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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 91 records · Page 5Linked to original sources
PubMed2001

Alpha2 adrenergic agonists for the management of opioid withdrawal.

BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. OBJECTIVES: To assess the effectiveness of interventions involving the use of alpha2 adrenergic agonists (clonidine, lofexidine, guanfacine, guanabenz acetate) to manage the acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched and relevant pharmaceutical companies contacted. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared alpha2 adrenergic agonists with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all four reviewers. MAIN RESULTS: Twenty-four studies, involving 1956 participants, were included. Nineteen were randomised controlled trials; in two allocation was by participant choice, one used alternate allocation and in two the method of allocation was unclear. Ten studies compared a treatment regime based on an alpha2 adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis. From the comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone, withdrawal intensity is similar to, or marginally greater with alpha2 adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects (low blood pressure, dizziness, dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. REVIEWER'S CONCLUSIONS: Treatment regimes based on the alpha2 adrenergic agonists clonidine and lofexidine, and those based on reducing doses of methadone over a period of around 10 days, have similar efficacy in the management of withdrawal from heroin or methadone. Participants stay in treatment longer with methadone regimes and experience less adverse effects. The lower incidence of hypotension makes lofexidine more suited to use in outpatient settings than lofexidine. There are insufficient data available to support a conclusion on the efficacy of guanfacine.

Acute Disease↗
PubMed2001

HIV-positive patients with anal carcinoma have poorer treatment tolerance and outcome than HIV-negative patients.

PURPOSE: Anal carcinoma is being found in HIV-positive patients with increasing frequency. Most patients are treated with combined chemotherapy and radiation. It was our impression that HIV-positive patients do not fare as well as HIV-negative patients in terms of both response to and tolerance of therapy. METHODS: To test this hypothesis, we reviewed our experience with anal carcinoma and compared HIV-positive to HIV-negative patients by age, gender, sexual orientation, stage at diagnosis, treatment rendered, response to treatment, tolerance, and survival. From 1985 to 1998, 98 patients with anal neoplasms were treated. Seventy-three patients had invasive squamous-cell carcinoma (including cloacogenic carcinoma), and this cohort was analyzed. Thirteen patients were HIV positive and 60 were HIV negative. RESULTS: The HIV-positive and HIV-negative groups differed significantly by age (42 vs. 62 years, P < 0.001), male gender (92 vs. 42 percent, P < 0.001), and homosexuality (46 vs. 15 percent, P < 0.05). There were no differences by stage at diagnosis or radiation dose received. Acute treatment major toxicity differed significantly (HIV positive 80 percent vs. HIV negative 30 percent; P < 0.005). Only 62 percent of HIV-positive patients were rendered disease free after initial therapy vs. 85 percent of HIV-negative patients (P = 0.11). Median time to cancer-related death was 1.4 vs. 5.3 years (P < 0.05). A survival model did not show age, gender, stage, or treatment to be independent predictors. CONCLUSION: We found that HIV-positive patients with anal carcinoma seem to be a different population from HIV-negative patients by age, gender, and sexual orientation. They have a poorer tolerance for combined therapy and a shorter time to cancer-related death. A strong trend to poorer initial response rate was also seen. These results suggest that the treatment of HIV-positive patients with anal carcinoma needs to be reassessed.

Adult↗
PubMed2001

Laparoscopic inguinal hernia repair: lessons learned after 1224 consecutive cases.

BACKGROUND: Despite numerous attempts to improve the techniques used for hernia repair, current published series show that recurrence rates are as high as 5-20%. The complexity of inguinal anatomy, combined with multiple potential areas of weakness, has contributed to the difficulty in preventing recurrences. However, the laparoscopic approach to inguinal herniorrhaphy has allowed clear visualization of all preperitoneal fascial planes and anatomic landmarks, as well as the hernia defect(s) and the peritoneal reflection. In the course of our performance of a series of 1,224 laparoscopic inguinal hernia repairs, we have developed a total extraperitoneal approach that yields excellent results with a low initial recurrence rate. Herein we describe our experience. METHODS: After our initial 300 transabdominal preperitoneal (TAPP) hernia repairs, which resulted in six recurrences, two bowel injuries, one bladder injury, and six cutaneous nerve injuries, the total extraperitoneal approach (TEP) was adopted. RESULTS: The first 300 TEP repairs resulted in one recurrence, two bowel injuries, one bladder injury, and two cutaneous nerve injuries. All major complications occurred in patients who had had previous lower abdominal surgery. In the last 624 TEP herniorrhaphies we implemented some modifications to the technique, especially for patients with previous lower abdominal surgery. In this group we recorded one bladder injury, no cutaneous nerve injuries, and one recurrence. CONCLUSIONS: The total extraperitoneal approach for laparoscopic herniorrhaphy allows for a safe and effective repair with low rates of complication and recurrence. A thorough knowledge of the anatomy of the extraperitoneal space and especially the two- and three-dimensional inguinal anatomy of this space contributed greatly to the evolution of our technique.

Adolescent↗
PubMed2001

Durability of combined aortic and mitral valve repair.

BACKGROUND: This study was undertaken to determine the durability of combined aortic and mitral valve repair. METHODS: From 1979 through 1999, 158 patients underwent simultaneous aortic and mitral valve repair. Multivariable, multi-phase hazard function analysis was used to determine risk factors for the outcomes of death and reoperation. RESULTS: Hospital mortality was 3%. Survival after operation was 97%, 93%, 82%, and 62% after 30 days and 1, 5, and 10 years, respectively. Risk factors for late death included aortic stenosis (p = 0.0001), older age (p = 0.002), and abnormal left ventricular function (p = 0.007). Thirty-six patients required reoperation for valvular dysfunction, and freedom from reoperation was 94%, 82%, and 65% after 1, 5, and 10 years, respectively. Risk factors for reoperation included severe aortic regurgitation (p = 0.004), aortic cusp shaving (p = 0.05), mitral valve chordal transfer (p = 0.004), and bovine pericardial annuloplasty (p = 0.002). Five-year freedoms from endocarditis, thromboembolism, and hemorrhage were 97%, 98%, and 99%, respectively, with freedom from any of these valve-related morbidities of 99%, 95%, and 94% after 1, 5, and 10 years, respectively. CONCLUSIONS: Double valve repair is associated with acceptable late survival and excellent freedom from valve-related morbidity, but limited durability. Therefore, double valve repair should be reserved for patients who cannot be anticoagulated, and should be used with caution in patients with aortic stenosis, rheumatic valve disease, or anterior mitral leaflet pathology.

Adolescent↗
PubMed2001

Preliminary characteristics of the prothrombin converting enzyme from venom of Stephen's banded snake (Hoplocephalus stephensii).

Stephen's banded snake (Hoplocephalus stephensii) is an infrequently encountered Australian elapid species. The crude venom contains coagulant activity and the component responsible is a prothrombin activator requiring factor V for activity. SDS-PAGE of the isolated native protein revealed two bands at 23 and 36 kDa. These findings indicate that the procoagulant is similar to that found in the Australian tiger snake (Notechis scutatus) and thus resembles factor Xa.

Animals↗
PubMed2001

Listeria spinal cord abscess responsive to trimethoprim-sulfamethoxazole monotherapy.

OBJECTIVE: To describe an alternative antibiotic regimen for the treatment of central nervous system Listeria monocytogenes infection. BACKGROUND: Classical treatment of listeria infections of the brain and spinal cord has included ampicillin in combination with gentamicin and chloramphenicol. Antibiotic resistance to L. monocytogenes is extraordinarily low, and the combined risks of nephrotoxicity, ototoxicity, and agranulocytosis in an already critically ill patient make the potential use of trimethoprim-sulfamethoxazole monotherapy for coverage or treatment of listeria an important alternative. METHODS: Case report. RESULTS: A 58-year-old woman presented with a two-week history of progressive quadriplegia. Gadolinium enhanced MRI showed diffuse edema of the cervical and thoracic spine with ring-enhancing lesions. Cerebrospinal fluid and blood cultures both grew L. monocytogenes. Spinal cord biopsy of the lesion revealed inflammation with necrosis and also grew listeria. Intravenous trimethoprim-sulfamethoxazole (8 mg/kg in four divided doses) was administered for six weeks with resultant arrest of neurological symptoms and stabilization of the clinical course. Although the patient was quadraparetic she was able to be discharged to a rehabilitation facility. CONCLUSIONS: Trimethoprim-sulfamethoxazole monotherapy may be a potential alternative option for critically ill patients with central nervous system L. monocytogenes infection.

Anti-Infective Agents↗
PubMed2001

Sociotropic cognition moderates stress-induced cardiovascular responsiveness in college women.

This study examined the moderating effects of sociotropic cognition (SC), a nondefensive need for approval, on stress-induced cardiovascular responsiveness (CVR) in women. Sixty-seven college-age females had blood pressure (BP) and heart rate (HR) monitored during baseline, anticipation, story-telling (where participants were randomly assigned to a low or high threat condition), and recovery periods. SC showed a positive association with CVR only in the high interpersonal threat context during task and early stages of the recovery periods. SC was positively correlated with such variables as anxiety, ruminative style, dysphoria, and anger. This is the first report examining the moderating effects of SC on interpersonal stress-induced CVR prior to, during, and following a task, using an explicit manipulation of social evaluation. The data help define risk factors for CVR in women, which may aid in the understanding of how emotions and stress affect physical health and well-being.

Adolescent↗
PubMed2001

Multicolour imaging of post-Golgi sorting and trafficking in live cells.

The biogenesis and maintenance of asymmetry is crucial to many cellular functions including absorption and secretion, signalling, development and morphogenesis. Here we have directly visualized the segregation and trafficking of apical (glycosyl phosphatidyl inositol-anchored) and basolateral (vesicular stomatitis virus glycoprotein) cargo in living cells using multicolour imaging of green fluorescent protein variants. Apical and basolateral cargo segregate progressively into large domains in Golgi/trans-Golgi network structures, exclude resident proteins, and exit in separate transport containers. These remain distinct and do not merge with endocytic structures suggesting that lateral segregation in the trans-Golgi network is the primary sorting event. Fusion with the plasma membrane was detected by total internal reflection microscopy and reveals differences between apical and basolateral carriers as well as new 'hot spots' for exocytosis.

Adenoviridae↗
PubMed2001

Immunological adjuvants promote activated T cell survival via induction of Bcl-3.

Injection of soluble protein antigen into animals causes abortive proliferation of the responding T cells. Immunological adjuvants boost T cell responses at least in part by increasing the survival of activated T cells during and after the initial proliferative phase of their clonal expansion. To understand how adjuvants promote T cell survival, we used gene microarrays to analyze gene expression in T cells activated either with antigen alone or in the presence of two different adjuvants. Among the genes whose expression was increased by both adjuvants was the IkappaB family member Bcl-3. Retroviral infection experiments showed that expression of Bcl-3 increased survival of activated T cells in vitro and in vivo. Adjuvants may therefore improve survival of activated T cells via induction of Bcl-3.

Adjuvants, Immunologic↗
PubMed2001

Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease. HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a founder effect. Several non-Puerto Rican patients also have mutations in HPS1, which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation, implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes. Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the second example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation.

Alleles↗
PubMed2001

Contracting for smoking and pregnancy interventions: current practice across England.

In order to understand the commissioning of smoking and pregnancy interventions across England prior to the implementation of the Government's national strategy, "Smoking Kills: A White Paper on Tobacco" in 1998, a postal survey was undertaken amongst all 96 Health Authorities (purchasers) and 207 Maternity Service Provider Units (providers) in England. The main outcome measures included the type and duration of contract agreements/service specifications, the level and nature of smoking and pregnancy interventions, barriers to commissioning smoking and pregnancy interventions, data collection and monitoring of activity and quality. A quarter of health authorities were encouraging smoking cessation through contract agreements. The level and complexity of contract agreements and service specifications varied tremendously. Existing smoking and pregnancy interventions were diverse and ad hoc. Data collection and monitoring were haphazard and inconsistent making cross-country comparisons difficult. The commissioning of smoking and pregnancy interventions across England during 1997 and 1998 appeared to be inadequately prioritised. These findings offer a benchmark for observing changes in practice following the recent change of government policy.

Contract Services↗
PubMed2001

Is repair preferable to replacement for ischemic mitral regurgitation?

OBJECTIVE: This study was undertaken to compare mitral valve repair and replacement as treatments for ischemic mitral regurgitation. METHODS: From 1985 through 1997, a total of 482 patients with ischemic mitral regurgitation underwent either valve repair (n = 397) or valve replacement (n = 85). Patients more likely (P < or =.01) to undergo repair had functional mitral regurgitation or coronary revascularization with an internal thoracic artery graft; those more likely to receive valve replacement were in higher New York Heart Association functional classes or underwent emergency operations. These factors were used for multivariable propensity matching. Risk factors for early and late death were identified by multivariable, multiphase hazard function analysis. RESULTS: Within the propensity-matched better-risk group, survivals after valve replacement were 81%, 56%, and 36% at 30 days, 1 year, and 5 years, but survivals after repair were 94%, 82%, and 58% at these intervals (P =.08). In contrast, within the poor-risk group, survivals after repair and replacement were similar (P =.4). Risk factors (P < or =.01) included older age, higher functional class, greater wall motion abnormality, and renal dysfunction. Approximately 70% of patients were predicted to benefit from repair; the benefit lessened or was negated if an internal thoracic artery graft was not used, if a lateral wall motion abnormality was present, or if the mitral regurgitation jet pattern was complex. Freedom from repair failure at 5 years was 91%. CONCLUSION: Late survival is poor after surgery for ischemic mitral regurgitation. Most patients with ischemic mitral regurgitation benefit from mitral valve repair. In the most complex, high-risk settings, survivals after repair and replacement are similar.

Aged↗
PubMed2001

Quantitative ER <--> Golgi transport kinetics and protein separation upon Golgi exit revealed by vesicular integral membrane protein 36 dynamics in live cells.

To quantitatively investigate the trafficking of the transmembrane lectin VIP36 and its relation to cargo-containing transport carriers (TCs), we analyzed a C-terminal fluorescent-protein (FP) fusion, VIP36-SP-FP. When expressed at moderate levels, VIP36-SP-FP localized to the endoplasmic reticulum, Golgi apparatus, and intermediate transport structures, and colocalized with epitope-tagged VIP36. Temperature shift and pharmacological experiments indicated VIP36-SP-FP recycled in the early secretory pathway, exhibiting trafficking representative of a class of transmembrane cargo receptors, including the closely related lectin ERGIC53. VIP36-SP-FP trafficking structures comprised tubules and globular elements, which translocated in a saltatory manner. Simultaneous visualization of anterograde secretory cargo and VIP36-SP-FP indicated that the globular structures were pre-Golgi carriers, and that VIP36-SP-FP segregated from cargo within the Golgi and was not included in post-Golgi TCs. Organelle-specific bleach experiments directly measured the exchange of VIP36-SP-FP between the Golgi and endoplasmic reticulum (ER). Fitting a two-compartment model to the recovery data predicted first order rate constants of 1.22 +/- 0.44%/min for ER --> Golgi, and 7.68 +/- 1.94%/min for Golgi --> ER transport, revealing a half-time of 113 +/- 70 min for leaving the ER and 1.67 +/- 0.45 min for leaving the Golgi, and accounting for the measured steady-state distribution of VIP36-SP-FP (13% Golgi/87% ER). Perturbing transport with AlF(4)(-) treatment altered VIP36-SP-GFP distribution and changed the rate constants. The parameters of the model suggest that relatively small differences in the first order rate constants, perhaps manifested in subtle differences in the tendency to enter distinct TCs, result in large differences in the steady-state localization of secretory components.

Animals↗
PubMed2001

Spindle dynamics and the role of gamma-tubulin in early Caenorhabditis elegans embryos.

gamma-Tubulin is a ubiquitous and highly conserved component of centrosomes in eukaryotic cells. Genetic and biochemical studies have demonstrated that gamma-tubulin functions as part of a complex to nucleate microtubule polymerization from centrosomes. We show that, as in other organisms, Caenorhabditis elegans gamma-tubulin is concentrated in centrosomes. To study centrosome dynamics in embryos, we generated transgenic worms that express GFP::gamma-tubulin or GFP::beta-tubulin in the maternal germ line and early embryos. Multiphoton microscopy of embryos produced by these worms revealed the time course of daughter centrosome appearance and growth and the differential behavior of centrosomes destined for germ line and somatic blastomeres. To study the role of gamma-tubulin in nucleation and organization of spindle microtubules, we used RNA interference (RNAi) to deplete C. elegans embryos of gamma-tubulin. gamma-Tubulin (RNAi) embryos failed in chromosome segregation, but surprisingly, they contained extensive microtubule arrays. Moderately affected embryos contained bipolar spindles with dense and long astral microtubule arrays but with poorly organized kinetochore and interpolar microtubules. Severely affected embryos contained collapsed spindles with numerous long astral microtubules. Our results suggest that gamma-tubulin is not absolutely required for microtubule nucleation in C. elegans but is required for the normal organization and function of kinetochore and interpolar microtubules.

Amino Acid Sequence↗