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Sjögren's syndrome (SS) and sarcoidosis are diseases that can affect the salivary glands and result in the loss of salivary gland function. Most of the criteria used for the diagnosis of SS exclude sarcoidosis before establishing the diagnosis of SS. However, several reports have suggested the coexistence of both SS and sarcoidosis in the same patient.The purpose of this study was to present five cases that support a true coexistence of sarcoidosis and SS.Clinical and laboratory findings of patients with evidence of having both SS and sarcoidosis were reviewed. The diagnosis of SS was based on the European community criteria; the diagnosis of sarcoidosis was based on the presence of serological, radiographic and/or histopathologic findings that are consistent with sarcoidosis.All patients fulfilled the criteria for the diagnosis of both diseases.Our findings appear to support a true coexistence of sarcoidosis with SS. Therefore, it is reasonable to suggest removing the exclusion of sarcoidosis from the diagnostic criteria for SS.

To examine the effect of trimester specific and pregnancy average total trihalomethane (TTHM) exposure on infant birth weight, low birth weight, and intrauterine growth retardation in term births, as well as gestational age and preterm delivery in all births.Cross sectional analysis of 56 513 singleton infants born to residents of Massachusetts during 1990. City specific aggregate data were used to estimate maternal exposure to TTHM concentration; individual maternal information was used to adjust for confounding.Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables. Compared to/=60 micro g/l, pregnancy average TTHM exposure over 80 micro g/l was associated with a 32 g reduction in birth weight. There was a 23 g reduction in birth weight in infants born to mothers exposed to greater than 80 micro g/l TTHM during the second trimester. For each 20 micro g/l increase in TTHM, the estimated reduction in birth was 2.8 g for pregnancy average exposure and 2.6 g for second trimester exposure. An increased risk of small for gestational age births was found for pregnancy average (odds ratio (OR) 1.14; 95% CI 1.02 to 1.26) and second trimester (OR 1.13, 95% CI 1.03 to 1.24) TTHM levels greater than 80 micro g/l. There was no evidence of an association between preterm delivery and increased TTHM levels, but there were slight increases in gestational duration associated with TTHM concentrations.Maternal exposure to THMs may be associated with fetal growth retardation. Our findings are consistent with most previous work, although we generally found smaller effects of TTHMs on low birth weight and intrauterine growth retardation.

Oral pemphigoid, defined as cicatricial pemphigoid limited to the oral cavity, is a clinical subset of cicatricial pemphigoid. Like cicatricial pemphigoid, it occurs mostly in middle-aged women and it is uncommon in children under 20 years of age. There are 11 cases of childhood cicatricial pemphigoid published previously in the English language literature, and four of them are oral pemphigoid patients. We present a case of the youngest oral pemphigoid patient reported yet. Because of the rareness of cicatricial pemphigoid in children, delayed diagnosis and treatment have been shown in many cases reported earlier. Clinical awareness and early recognition are, therefore, emphasized.

Summary The effect of sublingual captopril on the pressor response to intubation was studied in 40 patients. Captopril was used in one of two doses (12.5 mg and 25 mg) 25 minutes before tracheal intubation. Both doses were associated with a significant reduction in the pressor response to intubation (p < 0.05) compared to placebo, but no significant difference existed between the two doses. Neither dose controlled changes in heart rate at intubation. Untoward hypotension occurred in the treatment groups. Caution is advised in the peri-operative use of angiotensin-converting enzyme inhibitors.

The structure of the heterochromatic bands in mitotic chromosomes of the important tropical aquaculture species of tilapia, Oreochromis niloticus, was investigated by the combination of the C-banding technique, chromosomal digestion with two restriction endonucleases and fluorescence in situ hybridization (FISH) of two satellite DNAs (SATA and SATB). The tilapia chromosomes presented heterochromatic bands in the centromeres and in the short arms of almost all chromosomes that were differentially digested by the restriction endonucleases HaeIII and EcoRI. FISH of SATA showed that this satellite sequence is distributed in the centromeric region of all chromosomes of tilapia. FISH also revealed an intense hybridization signal for SATB in only one chromosome pair, but less intense signals were also present in several other pairs. The digestion of tilapia chromosomes by HaeIII and EcoRI was positively correlated with the position of SATA and SATB in chromosomes as revealed by FISH. The results obtained may be useful in future molecular and genetic studies of tilapias.

Isoniazid, a highly effective drug for the chemoprophylaxis and treatment of tuberculosis, is associated with severe hepatotoxicity in 1-2% of individuals. In a rabbit model of isoniazid-induced hepatotoxicity, we have measured hepatic necrosis (quantitated by elevation of plasma argininosuccinic acid lyase (ASAL) activity), hepatic steatosis (quantitated by elevation of hepatic triglyceride content), and elevation in plasma triglyceride concentration in 15 rabbits. Eight of 15 rabbits were male, and 14 of 15 were rapid acetylators of sulfamethazine. Administration of isoniazid to rabbits resulted in a 27-fold increase in plasma ASAL activities, a 7.5-fold increase in hepatic triglyceride content, and a 13-fold increase in plasma triglyceride levels. This study demonstrated no effect of gender on these three pathological changes that occur in this model of isoniazid-induced hepatotoxicity in rabbits.

The antihypertensive effects of once-daily diltiazem CD over a 24 hour period were compared with twice-daily diltiazem SR in 95 patients with mild to moderate hypertension using ambulatory blood pressure monitoring. This trial was designed as a multicenter, double-blind, parallel-group study. Following a 2 to 4 week placebo run-in period, diltiazem was administered as once-daily CD or twice-daily SR, starting with 180 mg daily and increasing to a maximum of 360 mg daily, to achieve a seated diastolic blood pressure goal ofor = 90 mmHg as measured by cuff between 08:00 and 10:00 in the morning. Following drug titration, patients received a maintenance dose of diltiazem for an additional 6 week follow-up phase. Twenty-four hour ambulatory blood pressure monitoring recordings were obtained at the end of the placebo, titration, and maintenance phases. Both diltiazem CD and diltiazem SR significantly reduced both systolic and diastolic blood pressure over the 24 hour day and maintained a normal circadian pattern. As well, treatment with once-a-day diltiazem CD significantly decreased the slope of the early morning rise of diastolic and mean blood pressure. Thus, diltiazem CD is as effective as diltiazem SR in lowering diastolic blood pressure over a 24 hour period and has the advantage of a once-daily formulation.

The efficacy and safety of optimally titrated once-daily (CD) and twice-daily (SR) diltiazem were compared in 111 patients with mild to moderate systemic hypertension [seated diastolic blood pressure (DBP)or = 95 mmHg andor = 114 mmHg] in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial. Following a 4 week washout and placebo-controlled run-in period, patients were randomized to receive diltiazem CD 180 mg and matching placebo (n = 54), or diltiazem SR 90 mg bid (n = 57). Total daily doses were titrated from 180 mg to 360 mg to achieve a goal of seated DBP90 mmHg during a 6 week titration period. The patients continued to receive their optimal dose for a 6 week follow-up period. Ninety-six (96) patients (diltiazem CD: 47, diltiazem SR: 49) completed the study protocol, with 60% of the diltiazem CD and 55% of the diltiazem SR patients achieving the goal of seated DBP of90 mmHg (p = 0.685). Although significant decreases occurred in seated and standing measurements of diastolic and systolic BP and heart rate with treatment in both groups, there were no significant differences between treatment groups. Both medications were well tolerated, with a similar frequency of adverse effects [diltiazem CD: 24/54 (37%) patients; diltiazem SR: 24/57 (42.1%) patients] with the most frequently reported adverse effects being headache and edema.

To investigate the acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients.The variations in level of plasma noradrenaline and adrenaline were measured in the supine and standing positions before and after the initial dose, and after 12 weeks of nitrendipine therapy. Following a washout placebo period, treatment was initiated by a single 20 mg dose of nitrendipine. This was followed by a double-blind randomization into two groups: one receiving 10 mg nitrendipine twice daily, the other receiving 20 mg once daily.Clinical investigation unit, University Hospital (University of British Columbia site), Vancouver, British Columbia.Sixteen patients (seven males and nine females), mean age 51 years (range 27 to 63), with mild to moderate, uncomplicated hypertension.Two hours after administration of the initial 20 mg nitrendipine dose to all patients, there was a significant fall in the supine and standing systolic and diastolic blood pressure - from 164 +/- 3/102 +/- 1 to 139 +/- 2/87 +/- 2 mmHg, and from 153 +/- 4/105 +/- 1 to 139 +/- 3/90 +/- 1 mmHg, respectively. The supine and standing heart rates were unchanged. After 12 weeks of nitrendipine therapy, blood pressure was reduced (2 h after the dose) to a similar extent as that seen after the initial dose. Acute and chronic nitrendipine administration significantly increased supine and standing noradrenaline, but not adrenaline. Two hours after the initial 20 mg dose, supine noradrenaline increased from 3404 +/- 585 to 4005 +/- 644 pmol/L and standing noradrenaline increased from 3769 +/- 609 to 5821 +/- 615 pmol/L. At the end of the 12 weeks of therapy, similar dose-dependent effects were observed 2 h after the dose, but not 12 or 24 h after the dose, in both groups. The percentage increase in noradrenaline produced by nitrendipine in the standing position was consistently greater than in the supine position.Chronic nitrendipine therapy results in a daily increase in plasma noradrenaline (2 h after the dose), and the effect is greater in the standing position.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

1. The effect of isoniazid given daily for 7 days on paracetamol (acetaminophen) kinetics and metabolism was studied in 10 healthy volunteers. Paracetamol, 500 mg, was given before isoniazid, on day 7 of isoniazid administration, and 2 days after the last dose of isoniazid. 2. On day 7, isoniazid markedly inhibited the formation clearance of the glutathione and catechol metabolites by 69.7% and 62.2%, respectively. Total paracetamol clearance was lowered by 15.2%. There was no effect of isoniazid on the non-oxidative pathways of paracetamol elimination. 3. Two days after isoniazid was discontinued, paracetamol metabolism had returned to pre-isoniazid values.

We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible.

A seroepidemiological survey was undertaken in Addis Ababa to assess the prevalence of chlamydial genital infections among patients attending a sexually transmitted diseases (STD) clinic and patients with no overt genital symptoms. In the STD clinic patients antibodies to Chlamydia trachomatis serotypes D to K (genital types) were detected in 68 of 210 (32.4%) men and in 72 of 159 (45.3%) women, a rate of exposure as high or higher than that found in Europe. Serological evidence of active chlamydial infection was present in 26.7% of men and 28.9% of women. Women were at risk of contracting STD, including chlamydial infections, at the age of 14 years or earlier. The titres of antichlamydial IgG were extremely high in some patients attending the STD clinic, with titres of between 1/512 and 1/8192 in 9.5% of men and 13.2% of women. This suggests that some patients had severe or disseminated chlamydial disease. The prevalence of exposure to chlamydial genital infections among 148 patients with no overt genital disease was 14.2%, which is significantly higher than that found in the United Kingdom. Among the total of 517 patients tested the prevalence of exposure to trachoma, lymphogranuloma venereum, and Chlamydia psittaci agents was very low.

Ten patients with clinically definite multiple sclerosis (MS) and action tremor were treated with isoniazid (INH) in a double-blind single crossover trial. The daily dose of INH administered during the 4-week treatment phase of the trial was determined by acetylator phenotype with slow acetylators receiving 12 mg/kg per day and rapid acetylators 20 mg/kg per day. Six of eight patients who completed the trial showed clinical improvement in the postural (alternating) tremor while on INH but the degree was minimal in all cases. Results of tremograms indicated that improvement also occurred in the intentional (synchronous) component of three patients while on INH, but this did not achieve statistical significance. Cerebrospinal fluid (CSF) levels of gamma-aminobutyric acid (GABA) homocarnosine and ornithine were markedly elevated with INH therapy (providing evidence for substantial inhibition of GABA aminotransferase activity and increase in GABA in the CNS), but no correlation was found between the degree of GABA elevation in the CSF and the clinical response. Side effects were minimal and well tolerated. Although INH appears to have a limited therapeutic role, a trial is warranted in MS patients with postural tremor.

Changes in the dimensionality of the moral criteria, i.e. of those aspects of an action-sequence to which a person pays attention when judging how good/bad (nice/naughty) the agent is, were studied with 7-, 10-, and 13-year-old girls and adult subjects. Action sequences varying in respect to potential moral criteria were presented as cartoons. A proximity setting technique and Kruskal's (1964) method of analysis were used. In the younger age groups a remorse-spite-dimension was obtained, the motive criterion becoming more dominant and differentiated with age. Methodological problems are discussed.

Seventy-three adult lymphedema patients with 78 affected lower extremities were treated with the Wright Linear Pump. All patients were admitted for a 48-hour clinical trial. Comparison of circumferential limb measurements before and after a 48-hour treatment period using a repeated measures analysis of variance showed statistically significant improvement (p less than 0.00005). Although the improvement appeared to be somewhat more pronounced for men than for women, both sexes experienced an important reduction in leg circumference after therapy. Other factors such as age, etiology, previous use of the Jobst pump, or duration of lymphedema did not appear to influence the extent of improvement. These data clearly indicate that the Wright Linear Pump is an effective treatment for lower extremity lymphedema in adults.

Clostridium difficile has been detected in the stools of some patients with relapse of Crohn's disease. The authors looked prospectively for present or previous exposure to C. difficile cytotoxin in 10 patients with mild to severe Crohn's disease. None of 25 stool samples from these 10 patients was positive for C. difficile cytotoxin. These negative stool ultrafiltrates had mild cytotoxin neutralizing activity, but this finding did not differ from that in 30 cytotoxin-negative stools from patients with other diarrheal diseases. Serum from these patients also showed no cytotoxin neutralizing activity. Review of the literature reveals that C. difficile can cause complications ranging from diarrhea to toxic megacolon in a small but variable proportion of patients with Crohn's disease. There is no evidence that C. difficile plays a part in the pathogenesis of the disease.

Both cellulose acetate electrophoresis and citrate agar electrophoresis were performed on 834 blood samples collected on filter paper in Jamaica and shipped for testing to the National Hemoglobinopathy Standardization Laboratory at the U.S. National Center for Disease Control. Additionally, 30 blood samples collected locally were stored on filter paper, in microhematocrit capillary tubes, and as whole blood specimens; at selected times the samples were tested for stability to determine the best sample-collection technique for hemoglobin electrophoresis. Results were most nearly accurate when both cellulose acetate electrophoresis and citrate agar testing were used. The methods are easy to perform, but results are unreliable if the blood samples on filter paper are stored at 4 degrees C for longer than two weeks before they are tested.

To compare the antihypertensive efficacy of methyldopa administered once at bedtime with the same total dose given three times daily, a double-blind crossover study was performed in 14 patients previously well controlled on methyldopa. Each patient received a total daily dose of 0.37 gm, 0.75 gm, or 1.5 gm of methyldopa, depending on the dose of drug that had previously been successful in that individual. The trial design included either 12 wk of methyldopa three times daily (TID) followed by 12 wk of single daily bedtime (HS) doses of methyldopa or administration of drug in the reverse order. Supine and erect blood pressures were recorded 4 times daily (8 a.m., 12 noon, 4 p.m., and 8 p.m.) every 4 wk throughout the study. Blood pressure control was excellent in all patients whether the drug was administered three times daily or at bedtime. Systolic pressures were slightly lower at 8 a.m., when methyldopa was given at bedtime than on doses three times daily, and systolic and diastolic pressures were slightly higher at 8 p.m. that at 8 a.m. on the bedtime regimen.

Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.

Recall of spatial location was studied with 5, 8, 12--13, and 17--18 year old subjects. Pictures of objects were shown one at a time in one of the four quadrants of a projection screen which was either blank (NF) or divided by a cross into four quadrants (F). The presence of the frame (F) did not affect item recall, but facilitated location recall more, the younger the subjects. Intentional learning of location was superior to incidental learning in the youngest but not in older children. The results are in agreement with Bryant's (1974) analysis of perceptual development which emphasizes the use of external spatial frames of reference in the encoding of attributes of visual objects in young children.