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BACKGROUND: Motor neuron degeneration and malnutrition alter body composition in amyotrophic lateral sclerosis (ALS). Resulting losses of weight, fat mass (FM), and fat-free mass (FFM) shorten survival. Nutritional management relies on body weight or BMI; neither reliably indicates malnutrition nor differentiates body compartments. OBJECTIVES: We aimed to 1) develop an equation to compute FM and FFM using clinical data, validated against DXA; and 2) examine the effect of computed FM and FFM on disease course and survival. METHODS: We studied 364 ALS patients from 3 cohorts. In Cohort #1 we used logistic regression on clinical and demographic data to create an equation (test cohort). In Cohort #2 we validated FM and FFM computed using this equation against DXA (validation cohort). In Cohort #3, we examined the effect of computed body composition on disease course and survival. RESULTS: In Cohort #1 (n = 29) the model incorporated sex, age, BMI, and bulbar-onset to create an equation to estimate body fat: % body fat = 1.73 – [19.80*gender (1 if male or 0 if female)] + [0.25*weight (kg)] + [0.95*BMI (kg/m(2))] − (5.20*1 if bulbar-onset or *0 if limb-onset). In Cohort #2 (n = 104), body composition using this equation, compared to other published equations, showed the least variance from DXA values. In Cohort #3 (n = 314), loss of body composition over 6 mo was greater in males. Adjusted survival was predicted by low baseline FM (HR: 1.39; 95% CI: 1.07, 1.80), and loss of FM (HR: 1.87; 95% CI: 1.30, 2.69) and FFM (HR: 1.73; 95% CI: 1.20, 2.49) over 6 mo. CONCLUSIONS: Our equation broadens the traditional nutritional evaluation in clinics and reliably estimates body composition. Measuring body composition could target FM as a focus for nutritional management to ensure adequate energy intake and complement measures, such as the ALS functional rating scale-revised score and forced vital capacity, currently used.

Introduction A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti-muscle-specific kinase (MuSK)-MG. Methods The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK-MG. Results Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12-1.53, P = 0.19). Discussion Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK-MG patients. Muscle Nerve 59:404-410, 2019.

We present a study of hydration in ALS patients and its effects on survival. This was a multicenter study over 48 weeks in 80 ALS patients who underwent 250 individual measurements using doubly labeled water (DLW). Total body water (TBW) and water turnover (a surrogate for water intake) were 3.4% and 8.6% lower, respectively, in patients compared to age- and gender-matched healthy controls, and both significantly decreased over study duration. In 20% of patients, water turnover measured over 10 d was 2 standard deviations below the mean value in healthy controls. In a separate clinic cohort of 208 patients, water intake estimated from a de novo equation created from common clinical endpoints was a prognostic indicator of survival. Regardless of nutritional state assessed by BMI, survival was two-fold longer in the group above the median for estimated water intake, suggesting that hydration may be a more important predictor of survival than malnutrition. Risk factors for poor hydration were identified. Water intake equations recommended by US Centers for Medicare and Medicaid Services in healthy elderly were inaccurate for use in ALS patients. We developed equations to estimate TBW and water intake in ALS patients for use in clinics to accurately estimate hydration and improve clinical care.

The purpose of this study was to evaluate a new care model to reduce chemotherapy-induced neuropathic symptoms. Neuropathic symptom usual care was prospectively compared to an automated symptom-monitoring and coaching system, SymptomCare@Home (SCH), which included nurse practitioner follow-up triggered by moderate to severe symptoms. Patients beginning chemotherapy were randomized to usual care (UC) or to the SCH intervention. This sub-analysis included only taxane/platin therapies. Participants called the automated telephone symptom-monitoring system daily to report numbness and tingling. The monitoring system recorded patient-reported neuropathic symptom severity, distress, and activity interference on a 0–10 scale. UC participants were instructed to call their oncologist for symptom management. SCH participants with symptom severity of ≥ 4 received automated self-care strategies, and a nurse practitioner (NP) provided guideline-based care. There were 252 participants, 78.6% of which were female. Mean age was 55.1 years. Mean follow-up was 90.2 ± 39.9 days (81.1 ± 40.3 calls). SCH participants had fewer days of moderate (1.8 ± 4.0 vs. 8.6 ± 17.3, p

Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P

The infectious dose of Listeria monocytogenes F5817, a serotype 4b human patient isolate, was determined following oral challenge in normal and compromised C57B1/6J mice. In an attempt to mimic human populations previously shown to be at risk to ingestion of L. monocytogenes , groups of mice used in this study consisted of the following: mice pretreated with hydrocortisone acetate or cimetidine; pregnant mice (12-14 d gestation); or beige mutants of C57B1/6J mice (deficient in lysosome production within monocytes and granulocytes). Mice were gavaged with varying levels of L. monocytogenes suspended in sterile 11% non-fat milk solids (NFMS). Upon expiration, the spleen, liver, lung, and brain were aseptically removed from mice. Organs were plated on LPM agar, and colonies were enumerated and biochemically confirmed as L. monocytogenes . Mice were considered infected if L. monocytogenes was recovered from at least one of the examined organs. In normal resistant C57B1/6J mice, the infectious dose 50 (ID50) ranged from 3.24-4.55 log10 CFU. In comparison, the ID50 for mice treated with 2.5 mg hydrocortisone acetate/day for 3d prior to infection decreased to 0.41 log10 CFU (range -1.91-2.74 log10 CFU). Administration of 0.25 mg hydrocortisone acetate/day for 3d prior to infection resulted in an ID50 similar to that calculated for normal mice. The ID50 calculated for pregnant mice was 2.48 log10 CFU, a value not significantly different from that of normal control mice. The response of beige mutants and cimetidine treated mice was comparable to that of normal controls, with ID50 values of 4.00 and 3.30 log10 CFU, respectively.

Milk from bulk tanks of 2,931 dairy herds were sampled and evaluated using trypticase blood-esculin agar, somatic cell, standard plate and preliminary incubation counts. Percent samples with trypticase blood-esculin agar counts >1 × 102 colony forming units/ml by organisms were Staphylococcus aureus , 33; Staphylococcus spp., 84; Streptococcus agalactiae , 47; esculin-positive streptococci, 72; coliforms, 73; and other microbes, 89. Trypticase blood-esculin agar counts were useful for identifying primary bacterial contaminants. Correlations were low between trypticase blood-esculin agar counts of specific bacterial groups and somatic cell, standard plate and preliminary incubation counts.

Objective The diagnosis of multiple sclerosis (MS) presently relies on radiographic assessments of imperfect specificity. Recent data using T2* methodology for the detection of the “central vessel sign” (CVS) in MS lesions suggests this novel MRI technique may distinguish MS from other disorders. Our aim was to determine if evaluation for CVS on 3T FLAIR* MRI differentiates MS from migraine. Methods Patients with MS or migraine and a prior brain MRI demonstrating at least two hyperintense lesions ≥3 mm were recruited. Exclusion criteria included any additional comorbidity known to cause brain MRI abnormalities. 3T MRI was performed in each participant with administration of gadopentetate dimeglumine, and FLAIR* images were generated in postprocessing. The total number of discrete ovoid lesions ≥3 mm were counted on FLAIR, per participant, and subsequently evaluated for presence of CVS on FLAIR*. An exploratory method evaluating for CVS in a maximum of 12 lesions per subject was also completed. Results Ten participants with MS and 10 with migraine completed the study. The median percentage (quartiles) of lesions in MS participants with CVS was 84 (79, 94) compared to 22 (15, 54) in migraine (P = 0.008). In a subanalysis by brain region, in the subcortical and deep white matter, the median percentage (quartiles) of lesions in MS participants with CVS was 88 (81, 100) compared to 19 (11, 54) in migraine (P = 0.004). This difference was not identified in juxtacortical, periventricular, or infratentorial regions. Interpretation Identification of CVS using FLAIR* on 3T MRI helps differentiate MS from migraine, particularly in the subcortical and deep white matter.

Objective:To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG).Methods:This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs.Results:Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005).Classification of evidence:This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20

Objective: To characterize patients misdiagnosed with multiple sclerosis (MS). Methods: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Results: Of 110 misdiagnosed patients, 51 (46%) were classified as “definite” and 59 (54%) “probable” misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Conclusions: Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.

Background: The use of air for the initial resuscitation of newborn infants has been shown to reduce neonatal mortality. However, a precise estimate of the neurodevelopmental status upon follow-up of infants resuscitated in air is lacking. Objective: To perform a meta-analysis of all studies reporting resuscitation of newborn infants with air or 100% oxygen that included follow-up data. Methods: Bibliographic databases were searched. In addition, we estimated the effect of loss to follow-up on our analysis of abnormal neurodevelopmental outcome. Results: We identified 10 studies in which newborn infants had been randomly or quasi-randomly assigned to resuscitation with air or 100% oxygen. Three of these 10 studies had available follow-up data. A total of 678 infants were enrolled at centers that performed follow-up of these infants. Of these, 113 died, leaving 565 infants potentially eligible for follow-up. A total of 414 children were evaluated (73% of eligible children; 195 resuscitated with air and 219 with 100% oxygen). In the air group, 12.8% of infants had an abnormal neurodevelopmental outcome, compared with 10.5% in the 100% oxygen group [typical relative risk (RR) 1.24, 95% confidence interval 0.73–2.10]. This is consistent with an RR of abnormal development as low as 0.41 or as high as 2.28. Conclusions: Long-term follow-up did not detect any significant differences in these two groups regarding abnormal development. However, the results are imprecise and could be consistent with significant harm or benefit.

The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight (ELBW) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age (PMA). Other important outcome measures, such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated.We conducted a multicenter randomized controlled double-blinded clinical study. The probiotics-supplementation (PS) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks (PMA). The control (C) group received unsupplemented feedings. Infant weight and feeding volumes were recorded daily during the first 28 days of study period. Weights were also recorded at 34 weeks PMA.A total of 101 infants were enrolled (PS 50 versus C 51). There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA (PS group 58% versus C group 60%, (P value 0.83)) or in the average volume of feeding during 28 days after study entry (PS group 59 ml kg(-1) versus C group 71 ml kg(-1), (P value 0.11)). Calculated growth velocity was higher in the PS group compared with the C group (14.9 versus 12.6 g per day, (P value 0.05)). Incidences of necrotizing enterocolitis (NEC), as well as mortality were similar between the two groups.Although probiotic-supplemented feedings improve growth velocity in ELBW infants, there was no improvement in the percentage of infants with growth delay at 34 weeks PMA. There were no probiotic-related adverse events reported.

Objective To determine whether buprenorphine maintenance alters intrapartum or postpartum pain or medication requirements. Methods Sixty three patients treated with buprenorphine for opioid dependence during pregnancy (vaginal n = 44; cesarean n = 19) were matched retrospectively to control women. Analgesic medication and pain scores (0–10) were extracted from the medical record. Primary endpoint: opioid utilization postpartum (oxycodone equivalents). Secondary endpoints: pain scores and intrapartum analgesia. Results There were no differences in intrapartum pain or analgesia. Following vaginal birth, buprenorphine maintained women had increased pain (buprenorphine 2.7 (1.7, 4.0); control 2.1 (1.2, 3.0), p = 0.006) but no increase in opioid utilization (buprenorphine: 11.8 ± 24.8; control 5.4 ± 10.4 mg/24 h, p = 0.10); following cesarean delivery both pain (buprenorphine: 5.1 (4.1, 6.1); control: 3.3 (2.5, 4.1), p = 0.009) and opioid utilization (buprenorphine: 89.3 ± 38.0, control: 60.9 ± 13.1 mg/24 h, p = 0.004) were increased. Conclusion Buprenorphine maintained women have similar intrapartum pain and analgesic needs during labor, but experience more postpartum pain and require 47% more opioid analgesic following cesarean delivery.

Background: Physicians and parents face significant uncertainties when making care decisions for extremely low birth weight (ELBW) infants. Many published estimates of death and developmental outcome are from well-funded university programs and may not reflect outcomes of infants from a variety of settings. The best estimates of the probabilities of death and severe disability combine local experience and published data. Objective: To describe the neurodevelopmental outcome of ELBW infants from centers of the ELBW Infant Follow-Up Group of the Vermont Oxford Network (VON) and to identify characteristics associated with severe disability. Methods: Predefined measures of living situation, health and developmental outcome were collected at 18–24 months’ corrected age for infants born from July 1, 1998 to December 31, 2003 with birth weights of 401–1,000 g at 33 North American VON centers. Logistic regression was used to identify characteristics associated with severe disability. Results: 6,198 ELBW infants were born and survived until hospital discharge; by the time of follow-up, 88 infants (1.4%) had died. Of the remaining 6,110 infants, 3,567 (58.4%) were evaluated. Severe disability occurred in 34% of the assessed infants. Multivariate logistic regression suggested cystic periventricular leukomalacia, congenital malformation and severe intraventricular hemorrhage were the characteristics most highly associated with severe disability. There were marked variations among the follow-up clinics in the attrition rate. Conclusion: ELBW infants completing evaluation were at a high risk for severe disability. There are considerable differences among participating centers in attrition at follow-up. Further resources will be needed to study the effect of follow-up care for this group of infants.

To determine whether methadone maintenance alters intrapartum or postpartum pain or medication requirements.Sixty-eight patients treated with methadone for opiate dependence during pregnancy (vaginal n=35; cesarean n=33) were matched retrospectively to control women. Analgesic medication and pain scores (0-10) were extracted from the medical record. The primary endpoint was opiate use postpartum (oxycodone equivalents). The secondary endpoints were pain scores and intrapartum analgesia.There were no differences in intrapartum pain or analgesia. After vaginal birth, methadone-maintained women experienced increased pain (methadone, 2.7 [1.9-5.0]; control, 1.4 [0.5-3.0], P=.001) but no increase in opiate use ([mean+/-standard deviation] methadone 12.7+/-32.1; control 6.8+/-12.7 mg/24 h, P=.33); after cesarean delivery both pain (methadone, 5.3 [4.1-6.0]; control, 3.0 [2.2-3.9], P=.001) and opiate use (methadone, 91.6+/-51.8; control, 54.0+/-18.6 mg/24 h, P=.001) increased.Methadone-maintained women have similar analgesic needs and response during labor, but require 70% more opiate analgesic after cesarean delivery.II.

Objectives. To determine the accuracy of knowledge of different health care providers regarding survival and long-term morbidity rates for very premature infants and to examine whether a focused educational intervention improves the accuracy of this knowledge and influences health care decisions.Methods. Using hypothetical case scenarios with infants at ≤28 weeks of gestation, we surveyed a variety of caregivers involved in perinatal communication and decision-making processes at a tertiary center that provides intensive care for neonates. We asked physicians from the pediatrics and obstetrics services and nurses and nurse practitioners from the NICU and obstetrics ward for their best estimates of survival and major long-term disability rates and for their opinions regarding the appropriateness of resuscitation and life support at each week of gestation of Results. Fifty-one health care providers were involved in the baseline survey. The response rates for the postintervention survey were 100% for physicians (20 of 20 subjects) and nurses (20 of 20 subjects) and 91% (10 of 11 subjects) for the nurse practitioners. In the baseline survey, statistically significant underestimates of survival rates were seen for physicians and nurses at 23 to 28 weeks of gestation and for nurse practitioners at 23 to 27 weeks of gestation. Statistically significant overestimates of disability rates were seen for physicians and nurse practitioners at ≤26 weeks of gestation and for nurses at ≤28 weeks of gestation. After the intervention, respondents demonstrated significant improvements in the accuracy of survival and disability estimates at many, but not all, gestational ages. Although underestimation of survival rates and overestimation of disability rates decreased after the intervention, it persisted to some degree. After the intervention, a larger proportion of physicians (53% vs 21%) and a smaller proportion of nurses (10% vs 37%) were likely to recommend resuscitation for infants born at 23 weeks of gestation.Conclusions. Physicians, nurses, and nurse practitioners underestimated survival rates and overestimated long-term disability rates for very premature infants. After education, their estimates of survival and long-term disability rates for these infants improved significantly. More accurate estimates of survival and disability rates affected physicians' and nurses' theoretical decision-making regarding the appropriateness of resuscitation at 23 weeks of gestation.

OBJECTIVE To determine whether a single outpatient dose of intravaginal misoprostol (versus intracervical dinoprostone gel) reduces the oxytocin use for induction. Despite the numerous trials examining misoprostol for induction, the efficacy of a single outpatient dose of misoprostol followed by oxytocin induction is unknown. METHODS Patients with a term, vertex, singleton pregnancy and a Bishop score of 6 or less were randomly assigned to receive misoprostol (n = 42, 0.25 microg intravaginally) or dinoprostone gel (n = 42, 0.5 mg intracervically) the evening before oxytocin induction. Patients were monitored for 3 hours after administration and discharged to home if fetal assessment was reassuring, for readmission the next morning for oxytocin. Primary outcomes were oxytocin dose, time, and dose intensity (dose divided by duration). Secondary outcomes were incidence of labor, uterine hyperstimulation, cesarean delivery, Apgar score. Statistics used were chi(2), Student t test, Mann-Whitney rank sum test, and Fisher exact test. P < .05 was accepted as statistically significant. RESULTS A single dose of misoprostol significantly decreased the cumulative dose of oxytocin, the cumulative time of oxytocin administration, and the dose intensity of oxytocin (dose divided by time). Data are as follows (mean +/- standard error of the mean): oxytocin dose-dinoprostone 10,929 +/- 219 mU, misoprostol 6,081 +/- 170 mU, P = .008; oxytocin time-dinoprostone 798 +/- 11 minutes, misoprostol 531 +/- 11 minutes, P = .009; dose intensity-dinoprostone 11.3 +/- 0.1 mU/min, misoprostol 7.4 +/- 0.2 mU/min, P = .003. Misoprostol induced labor during the ripening period in 19 of 41 of patients, compared with 6 of 42 after dinoprostone (P = .002). There was no difference in cesarean delivery (dinoprostone, 8/42; misoprostol, 9/42; P = 1.00). There was no difference in short-term neonatal outcome. No patient had hyperstimulation or required cesarean delivery for nonreassuring fetal assessment during the ripening period. CONCLUSION A single dose of misoprostol administered in the outpatient setting significantly decreases oxytocin use, largely due to labor within the ripening period.

Although i.v. t-PA has proven successful in reducing neurologic deficits in acute ischemic stroke, the disadvantages of a narrow therapeutic time window and the failure of thrombolysis in more than 50% of patients treated have necessitated an examination of adjuvant therapies to improve the rate of thrombolysis. Experimentally, the combination of aspirin therapy with t-PA has resulted in a paradoxical antagonism of thrombolysis. Reversal of this antagonism with nitric oxide (NO) donors suggested that aspirin may inhibit/ antagonize NO-related mechanisms. Using this rabbit model of thromboembolic stroke, this hypothesis is now expanded to compare two clinically relevant anti-hypertensive agents, atenolol (NO-dependent) and hydralazine (NO-independent), for their ability to improve t-PA-mediated clot lysis following aspirin pre-treatment. Thirty rabbits (10 per group) were pre-treated with aspirin (20mg kg(-1), i.v.) and then randomized to receive either vehicle, atenolol (20 microg kg(-1) h(-1), i.v.) or hydralazine (10 microg kg(-1) min(-1), i.v.) beginning 30 min following autologous clot embolization. All rabbits then received t-PA (6.3 mg kg(-1), i.v.) beginning 1 h after embolization, with completion of the protocol 4 h after embolization. Aspirin therapy reduced regional cerebral blood flow (rCBF) from 82.8m +/- 4.7 to 62.5 +/- 6.6 (n = 30; p = 0.0005). In the aspirin control group only 30% (3 of 10) rabbits demonstrated complete clot lysis, whereas the combined atenolol (60%) and hydralazine (70%) groups experienced a clot lysis rate of 65% (13 of 20 rabbits), similar to clot lysis rates previously observed with t-PA alone. In a separate series of experiments, all agents able to reverse aspirin antagonism of thrombolysis demonstrated an improvement in rCBF, suggesting a common mechanism for this diverse group of agents in reversing aspirin's antagonism of thrombolysis.

OBJECTIVE: Activated polymorphonuclear leukocytes (PMNs) have been suggested to contribute to the development of increased intracranial pressure (ICP). We recently demonstrated that human PMNs produce a novel cytochrome P450-derived arachidonic acid metabolite, 1 6(R)-hydroxyeicosatetraenoic acid [16(R)-HETE], that modulates their function. It was thus of interest to examine this novel mediator in an acute stroke model. METHODS: 16-HETE was assessed initially in a variety of human PMN and platelet in vitro assays and subsequently in an established rabbit model of thromboembolic stroke. A total of 50 rabbits completed a randomized, blinded, four-arm study, receiving 16(R)-HETE, tissue plasminogen activator, both, or neither. Experiments were completed 7 hours after autologous clot embolization. The primary end point for efficacy was the suppression of increased ICP. RESULTS: In in vitro assays, 16(R)-HETE selectively inhibited human PMN adhesion and aggregation and leukotriene B4 synthesis. In the thromboembolic stroke model, animals that received 16(R)-HETE demonstrated significant suppression of increased ICP (7.7 +/- 1.2 to 13.1 +/- 2.7 mm Hg, baseline versus final 7-h time point, mean +/- standard error), compared with either the vehicle-treated group (7.7 +/- 0.9 to 15.8 +/- 2.6 mm Hg) or the tissue plasminogen activator-treated group (7.6 +/- 0.6 to 13.7 +/- 2.1 mm Hg). The group that received the combination of 16(R)-HETE plus tissue plasminogen activator demonstrated no significant change in ICP for the duration of the protocol (8.6 +/- 0.6 to 11.1 +/- 1.2 mm Hg). CONCLUSION: 16(R)-HETE suppresses the development of increased ICP in a rabbit model of thromboembolic stroke and may serve as a novel therapeutic strategy in ischemic and inflammatory pathophysiological states.

Increased platelet reactivity is a descriptor of the risk of cardiovascular events in healthy men and in patients with overt coronary artery disease. We sought to determine if differential thresholds exist for activation of platelets with respect to alpha-granule degranulation and fibrinogen binding in healthy volunteers and in patients with acute coronary syndromes. We also sought to characterize the effect of aspirin on activation. Platelet activation was assessed with flow cytometry in whole blood anticoagulated with corn trypsin inhibitor and incubated with fluorescein isothiocyanate conjugated fibrinogen (to define activation of glycoprotein IIb-IIIa), a phycoerythrin conjugated antibody to P-selectin (a marker of alpha-granule degranulation), and selected concentrations of adenosine diphosphate (ADP) or thrombin receptor agonist peptide. ADP-induced fibrinogen binding was found to be a low threshold activation event (40% of platelets bound fibrinogen in response to 0.2 microM ADP). Alpha-granule degranulation was a higher threshold event (33% of platelets expressed P-selectin in response to 1.0 microM ADP). Intra- and interindividual variability were most apparent with low concentrations of agonist (0.2 microM ADP). Patients with acute coronary syndromes (on aspirin) had significantly increased P-selectin expression in response to ADP compared with healthy subjects (on aspirin), but no difference in ADP-induced fibrinogen binding was observed. Daily ingestion of 325 mg of aspirin had no effect on either P-selectin expression or fibrinogen binding in healthy subjects. Analysis of platelet reactivity with flow cytometry characterizes activation with respect to specific components of the process and should facilitate development and optimal titration of antiplatelet therapy.

Background: The measurement of exposure to war in large epidemiological studies necessitates the use of easily administered and reliable questionnaires that cover a range of war events. The War Event Questionnaire (WEQ) was designed by our group to address these issues and has proved to be quite easy to administer. The aim of this study is to establish the inter-rater reliability of the WEQ. Method: Two trained interviewers alternated in administering parts I and II of the WEQ. Results: The Kappa statistics used to calculate the degree of agreement between the two raters ranged from 0.281 to 0.774 for part I events and from 0.189 to 1.000 for part II events. Conclusion: The WEQ has proved to be a useful instrument that addresses both objective and the subjective war experiences; it is a fairly reliable instrument and has helped us avoid tautological assessment of the mental health effects of war.

Objectives. To determine whether augmented activation (degranulation) of platelets might contribute to the association between higher concentrations of fibrinogen and risk of myocardial infarction, we characterized adenosine diphosphate (ADP)-induced expression of P-selectin by platelets in whole blood as a function of this exposure to selected concentrations of fibrinogen. Background. An increased risk of myocardial infarction has been associated with increased concentrations of fibrinogen. Methods. Fibrinogen was added to blood anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa without effect on other coagulation factors). Degranulation of platelets was identified by flow cytometry. Results. Addition of fibrinogen to blood did not activate platelets under basal conditions (without ADP). By contrast, a concentration-dependent increase in ADP and thrombin receptor agonist peptide (TRAP)-induced activation occurred with increasing concentrations of fibrinogen. Increased ADP-induced degranulation was apparent with the addition of 100 mg/dl of fibrinogen (p ≤ 0.001 for 1.5 μmol/liter ADP, n = 10 subjects). Inhibition by abciximab of binding of fibrinogen to the surface glycoprotein IIb-IIIa did not attenuate the observed augmentation of reactivity induced by fibrinogen. Augmented degranulation was associated with uptake of fibrinogen into α-granules without surface binding despite pretreatment with abciximab as shown by laser scanning confocal microscopy. Conclusions. Fibrinogen in blood augments degranulation of platelets in response to ADP and is accompanied by uptake of fibrinogen into α-granules. Thus, elevated concentrations of fibrinogen secondary to inflammation implicated in cardiovascular risk may operate, in part, by increasing reactivity of platelets.

BACKGROUND: Observational studies on pediatric anesthesia neurotoxicity have been unable to distinguish long-term effects of general anesthesia (GA) from factors associated with the need for surgery. A recent study on elementary school children who had received a single GA during the first year of life demonstrated an association in otherwise healthy children between the duration of anesthesia and diminished test scores and also revealed a subgroup of children with “very poor academic achievement” (VPAA), scoring below the fifth percentile on standardized testing. Analysis of postoperative cognitive function in a similar cohort of children anesthetized with an alternative to GA may help to begin to separate the effects of anesthesia from other confounders. METHODS: We used a novel methodology to construct a combined medical and educational database to search for these effects in a similar cohort of children receiving spinal anesthesia (SA) for the same procedures. We compared former patients with a control population of students matched by grade, gender, year of testing, and socioeconomic status. RESULTS: Vermont Department of Education records were analyzed for 265 students who had a single exposure to SA during infancy for circumcision, pyloromyotomy, or inguinal hernia repair. Exposure to SA and surgery had no significant effect on the odds of children having VPAA. (mathematics: P = 0.18; odds ratio 1.50, confidence interval (CI), 0.83–2.68; reading: P = 0.55; odds ratio = 1.19, CI, 0.67–2.1). There was no relationship between duration of exposure to SA and surgery and performance on mathematics (P = 0.73) or reading (P = 0.57) standardized testing. There was a small but statistically significant decrease in reading and math scores in the exposed group (mathematics: P = 0.03; reading: P = 0.02). CONCLUSIONS: We found no link between duration of surgery with infant SA and scores on academic achievement testing in elementary school. We also found no relationship between infant SA and surgery with VPAA on elementary school testing, although the CIs were wide.

This article examines the effect of war events and pre-war depression on the prevalence of major depression during war. A total of 658 subjects aged 18-65 years were randomly selected from four Lebanese communities differentially exposed to the Lebanon Wars and were interviewed using the Diagnostic Interview Schedule (Arabic version). The individual levels of exposure to war events were assessed through a War Events Questionnaire. The lifetime prevalence of the DSM-III-R-defined major depression varied across the four communities from 16.3 to 41.9%; the final parameters predicting major depression since the onset of the wars were: depression before the wars and exposure to the wars. Both, individual levels of exposure to war and a history of pre-war depression, predict the development of depression during war.

A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue T-lymphocyte infiltrates, versus a nonspecific infiltrate, reflect a response to the causative agent. Lyme arthritis can histologically resemble rheumatoid synovitis, particularly the prominent infiltration by T lymphocytes. This has raised speculation about whether Lyme synovitis represents an ongoing response to the causative spirochete, Borrelia burgdorferi , or rather a self-perpetuating autoimmune reaction. In an effort to answer this question, the present study examined the repertoire of infiltrating T cells in synovial fluid from nine Lyme arthritis patients, before and after stimulation with B. burgdorferi . Using a highly sensitive and consistent quantitative PCR technique, a comparison of the T-cell antigen receptor (TCR) β-chain variable (Vβ) repertoires of the peripheral blood and synovial fluid showed a statistically significant increase in expression of Vβ2 and Vβ6 in the latter. This is remarkably similar to our previous findings in studies of rheumatoid arthritis and to other reports on psoriatic skin lesions. However, stimulation of synovial fluid T cells with B. burgdorferi provoked active proliferation but not a statistically significant increase in expression of any TCR Vβ, including Vβ2 and Vβ6. Collectively, the findings suggest that the skewing of the TCR repertoire of fresh synovial fluid in Lyme arthritis may represent more a synovium-tropic or nonspecific inflammatory response, similar to that occurring in rheumatoid arthritis or psoriasis, rather than a specific Borrelia reaction.

The hypothesis that neutrophil activation exacerbates brain injury in acute stroke is currently receiving wide acceptance. However, the temporal relationship of neutrophil activation to the ischemic event in clinical states is not clear. Therefore, this study was undertaken to examine human neutrophil activation by the technique of luminol-dependent chemiluminescence in both acute bland and hemorrhagic stroke. Patients (bland, n = 18; hemorrhagic, n = 16) were entered into this study within six hours of the ictus. These results were compared to other clinical central nervous system insults: subarachnoid hemorrhage (n = 11), spinal trauma (n = 9) and isolated closed head injury (n = 19). All subjects were sampled upon presentation to the emergency room and 0.5, 1, 2, 3, 4 and 5 days following the event. Neutrophil activation, as determined by luminol-dependent chemiluminescence, was evident at day 1 following the ictus in the bland stroke group (p < 0.05), although this trend was not demonstrated for hemorrhagic stroke. Patients suffering a closed head injury demonstrated greater initial neutrophil activation with values being significantly lower than baseline at days 0.5 (p = 0.01) and 1 (p = 0.05). No significant change was demonstrated for the groups with spinal trauma or subarachnoid hemorrhage. These results support a role for neutrophil activation during various central nervous system insults and provide a temporal framework for considering drug therapy directed at transient suppression of neutrophil function.

Randomized trials of thrombolytic therapy in stroke have reported an improvement in neurologic outcome; however, the addition of aspirin has resulted in a significant increase in mortality and antagonism of clot lysis in clinical and animal studies, respectively. This finding is in contradistinction to the known synergy in mortality reduction for aspirin and thrombolytics in myocardial infarction. It is hypothesized that aspirin antagonism of clot lysis is related to inhibition of nitric oxide (NO) and may be reversed by providing a source of NO. Twenty rabbits were treated with aspirin (20 mg/kg, i.v.) prior to internal carotid clot embolization. One-half hour following embolization, rabbits were randomized to receive vehicle (n = 5), the NO precursor L-arginine (300 mg/kg, i.v. bolus at 0.5 and 2.5 h postembolus; n = 5), or a nitric oxide donor (nitroprusside, 1 mg/kg/h, i.a., or nitroglycerin, 10 microg/kg/min, i.v., n = 5 each agent). Tissue plasminogen activator (t-PA) (6.3 mg/kg) was administered from 1 to 3 h after embolization. Lysis of the tin-tagged clot was followed with serial X rays and gross examination. No rabbit in the control group experienced complete clot lysis. However, 2 of 5 rabbits in the L-arginine group and 6 of 10 rabbits in the nitric oxide donor (nitroprusside and nitroglycerin) groups noted complete clot lysis (P < 0.05, Fisher exact test). Thus, administration of an NO donor (nitroglycerin or nitroprusside) and, to a lesser extent L-arginine, reversed aspirin's antagonism of t-PA thrombolysis. This study may help explain the discrepant results seen with aspirin and thrombolytics.

This study investigated the efficacy and safety of delayed therapy with tissue-plasminogen activator (t-PA) in a rabbit model of thromboembolic stroke. The t-PA therapy was started 3, 4, or 5 hours after autologous clot embolization. New Zealand rabbits were randomized to receive a 2-hour intravenous infusion of either t-PA (6.3 mg/kg) or a saline solution (0.9% saline) after an autologous clot had embolized the anterior cerebral circulation. Regional cerebral blood flow (rCBF), intracranial pressure (ICP), and infarct size were measured to determine the effects of the delayed administration of the t-PA after intracranial embolization. Additionally, the following physiological parameters were monitored throughout the protocol: mean arterial pressure, hematocrit, arterial blood gases, glucose, and core and brain temperatures. All animals were studied for 4 hours after the administration of the t-PA or control solution; thus, the duration of each experiment was 7, 8, or 9 hours after autologous clot embolization. In control animals, brain infarct size and final ICP values were directly related to the length of time studied after clot embolization; among control animals, the largest infarct size and greatest rise in ICP were seen 9 hours after embolization. The start of the t-PA therapy 3 hours after clot embolization was associated with a trend toward smaller mean brain infarct size (31.6±6.4% [n=10] versus 44.2±8.6% [n=10] of the infarcted hemisphere; the mean±the standard error of the mean) and a significantly lower mean ICP (15.5±2.8 versus 22.0±3.1 mm Hg, P=0.02). A trend toward restoration of rCBF was also noted with the t-PA therapy given 3 hours after embolization. No benefit was noted for any parameter studied (ICP, infarct size, or rCBF) with further delay to the t-PA therapy (4 or 5 h). In the group receiving t-PA 4 hours after embolization, ICP (measured 8 h after embolization) was significantly higher (31.3±5.2 versus 21.6±2.6 mm Hg, P=0.01), although no significant difference in ICP was detected between the two groups at 9 hours after embolization. In this rabbit model of thromboembolic stroke, the administration of t-PA 3 hours after autologous clot embolization was associated with a reduction in brain injury. Despite significant clot lysis by t-PA in all groups, no benefit was noted when the t-PA therapy was delayed longer (4-5 h after embolization); no return of rCBF was noted in the t-PA group at 9 hours after embolization

Predicting individuals at risk for fracturing and modifying that risk are important in preventative health. Our aim was to quantify the impact of spine bone mineral density (BMD) on fracture risk prediction and determine the positive predictive value of fracture prediction using the lowest BMD value at the femoral neck, total hip, or lumbar spine. A retrospective cross-sectional analysis of 15,033 women was performed, assessing the contribution of age, body mass index, number of clinical risk factors, T-score, and osteoporosis category to the presence of fracture. In patients whose lumbar spine T-scores are 1 or 2 osteoporosis categories lower than femoral neck, there is an approximately 30% increased risk of fracture compared with the femoral neck alone. For patients younger than 60 years, the odds ratio of having a fracture based on the presence of lumbar spine osteoporosis was greater than that based on femoral neck osteoporosis. Osteoporosis at the total hip correlated best with the presence of fracture. When using FRAX, we recommend that the 10-yr fracture prediction be adjusted when lumbar spine T-score is 1-2 osteoporosis categories lower than the femoral neck T-score or when lumbar spine T-score is ≥1 standard deviation less than femoral neck T-score.

The goal of this study was to determine whether improved access to medication assisted therapy in the general population, with improved coordination of ancillary services for pregnant women, improved perinatal outcomes in a nonurban area.The cohort of women treated for opioid dependence during pregnancy with medication-assisted therapy and delivered at a single institution between 2000 and 2006 were retrospectively identified (n = 149 women; n = 151 neonates). Access to opioid agonist therapy for the general population was determined as the combined number of available treatment positions for medication-assisted therapy. Treatment during pregnancy (interim substitution therapy vs opioid treatment program) and pregnancy outcomes were noted from chart review. The primary outcome of trend of prenatal care indices and newborn birth weight over time was determined by Kendall's tau.As access to treatment in the general population expanded from 2000 to 2006, the number of women receiving treatment increased, the proportion of women receiving interim substitution therapy decreased (P0.001), gestational age at the initiation of treatment decreased (P0.001), and the proportion of women receiving treatment before pregnancy increased (P0.001). Infants delivered to mothers in a treatment program had improved birth weight z score compared with those receiving interim substitution therapy (P = 0.007). The proportion of infants discharged to the care of the mother and remaining in maternal care at 1 year improved both over time (P = 0.03; P = 0.004) and with treatment within a treatment program (P0.001; P = 0.004).Improved access to opioid agonist treatment programs for the general population in nonurban areas improves perinatal outcome and retention of maternal guardianship.

Transforming growth factor-beta 1 (TGF-beta 1), suggested in some studies to suppress astrocyte and neutrophil function, has also reduced ischaemic brain injury when administered immediately prior to clot embolization in models of thromboembolic stroke. The effect of TGF-beta 1 as a post-treatment paradigm was investigated in a rabbit model of thromboembolic stroke. Following clot embolization, regional cerebral blood flow fell to10 cc 100 g-1 min-1 in all animals. TGF-beta 1 (10 micrograms) or vehicle (n = 5 each group) was infused via the contralateral carotid artery. TGF-beta 1 administration resulted in a rapid and selective reduction in the peripheral neutrophil count as compared to a significant (p0.05) increase in control values (2336 +/- 817 vs 4320 +/- 928 neutrophils mm3, mean +/- SEM). Neutrophil aggregation was increased within 30 min of TGF-beta 1 infusion when compared to control (2.07 +/- 0.70 vs 1.09 +/- 0.17 ohms, p0.05); neutrophil chemiluminescence, an index of the oxygen respiratory burst was not significantly affected by TGF-beta 1 administration. No difference in platelet counts or aggregation was noted. There was no significant difference between the two groups regarding brain infarct size (47.5 +/- 10.9 vs 56.5 +/- 10.4, n = 4, TGF-beta vs control, mean +/- SEM), intracranial pressure, or brain excitatory amino acid levels (aspartate and glutamate) within ischaemic regions.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE To determine if the T cell antigen receptor V beta usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB). METHODS Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for V beta gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 V beta primers with a constant region C beta primer, and 2 C alpha primers that co-amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer. RESULTS There were consistent differences between the V beta gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA-DR haplotype. In all synovial specimens, V beta 2 was increased relative to the peripheral blood, while V beta 13.1 and V beta 13.2 were decreased. V beta 6 and V beta 21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF V beta bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, V beta gene usage of separated CD4+ and CD8+ synovial T cells showed that V beta 2 and V beta 6 were more highly expressed on CD4 cells. CONCLUSION Freshly isolated synovial T cells from inflamed (not end-stage) knees of patients with RA have a remarkably consistent biased V beta gene usage compared with PB T cells. V beta 2 and V beta 6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same V beta bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response.

The aim of this study was to examine the effect of transforming growth factor-beta 1, a cytokine shown to amelioriate cardiac ischemia, in a rabbit model of thromboembolic stroke. An autologous clot embolus was introduced intracranially through the right internal carotid artery in 21 New Zealand White rabbits, with seven in each group receiving either vehicle control (albumin) or 10 or 50 micrograms transforming growth factor-beta 1 administered as an intracarotid bolus immediately before autologous clot embolization. Multiple physiological parameters were monitored, including regional cerebral blood flow, arterial blood gases, hematocrit, glucose, core temperature, and mean arterial pressure. The brain was harvested 4 hours after embolization, and infarct size was determined planimetrically as a percentage of the entire hemisphere. Brain infarct size was reduced in both the 10-microgram (16.7 +/- 4.0% [mean +/- SEM], p < 0.05) and 50-microgram (21.7 +/- 4.5%) transforming growth factor-beta 1-treated groups when compared with the control group (31.9 +/- 6.6%). Regional cerebral blood flow did not show any significant intergroup or intragroup variation over time, although the 10-microgram transforming growth factor-beta 1 group experienced a greater return of cerebral blood flow in the first 2 hours after embolization. Transforming growth factor-beta 1 reduced brain infarct size in a rabbit model of thromboembolic stroke. This effect was not related to a direct effect on blood flow. Studies are ongoing to determine the mechanism by which transforming growth factor-beta 1 salvages ischemic brain.

A 2-year study was conducted on the distribution of parasitoids of gypsy moth,Lymantria dispar (L.) (Lep.: Lymantriidae), in mesic and adjacent higher elevation transition and xeric forest habitats in Vermont (U.S.A.). In both years, overall parasitism ranged from 12–18% in each habitat. When analyzed according to the life stage at which the host was collected, parasitism rates of greater than 40% were obtained among the late instars.Parasetigena silvestris (Robineau-Desvoidy) andPhobocampe disparis (Viereck) were recovered most commonly from the mesic habitat, andCotesia melanoscelus (Ratzeburg) andBlepharipa pratensis (= Sturmia scutellata) (Meigen) were most common in collections from the xeric area. Parasitism byCompsilura concinnata (Meigen) occurred at similar levels in all three habitats, and this species was responsible for the highest parasitism rates on the site, reaching 40% among the late instars in 1985. Percent parasitism byC. concinnata increased three-four-fold from 1984 to 1985, while parasitism by other species declined.

Both cell-wall chemistry and anatomical structure determine the digestion characteristics of cell types in forages. The objectives of this study were to determine the digestion kinetics of cell types apart from anatomical factors, and to relate these digestion kinetics to previously determined cell-wall constituents. Parenchyma and sclerenchyma cell walls, isolated from plant parts of orchardgrass (Dactylis glomerata L.) and switchgrass (Panicum virgatum L.) at four growth stages, were milled (digestion >150 µm) and incubated in buffered rumen fluid for 0 to 96 h. Lag time (L) of cell types ranged from 4.0 to 8.0 h, rate constant (k) from 0.035 to 0.100 h⁻¹, and indigestible residue (IR) from 89 to 595 g kg⁻¹. Differences between L of cell types were small. The k of parenchyma was ≈50% greater (P < 0.01) than that of sclerenchyma. The concentration of IR increased (P < 0.05) during plant maturation, particularly for stem cell types. The IR of orchardgrass parenchyma was less (P < 0.01) than that of sclerenchyma at immature growth stages, but not at late anthesis. In contrast, IR of switchgrass parenchyma was greater (P < 0.01) than that of sclerenchyma. Among cell types, IR concentrations were lowest (P < 0.05) for leaf sheath parenchyma and leaf blade sclerenchyma. The L and k of both cell types and IR of sclerenchyma were poorly correlated to neutral sugar, esterified phenolic acid, and lignin concentrations. The IR concentration of parenchyma was correlated (P < 0.01) with most cell-wall constituents, suggesting that fiber digestibility could be improved by altering the cell-wall composition of this cell type. The rate and extent of digestion of sclerenchyma was much greater than reported from histological studies, suggesting that the anatomical configuration of this cell type, rather than its cell-wall composition, is the major factor limiting its digestion. Contribution of the U.S. Regional Pasture Res. Lab. and the Dep. of Agronomy, The Pennsylvania State University.

Monthly bulk tank milk samples and veterinary records were analyzed for 1 yr on 15 Vermont dairy farms. Data were evaluated using ANOVA to compare effects of grazing management systems on milk quality and udder health. Systems evaluated were intensively managed rotational grazing, traditional continuous grazing, and confinement housing. Bulk tank samples were evaluated for standard plate count, bacterial type counts on tryptose-blood-esculin agar, and SCC. Veterinary records were evaluated for incidence of clinical mastitis, udder edema, and teat injuries. Within- and between-treatment group analyses were conducted by season, herd size, and udder sanitation systems. Mean standard plate counts were lower in rotationally grazed herds than counts of confined herds during the grazing season. Similarly, rotationally grazed herds with fewer than 60 cows had lower standard plate counts than confined herds of similar size. Mean bulk tank counts of streptococci other than Streptococcus agalactiae during the grazing season differed among treatments. The lowest counts occurred in rotationally grazed herds. Among herd using predip products recognized as efficacious, fewer streptococci other than S. agalactiae were isolated from bulk tank milk of rotationally grazed herds than confined herds. Rotationally grazed herds using postdips recognized as efficacious had lower SCC than those using unrecognized postdips. No udder health differences were observed among grazing treatments.

Quality of Vermont bulk tank milk was first surveyed in 1985 as part of a statewide milk quality enhancement program. In a second survey conducted in 1990, bulk tank milk from 1,971 farms was sampled and tested for standard plate count, bacterial type and species distribution, and somatic cell count. Test results from 1,203 duplicate bulk tank milk samples were compared between five Vermont milk processors and the University of Vermont Quality Milk Research Laboratory. Arithmetic mean standard plate count conducted by processors was 2.3 × 104 CFU/ml in 1990 compared with 3.0 × 104 CFU/ml in 1985 (Geometric mean went from 1.3 × 104 CFU/ml in 1985 to 1.1 × 104 CFU/ml in 1990). Trypticase blood-esculin agar was used at the Quality Milk Research Laboratory to determine distribution of bacteria types and species. Comparison of results with a 1985 survey appeared to demonstrate a reduction in the percentage of farms with Streptococcus agalactiae from 47% to 32%. Frequency of other organisms increased with the majority being environmental organisms. Arithmetic mean total raw bacteria count on blood agar was 1.9 × 104 CFU/ml. Correlation between standard plate count and blood agar raw bacteria count was low. Arithmetic mean somatic cell count appeared to decline from 5.4 × 105 cells/ml in 1985 to 3.4 × 105 cells/ml in 1990 (Geometric mean went from 4.1 × 105 cells/ml in 1985 to 2.9 × 105 cells/ml in 1990). Correlation between somatic cell counts conducted by milk processors and the Quality Milk Research Laboratory was high.

Mature sugar maples have been shown in a previous study to be consistent for sap sweetness when ranked against other trees in a population for many years. This study examined sap sweetness in young sugar maples in relation to basal area growth rates. A definite trend toward consistency for sap sweetness was found in young trees although there was greater variability than in mature trees. Reasons for this variability are postulated to be the continuing competitive growth of the younger trees and mortality due to natural causes and/or management. However, the trend toward consistency for sweetness warrants sap testing as a criterion in selecting potential crop trees for sap production. Annual correlations between sap sweetness and growth rates varied with no clear trend. North. J. Appl. For. 7(1):5-9, March 1990.

Background: In response to Gulf War veterans’ concerns of high rates of ALS, this investigation sought to determine if Gulf War veterans have an elevated rate of ALS. Methods: A nationwide epidemiologic case ascertainment study design was used to ascertain all occurrences of ALS for the 10-year period since August 1990 among active duty military and mobilized Reserves, including National Guard, who served during the Gulf War (August 2, 1990, through July 31, 1991). The diagnosis of ALS was confirmed by medical record review. Risk was assessed by the age-adjusted, average, annual 10-year cumulative incidence rate. Results: Among approximately 2.5 million eligible military personnel, 107 confirmed cases of ALS were identified for an overall occurrence of 0.43 per 100,000 persons per year. A significant elevated risk of ALS occurred among all deployed personnel (RR = 1.92; 95% CL = 1.29, 2.84), deployed active duty military (RR = 2.15, 95% CL = 1.38, 3.36), deployed Air Force (RR = 2.68, 95% CL = 1.24, 5.78), and deployed Army (RR = 2.04; 95% CL = 1.10, 3.77) personnel. Elevated, but nonsignificant, risks were observed for deployed Reserves and National Guard (RR = 2.50; 95% CL = 0.88, 7.07), deployed Navy (RR = 1.48, 95% CL = 0.62, 3.57), and deployed Marine Corps (RR = 1.13; 95% CL = 0.27, 4.79) personnel. Overall, the attributable risk associated with deployment was 18% (95% CL = 4.9%, 29.4%). Conclusions: Military personnel who were deployed to the Gulf Region during the Gulf War period experienced a greater post-war risk of ALS than those who were deployed to the Gulf.

Although there is considerable interest in the role of neutrophils and platelets in acute cerebral ischemia-reperfusion, there are very little data related to the effect of systemic thrombolytic therapy on these blood elements. In the present study a rabbit model was used to examine the effects of cerebral ischemia, tissue-plasminogen activator therapy, or both on neutrophil and platelet peripheral counts and activity, the latter studied by stimulated neutrophil and platelet impedance aggregation and neutrophil oxygen-free radical chemiluminescence. New Zealand white rabbits (n = 25) were randomized to receive either tissue-plasminogen activator (6.3 mg/kg IV; 20% bolus, remainder as a 2-hour infusion) or vehicle (0.9% saline) 3 hours following either autologous clot embolization or sham carotid artery isolation. Thus, four groups were examined: sham (n = 4), tPA only (n = 4), stroke only (n = 8), and stroke plus tPA (n = 9). Two hours after completion of thrombolytic therapy or vehicle infusion, the experiments were terminated, that is, 7 hours following autologous clot embolization or sham instrumentation. Blood was sampled from the thoracic aorta, and neutrophil and platelet peripheral counts and activity were determined prior to embolization and 0.5, 2.0, 4.0, and 7.0 hours following autologous clot embolization. No significant difference in platelet counts, either over time or between groups, was noted. In contrast to the platelet counts, the neutruphil count significantly increased over time, rising approximately 2.5-fold from baseline in all four groups (p0.001). No significant increase in neutrophil accumulation (myeloperoxidase assay; 10 (7) PMNs/g tissue; mean +/- SEM) was noted within infarcted regions of either the stroke (1.26 +/- 0.07; n = 5) or stroke plus tissue-plasminogen activator (1.26 +/- 0.09; n = 5) groups when compared to either viable brain regions within the ischemic hemisphere (1.29 +/- 0.03; n = 4) or in sham controls (1.36 +/- 0.35; n = 4). Neutrophil activity (aggregation, oxygen-free radical release) in both groups undergoing autologous clot embolization demonstrated a trend toward higher values when compared to the two sham-operated groups. Tissue-plasrninogen activator administration did not significantly affect ex vivo neutrophil activity. In contrast, platelet aggregation was significantly reduced by the administration of tPA with (p = 0.001) or without (p0.01) autologous clot embolization. Thus, in the present rabbit model platelet but not neutrophil activity is modulated by the administration of tissue-plasminogen activator, while autologous clot embolization results in a trend toward acute neutrophil activation.

{#article-title-2} Writ e Click correspondence this week includes an instructive exchange between author, commenter, and biostatistician regarding the need to control for type I error. In reference to the recent article by Newhouse et al., “Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial,” Dr. Gold warns of the possibility of type I error in the article's secondary outcomes analyses and against reading too much into the significant p values reported. The authors agree that, as an exploratory study, type I error was not controlled for as multivariate analysis would have been impractical. Our own …

The accuracy of using other free pools in lieu of tRNA for calculation of tissue protein synthesis in liver (L), skeletal muscle (SM), and heart (H) was assessed in six adult miniature swine using L-[1-13C]leucine and L-[ring-2H5]phenylalanine as tracers. L leucyl-tRNA enrichment was higher than arterial plasma leucine and ketoisocaproate (KIC) enrichments, and L phenylalanyl-tRNA enrichment was higher than arterial phenylalanine enrichment (P < 0.05). No such differences were noted in SM and H. Leucyl- and phenylalanyl-tRNA enrichments in L were best predicted by the respective amino acid enrichments in tissue fluid [TF; Leu: slope (m) = 0.954 +/- 0.035; Phe: m = 1.011 +/- 0.032] using linear regression analysis to determine the accuracy of the prediction, whereas plasma phenylalanine reasonably predicted phenylalanyl-tRNA (artery: m = 0.821 +/- 0.032; vein: m = 0.947 +/- 0.135). In SM, plasma KIC (artery: m = 0.846 +/- 0.046; vein: m = 0.881 +/- 0.043) and TF leucine (m = 0.788 +/- 0.034) predicted leucyl-tRNA with high accuracy. In H tissue, TF (m = 0.991 +/- 0.044) was the best predictor of leucyl-tRNA enrichment, whereas arterial phenylalanine (m = 0.912 +/- 0.015) was the most reliable predictor of phenylalanyl-tRNA enrichment. The relationships between aminoacyl-tRNA and other free pools in the same species under the same study conditions differ in different tissues. Use of KIC in lieu of leucyl-tRNA for calculating muscle protein synthesis is supported by this study.