Thymoma and pancytopenia

Thymomas are often associated with a variety of autoimmune disorders including various cytopenias. Rare cases have been associated with pancytopenia. We describe a patient with an invasive thymoma treated with thymectomy and subsequent radiation therapy. A few months later, rapidly progressing pancytopenia developed. Treatment with antibiotics, immunoglobulin, high-dose steroids and granulocyte-colony stimulating factor (G-CSF) had no effect, and the patient died within two months of overwhelming septicaemia complicated with intracranial haemorrhage. We review the literature and discuss therapies.     

Frequency, causes, and outcome of home ventilator failure

STUDY OBJECTIVES: The safety of home ventilators has been questioned. We collected data to study the following: frequency of home ventilator failure, apparent causes for the failure or malfunction, and adverse consequences following the failure. STUDY DESIGN: Information on all requests to correct home ventilator failures reported to a home respiratory equipment vendor was collected prospectively between November 1991, and November 1992. PATIENTS: There were 150 ventilator-assisted patients aged 2 to 77 years; 44 were < or = 18 years. They received 841,234 h of home mechanical ventilation (average, 15.4 h/d per ventilator-assisted patient). RESULTS: There were 189 reports of home ventilator failure. Defective equipment or mechanical failure was found in only 39% (73 reports), equivalent to one home ventilator failure for every 1.25 years of continuous use. Other causes of ventilator failure included the following: improper care, damage, or tampering with the ventilator by caregivers (13%), functional equipment improperly used by caregivers (30%), and equipment functional but the patient's condition changed, mimicking ventilator failure (3%). No problem could be identified in 16%. The following actions were required: ventilator replacement (44%), repair of a defective part (6%), replacement of a functioning ventilator for psychological comfort (14%), ventilator adjustments made (21%), caregiver reeducation (7%), caregiver anxiety or distress reduced (3%), and no action required (4%). Hospitalization was required only in two cases (1%). No adverse outcomes, deaths, or serious injuries were associated with home ventilator failure. CONCLUSIONS: We conclude that in 150 patients requiring home mechanical ventilation, ventilator failure occurred relatively infrequently, and there were no adverse outcomes as a result of equipment failure at home. We speculate that equipment failure is not a frequent or serious problem for ventilator-assisted patients treated at home.     

Comparison of binding parameters of sigma 1 and sigma 2 binding sites in rat and guinea pig brain membranes: novel subtype-selective trishomocubanes

Comparisons of binding parameters of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine (DTG) at sigma binding sites in guinea pig and rat brain membranes demonstrated that [3H](+)-pentazocine binds to a single high-affinity site, whereas [3H]DTG binds to two high-affinity sites in both species. The Kd values of the radioligands were similar in both types of membranes. However, the density of sigma 1 sites in guinea pig was significantly higher than that of rat. Novel trishomocubanes were tested for their affinities at sigma 1 and sigma 2 binding sites in guinea pig brain membranes using [3H](+)-pentazocine and [3H]DTG as the radioligands. N-(4-Phenylbutyl)-3-hydroxy-4- azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecane (ANSTO-14) showed the highest affinity for the sigma 1 site (Ki = 9.4 nM) and 19-fold sigma 1/sigma 2 selectivity, as a result of increasing the alkyl chain between the cubane moiety and the aromatic ring. N-(3'-Fluorophenyl)methyl- 3-hydroxy-4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11]dodeca ne (ANSTO-19), displayed the highest affinity for sigma 2 sites (Ki = 19.6 nM) and 8-fold sigma 2/sigma 1 selectivity due to a fluoro substitution in the meta position of the aromatic ring. These represent structurally novel lead compounds, especially for the development of selective sigma 2 receptor ligands.     

Physical interpretation of information entropy: Numerical evidence of the Collins conjecture

The effect of altering the dietary Ca:P ratio during critical points of growth (based on reproductive and skeletal age) on kidney calcification in female rats was investigated. Groups of weanling animals were fed one of three nutritionally complete but calcium-altered diets (0.25, 0.5 or 1.0 g Ca/100 g diet) from 4 to 12 wk of age (Phase 1). Phosphorus concentration remained constant at 0.4 g/100 g diet resulting in Ca:P molar ratios of 0.48, 0.96 and 1.92, respectively. During Phase 2, the same animals within each diet group were then rerandomized into one of the above diets and fed for an additional 25 wk. Each group contained five rats. The data from the nine treatment groups were analyzed statistically using a two-way ANOVA (Phase 1 dietary Ca level by Phase 2 dietary Ca level). The level of dietary Ca during Phase 1 only exerted a significant influence on kidney Ca accumulation. Rats fed the two lower dietary Ca levels, and hence lower dietary Ca:P molar ratios, during Phase 1 had two- to threefold greater kidney Ca concentration and kidney ash Ca concentration than rats fed the diet with the highest dietary Ca level (1.92 Ca:P molar ratio) during Phase 1, regardless of the Ca intake during Phase 2. In contrast, the dietary Ca:P molar ratio during Phase 2 had little effect either positively or negatively on the kidney Ca concentration that had been established during Phase 1. The results indicate that dietary-induced nephrocalcinosis in female rats is irreversible and is induced primarily before the completion of adolescence (approximately 12 wk of age) in Sprague-Dawley female rats.     

Hemostatic profile in nephrotic syndrome

OBJECTIVE: To evaluate the coagulation profile and its relation to steroid therapy, and the frequency of thromboembolic complications and its correlation with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based. SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups, namely, fresh cases, steroid dependent, remission after therapy and steroid resistant. An equal number of age and sex matched children served as controls. In all the study and control subjects, detailed clinical examination, liver function tests, renal function tests and detailed coagulation profile were done. Evaluation of renal veins and inferior vena cava for the presence of thrombosis was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected in 57.5% and the degree of thrombocytosis was directly related to the amount of proteinuria. The mean prothrombin and thrombin times were within normal range in the study children. The activated partial thromboplastine time (APTT) was prolonged in six cases (15%) and three out of these six children had thromboembolic complications. Antithrombin-III level was significantly lower (p < 0.001) whereas protein C and S were significantly elevated (p < 0.001) as compared to controls. The levels became normal with remission of the disease. Steroid therapy significantly increased the levels of proteins C, protein S. AT-III and fibrinogen as compared to controls. Thromboembolic complications were seen in 3 cases (7.6%) and were associated with very low levels of AT-III and protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The importance of coagulation profile in nephrotic syndrome is highlighted and a high index of suspicion for thromboembolic complications is warranted in patients with thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low levels of AT-III, protein C and protein S.     

Intravenous administration of L-kynurenine to rhesus monkeys: effect on quinolinate and kynurenate levels in serum and cerebrospinal fluid

The effects of 2-buten-4-olide (2-B40), an endogenous feeding suppressant, on the secretion of luteinizing hormone (LH) were studied in ovariectomized rats. Intraperitoneal (ip) administration of 2-B40: adult female ovariectomized Wistar rats were given daily ip injections of solution containing 2-B40 at 0, 50 or 100 mg/kg body wt for 14 days. This ip treatment with 2-B40 significantly decreased the mean LH concentration and pulse frequency of LH. Intravenous (iv) administration of 2-B40: a solution of 2-B40 (50 or 100 mg/kg body wt) was slowly injected through an intra-atrium catheter and blood samples were taken every 6 min for 2 h. This iv treatment significantly suppressed the LH pulse frequency but had no significant effect on the LH amplitude or mean LH. Injection of 2-B40 into the third cerebroventricle: the injection of 2-B40 into the third cerebroventricle of freely moving rats decreased the mean LH concentration and the frequency and amplitude of LH pulses. Third cerebroventricle injection of a corticotropin-releasing factor (CRF) receptor antagonist before third cerebroventricle injection of 2-B40: the specific CRF receptor antagonist alpha-helical-CRF (9-41) was injected into the third cerebroventricle of ovariectomized rats before injection of 2-B40. Administration of 2-B40 into the third cerebroventricle significantly decreased the mean LH, concentration and pulse frequency. Third cerebroventricle injection of the CRF antagonist at 50 micrograms/rat and then 2-B40 also resulted in significant suppression of the mean LH concentration and pulse frequency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of malaria--an overview

PURPOSE: To examine the anterior optic nerve vasomotor effects of nonselective and relatively beta-1-selective beta-adrenergic antagonists in rabbits, because different influences on optic nerve blood flow with these medications have been suggested. METHODS: After topical therapy for 30 days with either timolol maleate 0.5% (six rabbits), betaxolol hydrochloride 0.5% (six rabbits), or placebo (two rabbits), the microvasculature of the optic nerve was examined with an intraluminal microvascular corrosion casting technique. The investigators were masked to both the medication group and the treated eye. The constriction, in percent of the downstream vessel caliber, was measured at the vascular branching point of arterioles supplying the anterior optic nerve. An average constriction was calculated and compared between the medication groups and between the treated and the contralateral, untreated eyes. RESULTS: Constriction values from a total of 218 arterioles supplying the anterior optic nerve were obtained for the 14 rabbits. The means of the average constriction on the treated side were comparable between the groups treated with timolol maleate, betaxolol hydrochloride, and placebo (one-way analysis of variance, P = .64), as well as between the treated and untreated eyes (two-tailed t-test for paired variables, P = .68 for timolol maleate and P = .42 for betaxolol hydrochloride). The statistical power to find a difference of 5% or more average constriction was at least 90%. CONCLUSIONS: Both relatively selective and nonselective beta-adrenergic antagonists produce no observable optic nerve vasomotor effects in the rabbit eye.