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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 415 records · Page 23Linked to original sources

Peripheral nerve regeneration: the effects of postoperative irradiation.

The purpose of this study was to evaluate the effects of postoperative external cobalt-60 beam irradiation on nerve regeneration. Sixty-five 250-gm male Sprague-Dawley rats were studied. Peripheral nerve regeneration was measured by walking track analysis and histomorphology of the proximal, graft, and distal nerve segments. These 65 animals underwent a 1.5-cm interpositional nerve graft into the right posterior tibial nerve. The left leg served as a control. Each animal was then randomly allocated into one of four groups. Group 1 served as control. Groups 2 through 4 were subjected to external cobalt-60 gamma-ray irradiation through a 2.5-cm circular portal for a total fractionated dose of 30, 50, and 70 Gy beginning on postoperative day 3. Radiation was administered in 2-Gy fractions, 5 fractions per week, with a top-up dose of 16 Gy given at the end of the fractionated irradiation. Walking track analysis was performed at 30, 60, 90, and 120 days after nerve grafting. At the conclusion of 120 days, sections of the proximal, grafted, and distal nerve were harvested, stained, and examined histomorphologically. Hematoxylin and eosin stains also were obtained. Evaluation of the print-length index demonstrated no statistical difference between the unirradiated controls and the irradiated groups. The total number of axons per square millimeter and nerve fiber density per square millimeter were significantly decreased in the distal segment of all the irradiated groups when compared with controls. Despite the reduction in myelinated regenerating fibers, no reduction in function was observed, as measured by walking track analysis. We would therefore recommend immediate reconstruction of peripheral nerve defects in the face of postoperative irradiation.

Animals↗

Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery.

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.

Administration, Topical↗

Simultaneous determination of phenytoin and carbamazepine in human hair by high-performance liquid chromatography.

Drug detection in human hair has been regarded as a potentially useful technique for therapeutic drug monitoring and for the assessment of therapeutic compliance. An isocratic high-performance liquid chromatography (HPLC) assay for the simultaneous measurement of phenytoin and carbamazepine in human hair was used to assess therapeutic compliance in a population of patients with epilepsy. After alkaline digestion, phenytoin and carbamazepine were separated on a reverse-phase column by using a mobile phase of acetonitrile/methanol/water (9:37:54) and monitored at a wavelength of 214 nm with methylphenyl-5-phenylhydantoin as internal standard. The assay was linear in the range from 0 to 66.66 ng/mg hair, and recoveries of both drugs at concentrations of 8.33, 33.3, and 66.66 ng/mg hair from the hair matrix ranged from 91.2 to 104.0%. Inter- and intraassay coefficients of variation for both drugs (assessed at three concentrations in the calibration range) were < 10%. The limits of detection for phenytoin and carbamazepine were 2.0 and 1.33 ng/mg hair, respectively.

Anticonvulsants↗

Accountability and the accounting regime in the public sector. Some messages from the NHS.

In the UK, the government is keen to introduce private sector procedures into the public sector. The latest stage of this process has been to suggest the adoption of accruals accounting by those parts of the public sector where it is not already operated. This approach to accounting was introduced into the NHS as part of the reforms which implemented a quasi-market to match the demands of purchasers of health care with its providers. Outlines the assumptions which underlie accruals accounting and considers whether the environment created for NHS Trusts is sufficiently like that of the private sector to justify its use. Shows that the initial ideas of the extent to which Trusts could mimic private sector organizations have not been fulfilled in practice, and concludes that it is not possible to justify the use of accruals accounting in the public sector simply on the grounds that as it is the technique used in the private sector it must be superior to the available alternatives.

Accounting↗

Counselling implications of chromosomal abnormalities other than trisomy 21 detected through a maternal serum screening programme.

OBJECTIVE: To identify counselling requirements, we reviewed the frequency and type of non-trisomy 21 chromosome abnormalities found at amniocentesis after maternal serum screening for Down's syndrome. DESIGN: The study involved a review of the cytogenetic results of amniocenteses performed because of a raised maternal serum screening risk. SETTING: The maternal serum screening and amniocenteses were performed at hospitals in the Yorkshire region. SAMPLE: 1715 amniocenteses were performed as a result of a raised maternal serum screening risk for the period 1990 to 1993. METHODS: The cytogenetic results were classified into the main categories of numerical and structural chromosomal abnormalities. MAIN OUTCOME MEASURES: The nature and frequency of abnormal cytogenetic results were identified in which parental samples were required in order to determine if the abnormal finding was de novo or familial and/or for which specialist genetic counselling was required. RESULTS: Sixty-nine pregnancies of 1715 amniocenteses were identified with a chromosomal abnormality (4.0%): 35 (2.0%) with trisomy 21 and 34 (2.0%) with another chromosomal abnormality. For 20 of these 34 abnormalities, parental karyotypes were required and in 29 of the 34 specialist genetic counselling was required. CONCLUSIONS: Women undergoing maternal serum screening and, in particular, those proceeding to amniocentesis, should be informed that there is an equal chance that a chromosomal abnormality other than trisomy 21 will be found at amniocentesis, the nature of which usually requires parental samples and specialist counselling.

Amniocentesis↗

Acute radiation dermatitis following radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia.

Radiation exposure during fluoroscopic imaging poses potential risks to patients and physicians, especially during protracted cardiovascular or radiological interventional procedures. We describe a woman with refractory paroxysmal supraventricular tachycardia who underwent radiofrequency catheter ablation of the slow pathway involved in atrioventricular nodal reentrant tachycardia. The patient subsequently returned 4 weeks later with acute radiation dermatitis that was retrospectively attributed to a malfunction in the fluoroscopy unit that lacked a maximum current output cut-off switch. Using dose reconstruction studies and her estimated biological response, we determined that she received between 15 and 20 Gy (1 Gy = 100 rads) to the skin on her back during the procedure. The exposure will result in an increase in her lifelong risk of skin and lung cancer. This article underscores the potential for radiation-induced injury during lengthy therapeutic procedures using x-ray equipment.

Acute Disease↗

Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia.

Infections with fluconazole-resistant Candida albicans isolate have rarely been described in clinical settings other than oropharyngeal candidiasis in patients with late-stage AIDS. We report on two patients with leukemia who developed fungemia caused by fluconazole-resistant C. albicans after receiving fluconazole prophylaxis (400 mg/day) and empiric amphotericin B therapy (0.5 mg/kg of body weight per day). The fluconazole MICs for the isolates were > or = 64 micrograms/ml, and the isolates were resistant to other azoles and had membrane sterol changes consistent with a mutation in the delta 5,6-sterol desaturase gene. The lack of ergosterol in the cytoplasmic membrane of the fluconazole-resistant strains also imparted resistance to amphotericin B. Both patients were successfully treated with high-dose amphotericin B (1 to 1.25 mg/kg/day) and flucytosine (150 mg/kg/day).

Adolescent↗

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection.

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.

AIDS Vaccines↗

The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection.

Different patterns of viral replication correlate with the natural history of disease progression in humans and macaques infected with human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), respectively. However, the viral and host factors influencing these patterns of viral replication in vivo are poorly understood. We intensively studied viral replication in macaques receiving identical inocula of SIV. Marked differences in viral replication patterns were apparent within the first week following inoculation, a time prior to the development of measurable specific immune effector responses to viral antigens. Plasma viral RNA levels measured on day 7 postinoculation correlated with levels measured in the postacute phase of infection. Differences in the susceptibility of host cells from different animals to in vitro SIV infection correlated with the permissiveness of the animals for early in vivo viral replication and hence with the postacute set point level of plasma viremia. These results suggest that host factors that exert their effects prior to full development of specific immune responses are critical in establishing the in vivo viral replication pattern and associated clinical course in subjects infected with SIV and, by extension, with HIV-1.

Animals↗

The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort.

The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.

Aged↗

A prospective study of patients with lung cancer and hyponatremia of malignancy.

This study was undertaken to define the impact of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) on sodium homeostasis in patients with lung cancer. Patients had their serum and urine electrolytes and osmolality determined before and after a saline infusion of 500 ml. The plasma hormones, AVP, ANP, plasma renin activity (PRA), angiotensin II, and aldosterone were determined by radioimmunoassay every 15 min before, during and after the saline infusion. Fifty patients, 31 with small cell lung cancer and 19 with non-small cell lung cancer participated in this trial. All 11 patients (10 patients with small cell lung cancer and one patient with non-small cell lung cancer) who presented with hyponatremia had inappropriately elevated levels of AVP. Elevated plasma AVP levels were highly correlated with the presence of hyponatremia (p < 0.00001). Initial plasma ANP levels were not associated with hyponatremia (p = 0.73). Urinary sodium concentration increased during the saline infusion proportional to the initial plasma level of ANP (p = 0.0045). AVP appears to be elevated in nearly all patients with hyponatremia of malignancy. ANP plasma levels in patients with lung cancer are associated with the ability to excrete a sodium load but do not appear to downregulate renin, angiotensin II, and aldosterone production.

Adult↗

Mental health practices of Ontario family physicians: a study using qualitative methodology.

OBJECTIVE: To obtain descriptions of how family physicians detect and manage mental health problems commonly encountered in their practices and how they function in their role as mental health care providers. Also, to elicit their perceptions of barriers to the delivery of optimal mental health care. METHOD: Focus groups with standardized questions were used to elicit descriptive data, opinions, attitudes, and terminology. Convenience samples of 10 to 12 physicians were chosen in each of Ontario's 7 health care planning regions, with a mixture of rural, urban, and university settings. Discussions were audiotaped, transcribed, analyzed, and recurring themes were extracted. RESULTS: Family physicians' descriptions of the range of problems commonly encountered and their detection and management highlight the unique nature of mental health care in the primary care setting. The realities of family medicine, the undifferentiated nature of presenting problems, the long-term physician-patient relationship, and the frequent overlap of physical and mental health problems dictate an approach to diagnosis and treatment that differs from mental health care delivery in other settings. Difficulties in the relationship with local psychiatric services--accessing psychiatric care (especially for emergencies), poor communication with mental health care providers, and cumbersome intake procedures of many mental health services--were consistently identified as barriers to the delivery of optimal mental health care. CONCLUSIONS: This study confirms the importance of the family physician in the detection and management of mental health problems. It offers insights into how family physicians function in their role as mental health care providers and how they deal with diagnostic and management challenges that are specific to primary care. It also identifies barriers to the optimal delivery of mental health care in the primary care setting, including difficulties at the clinical interface between psychiatry and family medicine. Further studies are needed to explore these issues in greater depth.

Appointments and Schedules↗

cudA: a Dictyostelium gene with pleiotropic effects on cellular differentiation and slug behaviour.

The Dictyostelium cudA gene encodes a nucleoplasmic protein that is essential for normal culmination. There are no functionally characterised homologues in other organisms but there is a related gene of unknown function in Entamoeba histolytica. The cudA gene is expressed by the prestalk cells that constitute the slug tip (the pstA cells), it is not detectably expressed in the band of prestalk cells that lies behind the tip (the pstO cells) but it is expressed in the prespore cells. This unusual pattern of expression suggests a role on both the stalk and spore pathways of differentiation and cudA- mutant cells are indeed defective in both stalk and spore formation. Furthermore, the slugs formed by cudA- cells continue to migrate under environmental conditions where normal slugs culminate immediately. This aspect of their behaviour can be reversed when the cudA gene is selectively expressed in the pstA cells. This shows that processes occurring in the pstA cells regulate entry into culmination.

Animals↗

Unmet long-term care needs of elderly people in the community: a review of the literature.

The extent of unmet need, or the extent to which needed assistance is unavailable for insufficient, is an important issue in public policy and financing of health and support services. This article reviews the research of literature to assess how unmet method is measured, and the extent of unmet needs among elderly people in the community. Measurement difficulties include variable definitions and measures of need across studies, the relative dearth of studies which undertake to measure unmet needs, and varying methodologies used to estimate need and unmet need. In addition, some measures of status and need, such as cognitive impairment and care giver burden are excluded from many estimates. Estimates of unmet need range from around 2 percent to about 35 percent of community dwelling elders, depending on what is included or excluded from the definition. Unmet need is associated with higher disability levels and living alone. The literature suggests that estimates of future unmet need will be mitigated by declining disability levels and increased use of assistive devices among the elder population.

Activities of Daily Living↗

Snakebite injuries: contributing factors and intentionality of exposure.

The objective was to study the intent of exposure to snakes and other factors contributing to snakebite injuries in order to develop prevention strategies. We used a retrospective chart review and a follow-up telephone interview of snakebite victims who were admitted to a tertiary care center between 1985 and 1994. The data collected included demographics, intent of exposure and host and environmental factors. I performed descriptive analysis. Twenty-four males and six females ranging in age from 2 to 93 years sustained bites from a variety of snakes including rattlesnakes, copperheads, and Egyptian cobra, and others. Sixty-seven percent (20/30) of all bites resulted from intentional exposures to snakes: professional snake handlers (7), snake hunts (8), and playing with (aggravating) snakes in the wild (5). Sixty-five percent (13/20) of intentional exposures involved novices in a recreational/home setting, and 35% (7/20) occurred in an occupational setting. Unintentional exposures occurred while victims were walking in wooded areas, fishing by streams, gardening, and washing dishes indoors. Forty percent (12/30) of all victims had consumed alcohol before the snakebite, 92% (11/12) of whom were nonprofessionals with intentional exposures. Only eight victims (seven of whom were professional handlers) were using protective equipment. I concluded that the majority of snakebite injuries resulted from intentional exposures to snakes in which a variety of factors such as the use of alcohol and lack of protective equipment likely played a role.

Adolescent↗

Intestinal microsporidiosis.

Intestinal microsporidiosis is caused by the protozoan parasites Enterocytozoon bieneusi and Encephalitozoon intestinalis. The disease has been described within the past decade and is found predominantly in acquired immunodeficiency syndrome (AIDS) patients in association with diarrhea. There have been rare reports of infections in immunocompetent patients. Both species of microsporidia invade and multiply within the enterocytes of the small intestine; Encephalitozoon intestinalis also causes a disseminated infection. Electron microscopy has been the mainstay of diagnosis, but improved noninvasive methods of detecting spores in feces are in development. The biology and pathogenicity of the parasites and the pathology and treatment of the disease are poorly understood.

AIDS-Related Opportunistic Infections↗

Job sharing at the managerial level.

Job sharing restructures a full-time position-two individuals share the responsibilities and the benefits of the position. If nurses are committed to making it work, this arrangement can succeed at the managerial level.

Humans↗