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Biomedical subjects

J F Williams

Publications and source records attributed to J F Williams.

At least 19 recordsLinked to original sources
PubMed1992

Pulmonary arteriovenous fistula: mechanical ventilation and hypoxemia.

Pulmonary arteriovenous malformation (PAVM) is an uncommon congenital anomaly. As PAVM is a direct communication between branches of the pulmonary artery and vein, major disturbances in gas exchange can result. We present a patient with an unsuspected PAVM who came to our institution for drainage of a brain abscess. Arterial blood gas analysis during and after surgery demonstrated a large alveolar-arterial gradient for oxygen in the absence of any obvious pulmonary pathology while the patient was receiving positive pressure ventilation (PPV). Oxygenation improved considerably upon resumption of spontaneous ventilation. A diagnosis of PAVM was made subsequently. We conclude that positive pressure ventilation can worsen right to left shunting in patients with PAVM.

Adult↗
PubMed1992

Dirofilaria immitis: do filarial cyclooxygenase products depress endothelium-dependent relaxation in the in vitro rat aorta?

Endothelial cells modulate the function of their underlying smooth muscle. Thus, altered endothelial behavior could be important in the pathogenesis of vascular and lymphatic diseases, including human and animal filariasis. Endothelium-dependent relaxation is depressed in both in vivo canine femoral artery of dogs infected with Dirofilaria immitis and in vitro rat aorta exposed to adult D. immitis. The experiments reported here were designed to determine if filarial cyclooxygenase products could depress endothelium-dependent relaxation in vitro. Pretreatment of the parasites, but not the vascular ring, with either indomethacin or aspirin, prevented filarial-induced depression of relaxation. Analysis of heartworm-conditioned medium by gas chromatography--mass spectrometry revealed two peaks in the biologically active medium that were not present in the control. One peak had a retention time and chromatographic profile characteristic of derivatized PGD2 standard, and the other was not identified. Incubation of the vascular ring with PGD2 mimicked filarial-induced depression of endothelium-dependent relaxation at low, but not high, concentrations of acetylcholine. Thus, filarial PGD2 may be involved in altered endothelium-dependent relaxation seen in heartworm-infected dogs.

Acetylcholine↗
PubMed1992

The profile of IgG and IgG subclasses of onchocerciasis patients.

In this study Onchocerca gutturosa was compared with O. volvulus in an ELISA test to detect Onchocerca-specific IgG and IgG subclasses. The test was developed and standardized to detect Onchocerca-specific IgG and IgG subclasses in sera of onchocerciasis patients and endemic controls. Onchocerca volvulus and O. gutturosa crude water-soluble antigens showed no significant difference in detecting onchocerca-specific IgG antibody (T = 1.88, P greater than 0.05). The levels of IgG subclasses varied greatly. IgG4 showed the highest detected mean level (0.84 +/- 0.59) and the other three subclasses showed considerably lower mean levels (IgG1 = 0.27 +/- 0.16, IgG2 = 0.24 +/- 0.17, IgG3 = 0.28 +/- 0.12). The status and score of skin lesions were found to have significant effect on the IgG and IgG subclasses levels (all P less than 0.001). IgG4 showed a positive correlation with the microfilarial (Mf) load (r = 0.21, P less than 0.03). IgG3 levels have a significant negative correlation with the Mf load (r = -0.23, P less than 0.02). The biological significance of these IgG and IgG subclasses in onchocerciasis is discussed.

Adolescent↗
PubMed1992

Alcoholism prevalence and utilization of medical services by Mexican Americans.

BACKGROUND: Alcoholism is a common disorder that often results in increased use of medical services. Research describing alcoholism among both outpatients and ethnic minorities has been sparse. METHODS: In this study, the Short Michigan Alcoholism Screening Test was used as part of a health screening interview of patients attending a South Texas family health clinic. Screening was used to detect alcoholism and identify the health care needs in this predominantly Mexican American population. RESULTS: Consistent with other studies, alcoholism was more prevalent among men than among women. The prevalence of 24.4% among Mexican American men was similar to that among men from other ethnic backgrounds. The 4.2% prevalence among Mexican American women was comparable to that among other women. Equal percentages of alcoholics were identified in the primary care clinic and the "walk-in" clinic. Compared with nonalcoholic patients, alcoholic patients were more often unemployed or disabled, and reported more hospitalizations during the previous year. CONCLUSIONS: These findings suggest that alcoholism is as prevalent and costly a disease among Mexican Americans as it is in other ethnic groups in our society. Alcoholism can readily be detected in a variety of outpatient settings when screening is used. Employment status might serve as an indicator for alcoholism screening, but ethnicity did not. Research into socio-economic and cultural influences on alcoholism may improve the effectiveness of diagnosis and treatment of this prevalent disease.

Adult↗
PubMed1991

Effect of interleukin 6 on phenobarbital induction of cytochrome P-450IIB in cultured rat hepatocytes.

Human recombinant interleukin 6 (rhIL-6) caused a dose dependent decrease in the phenobarbital induction of benzyloxyresorufin O-deethylase activity in cultured rat hepatocytes. Decreased enzymatic activity was associated with a decrease in the amount of immunoreactive P-450IIB1/2. rhIL-6 also prevented the PB-induced increase in the steady state level of P-450IIB mRNA. These results suggest that altered P-450 levels observed in vivo during the acute phase reaction may be due to interleukin 6.

Animals↗
PubMed1991

The effect of orotic acid on the response of the recently infarcted rat heart to hypothermic cardioplegia.

Patients with a recent myocardial infarction have a higher morbidity and mortality than comparable patients with chronic myocardial ischaemia. We postulated that this might be due to a reduced overall tolerance of the heart to cardioplegic arrest in the presence of a recent infarct. We postulated that orotic acid, a pyrimidine precursor which augments the rate of protein synthesis, might improve the response of the recently infarcted heart to cardioplegic arrest. Myocardial infarction was produced in rats by coronary ligation. The rats were then divided into two groups according to whether they were treated with oral orotic acid (10 mg/kg per day) or untreated. A sham-operated (non-infarcted) group served as normal controls. After 2 days, the hearts (n = 12 per group) underwent 1 h of cardioplegic arrest at 23 degrees C on the isolated working heart apparatus. Before arrest, maximum cardiac function in the untreated infarct group was lower than in the normal group (P less than 0.05), whereas in the treated group, function was similar to the normal group. After arrest there was severe depression of cardiac function in the untreated infarct group: only 57% recovery of the pre-arrest value compared with 86% in the normal group (P less than 0.001). In the orotic acid treated group, recovery (90%) was significantly greater than in the untreated group (P less than 0.001) and equivalent to the normal group. Oxygen utilisation, when corrected for external work, was higher in both infarct groups than in the normal group before and after arrest (P less than 0.05 in both cases). Total uridine nucleotide content of the infarcted and non-infarcted zones of the heart was increased. Treatment with orotic acid produced a further upward trend in uridine nucleotide levels. We conclude that an established, recent infarct reduces the overall tolerance of the heart to hypothermic cardioplegia. Treatment with orotic acid improves the function of the infarcted heart following cardioplegic arrest, and may therefore improve the results of urgent cardiac surgery in patients with myocardial infarction.

Animals↗
PubMed1991

Uptake of chloroquine by Onchocerca volvulus in vivo and in vitro.

Patients infected with Onchocerca volvulus in the Cayapa River focus in north-east Ecuador were given 500 mg chloroquine diphosphate (CQ) orally prior to nodulectomy. The concentrations of CQ were determined in parasite fragments and host tissue dissected from the nodules, in skin overlying the nodules, and in plasma at 3, 4, 7, and 24 hours after dosing. Onchocerca volvulus took up CQ rapidly, in some cases accumulating the drug to concentrations of over 600 pmol mg-1 worm tissue by three hours, and maintaining similar concentrations through 24 hours. These amounts were markedly higher than peak concentrations in plasma (3.16 pmol microliters-1) and in host tissues (78 pmol mgm-1) and skin (up to 93 pmol mg-1). In vitro uptake of CQ by females of O. volvulus was greater under alkaline conditions (pH 8.4) than at pH 6.8 and 7.4. Uptake reached equilibrium after one to two hours, with final concentrations being approximately 10 times lower than those reached in vivo. Inhibitory effects of chloroquine and its major metabolite desethylchloroquine on the motility of O. volvulus and other filariae have been observed previously in vitro; whether or not the drug had adverse effects on adult parasites in vivo was not determined in these experiments. However, the results illustrate the accessibility of O. volvulus to blood borne agents in vivo, and the potential importance of pharmacodynamic characteristics in the search for new macrofilaricidal agents.

Animals↗
PubMed1991

Use of femoral venous catheters in critically ill adults: prospective study.

OBJECTIVE: To determine the frequency of clinically important complications of femoral venous catheters. DESIGN: Prospective survey of major and minor complications. SETTING: A mixed medical/surgical ICU in a university hospital. PATIENTS: One hundred twenty-three patients admitted to the ICU who underwent femoral venous catheterization over a 2-yr period. MEASUREMENTS AND MAIN RESULTS: There were 150 catheters inserted in 123 patients for a mean duration of 6.4 days. There were no major complications including catheter-related sepsis. Minor complications consisted of arterial puncture (9.3%), local bleeding (10%), and local inflammation (4.7%). Critical care fellows had a significantly lower rate (6%) of insertion complications than interns or medical students (16%). We did not specifically look at the frequency of deep venous thrombosis. CONCLUSIONS: Femoral venous catheterization offers an alternative site of insertion to the subclavian and jugular veins for central venous access in the critically ill. The occurrence rate of clinically important complications is acceptably low.

Adult↗
PubMed1991

Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis.

Characterization of in vitro lymphocyte responsiveness was performed on selected groups of onchocerciasis patients from Sudan and Sierra Leone. These patients manifested a very broad range of clinical signs and showed widely divergent parasite infection intensities. Lymphocyte proliferative responses to soluble Onchocerca volvulus antigen (sAg) were poor in infected persons; mitogen and PPD responses were maintained in the normal range in one group of patients from southwestern Sudan, but were profoundly depressed in a group from N.E. Sudan. Proliferative responses and interferon-gamma (INF-gamma) secretion were very significantly depressed in the presence of live microfilariae of O. volvulus or secretions/excretions (S/E) from microfilariae (mf) or from female, but not male, adult parasites. Lymphocyte responses were maintained near normal when exogenous IL-2 was added to these cultures. The results indicate that O. volvulus infection and its clinical consequences are not consistently associated with systemic deficits in immune responsiveness. However, suppression of lymphocyte reactivity by mf and S/E in vitro suggests that direct parasite intervention in host cell responses could be taking place in vivo, perhaps at the local microenvironment level; mediated by effects on cytokine production.

Animals↗
PubMed1991

Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis.

A role for altered endothelial cell function is emerging in the pathogenesis of disease. We have previously demonstrated that Dirofilaria immitis, the canine heartworm, depresses endothelium-dependent responses and alters the mechanism of relaxation in the in vivo femoral artery of infected dogs. Exposure of rat aorta to the parasite or parasite-conditioned medium selectively depresses endothelium-dependent relaxation. D. immitis is closely related to the major human filarial pathogens. This study was designed to examine the effect of chronic infection with the filarial nematode Brugia pahangi on endothelium-mediated responses of the rat aorta in vitro. We tested the hypothesis that endothelium-dependent responses are depressed in the aorta from rats infected with B. pahangi. Rings of thoracic and abdominal aorta were suspended in muscle baths for measurement of isometric tension. Dose-response relations to norepinephrine, endothelium-dependent dilators (acetylcholine, histamine, and A23187), and nitroglycerin were done. In some experiments, inhibitors of cyclooxygenase (indomethacin and aspirin), guanylate cyclase (methylene blue), and nitric oxide formation (N-nitro-L-arginine methyl ester; L-NOARG) were used. No differences in vascular reactivity were detected in the thoracic aorta. In contrast, endothelium-dependent responses in abdominal aorta of Brugia-infected rats were significantly depressed when compared with control aorta from noninfected rats. Acetylcholine relaxation was further depressed by indomethacin and aspirin. After L-NOARG, acetylcholine relaxation in control abdominal aorta was completely abolished; however, in abdominal aorta of Brugia-infected rats, acetylcholine still caused relaxation. Methylene blue inhibited acetylcholine relaxation in both control and Brugia-infected abdominal aorta; however, relaxation in Brugia-infected aorta was significantly greater than control. This study demonstrates that endothelium-dependent relaxation can be altered by chronic experimental filarial infection in the absence of direct contact between the blood vessel and the parasite. The mechanism of relaxation in the Brugia-infected abdominal aorta appears to be altered when compared with control, suggesting that parasites are capable of modulating vascular reactivity by inducing changes in endothelial cell behavior. The mechanism may involve parasite-induced local inflammation or alterations in endothelial cell metabolism. Understanding how chronic experimental filarial infection alters vascular reactivity may enhance our understanding of the pathogenesis of human filariasis.

Animals↗
PubMed1991

The human promyelocytic HL60 cell line: a model of myeloid cell differentiation using dimethylsulphoxide, phorbol ester and butyrate.

The release of the reactive oxygen species that accompanies the oxidative burst was studied in HL60 cells differentiated with either dimethylsulphoxide, butyrate or phorbol myristate acetate in order to establish the extent to which differentiated cells are phenotypically similar to human neutrophils, monocytes and macrophages. When phorbol myristate acetate was used as a stimulus, the rates of superoxide production by dimethylsulphoxide and butyrate differentiated HL60 cells was not significantly different from those observed in neutrophils and monocytes isolated from normal peripheral blood. Similar results were obtained when luminol-dependent chemiluminescence was measured in the presence of horseradish peroxidase using phorbol myristate acetate as the stimulus. However, in the absence of horseradish peroxidase, the luminol-dependent chemiluminescence in the dimethylsulphoxide and butyrate-differentiated HL60 cells was significantly lower than that of the control cells isolated from human blood, reflecting the absence of myeloperoxidase in the differentiated cells. In contrast, HL60 cells differentiated by phorbol myristate acetate failed to show any increased generation of superoxide or luminol-dependent chemiluminescence upon stimulation. Impaired release of lysosomal enzymes by the chemically differentiated cells suggests impairments in the extent of differentiation resulting in cells with defective azurophilic degranulation processes. It is concluded that HL60 cells differentiated by the above agents are somewhat controversial models of promyelocyte differentiation into typical neutrophilic, monocytic and macrophage-like cells.

Butyrates↗
PubMed1991

Cytochrome P450 isoforms. Regulation during infection, inflammation and by cytokines.

Multiple isoforms of cytochrome P450 (P450) have been discovered that are important biomedically to drug pharmacokinetics, chemical carcinogenesis, and metabolism of endogenous agents such as steroids, arachidonic acids, and prostaglandins. P450 level and activity are altered during infection and inflammation, apparently by cytokines released during activation of the immune system. Cytokines shown to affect P450 are interferon (IFN), interleukin 1 (IL-1), tumor necrosis factor (TNF), and interleukin 6 (IL-6). Understanding the enzymology and regulation of the P450 monooxygenation system in animals and humans may allow more accurate extrapolation of toxicity and cancer data from laboratory animals to clinical medicine as well as more rational selection of therapeutic regimens.

Animals↗
PubMed1991

A high-performance system for automation of the polymerase chain reaction.

A high-performance PCR system has been developed which reduces the time required for PCR, increases the throughput, reduces reagent consumption and ensures reproducibility of amplification. Integration of sophisticated temperature control with optimally designed vessels has resulted in an amplification system which produces unique benefits. These include rapid amplification, the elimination of the need for oil, even for small volumes, and a microplate format which provides liquid handling automation benefits.

Automation↗
PubMed1990

Characterization of an insulin receptor mutant lacking the subunit processing site.

An insulin receptor mutant was constructed utilizing site-directed mutagenesis to delete the Arg-Lys-Arg-Arg basic amino acid cleavage site (positions 720-723) from the cDNA encoding the human insulin proreceptor. This mutant was transfected into Chinese hamster ovary cells. Immunoprecipitation of metabolically labeled cells revealed a 205-kDa proreceptor which bound to wheat germ agglutinin. Processed 130-kDa alpha and 95-kDa beta subunits were also observed and contained approximately 20% as much protein as the proreceptor on a molar basis. Trypsin digestion of intact metabolically labeled cells decreased the proreceptor band by 80%. Pulse-chase studies revealed a half-life of 28 h for the proreceptor. When cells were photolabeled with 125I-B2(2-nitro-4-azidophenylacetyl)-des-PheB1 (NAPA)-insulin, the proreceptor incorporated 10% as much label as the 130-kDa alpha subunit in spite of a 5-fold molar excess. Incubation of NAPA-labeled cells at 37 degrees C for 20 min resulted in 60% of the labeled subunits, but little labeled proreceptor, becoming resistant to trypsin degradation. Immunoprecipitation of NAPA-insulin-stimulated cells with anti-phosphotyrosine antibodies revealed that 62% of the processed labeled receptors, but very little proreceptor, contained phosphotyrosine. Thus, this mutant receptor is synthesized, glycosylated, and expressed on the cell surface as uncleaved proreceptor, although some processing to alpha and beta subunits still occurs. It exhibits a markedly decreased affinity for insulin, and when insulin is bound to, demonstrates defective internalization, down-regulation, and autophosphorylation. These data suggest that cleavage of the mutant proreceptor into subunits is required not only for the development of high affinity binding sites, but also for normal transduction of the signal which activates the beta subunit tyrosine kinase.

Affinity Labels↗
PubMed1990

Right ventricular infarction.

Right ventricular infarction commonly occurs in association with acute inferior left ventricular infarction, but is uncommon when infarction involves other areas of the left ventricle. Evidence of right ventricular infarction often can be detected by physical examination, electrocardiography, echocardiography, or radionuclide ventriculography. However, hemodynamically significant infarction (i.e., hypotension or shock) is much less frequent, occurring in approximately 10% of patients with other evidence of right ventricular infarction. Right ventricular infarction increases ventricular stiffness, thereby impeding diastolic filling. This results in hemodynamic changes similar to those found in constrictive pericarditis: elevated systemic venous pressure, a Y descent greater than the X descent, and an inspiratory increase in venous pressure. The increase in venous pressure generally equals or even exceeds left atrial pressure. When hypotension or shock occurs, expansion of vascular volume is generally employed as initial therapy. In nonresponders, dobutamine or similar inotropic agents may be helpful. The prognosis during the acute phases is guarded, but, in survivors, prognosis is favorable and generally related to the extent of left ventricular involvement.

Cardiotonic Agents↗
PubMed1990

Continuous positive airway pressure by face mask in Pneumocystis carinii pneumonia.

We used continuous positive airway pressure (CPAP) by face mask to treat 18 AIDS patients with Pneumocystis carinii pneumonia (PCP) who were in hypoxic respiratory failure. Candidates for mask CPAP were conscious, not hypercarbic, and able to protect their airway on ICU admission. Treatment was effective and well tolerated. Mean Po2 rose from 62 to 158 torr, respiratory rate decreased from 51 to 32 breath/min, and Pco2 was unchanged. Mean duration of treatment was 4.5 days. Only one patient developed a pneumothorax; there were no other major complications. Hospital mortality was 55%. CPAP by face mask allows speech and permits discussion of therapeutic limits. We present our protocol for using CPAP by face mask and conclude that CPAP is effective supportive therapy in hypoxic respiratory failure complicating PCP and AIDS.

Acquired Immunodeficiency Syndrome↗