Search PubMed⌕ Search

Biomedical subjects

J Hoffman

Publications and source records attributed to J Hoffman.

At least 73 records · Page 4Linked to original sources

Salt and water balance in the toad Bufo viridis during recovery from two different osmotically stressful conditions.

Toads, Bufo viridis, were subjected to two modes of osmotic stress: on soil of water potential approximately 5 atm and continuous partial immersion in 250 mmol/l NaCl solution. In both conditions, plasma osmolality was greatly elevated involving a large increase in urea concentration and was maintained hyperosmotic to the external environment. After acclimation to either condition, toads were allowed access to tap water, and the concentrations of body fluids and gross body weight were followed over a 7-day period. The toads bathed only until preacclimation gross weight was regained, although plasma osmolality remained elevated. Weight remained stable thereafter. Excess plasma Na+ and Cl- were eliminated within a few days, whereas the urea level diminished very slowly. K+ was closely controlled throughout, both during acclimation and recovery. The results suggest that B. viridis is equipped with a series of set points for osmotic pressure that enable it to maintain different steady states according to the prevailing conditions, the magnitude of the shift depending on the level of the imposed osmotic stress.

Acclimatization↗

Chitooligosaccharides stimulate Atlantic salmon, Salmo salar L., head kidney leukocytes to enhanced superoxide anion production in vitro.

Chitosans and chitooligosaccharides stimulated Atlantic salmon, Salmo salar L., head kidney leukocytes in vitro to produce elevated levels of superoxide anion. Both soluble and insoluble chitooligosaccharides were stimulatory 2 and 7 days after addition. Protein-chitooligosaccharide conjugates were also stimulatory in vitro both at 2 and 7 days after addition. Deacetylation seemed to be of little importance for the stimulatory capacity. High concentrations of the 80% deacetylated chitosan/chitooligosaccharides were toxic to the leukocytes as judged by reduced reduction of nitroblue tetrazolium and morphology.

Acetylation↗

Nursing wound care survey: sterile and nonsterile glove choice.

PURPOSE: The application of sterile and clean procedure to the practice of wound care nursing was examined. DESIGN: This prospective, descriptive study surveyed staff nurses regarding glove use. SUBJECTS AND SETTING: Seven hundred forty-three staff nurses from five health care agencies in the San Francisco Bay Area responded to the survey. INSTRUMENTS: A self-report wound care survey instrument was developed by Nursing Consortium for Research and Practice members from information adapted from the wound care literature. The questionnaire comprised 31 questions and required approximately 10 minutes to complete. METHODS: Nursing Consortium for Research and Practice members obtained approval from their respective institutional human subjects committees and distributed questionnaires among all nurses engaged in direct care. Some agency representatives personally handed the survey instruments to subjects, but most distributed them through their agencies personnel mailing systems. RESULTS: Seven hundred twenty-three (38%) of 1900 questionnaires were completed and returned to the five site coordinators. Differences were found between acute care and home health nurses. Acute care nurses were more likely than home care nurses to use sterile gloves in all wound care situations. CONCLUSION: Greater variation was found with regard to sterile technique in wound care practice than in previously reported studies. Although patient risk factors and wound type significantly influenced the choice of sterile or clean gloves, additional environmental and personal factors exerted considerable influence. These included health care setting, degree of professional education, and nurses' experiential background. Attempts to modify practice through policy change alone may not be sufficient to overcome resistance to change. Instead, it may be necessary for nurses to "unlearn" lessons from basic nursing education before they can adopt to new practices and clinical policies.

Adult↗

Does differential neuroendocrine control of cytokine production govern the expression of autoimmune diseases in pregnancy and the postpartum period?

Pregnancy and the postpartum period are associated with significant changes in levels of several hormones, such as estrogen, progesterone, cortisol and possibly catecholamines. Moreover, several autoimmune diseases such as rheumatoid arthritis tend to remit, develop or exacerbate during pregnancy or the postpartum period. Thus, the question arises: are the changes in the hormones and the expression of autoimmune diseases during these periods causally linked, or are these associations an epiphenomenon? Here we suggest that a causal link might be provided through differential neuroendocrine regulation of Th1-type and Th2-type cytokine production.

Autoimmune Diseases↗

Twice a day quadruple therapy (bismuth subsalicylate, tetracycline, metronidazole plus lansoprazole) for treatment of Helicobacter pylori infection.

BACKGROUND: Quadruple therapy (bismuth, metronidazole and tetracycline (BMT) + proton pump inhibitor) is touted as being > 95% effective, regardless of metronidazole resistance. We tested a 10-day b.d. quadruple therapy for treatment of H. pylori infection. METHODS: Anti-H. pylori therapy consisted of lansoprazole 15 mg b.d. plus tetracycline 500 mg b.d., metronidazole 500 mg b.d., and swallowable Pepto-Bismol caplets (2 b.d.) for 10 days. H. pylori status was evaluated by culture and histology before and 4 or more weeks after therapy. RESULTS: The cure rate for intention-to-treat was 70%. Treatment success was calculated overall and separately in relation to antimicrobial resistance patterns. The cure rate among the metronidazole-sensitive isolates was 89.7% (26 of 29) vs. 41.2% (7 of 17) of the metronidazole-resistant isolates (P < 0.005). Moderate (n = 1) or severe (n = 3) side-effects were experienced in four patients with only one withdrawing because of side-effects. CONCLUSION: Twice a day quadruple therapy is effective for metronidazole-sensitive strains but its usefulness is markedly reduced by the presence of pre-treatment metronidazole resistance. Twice a day quadruple therapy can be recommended in locations where background metronidazole resistance is uncommon. Possibly, 14-day therapy or a higher dosage of metronidazole provide better results with metronidazole-resistant H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Syncope recurrence can better be predicted by history than by head-up tilt testing in untreated patients with suspected neurally mediated syncope.

BACKGROUND: Head-up tilt testing is widely used in the evaluation of patients with suspected neurally mediated syncope. Although it remains unclear which patients require medical therapy to prevent recurrent syncope, most centres initiate empiric medical therapy in all patients in whom neurally mediated syncope has been diagnosed. To determine the natural history of this condition, we followed 80 untreated patients. METHODS: All 80 study patients fulfilled the following inclusion criteria: (1) > or = 1 syncope in the upright position, (2) absence of structural heart disease, (3) unremarkable work-up for other known causes of syncope. Thirty-nine patients had a history of one episode of syncope (group A) and 41 > or = 2 episodes of syncope (group B). Head-up tilting was performed in all patients at 60 degrees for a maximum of 45 min without medical provocation ('Westminster Protocol'). RESULTS: Suspected neurally mediated syncope could be reproduced by tilt testing in four of 39 patients from group A vs 10 of 41 patients from group B (10% vs 24%, P = 0.1). Independent of the result of head-up tilt testing, all patients were prospectively followed without medical therapy. During 23 +/- 8 months follow-up, syncope recurred in four of 39 group A patients vs 22 of 41 group B patients (10% vs 54%, P < 0.05). The incidence of syncope during follow-up was not significantly different between patients with and without positive baseline tilt test (43% vs 30%, P = ns). CONCLUSIONS: (1) 90% of patients with a single episode of syncope remain free of recurrent syncope without medical therapy irrespective of the result of tilt testing. (2) About half of patients with a history of > or = 2 syncopal episodes have recurrent syncope and, thus, may be appropriate candidates for prophylactic medical therapy. (3) Although head-up tilt testing at 60 degrees for up to 45 min does not appear to be useful to predict recurrent syncope in untreated patients, it is still a useful test in its evaluation.

Adolescent↗

QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy.

QT dispersion was measured in the 12-lead standard electrocardiogram in 107 patients with idiopathic dilated cardiomyopathy (IDC) and 100 age- and sex- matched controls without structural heart disease. All 107 study patients with IDC were prospectively followed in order to determine possible associations between QT dispersion and arrhythmic events, i.e., sustained ventricular tachycardia, ventricular fibrillation, or sudden death. QT dispersion, rate-corrected QT dispersion, and adjusted QTc dispersion, which takes account of the number of leads measured, were significantly greater in patients with IDC than in controls. During 13 +/- 7 months follow-up, arrhythmic events occurred in 12 of 107 study patients with IDC (11%). QT dispersion was increased in patients with versus without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms; p=0.03). QTc dispersion and adjusted QTc dispersion were not significantly different between patients with and without arrhythmic events (80 +/- 21 vs 75 +/- 35 ms, and 27 +/- 6 vs 24 +/- 10 ms, respectively). Thus, although QT dispersion was increased in patients with IDC and arrhythmic events during follow-up, its usefulness for arrhythmia risk prediction was limited by the large overlap of QT dispersion between patients with and without arrhythmic events.

Anti-Arrhythmia Agents↗

Structural studies of the Vibrio salmonicida lipopolysaccharide.

The oligosaccharide part of the Vibrio salmonicida (strain NCMB 2262) lipopolysaccharide was isolated by mild acid hydrolysis followed by gel-permeation chromatography. The structure was established mainly by methylation analysis, mass spectrometry, and NMR spectroscopy. It is concluded that the oligosaccharide has the following structure, in which L-alpha-D-Hep p is L-glycero-alpha-D-manno-heptopyranose, D-alpha-D-Hepp is D-glycero-alpha-D-manno-heptopyranose, alpha-D-Fuc p4N is 4-amino-4,6-dideoxy-alpha-D-galactopyranose, alpha-NonA is 5-acetamidino-7-acetamido-3,5,7, 9-tetradeoxy-L-glycero-alpha-D-galacto-nonulosonic acid, BA is (R)-3-hydroxybutanoyl, and PEA is phosphoethanolamine. The substitution pattern of the branching heptosyl residue was deduced from 1H NMR chemical shifts and conformations of the branching region, obtained by molecular modelling. The absolute configuration for NonA was determined by NMR spectroscopy from NOE correlations to the neighbouring sugar and 13C NMR chemical shift data. It could also be shown that assignments of nonulosonic acids with the D-glycero-L-galacto configuration, reported by previous investigators, are erroneous and should be changed to L-glycero-D-galacto. The oligosaccharide is assumed to be linked to the 5-position of a Kdo residue, phosphorylated in the 4-position as observed for other lipopolysaccharides from Vibrionaceae. [formula: see text]

Carbohydrate Conformation↗

Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine ribonucleoside.

Inhibition of pyrimidine and purine synthesis has been demonstrated to potentiate 5-fluorouracil (5-FU) activity in preclinical models. Low-dose phosphonacetyl-L-aspartate (PALA) potentiates the incorporation of 5-FU into RNA, without detectably increasing its toxicity. 6-Methylmercaptopurine riboside (MMPR) results in inhibition of purine biosynthesis with elevation of phosphoribosyl pyrophosphate (PRPP), which in turn is believed to increase the phosphorylation and intracellular retention of 5-FU. We conducted a phase I clinical trial to determine the maximum tolerated dose of 5-FU in combination with low-dose PALA and a biochemically-optimized dose of MMPR. The regimen consisted of PALA 250 mg/m2 given on day 1, followed 24 h later by MMPR 150 mg/m2, and escalating doses of 5-FU from 1625 to 2600 mg/m2 by 24 h continuous infusion. This regimen was repeated weekly. A group of 29 patients with a diagnosis of malignant solid tumor were entered; their median performance status was 1. The dose-limiting toxicity was mucositis, while other gastrointestinal toxicity was minimal. Two patients also experienced ischemic chest pain during the 5-FU infusion. The maximum tolerated dose of 5-FU in this combination was 2600 mg/m2. Several responses were observed including a complete remission in a previously treated breast cancer patient and two partial responses in breast and colon cancer. MMPR pharmacokinetics were obtained from urine analyses in 21 patients on this trial; there was no correlation between the pharmacokinetics of MMPR and the toxicity observed. This regimen was well tolerated and phase II trials are warranted using PALA 250 mg/m2, MMPR 150 mg/m2, and 5-FU 2300 mg/m2 by continuous infusion over 24 h.

Adult↗

Modulation of cyclic AMP accumulation in glial cells by exogenous phospholipase C.

Pretreatment of 1321N1 human astrocytoma cells with exogenously added bacterial phospholipase C (PLC) induced an increase in subsequent stimulation of cyclic AMP accumulation by the beta-adrenergic receptor agonist isoproterenol and by the direct adenylyl cyclase activator forskolin, a phenomenon referred to as sensitization. The direct protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induced a similar sensitization. In contrast, in C62B rat glioma cells both PLC and PMA induced a decrease in subsequent cyclic AMP accumulation stimulated by isoproterenol and little or no change in stimulation by forskolin. Although the effects of PMA were completely abolished by pretreating cells overnight with PMA to down-regulate protein kinase C activity, the effects of PLC were inhibited only partially or not inhibited. Pertussis toxin pretreatment did not inhibit the sensitization induced by PLC, whereas sensitization induced by lysophosphatidic acid (previously shown to involve pertussis toxin-sensitive GTP binding proteins) was completely inhibited. Further studies of these phenomena may reveal novel pathways for regulation of the cyclic AMP signalling pathway.

Adenylate Cyclase Toxin↗

Repeated isolation in the neonatal rat produces alterations in behavior and ventral striatal dopamine release in the juvenile after amphetamine challenge.

Rat pups were isolated from the mother and nest for 1 hr per day from Postnatal Day (PN) 2 to 9 At PN 27, rats were tested for behavioral responsiveness to 2.0 or 7.5 mg/kg amphetamine. Only isolated rats receiving the 7.5 mg/kg dose displayed increased activity scores, compared with nonisolated and nonhandled controls. Their increased activity is attributed to a slower latency to enter into stereotypy. In a second experiment, similarly treated groups were challenged by the 7.5 mg/kg dose during a session in which a microdialysis probe implanted in the ventral striatum was being perfused. The challenge drug elicited a much greater increase in dialysate dopamine in isolated vs. nonisolated groups. Results are discussed with regard to dissociation between sensitized and subsensitized responses.

Amphetamine↗

Phase I trial of buthionine sulfoximine in combination with melphalan in patients with cancer.

PURPOSE AND METHODS: Resistance to alkylating agents and platinum compounds is associated with elevated levels of glutathione (GSH). Depletion of GSH by buthionine sulfoximine (BSO) restores the sensitivity of resistant tumors to melphalan in vitro and in vivo. In a phase I trial, each patient received two cycles as follows: BSO alone intravenously (i.v.) every 12 hours for six doses, and 1 week later the same BSO as cycle one with melphalan (L-PAM) 15 mg/m2 i.v. 1 hour after the fifth dose. BSO doses were escalated from 1.5 to 17 g/m2 in 41 patients. RESULTS: The only toxicity attributable to BSO was grade I or II nausea/vomiting in 50% of patients. Dose-related neutropenia required an L-PAM dose reduction to 10 mg/m2 at BSO 7.5 g/m2. We measured GSH in peripheral mononuclear cells (PMN), and in tumor biopsies when available, at intervals following BSO dosing. In PMNs, GSH content decreased over 36 to 72 hours to reach a nadir on day 3; at the highest dose, recovery was delayed beyond day 7. The mean PMN GSH nadirs were approximately 10% of control at BSO doses > or = 7.5 g/m2; at 13 and 17 g/m2, all but two patients had nadir values in this range. GSH was depleted in sequential tumor biopsies to a variable extent, but with a similar time course. At BSO doses > or = 13 g/m2, tumor GSH was < or = 20% of starting values on day 3 in five of seven patients; recovery had not occurred by day 5. We measured plasma concentrations of R- and S-BSO by high-performance liquid chromatography (HPLC) in 22 patients throughout the dosing period. Total-body clearance (CLt) and volume of distribution at steady-state (Vss) for both isomers were dose-independent. The CLt of S-BSO was significantly less than that of R-BSO at all doses, but no significant differences in Vss were observed between the racemates. Harmonic mean half-lives were 1.39 hours and 1.89 hours for R-BSO and S-BSO, respectively. CONCLUSION: A biochemically appropriate dose of BSO for use on this schedule is 13 g/m2, which will be used in phase II trials to be conducted in ovarian cancer and melanoma.

Adult↗

A survey of physician knowledge of drug costs.

Previous studies have indicated that physicians have inadequate knowledge of drug costs. This study was designed to determine actual pharmacy prices of 12 nonsteroidal anti-inflammatory drugs (NSAIDs) and physicians' knowledge of these prices. Pharmacists (N = 67) in a large urban area were surveyed to determine the lowest retail price of commonly prescribed medications. Pain clinic and orthopedic physicians (N = 95) were surveyed to determine their knowledge of prices for 12 NSAIDs. There was wide variation between pharmacies in the cost of medications. Eighty-one percent of physicians agreed that cost is an important factor to consider. Only 25% of physicians estimated at least one-half of the medications between the highest and lowest pharmacy price. The results of this study indicate that physicians need more information about prices of medications they prescribe.

Anti-Inflammatory Agents, Non-Steroidal↗

Intravenous regional guanethidine in the treatment of reflex sympathetic dystrophy/causalgia: a randomized, double-blind study. Guanethidine Study Group.

This double-blind, randomized, multicenter study was designed to determine the short-term and long-term efficacy of intravenous regional block with guanethidine in patients with reflex sympathetic dystrophy (RSD)/causalgia. Sixty patients were enrolled to receive four intravenous regional blocks at 4-day intervals with either guanethidine or placebo in 0.5% lidocaine. Each patient was randomized to receive either one, two, or four blocks with guanethidine. Follow-up visits were scheduled for 4 days, 1 mo, 3 mo, and 6 mo after their final block. At 4 days after the initial block, the group treated with placebo experienced a greater decrease in pain scores than those treated with guanethidine, although this difference was not statistically significant. On long-term followup there was no difference in pain scores between groups receiving one, two, or four guanethidine blocks. Overall, only 35% of patients experienced clinically significant relief on long-term followup even though all were treated early in the evolution of RSD.

Adult↗

Failure of electron paramagnetic resonance spectroscopy studies to detect elevated free radical signals in liver biopsy specimens from patients with alcoholic liver disease.

Electron paramagnetic resonance spectroscopy (EPR) was used to study free radicals and transition metal complexes in liver tissue taken from patients with liver disease. Samples were frozen to 77K directly following biopsy to prevent deterioration. Our major aim was to compare signals from patients suffering from alcohol abuse with those from patients having liver damage not induced by alcohol. Samples were obtained from 19 chronic alcohol abusers and 7 non-alcoholic liver disease patients. Of the 19 alcoholic patients, 18 had an increased fat content, 6 had Mallory's hyaline, 12 had an acute inflammatory response, 9 had increased stainable iron and 4 had evidence of fibrosis. A signal derived from free radicals with a spectroscopic splitting factor of g = 2.0045 was found in all samples. This signal in the alcoholic patients had a mean amplitude of 2.96 cm (+/- 1.42 SD), and in patients with non-alcoholic liver disease 2.12 cm (+/- 0.82) (p = 0.10 NS), measured under identical instrument settings. The molar proportion of diene conjugated linoleic acid (DCLA), a free radical marker, in the sera of alcoholic patients was 2.68% (+/- 1.93), but did not correlate with the free radical signals obtained by EPR spectroscopy. Also, there was no correlation between the free radical derived EPR signal and fat content, Mallory's hyaline, inflammatory infiltrate, iron or fibrosis in the liver biopsy specimens. Similarly the concentrations of aspartate transaminase, albumin, and gamma-glutamyl transferase in serum samples showed no correlations with free radical concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗