Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women.

UNLABELLED: We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. INTRODUCTION: To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. METHODS: In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. RESULTS: The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART. CONCLUSIONS: In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.

Decreased digoxin cardioinactive-reduced metabolites after administration as an encapsulated liquid concentrate.

The generation by intestinal bacteria of large amounts of cardioinactive metabolites of digoxin with a reduced lactone ring (digoxin reduction products, or DRP) may be associated with increased dosage requirements. Since DRP excretion varies inversely with bioavailability, we compared the 6-day urinary excretion (CUE) of digoxin and DRP after 0.4-mg doses of an encapsulated liquid concentrate and a standard tablet in 22 normal subjects known to form substantial amounts of DRP. Mean (+/- SE) CUE of digoxin was greater with the capsules than the tablets (195.9 +/- 8.6 and 137.5 +/- 6.3 micrograms). CUE of DRP was less after the capsules (60.8 +/- 5.5 and 102.7 +/- 9.5 micrograms). Percent DRP was greater after the tablets in every subject (mean for tablets, 41.2 +/- 2.7%; capsules, 23.5 +/- 1.8%). Patterns of DRP excretion differed with the two preparations, probably reflecting differences in the routes whereby digoxin reached the colon. The use of highly bioavailable capsules in subjects with heavy DRP production should minimize metabolic inactivation during digoxin therapy.

Neurologic disease in human immunodeficiency virus-infected drug abusers.

Previous studies of human immuno-deficiency virus-related neurologic disease have been either retrospective or have included mostly homosexual patients. We sought to determine (1) the true prevalence of neurologic abnormalities in patients with acquired immunodeficiency syndrome or lymphadenopathy acquired immunodeficiency-related complex, and (2) whether differences in prevalence or type of neurological abnormality exist between parenteral drug abusers and non-parenteral drug abusers. We prospectively evaluated 190 adult inpatients with either acquired immunodeficiency syndrome (129) or lymphadenopathy acquired immunodeficiency-related complex (61); 151 (80%) were parenteral drug abusers, and 172 patients (91%) had neurologic symptoms or signs. There was no significant difference in prevalence of neurologic disease between parenteral drug abusers and non-parenteral drug abusers, or between patients with acquired immunodeficiency syndrome and those with lymphadenopathy acquired immunodeficiency-related complex. The prevalence of neurologic symptoms in these patients with lymphadenopathy acquired immunodeficiency-related complex and acquired immunodeficiency syndrome is the highest reported to date and appears to reflect the prospective nature of the study.

Large subcortical hemispheric infarctions. Presentation and prognosis.

A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.

Glucose uptake by gliomas after treatment. A positron emission tomographic study.

Positron emission tomographic scanning with fludeoxyglucose F 18 (18F-fluorodeoxyglucose) was used to study acute changes in gliomas after chemotherapy. In six experimental subjects, scans were obtained before and at days 1, 7, and 30 after treatment. Five control patients with gliomas who did not undergo chemotherapy had two scans, 1 month apart. Ratios were calculated between peak tumor regional cerebral metabolic rate for glucose and contralateral white matter. The percent change in ratios relative to each patient's baseline scan was calculated. Ratios in three stable controls remained unchanged over the study interval; in two controls it increased 155% and 36% and both died of tumor progression. In experimental subjects, ratios increased 20% to 100% 24 hours after chemotherapy and then decreased until at 28 days they varied between 22% above and 35% below baseline. The increased fludeoxyglucose F 18 uptake at 24 hours could be from uncoupling oxidative phosphorylation or shunting glucose to ribose phosphates for salvage nucleoside synthesis.

Evidence for transhemispheric diaschisis in unilateral stroke.

Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis.

Nonspecificity of ring enhancement in "medically cured" brain abscess.

Since the introduction of computed tomography (CT), there have been numerous reports of brain abscess treated successfully without surgery. Because pathologic confirmation was lacking in these patients, diagnosis was based on CT abnormalities, usually ring enhancement. However, our recent clinical experience and the experimental work of others indicate that the "ring sign" on contrast-enhanced CT is not absolutely diagnostic of encapsulated brain abscess. Moreover, in the reported cases of alleged brain abscess cured medically, atypical clinical features suggest that some patients may have had cerebral infarction or cerebritis. Stricter clinical and radiologic criteria are needed before concluding that encapsulated brain abscess can be cured by medical therapy alone.

Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. The Peptide T Neuropathy Study Group.

OBJECTIVE: To assess the safety and efficacy of Peptide T in the treatment of painful distal symmetrical polyneuropathy (DSP) associated with human immunodeficiency virus (HIV) infection. BACKGROUND: Painful DSP is a frequent complication of HIV infection, although its etiology and optimal treatment are unknown. Peptide T (D-(alpha 1)-Peptide T-amide) has been found in phase I trials and anecdotal reports to relieve neuropathic pain in AIDS patients. DESIGN/METHODS: In this multicentered, double-blind, randomized study, subjects received intranasal Peptide T 6 mg/day or placebo for 12 weeks. The primary outcome measure was change in the modified Gracely pain score. Secondary efficacy variables were results of neurologic examination, neuropsychological and electrophysiologic studies, global evaluation, and CD4 lymphocyte counts. RESULTS: Of 81 evaluable subjects, 40 received Peptide T and 41 received placebo. The change in pain scores was not significantly different (p = 0.32) in the Peptide T group (-0.24) as compared to placebo (-0.39). Group comparisons were not significantly different for change in any clinical examination or neuropsychologic measure, sural nerve amplitude or conduction velocity, or CD4 lymphocyte count. No significant drug-related adverse effects occurred in either group. CONCLUSION: Intranasal Peptide T is safe but ineffective in the treatment of painful DSP associated with AIDS.

Cerebral vasocapacitance and TIAs.

We report the vasocapacitance of the cerebral circulation, as determined by cerebral blood flow reactivity to induced hypercapnia using fluoromethane positron emission tomography, in 32 patients with unilateral anterior circulation transient ischemic attacks. A hemodynamic subset of eight patients, defined based on exertional, positional, orthostatic, or cardiac dysrhythmic induction of symptomatology, is characterized by multiple (median, 4.5 attacks per patient), brief (median, 2.5 minutes per attack), continued episodes of hemispheric ischemia including focal limb shaking. Symptomatic middle cerebral artery flow territories show significantly lower (p less than 0.04) and more asymmetric (p = 0.036) vasodilatory responses in the hemodynamic subset. Although ipsilateral internal carotid artery occlusion is more prevalent in the hemodynamic subset, the features of age, mean arterial blood pressure, carbon dioxide values, serum glucose, serum hematocrit, and number or type of risk factors do not differ significantly between groups. These studies of vasocapacitance help validate clinical criteria for cerebral hemodynamic events with an objective physiologic measurement.

Occult polymicrobial endocarditis with Haemophilus parainfluenzae in intravenous drug abusers.

PURPOSE AND PATIENTS AND METHODS: Fewer than 8 percent of intravenous drug abusers are found to have polymicrobial endocarditis. We report on cases of occult polymicrobial infective endocarditis with Haemophilus parainfluenzae in 10 intravenous drug abusers. Clinical and laboratory data on all 10 patients were obtained from hospital charts, and information on illicit drug use methods was given by five patients. Blood cultures were performed, as well as susceptibility testing to antibiotics. Subsequent molecular epidemiologic studies were performed on selected Staphylococcus aureus and H. parainfluenzae strains. Phage typing of S. aureus and biotyping of H. parainfluenzae strains were also done. RESULTS: Results of the initial blood cultures were positive on the second to fifth days (mean, 2.6 days), demonstrating a gram-positive pathogen in nine patients and Bacteroides asaccharolyticus in one. Significantly, in each case, H. parainfluenzae alone was subsequently identified from additional blood cultures, with a mean delay of 20.4 days (range, five to 57 days) to the isolation of this organism. Epidemiologic data indicated that our cases did not represent a point-source outbreak. Antibiotic therapy uniformly failed until an agent active against H. parainfluenzae was added. The constellation of clinical, microbiologic, and epidemiologic findings was similar, and permitted prospective diagnosis and therapy in three patients. Despite the absence of S. aureus bacteremia in four, all 10 patients had right-sided endocarditis with septic pulmonary emboli. Five patients had initial blood cultures that were positive for two facultative gram-positive cocci (S. aureus and commensal oral streptococcal species). CONCLUSION: Our findings suggest that polymicrobial endocarditis with H. parainfluenzae in intravenous drug abusers is a distinct clinical syndrome, and should be considered in all patients if the response to appropriate antibiotics is atypical or if pulmonary emboli continue with therapy.

Digoxin inactivation by the gut flora in infancy and childhood.

Inactivation of digoxin by reduction of the lactone ring has recently been shown to occur in one third of adults and to be mediated by anaerobic intestinal bacteria. Children from birth through adolescence were studied to determine the pattern of development of this gut flora-mediated process. None of 36 digitalized infants 8 months of age or less excreted reduced digoxin metabolites in the urine. The adult pattern of digoxin reduction product excretion by one third of patients was observed after 16 months of age; however, high levels of digoxin reduction products such as are found in 10% of adults were not encountered in children less than 9 years of age. Even though reduced metabolites were not formed in vivo early in life, stool cultures of 20 of 73 infants younger than 8 months of age contained digoxin reduction product-forming bacteria at high concentrations, in some instances as early as the second week of life. Maturation of the gut flora with respect to digoxin metabolism appears to be a protracted process. The relative digoxin resistance of infants and children is not due to bacterial inactivation.

Modulation of the multidrug resistance P-glycoprotein: detection with technetium-99m-sestamibi in vivo.

UNLABELLED: Overexpression of the multidrug resistance (MDR1) P-glycoprotein (Pgp) has been documented in nearly all forms of human cancers and increased levels of Pgp in some tumors correlate with poor response to treatment. Technetium-99m-sestamibi has recently been validated as a Pgp transport substrate. Pgp is also normally expressed along the biliary canalicular surface of hepatocytes and the luminal side of proximal tubule cells in the kidney, while not expressed in heart. METHODS: Focused on these organs with known Pgp status, we present the findings on 99mTc-sestamibi scintigraphy of three patients with refractory cancer who were imaged before and after administration of SDZ PSC 833, a second-generation, high-potency modulator of Pgp. RESULTS: Before treatment with SDZ PSC 833, scintigraphy using 99mTc-sestamibi showed normal, prompt clearance of the radiotracer from the liver and kidneys relative to the heart. After administration of the Pgp modulator, 99mTc-sestamibi was selectively retained in the liver and kidneys. CONCLUSION: Hepatobiliary and renal clearance of 99mTc-sestamibi are Pgp-mediated, and inhibition of Pgp transport in these organs can be successfully imaged using 99mTc-sestamibi in patients. Similar results might be expected with this and related radiopharmaceuticals for functional imaging of Pgp transport and modulation in tumors.

Preclinical evaluation of fluorine-18-labeled androgen receptor ligands in baboons.

UNLABELLED: A noninvasive method for detecting and quantifying androgen receptors (AR) in metastatic prostate cancer may be helpful in choosing the method of treatment and in better understanding the pathophysiology of this disease. Nine previously synthesized fluorinated androgens exhibited high affinity binding to AR and showed AR-mediated uptake in the ventral and dorsal prostate of the rat. Further evaluation of these agents for PET imaging is needed since sex hormone binding globulin (SHBG), a glycoprotein which binds androgens with high affinity, is absent in rat blood but is present at high levels in the blood of primates. We chose to study three of the nine fluoro-androgens by PET in the baboon. METHODS: In this study, 16beta-[18F]fluoro-5 alpha-dihydrotestosterone (I), 16beta-[18F]fluoromibolerone (II) and 20-[18F]fluoromibolerone (III) were synthesized and studied in both a young and old male baboon using PET. Blood samples were withdrawn in three of the 10 studies and analyzed for total radioactivity and percent unmetabolized radioligand. Tissue radioactivity was evaluated semiquantitatively, using prostate absolute, standard and target to nontarget uptake values. RESULTS: Prostate uptake was observed with all three 18F-androgens. At 60 min postinjection, compound I gave the highest prostate to soft tissue ratios in both baboons and prostate uptake was shown to be AR-mediated by blocking uptake through the coadministration of testosterone. Compound I gave the highest level of unmetabolized radioligand present in blood up to 45 min postinjection, and gave a 37-fold greater prostate-to-bone ratio at 2 hr postinjection in baboons compared to rats. The favorable behavior of this compound in the baboon may be related to its high affinity for SHBG. CONCLUSION: All three compounds can be used to determine AR-positive tissue in primates. Compound I was selected for the evaluation of AR in men with prostate cancer using PET.

Antitussive effect of the GABA-agonist baclofen.

BACKGROUND: gamma-Aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in peripheral tissues, including the lung. The GABA-agonist baclofen has been shown, in animal studies, to inhibit cough via a central mechanism, but has not been investigated in humans (to our knowledge). STUDY OBJECTIVE: To evaluate the antitussive effect of baclofen in normal human subjects. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic medical center. PARTICIPANTS: Twenty healthy, adult volunteers. INTERVENTIONS: Subjects underwent cough challenge with inhaled capsaicin before and after a 14-day course of baclofen, 10 mg three times daily, or placebo. Capsaicin cough threshold (C5) was defined as the concentration of inhaled capsaicin inducing five or more coughs. RESULTS: Subjects receiving baclofen (n=10) demonstrated a significant elevation of capsaicin cough threshold compared with placebo subjects (n=10). Mean delta log C5 after treatment was 0.48+/-0.19 (SEM) for the baclofen group, and -0.06+/-0.12 for the placebo group (p=0.024). Six of 10 subjects receiving baclofen, but none of the 10 subjects receiving placebo, demonstrated a fourfold or greater increase in capsaicin cough threshold (p=0.0054). CONCLUSION: The antitussive activity of low-dose, oral baclofen demonstrated in this study supports further investigation of this drug, or other GABA-agonists, for a potential therapeutic role in the treatment of pathologic cough.

Reduction in tuberculin skin-test conversions among medical house staff associated with improved tuberculosis infection control practices.

OBJECTIVE: To assess the efficacy of an infection control program as measured by tuberculin skin-test (TST) conversion rates in medical house staff. DESIGN: Observational study. SETTING: University-based hospital in New York City serving a large indigent population. PARTICIPANTS: Medical house staff. INTERVENTIONS: TST conversions were measured every 6 months in medical house staff from June 1992 to June 1994. Compliance with the isolation policy was measured by identifying room locations 24 hours after admission of patients who had Mycobacterium tuberculosis recovered from respiratory specimens. RESULTS: The TST conversion rate decreased from 5.8 to 0, 2.3, and 0 per 100 person years of exposure in successive 6-month periods. The estimated annual TST conversion rate among interns fell from 7 per 100 person years in June 1992 to 0 per 100 person years in June 1993 and 0 per 100 person years in June 1994 (P < .029). The proportion of patients with pulmonary tuberculosis who were isolated in negative-pressure rooms increased from 38% to 75% over the study period (P < .01). CONCLUSION: Development of a multifaceted infection control program can decrease the risk of nosocomial tuberculosis infection in medical house staff.

Effect of angiotensin-converting enzyme inhibition on bronchial responsiveness.

The effect of angiotensin-converting enzyme (ACE) inhibition on bronchial responsiveness has not been clearly established. Because ACE degrades bradykinin and substance P, inhibition of the enzyme may lead to accumulation of these potent bronchoconstrictors in the lung, potentially leading to enhanced bronchial reactivity or bronchospasm. Previous studies of the effect of ACE inhibition on airway responsiveness have yielded conflicting results. A randomized, double-blind, placebo-controlled study was therefore conducted to evaluate the effect of a 14-day course of oral lisinopril (10 mg for days 1-3, 20 mg for days 4-14) on bronchial responsiveness to inhaled methacholine in a group of healthy volunteers. No significant change in methacholine responsiveness occurred in any of the participants receiving lisinopril. The mean ( +/- SD) concentration of methacholine producing a decrease in FEV1 of 20% from baseline (PC20; mg/mL) was 23.3 +/- 5.0 before the study and 23.5 +/- 4.5 at the end of the study for the lisinopril group, and 23.0 +/- 4.6 before the study and 21.8 +/- 6.9 after the study for the placebo group. The 14-day course of ACE inhibitor therapy did not enhance nonspecific bronchial responsiveness in healthy volunteers.

Inhibition of capsaicin-induced cough by the gamma-aminobutyric acid agonist baclofen.

Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in the lungs. The GABA-agonist baclofen has been shown to have antitussive activity via a central mechanism in animals. Recently it was demonstrated that a 14-day course of baclofen given three times daily significantly inhibits the cough reflex in healthy volunteers. Because of the prolonged antitussive effect of baclofen that has been previously observed, the present study was conducted to evaluate the antitussive effect of low-dose, oral baclofen given once daily. Forty-one healthy volunteers were randomly assigned in a double-blind manner to receive a 28-day course of baclofen, either 10 mg or 20 mg once daily, or placebo. Subjects underwent cough challenge testing with inhaled capsaicin to establish baseline cough reflex sensitivity, and subsequently after 14 and 28 days of therapy. Subjects receiving baclofen 20 mg daily demonstrated significant inhibition of cough sensitivity after 14 days and after 28 days of therapy compared with baseline. Neither placebo nor baclofen 10 mg daily had a significant effect on cough sensitivity. No serious side effects were experienced by any study participant. These results confirm the recent observation that baclofen has significant antitussive activity in humans. Further, once-daily administration of a relatively low dose of baclofen is sufficient to achieve significant cough inhibition, although at least 14 to 28 days of therapy may be required to attain maximal antitussive effect. These results support further investigation of baclofen or other GABA-agonists as potential therapeutic agents for chronic, nonproductive cough.

Pulmonary embolism: diagnosis and treatment.

Pulmonary embolism is a condition with a potentially high mortality that often goes unrecognized. Prompt diagnosis and treatment effectively reduce the mortality rate. Clinical judgment alone is insufficient for diagnosis; objective testing is needed. Once the diagnosis is made, effective treatment should be instituted. Treatments differ, based on several factors including disease severity, contraindications to treatment and pre-existing diseases. The major thrust of training should be to teach medical care workers how to prevent deep vein thrombosis and its most serious complication, pulmonary embolism.

123I-iodoamphetamine SPECT brain imaging in alternating hemiplegia.

Alternating hemiplegia of childhood is an unusual disorder characterized by early onset (occurring before 18 months of age); repeated attacks of hemiplegia involving both sides of the body; other paroxysmal phenomena, such as tonic stiffening, dystonic posturing, choreoathetoid movements, ocular motor abnormalities, and autonomic disturbances, in association with bouts of hemiplegia or occurring independently; and evidence of mental or neurologic deficits. A girl was examined because of left hemiplegia at the age of 16 months. The patient had begun exhibiting episodes of alternating hemiplegia at approximately 4 months of age. They consisted of tonic stiffening and dystonia of the right or left extremities, lasting from 30 min to several hours and followed by residual hemiparesis. They were invariably accompanied by ocular motor abnormalities. Magnetic resonance imaging, computed tomography, and angiography all were normal. Single proton emission computed tomography brain images during an acute episode of right hemiplegia demonstrated hypoperfusion of the left cerebral hemisphere. Following improvement of the hemiplegia, the patient was re-evaluated. The uptake of the radiotracer in the left hemisphere was increased. The scan did not demonstrate significant asymmetry in cerebral perfusion.

Detection of complications after liver transplantation by technetium-99m mebrofenin hepatobiliary scintigraphy.

Fifty-five hepatobiliary scintigraphic studies using 99mTc-Mebrofenin were performed in 52 orthotopic liver transplant patients to evaluate suspected biliary complications, namely biliary extravasation and extrahepatic obstruction. Final diagnosis was made by analysis of the clinical course and other procedures. Three out of three studies of biliary leak and four out of five studies of biliary obstruction were detected. There were no false positives in either complication. The sensitivity, specificity and accuracy were 100, 100, 100% for ectravasation and 80, 100, 98% for obstruction, respectively. Hepatobiliary scintigraphy appears to be an accurate means of detecting biliary leak and obstruction associated with the transplanted liver.