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Biomedical subjects

W Clark

Publications and source records attributed to W Clark.

At least 37 records · Page 2Linked to original sources
PubMed1998

Outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) using human sperm prepared via a new standardized swim-up technique fit for office use.

Objective: Recent developments in the assisted reproductive technology (ART) areas necessitate the use of new and more efficient and acceptable modes of gamete in vitro manipulation techniques. As established via the use of various forms of ART, the natural process of fertilization has been largely bypassed and the gametes are obtained and manipulated outside of the normal means of conception. For the male, improvements in sperm quality have involved the use of various techniques that aim to recover a small percentage of healthy spermatozoa that can be further used for the different ART procedures. Previous IVF results showed no differences in fertilization rates between ZSC and Percoll recovered sperm (Zarmakoupis-Zavos et al. ACOG, 1997). The current study was designed to study the fertilizing capacity of ZSC recovered spermatozoa and subsequent embryonic development and pregnancy rates established via IVF and ICSI procedures.Methods: Sperm specimens (n = 30) were prepared via the use of the standardized ZSC swim-up technique, which was designed to harvest almost all overlayered media at the end of the procedure to maximize the sperm recovery. The ZSC device consists of a column with a conical cavity where the semen is placed, and from where the sperm swim-up into the overlayered media and are subsequently recovered at the end of the procedure. Semen specimens were initially assessed and then prepared (0.5 mL each) via the ZSC swim-up technique. The enhancement of the routine semen parameters was assessed and the recovered specimens were used for either conventional IVF or ICSI.Results: The results of the fertilization and pregnancy via IVF and ICSI are shown below:The generated results point out that ZSC recovered specimens yielded acceptable levels of fertilization and pregnancy rates in our IVF and ICSI program. Furthermore, the IVF inseminations yielded higher fertilization rates with a slight increase in polyspermic oocytes when compared to the ICSI inseminations.Conclusion: The data generated in this study tend to point out that the ZSC, besides being a simple one-step standardized system, can also be effectively employed in an ART program and can generate adequate fertilization and pregnancy rates. We have previously shown that the quality and fertilizing capacity of ZSC recovered sperm is comparable to that recovered via Percoll gradients. However, the ZSC when compared to the Percoll method was less time consuming (5 minutes of actual labor) and less tedious by eliminating the dilution and centrifugation steps of Percoll preparation, since it washes the sperm while simultaneously selecting it. The ZSC is a standardized semen preparation method and could be the method of choice in an ART program.

Journal Article↗
PubMed1998

An oncogenic mutation uncouples the v-Jun oncoprotein from positive regulation by the SAPK/JNK pathway in vivo.

Stimulation of c-Jun transcriptional activity via phosphorylation mediated by the stress-activated or c-Jun amino-terminal (SAPK/JNK) subgroup of mitogen-activated protein kinases (MAP kinases) is thought to depend on a kinase-docking site (the delta region) within the amino-terminal activation domain, which is deleted from the oncogenic derivative, v-Jun [1] [2] [3]. This mutation markedly enhances v-Jun oncogenicity [4] [5]; however, its transcriptional consequences have not been resolved. In part, this reflects uncertainty as to whether binding of SAPK/JNK inhibits c-Jun function directly [6] [7] or, alternatively, serves to facilitate and maintain the specificity of positive regulatory phosphorylation [8]. Using a two-hybrid approach, we show that SAPK/JNK stimulates c-Jun transactivation in yeast and that this depends on both catalytic activity and physical interaction between the kinase and its substrate. Furthermore, c-Jun is active when tethered to DNA via SAPK/JNK, demonstrating that kinase binding does not preclude transactivation. Taken together, these results suggest that SAPK/JNK acts primarily as a positive regulator of c-Jun transactivation in situ, and that loss of the docking site physically uncouples v-Jun from this control. This loss-of-function model accounts for the deficit of v-Jun regulatory phosphorylation and repression of TPA response element (TRE)-dependent transcription observed in v-Jun-transformed cells and predicts that an important property of the oncoprotein is to antagonise SAPK/JNK-dependent gene expression.

Animals↗
PubMed1998

Drug abuse day treatment: a randomized clinical trial comparing day and residential treatment programs.

Clients entering a therapeutic community (TC)-oriented drug treatment program were randomly assigned to day or residential conditions and interviewed at 2 weeks and 6 months after admission. Outcomes included Addiction Severity Index composite scores and summary scores for the Beck Depression Inventory, Symptom Checklist-90-R, and a social support scale. Only clients who remained in treatment for at least 2 weeks were included. The mean age of the sample (N = 261) was 32.9 (SD = 6.7 years) and the mean education level was 12.1 years (SD = 1.9 years); 30% were women. Comparison of outcome scores at 6 months between groups, while controlling for baseline values, indicated greater improvement for residential clients on social problems and psychiatric symptoms. The groups were similar on the 8 remaining outcomes, including measures of alcohol and drug problems. Overall, the level of improvement among day treatment clients was not significantly different from that of residential clients.

Adult↗
PubMed1998

Citicoline treatment for experimental intracerebral hemorrhage in mice.

BACKGROUND AND PURPOSE: Citicoline sodium (cytidine-5'-diphosphocholine) has been shown previously to reduce ischemic injury in focal central nervous system models. Intracerebral hemorrhage (ICH) appears to be associated with an area of edema and ischemic injury surrounding the hematoma that may be reduced by neuroprotective therapy. The present study was designed to test whether treatment with citicoline reduces ischemic injury and improves functional neurological outcome in an experimental model of ICH. METHODS: In 68 Swiss albino mice (26 to 36 g), ICH was induced by collagenase injection into the caudate nucleus. Animals were randomized to receive either: citicoline 500 mg/kg or saline IP prior to collagenase and at 24 and 48 hours. Animals were rated on a 28-point neurological scale and sacrificed at 54 hours. The brains were sectioned, and the volume of hematoma, total lesion, and surrounding ischemic injury was determined. RESULTS: In terms of functional outcome, animals treated with citicoline had improved neurological outcome scores compared with placebo-treated animals: 10.4+/-2.0 versus 12.1+/-2.4 (P<0.01). Regarding ischemic injury, although there was no difference in the underlying hematoma volumes, animals treated with citicoline had a smaller surrounding volume of ischemic injury than placebo-treated animals: citicoline, 13.8+/-5.8 mm3 (10.8+/-4.3% of hemisphere); placebo, 17.0+/-7.1 mm3 (13.3+/-5. 1%) (P<0.05). CONCLUSIONS: In this animal model of ICH, treatment with citicoline significantly improved functional outcome and reduced the volume of ischemic injury surrounding the hematoma. This study supports a potential role for citicoline in clinical ICH treatment.

Animals↗
PubMed1998

Clopidogrel: secondary prevention of vascular ischaemic events.

Atherosclerotic disease is one of the major causes of premature death. In patients with atherosclerotic disease, antiplatelet therapy with aspirin has been shown to decrease the risk of subsequent events by about 20%. In one large randomized controlled study, clopidogrel showed a marginal benefit over aspirin in the prevention of ischaemic vascular events in high-risk patients. Clopidogrel is therefore an alternative in secondary prevention for those patients who are unable to tolerate aspirin. A literature search was performed using MEDLINE, EMBASE, and the Cochrane library, using the keyword 'clopidogrel'. One published randomized, controlled trial was found which evaluated the effects of clopidogrel in the prevention of vascular ischaemic events.

Clopidogrel↗
PubMed1997

Event-related potential evidence for frontal cortex effects of chronic cocaine dependence.

We examined the effects of cocaine dependence and cocaine and alcohol codependence on the P3A event-related potential component. Ten chronic cocaine-dependent subjects, 10 chronic cocaine and alcohol codependent subjects, and 20 controls were studied in an auditory paradigm that included target, nontarget, and novel rare nontarget conditions. Substance-dependent subjects were abstinent from cocaine and/or alcohol for 2-6 weeks. Eighteen of these subjects (4 chronic cocaine-dependent subjects, 4 chronic cocaine/alcohol codependent subjects, and 10 normal controls) were also studied in an analogous visual paradigm. In the auditory modality, the latency of the P3A response in the novel rare nontarget condition was delayed and its amplitude was reduced in both substance-dependent samples compared to controls. Comparable results were found for the smaller samples studied in the visual modality. These results suggest that chronic cocaine dependence produces deficits in frontal cortex functions.

Acoustic Stimulation↗
PubMed1997

Calibrating the physician. Personal awareness and effective patient care. Working Group on Promoting Physician Personal Awareness, American Academy on Physician and Patient.

Physicians' personal characteristics, their past experiences, values, attitudes, and biases can have important effects on communication with patients; being aware of these characteristics can enhance communication. Because medical training and continuing education programs rarely undertake an organized approach to promoting personal awareness, we propose a "curriculum" of 4 core topics for reflection and discussion. The topics are physicians' beliefs and attitudes, physicians' feelings and emotional responses in patient care, challenging clinical situations, and physician self-care. We present examples of organized activities that can promote physician personal awareness such as support groups, Balint groups, and discussions of meaningful experiences in medicine. Experience with these activities suggests that through enhancing personal awareness physicians can improve their clinical care and increase satisfaction with work, relationships, and themselves.

Attitude of Health Personnel↗
PubMed1997

Changes in HIV-related behaviors among heterosexual alcoholics following addiction treatment.

In order to measure changes in HIV-related behaviors among heterosexual alcoholics following treatment, we conducted a prospective cohort study of 700 self-identified alcoholics recruited from five public alcohol treatment centers, all of which included HIV risk-reduction counseling. Respondents underwent an HIV antibody test and interviewer-administered questionnaire at entry to alcohol treatment and after a mean of 13 months later. Compared to baseline, at follow-up there was an overall 26% reduction in having sex with an injection-drug-using partner (23% versus 32%, P < .001) and a 58% reduction in the use of injection drugs (15% versus 37%, P < .001), along with smaller improvements in other behaviors. Respondents also showed a 77% improvement in consistent condom use with multiple sexual partners (35% versus 20%, P < .01) and a 23% improvement in partner screening (71% versus 57%, P < .001). Respondents who remained abstinent showed substantially greater improvement than those who continued to drink.

Adult↗
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↗