Group B streptococcal bacteremia in adults. Five years' experience and a review of the literature

The importance of group B streptococcus (GBS) as a cause of serious infectious disease among adults is not widely appreciated. In adults, the modes of acquisition and transmission are unknown. Since most hospital-based studies of GBS bacteremia in adults consist of small numbers of patients, the clinical spectrum of disease is not well described. Our retrospective study reviews the clinical features, antimicrobial therapy, and risk factors for mortality of 32 adult patients (18 women and 14 men) with GBS bacteremia and compares the proportion of isolates from the different beta-hemolytic streptococci sero-groups. We found that 39% of isolates from adult blood cultures were group B, a frequency nearly identical to that of group A streptococcal bacteremia. Most (66%) adult patients were more than 50 years old. Primary bacteremia was the most frequent clinical diagnosis, occurring in 7 (22%) of 32 patients. Nonhematologic cancer was the most frequently associated condition (25%). Nineteen percent of the patients had diabetes mellitus. The overall mortality rate was 31% and was significantly associated with increasing age. Our results are compared to those obtained by a review of all 5 previous comparable studies and demonstrate that GBS bacteremia is a serious infection in adults with increased mortality related to advancing age.     

Intradermal tophi in gout: a case-control study

OBJECTIVE: To describe the characteristics of intradermal tophi in patients with gout and search for factors associated with their development. METHODS: This is a case-control study of patients with gout: cases (Group A, n = 21) had intradermal (not subcutaneous) plaques of monosodium urate (MSU) crystals located in sites distant to articular or paraarticular structures, and controls (Group B, n = 42) had gout but no intradermal tophi. Both Group A and Group B were paired by sex, age (+/-5 years), and duration of the disease (+/-3 years). Analysis included serum and urinary uric acid levels at first visit, radiographic stage of gout, the presence of associated diseases, and previous therapy, specifically, chronic glucocorticoid and diuretic usage. RESULTS: Intradermal tophi were located in the legs, forearms, buttocks, thighs, arms, and abdominal wall. Patients in Group A had a greater number of nonintradermal tophi in common sites (11.9+/-12.5 vs. 4.2+/-7.9, mean +/- SD; p = 0.018), decreased glomerular filtration rate (46.74+/-25.11 vs. 70.87+/-30.18 ml/min; p = 0.042), advanced radiographic changes (57.2 vs. 7.1%; p = 0.0001), and longterm glucocorticoid self-medication (76 vs. 36%; p = 0.006). We found no differences in other associated diseases between groups. CONCLUSION: Intradermal tophi were commonly found in the legs and forearms, and less frequently in the buttocks, thighs, and abdominal wall of gouty patients, and were associated with longterm self-prescribed glucocorticoids and chronic renal failure. The occurrence of intradermal tophi in these patients appeared to correlate with advanced disease.     

Pulmonary atresia with ventricular septal defect in adults

BACKGROUND: Multistage surgery culminating in completed hemodynamic repair is now performed for pulmonary atresia with ventricular septal defect (PA-VSD). Justification for operation in patients with an adequate collateral pulmonary circulation is controversial. Data on natural adult survival are scant but are necessary to provide the rationale for multistage reconstructive procedures. METHODS AND RESULTS: All cyanotic adults with PA-VSD in the UCLA Adult Congenital Heart Disease Center Registry from 1978 through 1992 formed the basis for this study. Registry data and echocardiographic, hemodynamic, and angiographic information were used to determine longevity, clinical course, and operative feasibility. Of 26 patients, 16 were unoperated when referred (group A), and 10 had been palliated before age 18 years (group B). Two thirds were 18 to 29 years old. Only 2 patients survived beyond age 40 years. Six died during follow-up at a mean age of 31 years (+/- 12.1 SD). Eight group A patients were in New York Heart Association class II, and 8 were in class III. Of the 26 group A and B patients, 20 had aortic regurgitation, which was moderate or severe in 10. Eight had cardiac failure. Of 11 group A patients who remained unoperated, 5 died. Twelve patients were considered eligible for surgery at > or = 18 years of age. Ten underwent completed hemodynamic repair with a mean post-operative right ventricular-to-left ventricular systolic pressure ratio of 0.45 (+/- 0.16 SD), and there were no early or late deaths. CONCLUSIONS: Even when collateral blood flow permits adult survival, all such patients are symptomatic. Mean life expectancy without operation did not exceed three decades. Aortic regurgitation and cardiac failure are significant negative variables. Nearly half of unoperated adults died during follow-up. Staged hemodynamic repair can be performed with a low surgical risk in properly selected adults with PA/VSD.     

Bacterial meningitis in the United States in 1995. Active Surveillance Team

BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.     

Invasive pulmonary aspergillosis: a study of 33 cases

Invasive pulmonary aspergillosis (IPA) is an infectious complication appearing mainly in immunosuppressed patients, whose diagnosis is often difficult and lately made, and that usually bears a dismal prognosis. Patients diagnosed as having IPA from 1989 to 1994 were retrospectively analyzed. Probable IPA was diagnosed on the basis of a positive culture for Aspergillus together with a consistent radiological image. Confirmed IPA was diagnosed if there was, in addition to the former, a pathological examination showing Aspergillus hifae invading pulmonary parenchyma and/or pulmonary vessels. There were 25 men and 8 women with a mean age of 53.7 +/- 16.9 years (range: 22-86 years). IPA was confirmed in 11 cases and probable in 22. Sixty three percent of the patients had hematologic malignancy or solid cancer, whereas 30.3% did not have prior granulocytopenia or immunosuppressive therapy. The mean (SD) interval between admission and diagnosis was 40.2 (37.1) days (range: 1-180 days), and the diagnosis was made while the patient was still alive in 75% of the cases. Fifteen percent of the patients had extrapulmonary aspergillosis. The most frequent finding both on X-ray film of the chest and pulmonary computed tomography were bilateral multiple pulmonary nodules. Thirteen patients were treated with itraconazole, 6 with amphotericin B, 5 received both drugs, and 2 received fluconazole. Nineteen patients (57.6%) died and the case-fatality rate among treated patients was 46.1%. IPA presents mainly in immunosuppressed patients, but there was a not negligible proportion of patients lacking the classical risk factors. IPA is often a lately made diagnosis and in a quarter of the patients it is not made when the patient is alive. The most frequent radiological presentation are multiple bilateral nodules. The case-fatality rate of IPA is exceedingly high, even when if the patient has been adequately treated.     

The soluble 60-kDa tumour necrosis factor receptor: no difference found between patients with relapsing-remitting multiple sclerosis and controls: increasing levels are associated with the recovery from Guillain-Barré syndrome

We determined serum and cerebrospinal fluid (CSF) levels of the soluble 60-kDa tumour necrosis factor (TNF) receptor (sTNF-R p60) in 50 patients with relapsing-remitting multiple sclerosis (MS) and in 18 patients with Guillain-Barré syndrome (GBS). Neither in serum nor in CSF samples was there a statistically significant difference between mean receptor concentrations of patients with MS (serum: 1064, SD 262 pg/ml; CSF: 555, SD 130 pg/ml), with other noninflammatory neurological diseases (serum: 1008, SD 248 pg/ml; CSF: 530, SD 112 pg/ml) and with healthy control subjects (serum: 918, SD 180 pg/ml). In order to determine disease activity, magnetic resonance imaging (MRI) of the brain was performed in all MS patients. The mean sTNF-R p60 levels of patients who showed gadolinium DTPA enhancement on MRI were not different from those without enhancement (1034, SD 274 pg/ml vs 1099, SD 248 pg/ml in serum samples and 546, SD 109 pg/ml vs 565, SD 152 pg/ml in CSF samples). In GBS, the sTNF-R p60 levels of serum and CSF samples were significantly higher than in MS and all control groups except for the group with viral meningitis (VM) (GBS: 1544, SD 834 pg/ml in serum, 882, SD 147 pg/ml in CSF; VM: 1518, SD 375 pg/ml in serum, 1131, SD 611 pg/ml in CSF; P < 0.001 for serum samples and P < 0.005 for CSF samples). Serial serum sTNF-R p60 measurements in 13 patients with GBS showed an increase in receptor levels parallel with the recovery from the disease (1276, SD 374 pg/ml at the time of disease onset, 1554, SD 482 pg/ml 14-24 days later and 1787, SD 525 pg/ml after 28-32 days). From our results and the conflicting data of previous studies, we could not agree with the suggestion that the assessment of sTNF-R p60 in MS patients is a useful marker for disease activity. In GBS, subsequently increasing sTNF-R p60 levels are associated with recovery from the disease. It remains to be shown whether they might represent a relevant pathogenetic factor during this stage of GBS.     

The impact of advanced age on the results of carotid endarterectomy: an outcome analysis

BACKGROUND: This study examined whether advanced age adversely influences the outcome of carotid endarterectomy. STUDY DESIGN: The records of 173 patients who underwent 187 carotid endarterectomies performed by the author from January 1990 through December 1995 were retrospectively reviewed. Group 1 included 58 patients, ranging in age from 75 to 92 years (mean, 79.4 years), who underwent 63 procedures, and group 2 included 115 patients, ranging in age from 41 to 74 years (mean, 66.3 years), who underwent 124 procedures. The operation was performed for symptomatic disease in 67 percent of the cases in each group. The operated lesion was more than 80 percent stenotic in 85 percent of the group 1 and 79 percent of the group 2 cases. RESULTS: No significant differences were found in the operative mortality (1.6 percent compared with 1.6 percent), incidence of perioperative stroke (4.8 percent compared with 1.6 percent), or rate of major cardiac complications (7.9 percent compared with 7.3 percent) between groups 1 and 2. No significant difference was found in the mean postoperative length of hospital stay between the group 1 and group 2 patients (4.13 +/- 2.58 days compared with 3.68 +/- 1.40 days). However, during the last 2 years of the study, the mean postoperative length of stay among the group 2 patients (3.06 +/- 1.44 days) was significantly shorter than among the group 1 patients (4.15 +/- 1.45 days) (p < .05). CONCLUSIONS: Advanced age does not adversely affect the results of carotid endarterectomy. However, the very elderly may be expected to experience a longer postoperative length of stay because of associated comorbid conditions.     

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group. In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002). The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations. Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis.     

Estimation of ASO titer as an indicator of streptococcal infection precipitating acute adenolymphangitis in brugian lymphatic filariasis

Recurrent episodes of acute adenolymphangitis (ADL) are important clinical manifestations of lymphatic filariasis which contribute significantly to the progression of lymphedema. It is increasingly being recognized that secondary bacterial infections play an important role in the etiology of ADL. We examined the role of streptococcal infection as a precipitating factor of ADL in brugian filariasis, by determining the anti-streptolysin O (ASO) titers and by isolating the causative organism wherever possible. The study population consisted of 30 patients with filariasis related ADL (Group A), 30 patients with chronic filarial edema (Group B) and 60 age and sex matched healthy adults (Group C). ASO titer was estimated by the latex agglutination method at the time of entry into the study, at the 15th day and at 3, 6 and 12 months. ASO titers were persistently elevated in 90% of patients in Group A and a portal of entry for bacterial infection was detected in all of these patients. In Group B only six patients had persistently elevated ASO titers. These patients had grade III lymphedema and three of them had monilial infections in the affected limb. In the control group none had persistently elevated ASO titers. The elevated ASO titers and the detection of a site of entry for bacteria in patients with ADL supports a streptococcal etiology for this condition.     

Urinary antigen test as a screen for the diagnosis of beta-hemolytic streptococcal infections in newborn infants

OBJECTIVE: To differentiate between neonates with high and low risk of infections caused by group B beta-haemolytic streptococci (GBS), by using the urinary group B streptococcal antigen test. DESIGN: Retrospective. SETTING: Medical Centre Leeuwarden and Public Health Laboratory, Friesland, the Netherlands. METHODS: In a period of two years clinical, haematological and microbiological (including urinary group B streptococcal antigen detection) data were collected in newborns and their mothers who met one or more of the following criteria: a previous affected child, prolonged (> or = 12 hrs) rupture of membranes, fever in labour, unexpected preterm delivery, unexplained perinatal asphyxia. On the basis of surveillance cultures a colonization rate was made. GBS infection was 'suspected' in an unwell infant with a 'high' colonization rate; infection with GBS was 'proved' by a positive blood culture with GBS. RESULTS: 6 of 342 neonates had an infection with GBS. Risk of invasive infection increased with higher colonization rates. Sensitivity of the antigen test to detect colonization was low, sensitivity to detect neonatal infection was high (51 versus 100%). The negative predictive value of urinary antigen testing was 100%. Prolonged rupture of membranes (1.5% risk of infection) and maternal fever (5%) were the most important risk factors. CONCLUSION: In healthy neonates with risk factors but with a negative antigen detection test the risk of GBS infection is extremely low. In children with a risk factor a positive test result can indicate heavy colonization or infection. These children should be carefully observed and examined.     

Change in anaesthesia practice and postoperative sedation shortens ICU and hospital length of stay following coronary artery bypass surgery

We randomized prospectively 144 patients, undergoing elective coronary artery bypass surgery, to either early or to routine extubation [mechanical ventilatory support for 4-7 h (Group A), or 8-14 h (Group B)]. Anaesthesia was modified for both groups. The groups were well matched in terms of sex, age, NYHA class, preoperative left ventricular ejection fraction, bypass time and aortic cross-clamp time, number of grafts used, and blood units transfused. All patients had normal preoperative respiratory, renal, hepatic and cerebral functions. Mechanical ventilatory support (mean +/- SD) was 6.3 +/- 0.7 h for Group A and 11.6 +/- 1.3 h for Group B. Mean ICU stay was 17 +/- 1.3 h for Group A and 22 +/- 1.2 h for Group B, while the mean hospital stay was 7.3 +/- 0.8 days and 8.4 +/- 0.9, respectively. There were no statistically significant differences in the frequency of all postoperative complications among the two groups. There were no reintubation, readmission to the ICU or death in either group. We concluded that change in anaesthesia practice and early postoperative sedation in patients undergoing elective coronary artery bypass graft (CABG) surgery resulted in earlier tracheal extubation, shorter ICU and hospital length of stay without organ dysfunction or postoperative complications. Early extubation was only possible due to the modification of anaesthesia and ICU sedation regime.     

Intracranial meningiomas of the first two decades of life

Meningiomas arising in the first two decades of life are uncommon and their characteristics are controversial. Some authors believe meningiomas in younger patients occur in different locations, have more malignant histological features, and have a worse prognosis than those in adults. To address this controversy, the authors retrospectively reviewed 23 cases of meningiomas in patients under 21 years of age at diagnosis who were operated on at the University of Turin (1948 to 1990) or at the University of California, San Francisco (1970 to 1989). These tumors represented 2.9% of all tumors in this age group and 1.8% of all meningiomas during the study period at the two institutions. There were 14 males and nine females. The mean age at surgery was 13.3 +/- 5.6 years; nine cases occurred in the first decade and 14 in the second. The most common neurological symptoms were a focal neurological deficit (33%) and seizures (25%). Seventy percent of the tumors were supratentorial. A gross total resection was performed in 60% of the cases. Histologically, the majority (74%) of the tumors were meningothelial or mixed. An increased number of mitoses was observed in 33% of the tumors, focal necrosis in 29%, and invasion of adjacent brain in 14%; however, none of the tumors was classified as a Grade III (anaplastic) meningioma. All patients are alive without evidence of recurrent disease 3 to 22 years (mean +/- standard deviation: 10 +/- 7.3 years) after surgery. This study confirms the rarity of meningiomas of the first two decades of life and the absence of the female predominance associated with meningiomas in adults. The location and histological features of these tumors are similar to those in adults; they have a low recurrence rate, and the outcome and survival rate are excellent.     

Acute bacterial meningitis in adults: a clinical and developmental analysis of 100 cases

BACKGROUND: Characterize clinical findings and outcome of acute bacterial meningitis (ABM) in adults, with special emphasis on nosocomial meningitis and meningitis in the elderly. METHODS: We reviewed the charts of all persons 14 years of age or older in whom ABM was diagnosed in our hospital during a 12 and a half-year period. RESULTS: Ninety-seven patients were treated for 100 episodes of ABM, of which 23 percent were nosocomial and 27 percent occurred in elderly persons. Predisposing factors were present in 59 percent of the episodes. Fifty-four percent had the classic triad of fever, nuchal rigidity, and change in mental status. Cerebrospinal fluid pleocytosis with a neutrophilic predominance, hypoglycorrhachia, and elevated protein levels were present in 62 percent of the episodes. A pathogen was identified in 62 percent of the cases, in a higher frequency in elderly persons (p < 0.05) and in patients who had not received antibiotics before the lumbar puncture (p < 0.05). Causal agents more frequently identified were: Streptococcus pneumoniae (27 percent) in community-acquired meningitis, coagulase-negative Staphylococci (35 percent) in nosocomial meningitis, and Strep. pneumoniae (33 percent) in elderly persons. Central nervous system (CNS) complications occurred in 18 percent of episodes, and 15 percent developed systemic complications. The overall mortality rate was 9 percent, higher among patients in whom CNS complications began within 24 hours of admission (p < 0.05). CONCLUSIONS: A high proportion of cases of ABM in adults are nosocomial, or affect elderly persons. The fatality rate is high, particularly among those who develop CNS complications at the onset of the disease.     

Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men

OBJECTIVE: Verapamil has been associated with hyperprolactinaemia, but there have been no population-based studies. Our objective was to determine the prevalence and degree of hyperprolactinaemia associated with verapamil in the clinical setting. DESIGN: Observation with cross-sectional and longitudinal components in the setting of an urban teaching hospital and its satellite out-patient clinics. PATIENTS: Male out-patients excluding those taking other drugs known to raise PRL, renal failure and known primary hypothyroidism (1265 eligible subjects). Control subjects were drawn from eligible out-patients not taking verapamil. MEASUREMENTS: Serum PRL levels, frequency of persistent hyperprolactinaemia and total testosterone levels. RESULTS: Prolactin levels were obtained in 449 subjects on verapamil (35.5% response rate) and 166 controls. The proportions of individuals with hyperprolactinaemia (PRL > 460 mU/l) were 0.085 and 0.030 in the verapamil and control groups, respectively (P = 0.012, X2-test). The mean (+/- SD) serum PRL levels were 267 +/- 205 and 203 +/- 118 mU/l in the verapamil and control groups, respectively (P < 0.001, independent t-test). Of the 38 patients with previously determined elevated PRL levels, follow-up data were obtained in 25 (65.8%); one was found to have a pituitary adenoma and was excluded from the analysis. Fifteen of the 24 were still on verapamil (Group 1) and 14 (93.3%) continued to be hyperprolactinaemic. In 9 patients verapamil had been discontinued (Group 2) and all had normal PRL levels. Continued verapamil use was associated with persistent hyperprolactinaemia (odds ratio > 120, P < 0.00001). The mean +/- SD serum testosterone levels at follow-up were significantly lower in Group 1 (6.16 +/- 2.52 nmol/l) than in Group 2 (9.42 +/- 3.92 nmol/l, P = 0.029, independent t-test). CONCLUSIONS: The prevalence of hyperprolactinaemia associated with verapamil use in this study of male out-patients was 8.5% (95% CI 5.9-11.1%). The persistence of hyperprolactinaemia when verapamil was continued (Group 1) and the return to normal PRL levels when verapamil was discontinued (Group 2) confirm verapamil's causal role in the development of hyperprolactinaemia. While low testosterone levels were common in both groups, testosterone levels were lower in patients on verapamil. Our data suggest that screening for hyperprolactinaemia should be considered in male patients taking verapamil.     

Long-term effect of Helicobacter pylori eradication on gastric metaplasia in patients with duodenal ulcer

Thyroid functions were analyzed before, during and after interferon (IFN) therapy in patients with chronic hepatitis C. According to the results of routine thyroid function tests and measurements of the levels of anti-thyroid autoantibody prior to the therapy, patients were divided into 2 groups; Group A (19 patients) had at least one abnormal finding related to the thyroid, and Group B (40 patients) did not show any abnormality. Five patients (26%) in Group A and 4 (10%) in Group B showed thyroid dysfunctions which were very clearly reflected by thyrotropin (TSH) measurements. Interestingly, the time of peak TSH elevation in Group A (mean +/- SD, 4.3 +/- 0.8 months) was significantly earlier than that in Group B (6.8 +/- 0.8). Most patients in Group B were diagnosed as having destructive thyroiditis. These findings may suggest that the pathogenesis of IFN-induced thyroid dysfunction consists not only of exacerbation of pre-existing thyroid autoimmunity but also of de novo destructive changes even in the intact thyroid before IFN therapy.     

Emergence of drug-resistant tuberculosis in Jerusalem: ten-year retrospective review

Drug-resistant tuberculosis (TB) has emerged as a worldwide problem. The annual incidence of TB has increased in Israel in the last decade, mainly due to successive waves of immigration. Few data are available on drug-resistant TB in Israel A 10-year retrospective review was conducted on all patients who had been infected with culture-proven Mycobacterium tuberculosis and had been admitted to our hospital. Forty-seven patients had culture-positive TB; 27 (57%) were male, 20 (43%) were female; mean age (+/- SD) was 56 +/- 23 years. Twenty patients (43%) had pulmonary TB. Three patients (6.4%) had single-drug resistance; 4 patients (8.5%) had multi-drug resistance. Six of the seven patients (86%) with drug-resistant TB had been diagnosed after 1990. Six of the 20 patients (30%) with pulmonary TB had drug-resistant organisms. Six of the 7 patients (86%) with drug-resistant TB had pulmonary infection, as compared to 15/40 (37%) of the patients with drug-susceptible TB (p < 0.001). Six of the 7 patients (86%) with drug-resistant TB had a history of TB. Fifteen percent (14.9%) of all new cases diagnosed with TB in our hospital in the last 10 years had drug-resistant M. tuberculosis. Thirty percent of patients with pulmonary TB had drug-resistant organisms. Drug-resistant TB has evidently emerged in Israel and poses a serious clinical and social threat. A strong case for directly-observed treatment in Israel should be made, especially since the incidence of TB here is still small.     

Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function

The dose proportionality of lubeluzole, a drug in clinical development for the treatment of acute ischemic stroke, was evaluated in a Phase I, single-center, open-label, randomized-dosing-sequence, three-way crossover clinical trial in 12 healthy adults. An equal number of male and female volunteers were enrolled in the trial, with a mean weight (+/- SD) of 73.2 +/- 11.9 kg, mean height (+/- SD) of 66.8 +/- 4.6 inches, and a mean age of 36.1 +/- 5.2 years. Subjects received intravenous infusions of 5 (A), 10 (B), and 15 mg (C) of lubeluzole over 1 hour on three separate occasions, with a minimum washout period of 2 weeks. The treatment sequences were A-B-C; A-C-B; B-A-C; B-C-A; C-A-B; and C-B-A. One male and one female were assigned to each sequence. After the 5-, 10-, and 15-mg doses, maximum concentration (Cmax) was 58.1, 113, and 138 microg/L, respectively, and the area under the curve from 0 to (AUC(0-infinity)) was 771, 1384, and 2025 microg x h/L. There were no statistically significant differences among the groups in mean terminal half-life, steady-state volume of distribution, total plasma clearance, or dose-normalized AUC(0-infinity). Dose-normalized values of Cmax differed significantly between the groups. No serious adverse events were reported, and no changes were observed in cardiac function, as judged by the QT(c) interval. The pharmacokinetics of lubeluzole appear to be linear at intravenous infusion doses of 5, 10, and 15 mg, and these doses are well tolerated by healthy adults.     

Inhibition of peripheral blood mononuclear cell proliferation by cardiac glycosides

We prospectively studied the epidemiologic, clinic signs and outcome of bacterial meningitis in 125 children who were admitted into a PICU (Pediatric Intensive Care Unit) of 11 hospitals of Spain and whose meningitis was diagnosed between May 1994 and April 1995. RESULTS: The median age of the children was 3.55 +/- 3.32 years (range 1 month to 16.5 yrs). Eighty-eight were bacterial meningitis, probably bacterial 30 and aseptic 7. The most frequently isolated organisms were N. meningitidis (52), H. influenza type b (17) and S. pneumoniae (8). Twenty-five percent of N. meningitidis had C serotype. Incidence rate of each germen was depending of age. All patients diagnosed of H. influenza type b meningitis were less than 3 years old. H. influenza type b and meningococcus had similar incidence rate during the first year of life (27% versus 31%). During the first three years of life H. influenza type b produced one third of bacterial meningitis. A mortality rate of 5.6% (seven patients: 3 S. pneumoniae, 1 N. meningitidis, 1 H. influenza type b and 2 unknown germen) was observed. Patients who die had lower Glasgow coma score (p = 0.034) and seizures (p = 0.001) at admission. At discharge of PICU, 9 survivors (7.2%) had sequelae: mental retardation in 7 patients and hearing loss in two. One third of patients needed hemodynamic support and a 15% of them ventilatory support. CONCLUSIONS: Age is an important epidemiological factor in the etiology of pediatric acute meningitis. H. influenza type b and N. meningitidis had similar incidence rate during the first year of life. S. pneumoniae had the highest mortality rate (37.5%). The presence of coma and seizures at admission were associated with mortality.     

Poor long-term survival after acute myocardial infarction among patients on long-term dialysis

BACKGROUND: Cardiovascular disease is common in patients on long-term dialysis, and it accounts for 44 percent of overall mortality in this group. We undertook a study to assess long-term survival after acute myocardial infarction among patients in the United States who were receiving long-term dialysis. METHODS: Patients on dialysis who were hospitalized during the period from 1977 to 1995 for a first myocardial infarction after the initiation of renal-replacement therapy were retrospectively identified from the U.S. Renal Data System data base. Overall mortality and mortality from cardiac causes (including all in-hospital deaths) were estimated by the life-table method. The effect of independent predictors on survival was examined in a Cox regression model with adjustment for existing illnesses. RESULTS: The overall mortality (+/-SE) after acute myocardial infarction among 34,189 patients on long-term dialysis was 59.3+/-0.3 percent at one year, 73.0+/-0.3 percent at two years, and 89.9+/-0.2 percent at five years. The mortality from cardiac causes was 40.8+/-0.3 percent at one year, 51.8+/-0.3 percent at two years, and 70.2+/-0.4 percent at five years. Patients who were older or had diabetes had higher mortality than patients without these characteristics. Adverse outcomes occurred even in patients who had acute myocardial infarction in 1990 through 1995. Also, the mortality rate after myocardial infarction was considerably higher for patients on long-term dialysis than for renal-transplant recipients. CONCLUSIONS: Patients on dialysis who have acute myocardial infarction have high mortality from cardiac causes and poor long-term survival.     

Tuberculosis among Filipino patients with systemic lupus erythematosus

A retrospective review of the clinical records of 54 patients with systemic lupus erythematosus (SLE) and documented tuberculosis (TB) infection seen at the University of Santo Tomas Hospital was accomplished. There were 53 women and one man, with a mean age of 32.2 +/- 10 years and a total of 57 TB occurrences. Pulmonary involvement was recorded in 42 (74%): upper lungfield in 25, mid to lower lungfield in 7, and miliary pattern or diffuse infiltrates in 10. TB arthritis was noted in 8, osteomyelitis in 4, and soft tissue abscesses in 4. Central nervous system involvement consisted of brain abscesses (tuberculomas) in two and meningitis in one. Two patients each had TB lymphadenitis, genitourinary TB, ileocecal TB, and TB peritonitis. Hepatobiliary and cutaneous TB occurred in one patient each. Eight of 10 patients with disseminated or miliary TB died primarily of respiratory failure; six of these eight patients also had some form of extrapulmonary involvement. Using the Wilcoxon rank-sum test, there were significant differences in the mean SLE Disease Activity Index (SLEDAI) and Severity of Disease Index (SDI) scores between those with limited TB (SLEDAI 24 +/- 7 SD; SDI 19 +/- 18 SD) versus those with extensive TB (SLEDAI 41 +/- 16 SD; SDI 36 +/- 21 SD), P < .05. There was no significant difference in the average daily prednisone dose (mg) between those with limited TB (25 +/- 17 SD) versus those with extensive TB (31 +/- 16 SD). The contributory role of tuberculous infection in the morbidity and mortality of patients with SLE must be emphasized, especially in areas endemic for TB.