Department of Medicine faculty members published more than 3,300 peer-reviewed articles in 2016-2017.
Acute-onset persistent olfactory deficit resulting from multiple overexposures to ammonia vapor at work.
Obstructive pulmonary disease. The clinician's perspective.
This article reviews the differential diagnosis of obstructive lung disease, including lesions that may mimic chronic obstructive pulmonary disease, as well as the tools on which the clinician relies for making a proper diagnosis. The clinician's view of the radiologist's role is briefly discussed, but the details of specific radiologic techniques are discussed elsewhere in this issue.View on PubMed
A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial.
Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).View on PubMed
Primary immunodeficiency diseases.
Integrin alpha v beta 6 enhances coxsackievirus B1 lytic infection of human colon cancer cells.
Viral entry into host cells depends upon specific interactions between virus attachment proteins and cell surface receptors that enable virus binding and internalization of virus and/or the virus-receptor complex. We have recently reported that the ubiquitous cell surface molecule, decay-accelerating factor (DAF), is a major cell attachment receptor for Coxsackieviruses B1, B3, and B5. However, DAF permits only virus binding and not virus internalization, invoking the presence of secondary or accessory receptors. Among the known receptors for enteroviruses are members of the cell adhesion molecule family known as integrins. In the present study, we found that expression of the epithelial-restricted integrin, alpha v beta 6, on colonic epithelial cells significantly enhanced Coxsackievirus B1-mediated cell lysis. Importantly, the viral-mediated cell killing required the presence of the 11-amino-acid C-terminal cytoplasmic extension unique to the beta 6 subunit, providing the first evidence of regulation of viral infectivity by integrin cytoplasmic domains. These results indicate that alpha v beta 6 expression on intestinal epithelial cells critically affects Coxsackievirus B1 infectivity. This may be essential in the conversion of asymptomatic enterovirus infection into clinically apparent disease.View on PubMed
Membrane transporters in drug disposition.
Many clinically used drugs and their metabolites as well as a variety of environmental toxins are organic cations at physiologic pH. Secretion in the renal proximal tubule constitutes a major pathway in the elimination of organic cations. In this report, the results of studies recently performed in this laboratory are presented. First, the molecular cloning of a novel splice variant of organic cation transporter from rat kidney (rOCT1A) is described. The functional characteristics of the transporter are discussed along with the implications of RNA splicing in enhancing transporter diversity. Second, the molecular cloning of the first human organic cation transporter (hOCT1) is described. Distinct interspecies differences in the tissue distribution and function of this transporter is presented. These studies have paved the way for elucidating molecular structure function relationships of organic cation transporters and for determining their physiologic role in drug absorption and elimination. The cloned transporters can be used in mammalian expression systems for screening candidate compounds identified during drug discovery and development and in the in vivo prediction of the pharmacokinetics of therapeutic agents.View on PubMed
Na(+)-dependent purine nucleoside transporter from human kidney: cloning and functional characterization.
Many purine nucleosides and their analogs are actively transported in the kidney. Using homology cloning strategies and reverse transcriptase-polymerase chain reactions, we isolated a cDNA encoding a Na(+)-dependent nucleoside transporter, hSPNT1, from human kidney. Functional expression in Xenopus laevis oocytes identified hSPNT1 as a Na(+)-dependent nucleoside transporter that selectively transports purine nucleosides but also transports uridine. The Michaelis constant (K(m)) of uridine (80 microM) in interacting with hSPNT1 was substantially higher than that of inosine (4.5 microM). hSPNT1 (658 amino acids) is 81% identical to the previously cloned rat Na(+)-nucleoside transporter, SPNT, but differs markedly from SPNT in terms of its primary structure in the NH2 terminus. In addition, an Alu repetitive element (approximately 282 bp) is present in the 3'-untranslated region of the hSPNT1 cDNA. Northern analysis revealed that multiple transcripts of hSPNT1 are widely distributed in human tissues including human kidney. In contrast, rat SPNT transcripts are absent in kidney and highly localized to liver and intestine. The hSPNT1 gene was localized to chromosome 15. This is the first demonstration of a purine nucleoside transporter in human kidney.View on PubMed
Pulmonary and allergy subspecialty care in adults with asthma. Treatment, use of services, and health outcomes.
To study the relationship between physician subspecialty practice type and health measures in patients with adult asthma, we prospectively studied 601 adults with asthma. The subjects were recruited from a random sample of board-certified pulmonary or allergy internal medicine subspecialists practicing in northern California; 539 patients (90%) were restudied after 18 months. Structured telephone interviews were used to elicit demographics, clinical variables, and measures of asthma severity, asthma-specific quality of life, and physical function status. At baseline and follow-up, 283 subjects (53%) reported their principal asthma care provider type as a pulmonary specialist throughout and 150 (28%) as an allergy specialist throughout, 53 (10%) switched provider type during follow-up, and 53 (10%) reported that their principal asthma care physician was from neither subspecialist group. Taking into account illness severity and other demographic and clinical covariates, the group whose principal asthma care came from an allergy subspecialist was more likely than the pulmonary specialist-care group to report possessing a peak expiratory flow rate meter (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8 to 4.6) and less likely to be receiving high-dose inhaled steroids (OR, 0.3; 95% CI, 0.1 to 0.6). Taking into account demographic and clinical covariates, allergists' care was related to worse subject-reported asthma-specific quality of life (P = 0.02), but not to statistically increased risk of hospitalization, decreased physical function, or an increased number of reported health-related restricted-activity days. We observed subject-reported specialist variation in management and health outcomes among adults with asthma not accounted for by differing disease severity or other clinical and demographic variables.View on PubMed
Use of herbal products, coffee or black tea, and over-the-counter medications as self-treatments among adults with asthma.
There are few data on the use of alternative therapies in adult asthma and their impact on health outcomes.
The objective of this study was to study the prevalence and morbidity of asthma self-treatment with herbs, coffee or black tea, and over-the-counter (OTC) medications containing ephedrine or epinephrine.
We carried out a cross-sectional analysis of interview data for 601 adults with asthma recruited from a random sample of pulmonary and allergy specialists. We estimated the 12-month prevalence of reported use of herbal products, coffee or black tea, or OTC products to self-treat asthma and their association with emergency department visits and hospitalization.
Herbal asthma self-treatment was reported by 46 (8%; 95% confidence interval [CI] 6% to 10%); coffee or black tea self-treatment by 36 (6%; 95% CI 4% to 8%), epinephrine or ephedrine OTC use by 36 (6%; 95% CI 4% to 8%), and any of the three practices by 98 subjects (16%; 95% CI 13% to 19%). Adjusting for demographic and illness covariates, herbal use (odds ratio [OR] 2.5; 95% CI 1.1 to 5.6) and coffee or black tea use (OR 3.1; 95% CI 1.2 to 7.8) were associated with asthma hospitalization; OTC use was not (OR 0.8; 95% CI 0.3 to 2.5).
Even among adults with access to specialty care for asthma, self-treatment with nonprescription products was common and was associated with increased risk of reported hospitalization. This association does not appear to be accounted for by illness severity or other disease covariates. It may reflect delay in utilization of more efficacious treatments.View on PubMed
Transjugular intrahepatic portosystemic shunts (TIPS) in children.
The transjugular intrahepatic portosystemic shunt procedure is an accepted treatment for adults with complications of portal hypertension. We performed a retrospective review of all pediatric TIPS placements performed at the University of California, San Francisco between 1990 and 1996. Twelve procedures were attempted in nine children, with a mean age (+/- SD) of 9.4 +/- 3.9 years (range, 5 to 15 years) and a mean weight of 31 +/- 18 kg (range, 16 to 70 kg). The indications for TIPS placement were portal hypertension complicated by chronic variceal hemorrhage not controlled with sclerotherapy (n = 7) and hypersplenism with thrombocytopenia (n = 2). TIPS placement was successfully completed initially in seven of nine (78%) patients. Unfavorable vascular anatomy was the cause of failure in two cases. The seven patients who underwent successful TIPS placement were followed up for an average of 136 days (range, 1 to 800 days); two still have patent shunts, three underwent liver transplantation, one had a splenorenal shunt after stenosis, and one died of underlying liver disease. Variceal bleeding was controlled in four of five patients who successfully underwent TIPS placement. Shunt occlusion occurred in four patients; patency was restored by transjugular shunt revision in three, and a splenorenal shunt was performed in one.View on PubMed