The effect of hyperthyroidism on gastric emptying rates and pancreatic exocrine and biliary secretion in man

Malabsorption and diarrhea in hyperthyroidism has been attributed in part to an increased rate of gastrointestinal transit as measured with barium sulfate suspension. Data are unavailable on the effect of hyperthyroidism on gastric emptying rates of normal food and pancreatic enzyme secretion. These functions have been studied in 4 hyperthyroid patients and compared to results obtained when treatment achieved euthyroidism. Pancreatic trypsin secretion was half the euthyroid level in the hyperthyroid state. No significant change in bile salts occurred, although there was a tendency for a greater proportion of dihydroxy bile salts while hyperthyroid. Gastric emptying rates of a mixed fat, protein, and carbohydrate liquid meal were normal. Similarly the gastric emptying rate of a beef stew plus chicken liver meal was normal. We conclude that in hyperthyroidism gastric emptying rates of physiologically active food is normal. Pancreatic enzyme secretion is depressed in hyperthyroidism and may contribute to maldigestion.Supported by the Medical Research Service of the Veterans Administration and Apprenticeships for Carrer Exploration (KML).     

Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme.

Captopril, a specific oral inhibitor of angiotensin-converting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may maintain blood pressure in essential hypertension. This does not necessarily imply that the renin-angiotensin system is the cause of the high blood pressure.     

Dipyridamole bioavailability in subjects with reduced gastric acidity

Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increased gastric pH that occurs with commonly prescribed antacids. An extended-release (ER) formulation of DP that employs tartaric acid to improve bioavailability of DP in the presence of elevated gastric pH was developed as a combination antiplatelet product with immediate-release aspirin. This crossover-designed study examined the relative bioavailability of DP from the composite product compared to conventional DP tablets during reduced gastric acidity. Gastric pH was increased (pH > 4.0) in 20 healthy subjects with lansoprazole (30 mg/d for 5 days). Dipyridamole systemic exposure over 12 hours was compared after oral administration of a single composite ER capsule (200 mg DP + 25 mg aspirin) versus two 100-mg conventional DP tablets given 6 hours apart combined with 81 mg aspirin. DP relative bioavailability was reduced 53% with conventional tablets compared to the composite buffered ER capsule in reduced gastric acid conditions. Peak DP plasma concentrations were 57% lower with immediate-release tablets compared to the composite formulation with high stomach pH. Substituting generic DP plus low-dose aspirin may be less effective than the buffered DP composite product in patients with concomitant antacid therapies.     

A case of mucormycosis limited to the parotid gland

BACKGROUND: Mucormycosis is a rare fungal infection commonly affecting structures in the head and neck such as air sinuses, orbits, and the brain. Common predisposing factors include diabetes and immunosuppression. To date, only one case of mucormycosis involving the parotid gland has been reported, and this infection was associated with a fatal outcome. METHODS: We report a case of parotid gland mucormycosis in a 45-year-old woman with type 2 diabetes, who was successfully treated with a superficial parotidectomy and intravenous amphotericin B. RESULTS: After initial surgical and antifungal therapy, the patient was left with a residual facial nerve palsy for which multiple sling procedures were performed. She is currently alive and well 6 years after the diagnosis of mucormycosis. CONCLUSIONS: Mucormycosis of the parotid gland is a rare form of this often-fatal infection. In this case, infection remained isolated to the parotid gland and was diagnosed soon after presentation. The patient most likely survived because of the early diagnosis, successful surgical removal of all infected tissue, use of intravenous amphotericin therapy, and the aggressive management of comorbidities such as her diabetes.     

Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers

Loperamide (LOP) is a peripherally acting opioid receptor agonist used for the management of chronic diarrhea through the reduction of gut motility. The lack of central opioid effects is partly due to the efflux activity of the multidrug resistance transporter P-glycoprotein (P-gp) at the blood-brain barrier. The protease inhibitors are substrates for P-gp and have the potential to cause increased LOP levels in the brain. Because protease inhibitors, including tipranavir (TPV), are often associated with diarrhea, they are commonly used in combination with LOP. The level of respiratory depression, the level of pupil constriction, the pharmacokinetics, and the safety of LOP alone compared with those of LOP-ritonavir (RTV), LOP-TPV, and LOP-TPV-RTV were evaluated in a randomized, open-label, parallel-group study with 24 healthy human immunodeficiency virus type 1-negative adults. Respiratory depression was assessed by determination of the ventilatory response to carbon dioxide. Tipranavir-containing regimens (LOP-TPV and LOP-TPV-RTV) caused decreases in the area under the concentration-time curve from time zero to infinity for LOP (51% and 63% decreases, respectively) and its metabolite (72% and 77% decreases, respectively), whereas RTV caused increases in the levels of exposure of LOP (121% increase) and its metabolite (44% increase). In vitro and in vivo data suggest that TPV is a substrate for and an inducer of P-gp activity. The respiratory response to LOP in combination with TPV and/or RTV was not different from that to LOP alone. There was no evidence that LOP had opioid effects in the central nervous system, as measured indirectly by CO2 response curves and pupillary response in the presence of TPV and/or RTV.     

Heparin receptors on mouse macrophages

This study deals with the nature of the attachment between the macrophage cell membrane and heparin molecules. Treatments intended to remove or internalise macrophage receptors (trypsinisation and stimulation of phagocytosis respectively) were shown to considerably modulate the attachment of heparin. An excess of heparin fractions ranging in mean molecular weight from 8100 to 25700 all inhibited attachment of 35S heparin as did a mixed isomer chondroitin sulphate preparation. Our study provides evidence for the presence of receptors for sulphated glycosamino-glycans on the mouse macrophage cell membrane.     

Kabuki syndrome: new ocular findings but no evidence of 8p22-p23.1 duplications in a clinically defined cohort

The underlying cause of the multiple congenital anomalies/mental retardation syndrome Kabuki syndrome (KS, OMIM 147920) has not yet been established. We identified seven patients who fulfilled the classical clinical criteria for this syndrome and undertook a detailed clinical, ophthalomological and molecular cytogenetic review. Three of the seven patients had previously undetected ocular anomalies including myopia, ptosis, strabismus and tilted discs. The identification of preventable causes of loss of vision underlines the value of detailed ophthalmologic examination of KS patients. Using BAC fluorescence in situ hybridisation, there was no evidence of the duplication of 8p recently reported by Milunsky and Huang. We conclude that the cause of KS has yet to be established.     

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs. Only 21% of the 19 patients entered on suspicion of having DMAC grew MAC from blood or marrow. Neither clinical presentation nor laboratory tests differentiated those culture-positive from those culture-negative patients. However, prior PCP or multiple other opportunistic infections were more common in the DMAC group. MAC was isolated from 82% of marrow and 50% of blood specimens from the DMAC group. Respiratory or gastrointestinal colonization was present in 36% of DMAC subjects, but only 5% of non-DMAC subjects with CD4 counts <50 cells/microl. CD8+ cells were more frequent in bone marrow, and CD4 cells recognizing MAC antigen were more frequent in blood from DMAC subjects vs. controls. Results suggest an early stage of tissue dissemination preceding persistent bacteremia, and mucosal entry without persistence of colonization. MAC-specific T cell responses apparently develop and persist during DMAC, but are dysfunctional or too infrequent to prevent persistence.