Antigenic determinants detected on adenoid lymphocytes

This study was undertaken to detect the antigenic determinants expressed by adenoid lymphocytes. For this purpose, adenoid and peripheral blood lymphocytes obtained from the same patient were subsequently tested with human and hetero antisera. The research was based upon microlymphocytotoxicity where the various lymphocyte subsets were incubated with the antiserum and complement. The reactions were scored by the dye exclusion technique. The results indicated that: 1) compared with peripheral blood, the expression of the major histocompatibility gene products is enhanced by adenoid lymphocytes; 2) adenoid T lymphocytes express DRw antigens. These antigens were thought to be restricted to B lymphocytes and macrophages but have later been detected in T lymphocytes activated in vitro. Thus, lymphocytes derived from hypertrophied adenoids may simulate a culture activated in vivo; 3) because of their higher sensitivity to antibodies and complement-mediated cell lysis, adenoid lymphocytes may be useful in detecting minor histocompatibility gene products and differentiation antigens. It is concluded that adenoids represent a highly active lymphoid organ probably actively participating in the host's immunological defence mechanism.     

Decreased expression of the p21ras stimulatory factor hSOS in PBMC from inactive SLE patients

Expression of the p21 ras protooncogene is reported to be increased in animal models and in patients with SLE. However, the expression of p21ras regulatory elements has not been determined. We determined the expression of p21ras, and its regulatory elements p120-ras-GAP and hSOS, in PBMC of 10 patients with inactive SLE (mean SLEDAI score 1.8+/-0.53) and 10 age- and sex-matched healthy controls. No difference was found between the two groups in the levels of p21 ras (3760+/-513 and 3367+/-335, P=0.25) and ras-GAP (1048+/-261 and 1534+/-247, P=0.11) in patients and controls, respectively. In contrast, levels of hSOS were significantly decreased in patients as compared to controls: 955+/-218 and 2306+/-327, P = 0.002, respectively. The mitogen-induced proliferative response was comparable in the two groups: SI 20.8+/-4.2 and 15.03+/-4.9, P=0.135, in patients and controls, respectively. Taken together, our data demonstrate that nonactive SLE patients are characterized by reduced hSOS expression and underscore the need for a comprehensive evaluation of p21ras pathway in these patients.     

Anti-inflammatory drugs in the treatment of neurodegenerative diseases: current state

Increasing evidence indicates that inflammation is involved in the pathogenesis of many neurological, particularly neurodegenerative diseases. Even if inflammation is not a primary causative process, its presence may contribute to the continued loss of CNS neurons. Therefore, it seems reasonable to propose that use of anti-inflammatory drugs might diminish the cumulative effects of inflammation in the brain. Indeed, some epidemiological studies performed to date, especially in Alzheimer's disease, suggests that sustained use of anti-inflammatory drugs (AIDs) may prevent or slow down the progression of neurodegenerative diseases. However, small number of clinical trials carried out so far using AIDs, were minimal and equivocal in their outcome. Potential reasons for these mixed results include timing of AIDs administration, nonselective inhibition of cyclooxygenase (COX), inappropriate use of particular anti-inflammatory drugs for a given disease or disease progression/ severity, sub-optimal dose in target site, or limited penetration to the brain through the blood-brain barrier (BBB). Therefore, design of AIDs for the treatment of neurodegenerative diseases based upon better BBB penetration, and with minimal adverse events, would be appropriate. In addition, relevant genetic differences among patients should be considered planning new AIDs, for improved efficacy. Furthermore, due to the possible co-involvement of oxidative stress and excitotoxicity in the pathogenesis of these diseases, combination therapy with antioxidants or glutamate antagonists or a multi-potent drug might be much more effective in successfully treating neurodegenerative diseases.     

Beta1- or beta2-blockers to improve hemodynamics following endotracheal adrenaline administration

BACKGROUND: The recommended dose for endotracheal adrenaline (0.02 mg/kg) causes a pronounced initial decrease in diastolic blood pressure which is detrimental at the initial phase of cardiopulmonary resuscitation. This effect was previously attributed to an early and preferential stimulation of the beta-adrenergic receptors causing vasodilatation unopposed by an alpha-adrenergic vasoconstriction. We hypothesized that inhibition of the beta2-adrenoreceptors is responsible for prevention of the deleterious initial decrease in blood pressure that takes place following endotracheal administration of adrenaline. METHODS: Adrenaline (0.02 mg/kg) diluted with normal saline (5 ml) was injected into the endobronchial tree of anesthetized dogs 3 min following pretreatment with the non-selective beta-blocker propranolol, selective beta1-blocker metoprolol (0.1 mg/kg, i.v.), or without pre-treatment. Heart rate, blood pressure and arterial blood gases were monitored. RESULTS: The selective beta-blocker metoprolol was almost as effective as the non-selective beta-blocker propranolol in attenuating the initial decrease in blood pressure following endotracheally administered adrenaline, a phenomenon that was previously attributed to inhibition of beta-adrenoreceptors. CONCLUSIONS: The outcome of this study might be explained by a dose-related loss of cardioselectivity of metoprolol. Further studies are warranted to refine the pharmacological means to abort the initial blood pressure-lowering effect of endotracheally administered adrenaline.     

Physician speciality and adherence to guidelines for the treatment of unsubstantiated uncomplicated urinary tract infection among women

PURPOSE: To evaluate the variance in rates of physician adherence to guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommending either trimethoprim-sulfamethoxazole (TMP-SMX) or nitrofurantoin, in all relevant physician subspecialities practising in a managed care community setting in Israel. METHODS: Data were derived from the computerised medical records of Maccabi Healthcare Services, a health maintenance organisation (HMO) in Israel providing care to more than 1.6 million members nation-wide. The study population included women aged 18-75 years without risk factors for complicated UTI who were treated empirically with antibiotics for a diagnosis of acute cystitis or UTI. The data set consisted of 64,236 initial physician-patient encounters from July 2000 to June 2002. Physician adherence to guidelines was calculated by comparing the proportion of cases treated with each individual drug. A binary regression model was used to evaluate factors associated with suboptimal adherence to the guidelines. RESULTS: Nitrofurantoin was the most frequently prescribed drug (18.51%), followed by TMP-SMX (17.04%) for a crude rate of adherence of 35.6%. Adherence was observed to be highest in cases treated by urologists (OR=2.8, 95%CI: 2.4, 3.3), followed by gynaecologists (OR=1.9, 95%CI: 1.7, 2.31), with family practice as the referent speciality. The medical school attended was also found to be significant. CONCLUSIONS: Physician speciality was found to be significantly associated with rate of adherence to guidelines, with higher rates being observed amongst specialities such as urologists who presumably have greater familiarity with the subject matter.     

Five-year experience with the 'Sheba' model of comprehensive orthogeriatric care for elderly hip fracture patients

BACKGROUND AND PURPOSE: The Sheba model of orthogerioatric medicine is a unique model of in-hospital care for elderly hip fractured patients, based upon the concept that a hip fracture represents a geriatric, rather than an orthopedic disease. The nature and feasibility of such a comprehensive orthogeriatric unit, taking care of all surgical, medical and rehabilitation needs, in a single geriatric-based setting (rather than orthopedic-based), were questioned. The aim of the study is to describe the results of its operation during a five-year period. METHOD: A retrospective charts analysis of consecutive older patients with hip fractures, admitted from the emergency unit directly to the orthogeriatric unit of a department of geriatric medicine. RESULTS: A total number of 592 patients were admitted. Mean age of patients was 83.2 years, mostly women. A total of 538 (91%) were treated surgically. Delay to surgery was 3.6 +/- 2.9 days. A total of 65.6% were suitable for rehabilitation, and had a mean Functional Independence Measure (FIM) gain of 22.3 +/- 7.9. Mean total hospital length of stay was 29.9 days and 68.7% of patients returned to their previous living residence. Rates of major complications (4.1%) and in-hospital mortality (3.2%, equivalent to 30 days mortality) were low. CONCLUSIONS: Treatment within this unit was associated with low rates of major morbidity and mortality, short stay and acceptable functional outcomes. The data provide clinical evidence supporting the implementation of this model of comprehensive orthogeriatric care, being a practical, applicable and feasible service for elderly hip fractured patients, and covering the various needs of these patients. The present model of organization could also help in skillful use of economic resources, facilitating effective treatment strategies.     

Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives: a multicenter study

OBJECTIVE: To investigate the prevalence of autoimmune diseases in young patients (probands) with type 1 diabetes and their first-degree relatives, and to determine the spectrum of extrapancreatic manifestations in these subjects. RESEARCH DESIGN AND METHODS: The study population included 109 probands age 13 +/- 4.9 years and 412 first-degree relatives age 28.7 +/- 16.2 years. The prevalence rates of autoimmune thyroiditis and celiac disease were determined in all probands and in 100 of the 412 first-degree relatives. Control groups included 78 subjects age 14.9 +/- 10.4 years for the prevalence of autoimmune thyroiditis and 120,000 youth ages 16-17 years for the prevalence of celiac disease. Thyroiditis and celiac disease were diagnosed by abnormally high thyroid peroxidase (TPO), thyroglobulin (TG), antigliadin, and antiendomysial antibody titers. Celiac was confirmed by biopsy. A questionnaire was used to interview probands and relatives to determine the spectrum of autoimmune manifestations. RESULTS: The prevalence of autoimmune thyroiditis determined by high TPO and/or TG titers was 27 and 25% for probands and relatives, respectively. These rates were higher than those for control subjects (P < 000.1). The prevalence of celiac disease among probands and screened relatives was 8.3 and 6%, respectively. These rates were higher than those for control subjects and the 312 family members interviewed only (0.1 and 0.3%, respectively; P < 0.0001). Interviews of participants revealed a wide range of associated autoimmune diseases. The risk of developing an autoimmune disease was higher (P < 0.001) in families with a proband who had an additional autoimmune manifestation. CONCLUSIONS: Screening for autoimmune thyroiditis and celiac disease should be performed in patients with type 1 diabetes and their first-degree relatives, especially when the probands have an additional autoimmune manifestation.     

Endotracheal epinephrine: a call for larger doses

Endotracheal administration of epinephrine 0.02 mg/kg (twice the IV dose) is recommended when IV access is unavailable during cardiopulmonary resuscitation. The standard IV dose has been considered too small for the endotracheal route by causing a detrimental decrease of arterial blood pressure (BP), presumably mediated by the beta-adrenergic receptor unopposed by alpha adrenergic vasoconstriction. We conducted a prospective, randomized, laboratory comparison of increasing doses of endotracheal epinephrine to ascertain the yet undetermined optimal dose of endotracheal epinephrine that would increase BP. After injecting normal saline (control), saline-diluted epinephrine (0.02, 0.035, 0.1, 0.2, and 0.3 mg/kg) was injected into the endotracheal tube of five anesthetized dogs at least 1 wk apart. Arterial blood samples for blood gases were collected before and at 14 time points up to 60 min after the drug administration. Heart rate and arterial BP were continuously monitored with a polygraph recorder. Only the 0.3 mg/kg dose successfully caused an increase in BP, observed 2 min after administration, and lasting for 10 min. An early decrease in BP was obviated only at a dose equivalent to 10-fold the currently recommended one. IMPLICATIONS: We conducted a prospective, randomized, laboratory comparison of increasing doses of endotracheal epinephrine to ascertain the yet undetermined optimal dose of endotracheal epinephrine that would increase arterial blood pressure (BP). A decrease in BP was obviated only at a dose equivalent to 10-fold the currently recommended one. Clinical studies using larger doses of endotracheal epinephrine and their use as first-line therapy in cardiac arrest are warranted.