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Since the first reported case in early December 2019, severe acute respiratory coronavirus 2 (SARS‐CoV‐2) infection, known as Coronavirus Disease 2019 (COVID‐19), has spread all over the world (1‐3). As of June 4th, more than 6 million cases and 350,000 deaths have been reported worldwide (4). Treating these patients and containing the outbreak has become the main priority in any center, arising the risk of possible collateral damage on patients with other acute diseases due to the collapse of the pre‐ and intra‐hospital emergency care systems.

Background Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with an increasing incidence and unknown aetiology. Aim To identify possible environmental and hormonal factors related to FFA. Methods We conducted a multicentre case-control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease. Results For women, there was a statistical association between alopecia and history of pregnancy (OR = 1.6; 95% CI 1.06-2.41), use of facial sunscreen (OR = 1.6; 95% CI 1.06-2.41) and hormone replacement therapy (HRT) (OR = 1.76; 95% CI 1.11-2.8) or raloxifene (no controls exposed therefore OR was not calculated), exposure to alkylphenolic compounds (OR = 1.48; 95% CI 1.05-2.08), and presence of rosacea (OR = 1.91; 95% CI 1.07-3.39), lichen planus pigmentosus (LPP) (OR = 5.14; 95% CI 1.11-23.6) or hypothyroidism (OR = 1.73; 95% CI 1.11-2.69). For men, there was a statistical association between alopecia and use of facial sunscreens (OR = 11.6; 95% CI 1.7-80.9) or antiageing creams (OR = 1.84; 95% CI 1.04-3.23). Conclusions FFA seems to be associated with hormonal exposure (pregnancy, HRT and raloxifene), comorbidities (hypothyroidism, LPP and rosacea) and environmental factors (facial sunscreens, antiageing creams and occupational exposure). Further research is required to analyse the exact mechanism in which these environmental factors participate in the development of this alopecia.

International audience; Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections. In this study, we have evaluated whether adult mice gestated in hypothyroid mothers have an altered response to pneumococcal pneumonia. We observed that female mice gestated in hypothyroidism have increased survival rate and less bacterial dissemination to blood and brain after an intranasal challenge with Strepto-coccus pneumoniae. Further, these mice had higher amounts of inflammatory cells in the lungs and reduced production of cytokines characteristic of sepsis in spleen, blood, and brain at 48 hours after infection. Interestingly, mice gestated in hypothyroid mothers had basally increased vascular per-meability in the lungs. These observations suggest that gestational hypothyroidism alters the immune response and the physiology of lungs in the offspring, increasing the resistance to respiratory bacterial infections.

BACKGROUND AND PURPOSE The aim of this study was to describe the clinical and epidemiological characteristics of acute ischaemic stroke (AIS) in patients with atrial fibrillation (AF) previously treated with oral anticoagulants (OACs) according to the type of OAC prescribed. Also, to analyze the outcomes of the patients and the therapeutic approach adopted by the neurologist in the acute phase and for secondary prevention. METHODS We performed a multicenter, observational study based on prospective registries. We included patients with AF treated with OACs admitted for AIS over a 1-year period. Detailed clinical data and functional outcome at 3 months (modified Rankin Scale score) were collected. Patients were divided into two groups according to their pre-AIS anticoagulant therapy: vitamin K antagonists (AIS-VKA) and direct-acting OACs (AIS-DOAC). RESULTS We recruited 1240 patients (80.4% AIS-VKA and 19.6% AIS-DOAC). In the AIS-DOAC group, transient ischaemic attack was more frequent (18.1% vs. 10.8%; P = 0.001), symptomatic hemorrhagic transformation was less frequent (1.6% vs. 4.6%; P = 0.035) and hospital stay was shorter (median 6 vs. 7 days; P = 0.03). Intravenous thrombolysis was more commonly used in AIS-VKA (9.2% vs. 1.6%; P

The relative frequency of the non-Hodgkin lymphoma (NHL) subtypes varies around the world. The objective of this study was to describe the general features of patients with lymphoma in Colombia. A total of 819 patients with a new diagnosis of lymphoma were included. Nighty-nine (12 %) of them had Hodgkin lymphoma (HL) and 720 (88 %) had NHL. Most cases had advanced stage disease at presentation (63.6 %). Diffuse large B cell lymphoma (DLBCL) was the most frequent diagnosis; it was seen in 40 % of patients with NHL and in 35 % of patients in the whole series. Overall survival rates at 3 years were 77 % for HL and follicular lymphoma, 54 % for DLBCL, and 45 % for T cell lymphomas. In conclusion, the distribution of specific NHL subtypes is similar to what has been reported previously in other tropical countries.

Background. TheworldwideseroprevalenceofhumanBKpolyomavirus(BKV)inadultsis 80%.About10%e60%ofrenaltransplantrecipientsexperienceBKVinfection,nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. Methods. An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10 7 copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. Results. Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10 7 copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3e7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. Conclusions. This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

Background and Purpose— Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. Methods— Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel–Haenszel test statistic. Results— We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74–1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74–1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25–1.27). Conclusions— This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.

This study examined the effects of implicitly presented odors on the emotional content of memory narratives. Participants were exposed to low levels of perfumes or no odors while they reconstructed a memory from childhood and a recurrent dream. Narratives were analyzed for emotional content using the Linguistic and Inquiry Word Count program. Exposure to perfumes increased the percentage of positive emotion words used by participants in recalling both dreams and childhood memories. In addition, exposure to odors decreased the percentage of negative emotion words that men used in their narratives, whereas the opposite effect was found for women. Discussion focuses on gender differences in written emotional expression, possible ways by which perfumes may exert their effects, and the usefulness of using ambient odors and objective content analysis when studying emotions in memories.

Markku Kaste ja Filip Scheperjans työryhmän jäsenenä. Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP 90, 60-90, and Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs. Am J Kidney Dis. 68(1): 94-102. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license.

Purpose The goal of this study was to determine differences in work beliefs between people with epilepsy who work and those who do not work. Methods One hundred thirteen subjects (58 females, 55 males) 41.56 ± 11.42 years of age and with a seizure duration of 22.88 ± 12.96 years (means ± SD) were assessed. Results Forty percent worked full-time, 10% worked part-time, and 50% did not work. Twelve of the fifty-six who worked had more than one seizure per month, compared with 29 of 57 who did not work. There were significant differences between the working and nonworking groups: The nonworking group believed that (1) they had to work to be “normal,” (2) they did not have enough education, (3) not having a job was the only barrier to independent living, (4) their families feared work injuries, (5) working represented a risk of injury, (6) they would hurt others if they had a seizure at work, (7) their families did not want them to work, and (8) seizures would negatively affect job performance. Conclusion Work beliefs are important factors contributing to work status.

Background: Plasma cortisol, β-endorphin, corticotropin, corticotropin-releasing factor, and salivary cortisol concentrations, resting and after ingestion of 1 mg of dexamethasone, were investigated in depressed patients and controls. Methods: Fourteen outpatients from the psychiatric department diagnosed with depressive disorder (ICD-10 Classification) participated in the study. The comparison group consisted of 12 healthy volunteers from the hospital staff. All hormones were measured using direct iodine-125 radioimmunoassay, except corticotropin-releasing factor, which included a sample preextraction and concentration step. Results: The basal plasma cortisol and corticotropin-releasing factor levels in depressive disorder were significantly higher than in the healthy group. After dexamethasone administration, corticotropin-releasing factor plasma values decreased significantly in the depressed group, but showed no significant changes in the controls. In depressive disorder baseline values correlated significantly for salivary cortisol and plasma cortisol, salivary cortisol and plasma corticotropin-releasing factor and plasma corticotropin and β-endorphin. Similar correlations were found in the healthy subjects, except for salivary cortisol and plasma corticotropin-releasing factor. Conclusions: These findings indicate that the increased corticotropin-releasing factor plasma concentrations demonstrated in depressive disorder reflect the hypothalamic corticotropin-releasing factor hypersecretion evidenced in this illness. Therefore, measurements of plasma corticotropin-releasing factor levels can be considered a reliable tool for investigating the role of this peptide in the pathophysiology of depression.

Adeno-associated viruses (AAVs) display a highly conserved NGR motif on the capsid surface. Earlier studies have established this tripeptide motif as being essential for integrin-mediated uptake of recombinant AAV serotype 2 (AAV2) in cultured cells. However, functional attributes of this putative integrin recognition motif in other recombinant AAV serotypes displaying systemic transduction in vivo remain unknown. In this study, we dissect the biology of an integrin domain capsid mutant derived from the human isolate AAV9 in mice. The AAV9/NGA mutant shows decreased systemic transduction in mice. This defective phenotype was accompanied by rapid clearance of mutant virions from the blood circulation and nonspecific sequestration by the spleen. Transient vascular hyperpermeability, induced by histamine coinjection, exacerbated AAV9/NGA uptake by the spleen but not the liver. However, such treatment did not affect AAV9 virions, suggesting a potential entry/post-entry defect for the mutant in different tissues. Further characterization revealed modestly decreased cell surface binding but a more pronounced defect in the cellular entry of mutant virions. These findings were corroborated by the observation that blocking multiple integrins adversely affected recombinant AAV9 transduction in different cell types, albeit with variable efficiencies. From a structural perspective, we observed that the integrin recognition motif is located in close proximity to the galactose binding footprint on AAV9 capsids and postulate that this feature could influence cell surface attachment, cellular uptake at the tissue level, and systemic clearance by the reticuloendothelial system.

Background: The aim of this work was to investigate alterations of plasma corticotropin-releasing factor (CRF) levels in depressive states. We have also measured plasma cortisol and corticotropin (ACTH) concentrations and examined their correlation with the peripheral CRF values. Methods: Thirty-six outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having major depressive disorder ( n = 26) and dysthymic depressive disorder ( n = 10) were studied. Among the major depressed patients, 10 suffered from severe depressive disorder and 16 from mild or moderate depressive disorder. The comparison group consisted of 17 healthy volunteers. Cortisol, ACTH, and CRF concentrations were determined by iodine-125 radioimmunoassay; CRF measurements were performed on C 18 extracted samples. Results: CRF and cortisol plasma concentrations were significantly higher in major depression and dysthymia than in the comparison group. The major depressed patients did not show significantly different CRF and cortisol levels than the dysthymic. Severe major depressive disorder exhibited significantly higher CRF plasma levels than the mild or moderate episodes. Plasma cortisol and CRF concentrations correlated significantly. Conclusions: The results obtained indicate that plasma CRF values are altered in depressive disorders and suggest that these determinations could be important for understanding the pathophysiology in affective illness.

Cholecystokinin (CCK) levels were measured in cerebrospinal fluid (CSF) of patients with adult chronic hydrocephalus syndrome (ACHS) (n = 16) and compared with levels from a control group (n = 11). The CSF concentration of CCK in the ACHS group (0.79 +/- 0.53 fmol/mL) was significantly reduced (p = .002) with respect to the controls (1.55 +/- 0.54 fmol/mL). As CCK-8, the most prevalent from of CCK in the central nervous system, has been demonstrated to play a significant role in several physiological and behavioral actions, the reduced octapeptide values found in ACHS could be involved in the disturbances associated with this disorder. Continuous monitoring of intracranial pressure (ICP) demonstrated different ICP profiles in ACHS. We found that all patients with abnormal ICP records except one showed CCK values under the detection limit. Three of the 4 patients with normal ICP had CCK levels within the normal range. These preliminary studies could evidence that ICP alterations are responsible for part of the loss of brain neuropeptide levels in ACHS.

Research is ongoing on eighteen cases of Legionellosis, including four deaths, identified among tourists and employees in a hotel in Calp, Spain. Cases occurred during a period of two months, indicating the possibility of a point-source transmission at the hotel. An environmental investigation identified several positive samples in the hotel, which as a precautionary measure, was closed until requested improvements were made. Surveillance measures currently remain active.

Sarcoidosis is a chronic multisystemic granulomatous disease of unknown origin. Generalised eruptive histiocytosis is a rare, benign, self-healing, non-Langerhans' cell histiocytosis (non-LCH). We report the case of an 8-year-old girl with sarcoidosis who was misdiagnosed as non-LCH. She was treated with oral corticosteroids, methotrexate and adalimumab, but there was insufficient control of ocular disease. The introduction of infliximab achieved a control of the uveitis and enabled the corticosteroid dose to be tapered. In some cases of sarcoidosis the lack of well-organised granuloma formation at the beginning of the disease, and the presence of prominent giant cells may suggest alternative diagnoses, such as non-LCH. Although the experience of tumour necrosis factor-α antagonists use in children with sarcoidosis is limited, these drugs may be helpful for those patients experiencing a severe and refractory disease.

To present the diagnostic process of CD Celiac disease among adults showing variable signs of nutritional derangements assisted at two tertiary-level health care institutions in Havana City (Cuba) between 2004 - 2007 for non-exhaustively characterized gastrointestinal disorders.Clinical, serological, histo-pathological and nutritional findings were integrated into an ad hoc created scoring system. Weight gain was monitored during the study observation window.Twenty-eight presumptive celiac patients were identified among those assisted. CD diagnosis was as follows: Confirmed: 17.9% (Score: 9.2 +/- 0.4); Highly likely: 60.7% (Score: 6.6 +/- 1.1); Non-conclusive: 32.1% (Score: 4.7 +/- 0.5); respectively. Ninety-two point eight percent of subjects were malnourished at the moment of the first interview. Total intestinal villi atrophy was observed in less than one-third of the identified celiac patients. Tittering of antibodies associated with CD was as follows: Anti-gliadin: Completed: 25; Positive: 72.0%; Anti-transglutaminase: Completed: 11; Positive: 54.5%. Nutritional replenishment actions comprised: Diet gluten withdrawal (100.0%); Vitamins and minerals prescription (92.9%); supplementary Enteral Nutrition (57.2%); and Parenteral Nutrition (21.4%). Weight gain was of 400 grams in 80.8% of CD patients after 33.7 days of follow- up; and of 700 grams in 13 of them after 321 days. The scoring system presented in this study could be useful for diagnosis and treatment of CD: a condition that keeps baffling physicians and nutritionists alike.

Nutrient Energy Malnutrition (NEM) is a common feature among liver cirrhosis (LC) patients, and might constitute a negative predictor of patient's survival. A prospective descriptive study was carried out in order to assess the influence of LC patient's nutritional status on the occurrence of complications and mortality in a tertiary care health institution in Havana City (Cuba). One-hundred twenty-one patients were recruited for the study (Women: 52.9%; Younger than 60 years: 59.0%; Whites: 90.0%). C virus infection, alcoholism, and B virus infection accounted for 71.0% of LC cases. Ninety-two percents of the patients had less than 5 yearse of diagnosis. Subjective Global Assessment (SGA) of nutritional status returned a 45.0% of malnutrition. Malnutrition was associated with disease progression: twenty-one percent of A Child-Pugh Stage patients was malnourished, but this rate increased to become 90.0% among those in C stage. Fat and skeletal muscle compartments were reduced in 36.0 and 37.0% of the patients, respectively. Complications affected 44.6% of the patients. Sixty percent of them were malnourished (p0.01). One-year mortality rate was 11.0%. Ninety-two percent of deceased patients were malnourished (p0.01). LC malnourished patients have greater risk of complications and death as compared to well-nourished ones.

The cerebral haemodynamic reserve (HR) is a recognised predictive factor of brain ischaemia in subjects with carotid stenosis. Our objective is to establish normal parameters which may be used for comparison with deficit states.The haemodynamic reserve was calculated in healthy subjects who had no evidence of previous carotid, haematological or cardiovascular pathologies. Subjects were asked to inhale CO2. The HR was then calculated as a percentage of the increase in the mean velocity in the Silvian artery for each millimetre of mercury increase of the end-tidal CO2. The median and percentiles 5 and 95 were calculated for each hemisphere, sex and age group.100 subjects were studied (45 men and 55 women, mean age 51.6 years, range 18-79). Normal HR value was defined as percentile 5, with a value of 2% for men, and 2.5% for women. The only adverse reaction was dyspnea in 2 subjects.Values for the haemodynamic reserve of healthy subjects, which may serve as a reference for other ultrasonography laboratories, are established from an extensive control group.

The aim of the study is to determine the effect of short-term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin-suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 +/- s.e.m. 2.14 vs. 17.6 +/- s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short-term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.

Cerebral vasospasm is involved in the development of delayed ischemic lesions in patients with subarachnoid hemorrhage. We developed an integral theoretical model to explain the pathophysiology of cerebral vasospasm, in which endothelin-1 has a pivotal role in the development of both cerebral vasospasm and delayed ischemic neurological deficits (DIND).The objective of this study is to analyze the relationship between temporal profile of plasma endothelin-1 levels and the development of cerebral vasospasm and DIND.We analyzed sequentially plasma endothelin-1 levels in 17 patients with aneurysmatic subarachnoid hemorrhage. All the patients had complete clinical and neuroradiological studies. Patients were classified according to Fisher's score.Patients (4 males and 13 females, aged 48.1 +/- 20.3 years) had a good clinical condition (Hunt-Hess4, GCS10). Two weeks after bleeding, patients had higher plasma endothelin-1 levels than healthy volunteers (p = 0.024). Patients who developed DIND had higher plasma endothelin-1 levels (p = 0.034) and a different evolution (p = 0.0146) than patients without DIND. There is a significant correlation (p = 0.02) between basal plasma endothelin-1 levels and GOS score. Multiple regression analysis shows a significant dependence between plasma endothelin-1 levels and Fisher's score (p = 0.0195), development of DIND (p = 0.0095), and GOS score (p = 0.0319). Logistic regression analysis finds a predictive relation between Fisher's score and plasma endothelin-1 levels for the development of DIND (overall predicted = 74.24%; p = 0.0148).Plasma endothelin-1 levels are increased in patients after subarachnoid hemorrhage and are associated with the development of cerebral vasospasm and DIND.

Experimental studies suggest that leptin may be an important metabolic signal for energy regulation. Aim: To assess whether surgical stress produces changes in serum leptin concentration and to investigate and compare the effect of total parenteral nutrition and hypocaloric parenteral nutrition on serum leptin levels. Patients and methods: Twenty-two surgical patients (11 male and 11 female) in need of parenteral nutrition were recruited. Parenteral nutrition was always initiated 24 h after surgical procedure. Group I ( n =15) received total parenteral nutrition, while Group II ( n =7) were treated with hypocaloric parenteral nutrition. Serum leptin concentration was determined before surgical procedure (day −1), after surgery and before parenteral nutrition was started (day +1), and after 5 days of treatment with parenteral nutrition (day +6). Results: A tendency to increase serum leptin levels was observed after surgical procedure (6.0±1.9 vs 9.9±2.7 ng/ml; P = 0.07). After starting parenteral nutrition no significant changes on serum leptin concentrations were found in both groups, but a trend to raise serum leptin was observed in Group I (6.2±1.7 vs 8.3±2.7 ng/ml) whereas a trend to decrease serum leptin was detected in Group II (4.6±2.5 vs 1.6±0.5 ng/ml). On day +6 an increase of serum leptin and insulin levels was observed in Group I in comparison with Group II (8.3±2.7 vs 1.6±0.5 ng/ml; P ⪡ 0.05 and 58±41 vs 12±15 μU/l; P ⪡ 0.05 respectively). Finally, a positive correlation at day +6 between insulin and serum leptin levels was observed ( r = 0.66; P ⪡ 0.01). Conclusions: a) Surgical stress is associated to an increase of serum leptin concentrations; b) Total and hypocaloric parenteral nutrition produces quite different effects on serum leptin levels that could be related to distinct insulin response.

A case of group A streptococcal meningitis is reported and the 51 cases reported in the literature since 1966 reviewed. A total of 24 men and 24 women were included in the study; the mean age (+/-SD) was 20.9+/-25.5 years. Fifty-eight percent of the patients had comorbid conditions, 80% had a distant focus of infection, and 65.8% had blood cultures positive for group A streptococci. Seventy-five per cent of the patients were treated with penicillin. The overall case-fatality rate was 12% (6 patients). Sequelae were more prevalent among children (44%) than among adults (7.7%) (OR=9.43; 95% CI, 1.02-438.95; P=0.03). Group A streptococcus is a rare cause of pyogenic meningitis, affecting mainly children or adults with comorbidity. Although the case-fatality rate is relatively low, neurological sequelae are frequent among survivors, especially children.

A 25-year-old female with transfusion-associated acquired immunodeficiency syndrome (AIDS) treated with zidovudine (AZT) developed cervical lymph node enlargement. The histological study disclosed granulomas and the culture revealed M. tuberculosis. The patient was treated with isoniazid, rifampicin and pirazynamide and the lymphadenomegaly resolved. Five years later, with a CD4 cell count of 245, the lymph node enlargement reappeared, the biopsy and special studies confirming tuberculosis (TB). She was then given ciprofloxacin, azithromycin, ethambutol, amikacin and pirazynamide without success. In two instances the enlarged nodes were surgically removed. Facing progressive obstruction of both the airway and the esophagus, localized radiotherapy (1800 cGy in nine fractions) to the right aspect of the neck was delivered with dramatic resolution of the node enlargement; however, dissemination of the infection leading to a severe lung infiltration and respiratory failure ended the life of the patient.

Immunoreactive neurokinin A was measured in the cerebrospinal fluid of twelve patients with Parkinson's disease and eleven normal subjects, using a sensitive and precise extraction/concentration radioimmunoassay method. The mean value obtained in Parkinson's disease patients (13.2 +/- 4.6 pmol/l) was lower than that of the controls (17.4 +/- 5.9). The tendency toward a significant decrease (p = 0.085) found in this preliminary study could indicate that neurokinin A containing neurons are involved in the pathophysiology of Parkinson's disease. In addition, the establishment of reference values for neurokinin A in cerebrospinal fluid may provide a basis for further studies of this neuropeptide in neurological disorders.

Objective: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. Method: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N= 9) or endogenous (N= 1 1) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-i 25 radioimmunoassay with commercial kit reagents. Results: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. Conclusions: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression. (Am J Psychiatry 1991; 148:505-508)

Recombinant interferon beta (IFN-beta ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 x 10(6) IU to 14 patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-beta ser appears to have activity in human glioma and is well tolerated at this dosage and schedule.

The cerebrospinal fluid neuropeptide Y level was measured by radioimmunoassay in 20 patients with probable Alzheimer's disease and in 19 controls. The mean level was lower in patients (69.5 +/- 36.7 pg/ml) than in controls (103 +/- 21.8 pg/ml; p less than 0.001). Patients with a disease duration of greater than 2 years had cerebrospinal fluid neuropeptide Y levels lower than those with shorter disease duration (p less than 0.02). These results suggest that neuropeptide Y containing cells may be involved in Alzheimer's disease. No correlation was found between neuropeptide Y levels and degree of cognitive impairment or age at disease onset.

Basal serum cortisol, growth hormone, prolactin and immunoreactive (IR) plasma beta-endorphin levels were measured in 31 depressed patients (14 endogenous, 17 nonendogenous) undergoing the dexamethasone suppression test. The endogenously depressed patients had significantly higher (22.55 +/- 1.34 micrograms/dl) predexamethasone cortisol levels than the nonendogenous patients (16.34 +/- 1.93 micrograms/dl). The mean serum prolactin and growth hormone values of these two groups were not significantly different, while plasma IR-beta-endorphin levels of the endogenous group (40.11 +/- 3.57 pg/ml) were significantly lower than those of the nonendogenous group (120.33 +/- 27.98 pg/ml). Neither group showed a significant correlation between plasma IR-beta-endorphin and serum cortisol values. These results indicate that measurement of predexamethasone serum cortisol values and plasma IR-beta-endorphin could be valuable laboratory tests in the diagnosis of depression.

Previous studies have indicated that sodium diethyldithiocarbamate (DDTC) can reduce cisplatin's (CP) toxic effects without altering the antitumor activity. DDTC has also been shown to have immunostimulative properties. Sixty patients with objectively measurable recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck were randomized to receive either (A) CP at 120 mg/m2 over one hour on day 1, plus fluorouracil (5-FU) at 1,000 mg/m2 over 24 hours as a continuous infusion on days 1 through 5, or (B) CP/5-FU as in A, plus DDTC at 600 mg/m2 over 30 minutes administered intravenously (IV) exactly 30 minutes after CP infusion. Group B also received DDTC at 200 mg/m2 administered IV over 30 minutes on days 8 and 15. Each cycle was repeated at 3-week intervals. Objective responses were achieved in 41% of the CP/5-FU group and in 29% of the CP/5-FU with DDTC group (P = .26). Median survival was 9 months in group A and 10 months in group B. CP-related toxicity between the groups was equivalent with respect to nausea and vomiting, renal impairment, neurotoxicity, ototoxicity, and hematologic toxicity. The pharmacokinetics of reactive platinum species in plasma ultrafiltrate and urine samples obtained from both groups were comparable. The immune status of 48 patients was evaluated before and after completion of therapy. There were no significant differences in mean pretreatment and posttreatment values within or between groups A or B, except for absolute pretreatment OKT4 values (P = .02). We conclude that (1) the present dose and infusion schedule of DDTC did not significantly reduce CP-mediated toxic effects, (2) DDTC did not alter the disposition of ultrafilterable platinum species, (3) DDTC did not affect immune responses, and (4) the addition of DDTC improved neither the clinical response nor the survival of patients with recurrent SCC of the head and neck.

FMAU (1-[2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl]-5-methyluracil) a newly synthesized fluorinated nucleoside, has potent in vitro antiviral and antileukemic activity and is active in murine leukemia lines resistant to cytosine arabinoside. In the initial phase I trial neurotoxicity, characterized by extrapyramidal dysfunction, was found to be the dose-limiting toxic effect, and a dosage of 32 mg/m2/day for 5 days was suggested for phase II studies. We report a second phase I study of FMAU using this schedule. Mild, transient neurologic dysfunction was encountered in patients treated at the starting dose of 4 mg/m2/day x 5 days and became severe and irreversible in two patients who received the highest cumulative doses administered at the 8 mg/m2/day x 5 days level. Both severely affected patients died. Severe neurotoxicity developed and progressed in these patients despite serial neurologic examinations, including detailed neuropsychologic tests implemented in an effort to detect early neurotoxicity. Because of these findings, further study of this drug as an antileukemic agent cannot be recommended. If it is to be used as an antiviral agent, further phase I study at lower doses is advised.

Plasma arginine vasopressin (AVP) was measured in 24 patients with polyuria exceeding 3.5 l/day diagnosed as severe or partial diabetes insipidus according to the dehydration test. All patients with severe diabetes insipidus diagnosed by the dehydration test had very low or undetectable basal AVP values and always subnormal plasma osmolality. Patients with partial diabetes insipidus diagnosed by the dehydration test had a wide range of AVP and osmolality values. The stimulation test performed on these patients was able to differentiate patients with primary polydipsia from patients with partial diabetes insipidus. The measurement of basal plasma AVP is capable of diagnosing all patients with severe diabetes insipidus; when we combine the stimulation test with the measurement of AVP, we can differentiate partial diabetes insipidus from other forms of polyuria.

The objective was to assess the impact of transcranial magnetic stimulation (TMS) on pain and the autonomic nervous system (ANS) in migraine. Forty-two people [mean age 41.43+/-11.69 (SD) years, 36 females] were randomised into high vs. low TMS stimulation groups and received 2 brief pulses of TMS. Thirty-three (33/42) individuals had heart-rate variability assessed, before and after stimulation. No group effects were found. Pain decreased by 75%; 32% of people after 1 treatment reported no headache after 24 h. Mean heart rate decreased from 79.05+/-10.27 to 72.89+/-11.35 beats/min. The low-frequency (LF) and the high-frequency (HF) areas derived from power spectral analyses increased [mean 6522+/-1277 to 8315+/-1009 beats/min(2) (LF) (p=0.001) and mean 5600+/-1568 to 8755+/-3071 beats/min(2) (HF) (p=0.001)]. The LF:HF ratio decreased from mean 1.31+/-0.51 to 1.13+/-0.48 (NS). TMS produces immediate, sustained reductions in pain and modification of the ANS.

In order to evaluate the effects of amiodarone on thyroid function in chronically treated patients, 43 consecutive patients, who had been taking a mean weekly dose of 1420 +/- 488 mg for more than 9 months (mean 16.5 months), were studied. In a first evaluation, three patients with hypothyroidism and two with hyperthyroidism were discovered. In the remaining 38 patients, mean T4 (131 +/- 38 nmol/L) and rT3 (0.85 +/- 0.3 nmol/L) levels were significantly higher than reference values (p less than 0.05 and p less than 0.001, respectively), and mean T3 levels (1.89 +/- 0.73 nmol/L) were significantly lower (p less than 0.001). Thirteen patients showed hyperresponsiveness to thyrotropin-releasing hormone (TRH) stimulation testing. In a second evaluation, performed 12 to 18 months later, two new cases of hypothyroidism were discovered. T3 levels showed significantly lower values (p less than 0.02) than in the first evaluation, whereas basal thyroid-stimulating hormone levels and levels 30 and 60 minutes after TRH stimulation were significantly higher than those in the first evaluation (p less than 0.001). Five new hyperresponders to TRH were found. In the present series, the progressive appearance of clinical thyroid dysfunction with an elevated total incidence (16%) is demonstrated. Moreover, a progressively high prevalence of hyperresponsiveness to TRH stimulation is shown. These findings indicate that chronic amiodarone administration may carry a high risk of thyroid dysfunction.

Eleven patients at M.D. Anderson Hospital were referred for neurologic evaluation after having their internal or external iliac arteries catheterized for the treatment of localized pelvic or lower extremity tumors. Nine patients developed lumbosacral plexopathies and two patients, mononeuropathies. All symptoms occurred within 48 hours of the intra-arterial infusion. All patients received cis-dichlorodiammine-platinum (cisplatin; CDDP) intra-arterially, alone or in combination with other agents. Follow-up examinations revealed that only one patient had made partial recovery from the neurologic dysfunction. Chemotherapy-induced small vessel injury, with subsequent plexus or nerve infarction, appears to be the most likely cause, although a direct neurotoxic effect of CDDP cannot be excluded.

An improved radioimmunoassay was developed to determine estrone-3-glucuronide in daily urine. Resulting levels were compared with those of estradiol in plasma of 10 healthy women and 14 undergoing ovulation induction therapy with human menopausal gonadotropin and human chorionic gonadotropin. A highly significant correlation between plasma estradiol and urinary estrone-3-glucuronide in normal (r = .9209; P less than .01) and stimulated (r = .9229; P less than .01) women was demonstrated. These results proved that the pattern of excretion of estrone-3-glucuronide perfectly reflected the changes in plasmatic estradiol levels when monitoring ovarian induction and that estrone-3-glucuronide determinations can provide clinically useful information in human induction therapy.

Anatomical and angiocardiographic studies have made possible discussion of hypotheses of the development and differentiation of the conus and of the trunco-conal orientation of the septum. Three autopsy specimens and two angiocardiogrammes of intertwined great vessels with transposition and partial distortion of the great vessels were studied. The specimen of intertwined great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum. In the case of transposition the opposite situation was encountered with a muscular pulmonary infundibulum posterior to and greater than the sub-aortic infundibulum; the plane of the aortic valves was higher than that of the pulmonary valves. The specimen of partial distortion of the great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum with the aortic valve set higher and in fibrous continuity with the mitral valve. It is concluded that the relations of the great vessels between each other and with the ventricles depend on the orientation of the trunco-conal septum and on the process of incorporation of the cone. The presence or absence of a posterior muscular infundibulum is not related to the growth or differential reabsorption of the cone but to a process of cellular differentiation. There was no relation between the level of the valves and their spatial orientation and the length of the infundibulum. The continuity or discontinuity between the aortic and atrio-ventricular valves is not determined by the level of the aortic valves.

A patient with acute myelogenous leukemia in relapse developed reversible bilateral lateral rectus muscle palsy and cerebellar dysfunction after receiving chemotherapy with high-dose cytosine arabinoside and mitoxantrone. The differential diagnosis of this syndrome is reviewed.

Ninety unselected male patients with infertility were treated with clomiphene citrate, 25 mg/day, taken on 20 consecutive days each month for a period of 3 to 12 months. The patients were divided into two groups according to sperm counts. In 39 cases of oligozoospermia with sperm counts above 10 million/ml, six pregnancies were obtained (15.4%) while a significant improvement of sperm counts occurred in 22 cases (56.4%). On the other hand, in 51 cases with azoospermia or oligozoospermia below 10 million/ml only three pregnancies occurred (5.9%) and two patients (3.9%) had significantly improved sperm counts. The indications and form of administration of clomiphene citrate are commented upon.

The authors studied the saccharidase levels in the intestines of rats during the perinatal period. Sucrase and maltase values increase with advancing time, while lactase values decrease also age-dependently. The thyroid gland has a decisive role in the intestinal maturation of fats. In an assessment of circulating blood thyroxin levels, the authors found that the amount of thyroxin at birth is practically undetectable (less than 0,05 mug/100 ml expressed in iodine), rapidly increasing up to adult levels (3,8 mug/100 ml) 22 days after birth.