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Biomedical subjects

W Clark

Publications and source records attributed to W Clark.

At least 55 records · Page 3Linked to original sources
PubMed1997

Arthroplasty of rheumatoid metatarsophalangeal joints. An outcome study.

Deformity of the forefoot is a common disabling problem in chronic rheumatoid arthritis. The most common deformifies are hallux valgus, cockup toes, and depressed metatarsal heads. Resection arthroplasty has been improved by adding reconstructive procedures, for example, medial capsular arthroplasty in the great toe and plantar plate arthroplasty of the lesser toes with longitudinal pinning of all toes for 4 weeks. Results were compared with a series of silicone double hinge implants without grommets in the great toe and resection of lesser metatarsal heads and pinning. Patients were evaluated by questionnaire to evaluate outcome. There was no significant difference in the two series of patients. Overall good results were 85% to 95% and slightly favored the group without implants. These results were equal to those reported in the literature for patients who underwent fusion of the great toe and resection arthroplasty of lesser toes.

Adult↗
PubMed1997

Therapeutic advances: protease inhibitors for the treatment of HIV-1 infection.

BACKGROUND: Anti-retroviral treatment of human immunodeficiency virus (HIV) infection is undergoing great changes, brought about by a better understanding of the disease pathology. One of the most recent advances has been the introduction of the protease inhibitors, reversible inhibitors of HIV aspartic protease. Published data on the clinical efficacy of these drugs are limited, but preliminary results suggest that, in combination with one or more nucleoside analogues, they represent an important advance in the treatment of patients with advanced HIV infection. The adverse effects and potential for drug interactions, together with the additional cost associated with prescribing these drugs, mean that careful selection and supervision of these patients is imperative. AIM: To present an up-to-date review of the three most recently introduced protease inhibitors. METHODS: Based on a review of the literature, abstracts from relevant meetings and information from the pharmaceutical companies. CONTENT: A review including background data on HIV infection and the treatment options. Detailed information on ritonavir, saquinavir and indinavir. CONCLUSIONS: These new drugs are useful additions to the therapeutic current aims for the treatment of HIV infection. They need to be used under close supervision by specialists.

Anti-Bacterial Agents↗
PubMed1997

Effects of continuous venovenous hemofiltration on cardiopulmonary function in a porcine model of endotoxin-induced shock.

OBJECTIVE: To determine whether continuous venovenous hemofiltration, proposed to remove inflammatory mediators from circulation, would resolve cardiopulmonary derangements in a model of established endotoxic shock. ANIMALS: 16 clinically normal pigs. PROCEDURE: Endotoxin was infused, IV, into anesthetized pigs for a total of 50 minutes. Thirty minutes after termination of the infusion period, extracorporeal circulation was initiated through a 50-kd diafilter, or past the filter without ultrafiltrate formation. Cardiac and respiratory variables were monitored for a period of 4 hours. RESULTS: Infusion of lipopolysaccharide resulted in a severe hypodynamic circulatory state, with significant decreases in mean arterial pressure and cardiac output concurrent with a significant increase in pulmonary arterial pressure. Hemofiltration was not associated with any correction of lipopolysaccharide-induced cardiopulmonary derangements. CONCLUSIONS: Continuous venovenous hemofiltration, as used in this acute experiment, did not improve cardiopulmonary dysfunction during endotoxic shock. CLINICAL RELEVANCE: Continuous venovenous hemofiltration needs further investigation before it can be recommended as a clinically effective treatment.

Animals↗
PubMed1997

Transformation by v-Jun prevents cell cycle exit and promotes apoptosis in the absence of serum growth factors.

To gain insight into the mechanism of action of the v-Jun oncoprotein, we compared the growth and cell cycle behavior of normal and v-Jun-transformed fibroblasts. We show that v-Jun induces marked alterations in cell cycle regulation in both the presence and absence of serum growth factors. During asynchronous growth, v-Jun-transformed fibroblasts divide more rapidly than their normal counterparts, owing to a reduction in the length of the G1 phase of the cell cycle. When deprived of serum mitogens, normal fibroblasts exit the cycle and enter a reversible state of quiescence (G0). In contrast, v-Jun-transformed fibroblasts continue to cycle and maintain increased levels of retinoblastoma tumor suppressor protein phosphorylation and elevated expression of cell cycle-dependent markers such as cyclin A, cyclin-dependent protein kinase 2 (CDK2), and CDC2. v-Jun-transformed fibroblasts nevertheless remain wholly dependent on growth factors for cell multiplication, because cell cycle progression in the absence of serum is accompanied by high rates of apoptotic cell death. We conclude that v-Jun shares the capacity of the Myc, E1A, and E2F oncoproteins to promote both cell cycle progression and apoptosis under conditions of mitogen depletion.

Adenovirus E1A Proteins↗
PubMed1996

Efficacy of convective removal of plasma mediators of endotoxic shock by continuous veno-venous hemofiltration.

Continuous veno-venous hemofiltration (CVVH) has been reported to provide beneficial effects during endotoxic shock. This experiment was designed to determine if selective removal of plasma mediators occurs during CVVH and if plasma concentrations of these mediators are reduced. A swine endotoxic-shock model with three groups was used (lipopolysaccharide (LPS) only (n = 6); LPS followed by CVVH (n = 6); and LPS followed by sham CVVH (n = 4). Plasma and filtrate samples were collected at frequent intervals for 5 h. Lactic acid (LA), eicosanoids [prostacyclin (6-keto PGF1 alpha), thromboxane (TxB2), and prostaglandin E2 (PGE2)] and tumor necrosis factor (TNF) were measured in plasma and filtrate. Plasma concentrations of 6-keto PGF1 alpha, TxB2, TNF, and LA were not significantly different in any group. LA, PGE2, 6-keto PGF1 alpha, and TXB2 concentrations were similar in filtrate and plasma. TNF did not move across the membrane into the filtrate, CVVH, as used in this experiment, did not significantly reduce plasma concentrations of any of these mediators.

Animals↗
PubMed1996

Tacrolimus: immunosuppression following liver and kidney transplant.

Advances in transplantation have been impressive since the introduction of cyclosporin, however, there is still considerable debate on the most suitable immunosuppressant regimen. Tacrolimus, a new macrolide immunosuppressant, was marketed in the U.K. in 1994. Open studies have demonstrated its equal efficacy to cyclosporin in terms of patient and graft survival rates when used for primary immunosuppression following both liver and kidney transplantations. Tacrolimus also provides a valuable alternative for patients experiencing rejection in whom re-transplantation is often the only alternative. Unfortunately, in the studies to date, tacrolimus use was associated with increased nephrotoxicity and neurotoxicity compared to cyclosporin. Further trials are therefore required to define tacrolimus' true value in this complex field.

Graft Rejection↗
PubMed1996

Growth hormone treatment for growth hormone deficient adults.

Growth hormone (GH) deficiency in adults is now recognized as a clinical syndrome with characteristic signs and symptoms. Numerous trials with daily subcutaneous biosynthetic human growth hormone (hGH) have been conducted in this patient group. Generally, improvements in insulin-like growth factor levels, decreases in total fat mass and increases in lean body mass are recorded with no overall effect on total body weight. Variable effects on serum cholesterol, bone mineral density and quality of life have also been reported. The true place of GH replacement therapy in adults has yet to be defined. Several questions relating to the dose, duration of treatment, long-term side-effects, quality of life changes and health economic implications of treatment still need to be assessed.

Adult↗
PubMed1996

Therapeutic advances: riluzole for the treatment of motor neurone disease.

Amyotrophic laterial sclerosis is a fatal neurogenerative disorder, for which only symptomatic treatment was previously available. Riluzole was recently launched in the U.S.A. and Europe. This is the first drug to produce a modest increase in survival (approximately 3 months) in patients with this disease. Unfortunately, treatment causes a number of side-effects of which asthenia is particularly troublesome. Between 10 and 20 per cent of patients can be expected to withdraw from treatment due to these adverse effects. Data on the real time survival advantage and quality of life that can be expected whilst on treatment are needed to identify the place of riluzole in the management of this distressing disease.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Therapeutic advances: beta-interferon for multiple sclerosis.

Multiple sclerosis (MS) is a very distressing condition for which there is no effective treatment. Two randomized double-blind placebo-controlled trials of beta-interferon in mildly disabled patients with relapsing remitting MS have been published. Although promising, beta-interferon is not a cure for MS and the clinical significance of the small effect of beta-interferon on disease progression is not known. The high cost of beta-interferon, the distressing nature of MS and the small benefit demonstrated in clinical trials mean that purchasers and clinicians will face hard decisions in managing the introduction of these drugs.

Humans↗
PubMed1996

Adjunctive Use of Appetite Suppressant Medications for Improved Weight Management in Bariatric Surgical Patients.

BACKGROUND: Patients who undergo bariatric surgery sometimes experience late onset or weight gain, when they lapse into negative eating patterns, which adversely affect weight management. Long-term weight management is a process, with a surgical foundation, and requiring adjunctive strategies for best results. We sought to determine if appetite suppressant medications could be safely incorporated into a comprehensive program of weight management. METHODS: Subjects were at least 18 months postoperative, were accessible for weekly follow-up, and weighed at least 9 kg more than their ideal body weight. Phentermine and fenfluramine were prescribed in combination, at the lowest dose necessary to achieve comfortable appetite suppression. RESULTS: Weight losses ranged from 4.5 to 22.7 kg, over a 12-week course of treatment, corresponding to 8-65% of excess body weight. Most side-effects were minor, and did not require cessation of treatment. Two patients discontinued treatment due to side-effects which were unacceptable to them. CONCLUSION: Phentermine and fenfluramine are a safe and useful adjunct to a comprehensive program of weight management.

Journal Article↗
PubMed1996

Spontaneous intramural haematoma of the oesophagus: radiologic recognition.

Spontaneous intramural haematoma of the oesophagus (SIHO) is an uncommon disorder. It presents usually with acute chest pain followed by dysphagia. This condition may mimic spontaneous rupture of the oesophagus (Boerhaave Syndrome), dissection of the thoracic aorta or acute myocardial infarction. Hence early accurate confirmation of the diagnosis by radiology is vital for the appropriate acute management. The condition is frequently mistaken for acute myocardial infarction which may prompt inappropriate thrombolytic therapy. The appearances on contrast studies of oesophagus and on CT scanning are characteristic. Despite this, the diagnosis may easily be missed, if appropriate careful radiological technique is not used. This paper reports three consecutive cases of SIHO managed in one institution. These cases illustrate that early gastrografin contrast radiology followed by barium contrast radiology and if necessary by thoracic CT is diagnostic in all cases of this condition.

Aged↗
PubMed1995

Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial.

BACKGROUND AND PURPOSE: CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. METHODS: At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee-evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. RESULTS: Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of > or = 70 at the terminal visit. CONCLUSIONS: We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Acute Disease↗
PubMed1995

Alcohol-related risk factors associated with HIV infection among patients entering alcoholism treatment: implications for prevention.

OBJECTIVE: Reports suggest that alcoholics may be at risk for HIV infection. In this article we examine several alcohol-related risk factors for HIV infection among patients entering alcoholism treatment in an AIDS epicenter. Our objective was to identify key factors for HIV prevention and screening among populations receiving treatment for alcohol abuse or alcohol dependence. METHOD: Clients (N = 921) entering five alcoholism treatment centers in the San Francisco Bay area underwent an interview and blind serotesting for HIV antibodies (76% were male, 16% men who had sex with men, 50% black, 10% Latinos and 6.5% were HIV seropositive). Logistic regression was used to predict HIV serostatus from five possible alcohol-associated risk factors, controlling for demographics and traditional HIV risk factors. These were alcohol impairment, attitudes about socializing in bars, increased sexual risk expectancies when drinking, enhanced sexual expectancies when drinking and decreased nervousness when drinking. Male and female heterosexuals and men with a history of homosexuality were analyzed separately. RESULTS: Among male and female heterosexuals, HIV infection was positively associated with higher alcohol impairment (OR = 2.69, p = .031) and negatively associated with higher sexual risk expectancies when drinking (OR = 0.24, p = .075). Among men who had sex with men, HIV infection was positively associated with higher bar socializing orientations (OR = 10.06, p = .004). Infection was also negatively associated with higher alcohol impairment (OR = 0.34, p = .052) and higher sexual risk expectancies when drinking (OR = 0.26, p = .024) for these men. CONCLUSIONS: Since these associations were independent of demographics and traditional HIV risk factors, our research suggests it may be important to also focus HIV screening and prevention on alcohol-related risk factors in AIDS epicenters. For heterosexual alcoholics, the focus should be on those with higher alcohol dependence. For male alcoholics who had sex with men, the focus should be on those who primarily socialize in bars. Further research is needed to determine why higher sexual risk perceptions when drinking were associated with lower rates of HIV infection for both groups, since this discovery may have important prevention implications. The negative association between infection and alcohol impairment among homosexual men also warrants further investigation.

Adolescent↗
PubMed1994

HIV infection and risk behaviors among heterosexuals in alcohol treatment programs.

OBJECTIVE: To measure the prevalence of human immunodeficiency virus (HIV) infection and high-risk behaviors among heterosexuals in alcohol treatment. DESIGN: Cross-sectional survey. SETTING: Five public alcohol treatment centers. SUBJECTS: Consecutive sample of 888 heterosexual clients entering treatment between October 1990 and December 1991. Respondents were 51% black, 10% Hispanic, 33% white, and 76% male. The overall response rate was 68%. MEASUREMENTS: Structured interview and serotesting for HIV antibodies. RESULTS: The overall seroprevalence of HIV infection was 5% (95% confidence interval, 3% to 6%). There were no significant differences in rates of infection by age, gender, or race. The prevalence of infection in heterosexual respondents without a history of injection drug use was 3% in men and 4% in women, several times higher than published estimates from a similar community-based heterosexual sample. Unsafe sexual practices were common: 54% of respondents reported multiple sexual partners in the previous year, 97% of nonmonogamous respondents did not use condoms during all sexual encounters, and few respondents consistently asked new sexual partners about previous high-risk behaviors. CONCLUSIONS: There is a substantial prevalence of HIV infection among heterosexual clients in San Francisco (Calif) alcohol treatment programs, much of which is not associated with injection drug use. Because of this and the high prevalence of unsafe sexual behaviors, there is a relatively high likelihood of heterosexual spread of HIV among the large population of clients seeking treatment for alcohol dependency. Interventions to prevent HIV spread should become a standard part of alcohol treatment programs.

AIDS Serodiagnosis↗
PubMed1994

Levels of HIV testing and low validity of self-reported test results among alcoholics and drug users.

OBJECTIVES: To evaluate HIV testing behavior, validity of self-reported serostatus, and intention to test among alcoholics and drug users entering treatment. DESIGN: Longitudinal cohort study. METHODS: A total of 952 clients voluntarily entering three outpatient and two inpatient public alcohol treatment centers in San Francisco were enrolled. Seventy-six per cent were men, 50% black, 81% had used both alcohol and drugs during the last year, 43% had injected drugs and 9% of the men were homosexual. Subjects completed an interviewer-administered questionnaire and blindly-linked HIV-antibody test at entry and after 1 year (81% follow-up). RESULTS: Fifty-seven per cent of subjects reported that they had previously sought HIV testing. Factors associated with HIV testing included homosexual contact, injecting drug use, having a partner who had been tested, and using condoms. Hispanics were the least likely of all ethnic groups to report testing. Of 60 subjects with HIV antibodies, 47 (78%) said they had already been tested; however, 19 (40%) inaccurately reported that their serostatus was negative and another four (9%) had no collected their test results. Blacks were much more likely than other groups to misreport or be unaware of their HIV status. Only half of the 68% who said they planned to be tested during the following year did so. Five (42%) out of 12 HIV-positive individuals who were unaware of, or misreported their serostatus at baseline, and who sought another HIV test during the follow-up year continued to report themselves as uninfected. CONCLUSIONS: A large proportion of clients attending public alcohol treatment centers report having been HIV tested, much greater than that observed in other populations. However, misreporting of HIV test results was very common among seropositive subjects. Alcohol and drug treatment programs for this high-risk population should include interventions to optimize use of HIV testing for prevention and treatment, and improve understanding of test results.

Adolescent↗
PubMed1993

Transcription activation by Myc and Max: flanking sequences target activation to a subset of CACGTG motifs in vivo.

The Myc oncoprotein has been implicated in control of cell growth, division and differentiation. Although Myc contains a bHLH-LZ motif, it fails to bind DNA alone but can do so by forming heterodimers with an unrelated bHLH-LZ protein, Max. Max homodimers and Myc-Max heterodimers share the ability to bind CACGTG or CATGTG elements. Current models, based on experimentally induced overexpression of Myc and Max in mammalian cells, propose that Max-Max homodimers repress while Myc-Max heterodimers activate transcription through CACGTG binding sites. The interpretation of the results using mammalian cells is complicated by the presence of numerous unrelated CACGTG binding transcription activators and the existence of two alternative Max dimerization partners, Mad and Mxi-1. Thus, the mechanism whereby overexpression of Max leads to transcriptional repression remains to be established. Using a yeast system we show that Max homodimers have the potential to activate transcription through CACGTG motifs. Activation by Max requires DNA binding and amino acids outside the bHLH-LZ domain but is reduced compared with activation by Myc-Max heterodimers. Moreover, transcriptional activation by Myc-Max heterodimers, but not Max-Max homodimers, is strongly inhibited in vivo by specific sequences flanking the core CACGTG binding motif, presumably reflecting reduced DNA binding affinity. These results suggest a mechanism for directing the Myc-Max complex to a specific subset of CACGTG-containing target genes.

Amino Acid Sequence↗
PubMed1993

The development of guideline factors for the evaluation of disability in neck and back injuries. Division of Industrial Accidents, State of California.

This is the second article documenting the development of guideline factors for the evaluation of spine injuries by a committee supported by the Division of Industrial Accidents (DIA) in the State of California. The committee was asked to develop guidelines that incorporated cervical and thoracic spine injuries into the original guidelines developed for lumbar spine injuries (Clark et al, Spine 1988; 13:332). Multiple Independent Medical Examiners (IMEs) were requested to rate disability on 42 case reports submitted to the DIA. A tremendous variation existed in the disability rating recommended by physicians given the same set of facts. One hundred eighty-five IMEs then were asked to evaluate a series of potential factors influencing disability. Each factor was listed according to its perceived importance in determining disability. These factors then were subjected to an intensive search of the medical and scientific literature to determine their validity. A final list of 28 factors for the cervical and thoracic spine were developed and combined with the previously published factors for the lumbar spine. This led to the development of 37 factors or guidelines for the evaluation of spine disability. Testing of this schedule was performed by reviewing 159 submitted disability consultation reports. This review showed that there were no factors in the reports that were not included in the schedule. An average of 3.1 subjective factors and 2.3 objective factors were noted in the reports, with a very poor relationship between the number of factors and the level of disability given by the assessing physician. It is thought that the incorporation of the proposed guideline factors into the current disability rating system would allow for a more reproducible evaluation of disability and allow Workers' Compensation judges and administrators to make disability decisions based on documentable and reliable facts.

Back Pain↗