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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 55 records · Page 3Linked to original sources
PubMed2000

Which patients are treated for glaucoma? An observational analysis.

PURPOSE: More than one million patients in the United States are treated for glaucoma, although little is known about the typical clinical characteristics of this group of patients and the type of therapy they receive. This study was conducted to describe the demographic and diagnostic characteristics of patients beginning long-term drug therapy for glaucoma. METHODS: This cross-sectional study included 544 patients beginning topical glaucoma medication regimens who received care at a group model health-maintenance organization (HMO) located in central Massachusetts. The primary medical records of 544 patients beginning topical glaucoma medication between 1987 and 1990 were reviewed to ascertain the presence of three clinical findings: intraocular pressure (IOP) > or = 22 mmHg; optic disc changes including cup-to-disc ratio > or = 0.8, cup-to-disc asymmetry > or = 0.2, or morphologic disc changes consistent with glaucomatous optic neuropathy; and visual field defect consistent with glaucoma. RESULTS: A majority of the 544 patients (86%) were diagnosed as having primary open-angle glaucoma (POAG) by their physicians. Almost half (44.7%) of these patients had only an elevation in IOP without other clinical findings, and 9% met none of the above criteria for glaucoma according to information in the medical record. CONCLUSION: In this setting, most patients who were prescribed drug therapy for POAG were treated for an elevation in IOP alone in the absence of other ophthalmologic characteristics of glaucoma.

Adrenergic beta-Antagonists↗
PubMed2000

Effects of prolactin on osteoblast alkaline phosphatase and bone formation in the developing rat.

The purpose of the current study was to determine whether maternal prolactin (PRL) had any effects on bone formation in the developing rat pup. Because the most prevalent forms of PRL in rats are unmodified and phosphorylated PRL, both recombinant PRL and a molecular mimic of phosphorylated PRL (PP-PRL) were administered to pregnant animals. Blood samples from the dams showed normal estrogen and progesterone and no effect of extra PRL on parathyroid hormone (PTH), calcium, or alkaline phosphatase (AP). In newborn pups, however, there was a 30% decrease in blood AP in both PRL-treated groups, whereas PTH and calcium levels were not different from controls. When primary rat osteoblasts were exposed to both PRLs, AP activity was reduced, with PP-PRL being the more potent form of the hormone. Histological examination of pup bone formation showed reduced calvarial bone and reduced endochondral ossification in pups exposed to PP-PRL. These results are the first to show a direct inhibitory effect of PRL on osteoblast function.

Alkaline Phosphatase↗
PubMed2000

Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension.

BACKGROUND: The use of appetite suppressants in Europe has been associated with the development of primary pulmonary hypertension (PPH). Recently, fenfluramine appetite suppressants became widely used in the United States but were withdrawn in September 1997 because of concerns over adverse effects. MATERIALS AND METHODS: We conducted a prospective surveillance study on patients diagnosed with pulmonary hypertension at 12 large referral centers in North America. Data collected on patients seen from September 1, 1996, to December 31, 1997, included the cause of the pulmonary hypertension and its severity. Patients with no identifiable cause of pulmonary hypertension were classed as PPH. A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines. RESULTS: Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens. CONCLUSION: The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH.

Adult↗
PubMed2000

Cerebral circulation in REM sleep: is oxygen a main regulating factor?

In the transition from NREM to REM sleep, as in other instances of brain activation, a marked increase in cerebral blood flow and glucose uptake is observed, together with a lesser increase in O2 uptake. Brain activation also entails an increase in capillary PO2 and lactate production. The hypothesis of saturation of the oxidative machinery was advanced to explain anaerobic glycolysis and lactate production in the presence of high PO2, but data are available that cannot be explained by this hypothesis: hypoxic spots exist in the brain, augmenting in arterial hypoxia and disappearing in arterial hyperoxia, while tissue [H+] lowers as arterial PO2 increases beyond 100 mmHg. Additional hypotheses are thus required. We suggest that O2 diffusion limitation exists in the brain: microregions lying at mid-distance between capillaries may become hypoxic and partly resort to anaerobic glycolysis. These microregions are thought to enlarge with increasing metabolic rate or arterial hypoxia and give rise to vasodilatatory signals regulating local blood flow. REM sleep time is strongly reduced by hypoxic and increased by hyperoxic atmosphere, in accordance with the existence of an O2 diffusion limitation. Any pathological decrease in arterial PO2 and/or O2 delivery creates a specific risk in REM sleep.

Animals↗
PubMed1999

Repetitive hypoxia rapidly depresses cardio-respiratory responses during active sleep but not quiet sleep in the newborn lamb.

1. Arousal from sleep is an important protective response to hypoxia that becomes rapidly depressed in active sleep (AS) when hypoxia is repeated. This study questioned whether there might also be selective depression of cardio-respiratory responses to hypoxia during AS. 2. Nine newborn lambs (7-22 days of age) were studied over three successive nights. The first and third nights were baseline studies (inspired oxygen fraction, Fi,O2 = 0.21). During the second night, during every epoch of sleep, lambs were exposed to 60 s episodes of isocapnic hypoxia (Fi,O2 = 0.10). 3. During quiet sleep (QS), the probability of arousal in hypoxia exceeded the probability of spontaneous arousal (P < 0.001) throughout repeated exposures to hypoxia. Similarly, there were persisting increases in ventilation (135 +/- 25 %), blood pressure (3 +/- 1 %) and heart rate (3 +/- 1 %). 4. By contrast, rapid depression of all responses occurred during repetitive hypoxia in AS. Thus, the probability of arousal in hypoxia exceeded the probability of spontaneous arousal during the first 10 hypoxia exposures (P < 0.001) but not thereafter. Similarly, during the first 10 exposures to hypoxia, the changes in ventilation (88 +/- 15 %) and blood pressure (5 +/- 1 %) were greater than subsequent responses (P < 0.05). 5. We conclude that, when repeated, hypoxia rapidly becomes ineffective in stimulating protective arousal, ventilatory and blood pressure responses in AS, but not in QS. Selective depression of responses during AS may render the newborn particularly vulnerable to hypoxia in this state.

Animals↗
PubMed1999

Descriptive epidemiology of acute liver enzyme abnormalities in the general population of central Massachusetts.

OBJECTIVES: This study quantifies the incidence of liver enzyme abnormalities in the general population of central Massachusetts. METHODS: Computerized data files from a health maintenance organization were used to ascertain potential subjects during the study period of 1 July 1992-30 June 1993. Medical records and laboratory tests results were reviewed to confirm the diagnoses. RESULTS: The incidence rates were 40.6 cases per 100,000 persons per year for drug-associated liver enzyme abnormalities, 39.0 per 100,000 persons per year for liver enzyme abnormalities secondary to biliary pathologies, 25.2 per 100,000 persons per year for liver enzyme abnormalities secondary to mononucleosis, 25.2 per 100,000 persons per year for liver enzyme abnormalities of unknown aetiology, 15.4 per 100,000 persons per year for alcoholic liver enzyme abnormalities, 12.2 per 100,000 persons per year for liver malignancy, and 7.3 per 100,000 persons per year for viral hepatitis (HAV, HBV and HCV). Men were more commonly affected by alcoholic liver enzyme abnormalities and viral hepatitis, with respective incidence rates approximately 5 and 2 times higher than women. Liver enzyme abnormalities secondary to mononucleosis occurred predominantly between the ages of 15-24 years. In contrast, liver diseases secondary to biliary pathologies, liver malignancies and drug-associated liver enzyme abnormalities were found most frequently among the elderly. CONCLUSION: Liver enzyme abnormalities occurred with a higher incidence in this general population than reported previously in selected patients. Drug-associated liver enzyme abnormality was the most common type. The magnitude of drug-associated liver enzyme abnormality could be much higher as an appreciable proportion of the liver cases of unknown aetiology are potentially drug-attributable.

Journal Article↗
PubMed1999

A combination study design to examine mycophenolate mofetil (MMF) and PTLD in renal transplant patients.

Renal transplant recipients who are chronically immunosuppressed by drugs are at a higher risk of developing malignancies. Commonly observed malignancies are several forms of posttransplant lymphoproliferative disorders (PTLD), skin, lip and gynaecological cancers. The risk is associated with many risk factors including the extent of immunosuppression. Mycophenolate mofetil (MMF) is an immunosuppressant, indicated for the prophylaxis of organ rejection in patients receiving allogenic renal and heart transplants. During the European approval of MMF for renal transplantation, the question was raised as to whether the use of MMF was associated with an increased risk of PTLD in comparison with alternate immunosuppressive regimens. In response, F. Hoffman-La Roche Ltd set up a prospective observational cohort study with a companion case-control study. This paper describes the objectives and the methods of these studies along with the rationale of the methodology.

Journal Article↗
PubMed1999

The risk of serious cardiac arrhythmias among cisapride users in the United Kingdom and Canada.

PURPOSE: Serious, although rare, ventricular arrhythmias and deaths have been reported in patients taking cisapride monohydrate. Without quantification of the risk involved, it is impossible to develop rational therapeutic guidelines. SUBJECTS AND METHODS: Arrhythmic events (sudden deaths and other events compatible with serious ventricular arrhythmias) were sought among 36,743 patients prescribed cisapride in the United Kingdom and Saskatchewan, Canada. Prescriptions and cases were identified from computerized medical claims data and physicians' office records. We compared rates of events between periods of recent cisapride use and nonrecent use, using cohort analysis. Potential confounding factors, including concomitant treatment with agents that inhibit CYP3A4 metabolism or that prolong the QT interval, were assessed in a nested case-control study. RESULTS: In the cohort analysis, the incidence of the arrhythmic events was 1.6 times greater (95% confidence interval [CI]: 0.9 to 2.9) in periods of recent use. With adjustment for clinical history, use of CYP3A4 inhibitors, and use of drugs that prolong the QT interval, the odds ratio for cisapride and cardiac outcomes was 1.0 (95% CI: 0.3 to 3.7). There was no identifiable increase in risk when cisapride was dispensed at about the same time as QT-prolonging drugs or CYP3A4 inhibitors. QT-prolonging agents were associated with a 2.5-fold increase in the risk of arrhythmic events (95% CI: 1.1 to 5.8). CONCLUSIONS: Serious rhythm disorders were not associated with cisapride use, although the upper confidence bounds do not rule out an increase in risk.

Adolescent↗
PubMed1999

Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection.

Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent. We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population. Of 72 episodes, 44 (61%) were in Aboriginal patients. All 12 cases in children were Aboriginal. Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor. Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere.

Adolescent↗
PubMed1999

Classification trees and logistic regression applied to prognostic studies: a comparison using meningococcal disease as an example.

The authors used logistic regression and classification trees to develop prediction models for fatal outcomes in meningococcal disease in a cohort of 829 children hospitalized for meningococcal disease during 1989-1990 in Rio de Janeiro. The area under the receiver operator characteristic (ROC) curve was 92 per cent for logistic regression and 88 per cent for classification trees. Logistic regression may be preferred when the main objective is to obtain explicit measures for statistical inference and measures of the force of the association between each variable and the outcome. However, estimation of the probability of dying for each patient involves manipulation of the logistic regression formula, which would not easily be done in an emergency room. Classification trees provided comparable discrimination between fatal and non-fatal outcomes, and yielded a graphical display of the results that is easier to understand and is straightforward to apply in clinical settings.

Adolescent↗
PubMed1999

Outbreak of Escherichia coli O157 in a nursery: lessons for prevention.

OBJECTIVES: To identify risk factors for transmission of verocytotoxin producing Escherichia coli O157 (VTECO157) and means of prevention. STUDY DESIGN: Outbreak investigation: retrospective cohort study. SETTING: A nursery (child care centre) in North Wales. SUBJECTS: Children attending (n = 104). METHODS: Faeces were examined using sorbitol MacConkey agar (SMAC), with cefixime, tellurite, and rhamnose; enrichment in modified tryptone soya broth; and immunomagnetic separation. Symptoms and exposure data were obtained from questionnaires to parents/guardians and children's toiletting and feeding records kept at the nursery. MAIN OUTCOME MEASURE: A "case" was defined as a child with verocytotoxin producing E coli O157 isolated from faeces, or a history of haemolytic uraemic syndrome (HUS) and antibodies to E coli O157 lipopolysaccharide, during the period 10 August to 30 September 1995. RESULTS: The attack rate was 31 in 104. Two children developed HUS. There were higher attack rates among girls and friends who played together. Cases were more likely to attend the nursery more frequently. The mean number of recorded bowel motions/child/half day was 0.51 in cases and 0.21 in well children. Child to staff ratios were high preceding and during the outbreak. CONCLUSIONS: A sick child is the most plausible source of infection with subsequent person to person transmission. The record of children's toiletting discriminated between cases and well children and might have allowed earlier detection of the outbreak. This simple record could be considered by other child care facilities as a means of giving early warning of problems with infectious intestinal diseases.

Child↗
PubMed1999

Cerebral blood volume measured using near-infrared spectroscopy and radiolabels in the immature lamb brain.

Near-infrared spectroscopy (NIRS) is a technique that is increasingly being used for the noninvasive measurement of cerebral blood volume (CBV) in newborn infants, but it has not been fully validated against established methods. These experiments in immature lambs (gestation 92+/-1 d, mean+/-SEM) compared CBV measured using NIRS-derived estimates of oxygenated Hb (n = 5) with CBV estimated with radiolabeled indicators (125I-labeled serum albumin and 51Cr-labeled red blood cells, n = 10). Total brain CBV (mL/100 g tissue) measured using NIRS was 2.5+/-0.2 compared with 2.5+/-0.2 using radiolabels (NS). Regional tissue plasma, red blood cells, and whole blood volumes from radiolabels varied significantly (p < or = 0.05) throughout the brain. Whole blood volume (mL/100 g tissue) was largest in choroid plexus (16.2+/-2.1) and least in white matter (0.7+/-0.1) with a significant hierarchy evident among regions: choroid plexus > cerebellum > cortex > brain stem = midbrain > white matter. Regional plasma and red blood cell distributions were similar to whole blood, being highest in choroid plexus (13.0+/-1.6 and 3.2+/-0.9, respectively), and least in white matter (0.8+/-0.1 and 0, respectively). These data from the immature lamb brain indicate that total CBV measured with NIRS is essentially identical with the volumes obtained using intravascular radiolabels. Among cerebral regions, white matter contributes little to the global blood volume measured with NIRS because its red blood cell content is very low.

Animals↗
PubMed1999

Dissociation of Janus kinase 2 and signal transducer and activator of transcription 5 activation after treatment of Nb2 cells with a molecular mimic of phosphorylated prolactin.

We have previously demonstrated that phosphorylated PRL acts as an antagonist to the Nb2 proliferative activities of unmodified PRL. A molecular mimic of phosphorylated PRL, which substitutes an aspartate residue for the normally phosphorylated serine (serine 179), has the same properties. Because it takes less than one fourth the amount of phosphorylated hormone, or the aspartate mutant, to block the proliferative activity of unmodified hormone, we have investigated whether the high potency of the aspartate mutant is achieved by the production of an alternate and interfering intracellular signal cascade. Nb2 cells were exposed to 5 or 500 ng/ml human NIDDK PRL, wild-type recombinant PRL (unmodified PRL), or aspartate mutant PRL (pseudophosphorylated PRL) for 1, 5, or 10 min at 37 C. At 5 ng/ml and 10 min, wild-type recombinant PRL showed greater activation of Janus kinase 2 (JAK 2) than the NIDDK preparation. This is consistent with a previous report of higher proliferative activity for the wild-type hormone and is primarily a reflection of the presence of some phosphorylated hormone in the NIDDK preparation. At 500 ng/ml and 10 min, saturation eliminated any differences between responses to the two preparations. JAK 2 activation was not seen in response to the aspartate mutant at either concentration. Signal transducer and activator of transcription 5 (STAT 5) activation was, however, just as robust for the aspartate-treated cells as for the other two groups. Time course experiments eliminated the possibility that STAT 5 phosphorylation in response to the aspartate mutant was the result of JAK 2 activation at earlier time points. Experiments in the present study also interestingly showed preassociation of JAK 2 and STAT 5 in the absence of PRL and the absence of detectable phosphorylation of either JAK 2 or STAT 5. Like JAK 2, receptor phosphorylation was absent with the aspartate mutant. A comparison between STAT 5a and STAT 5b activation showed a marked reduction in STAT 5b phosphorylation in response to the aspartate mutant, with concomitant reduction in STAT 5a-STAT 5b heterodimers. STAT 5a activation, however, was indistinguishable between the wild-type and aspartate mutant. We conclude that the nonproliferative aspartate mutant signals and activates STAT 5 without, or with minimal, use of JAK 2 or receptor phosphorylation. The wild-type proliferative PRL, on the other hand, uses receptor phosphorylation and JAK 2 activation.

Aspartic Acid↗
PubMed1999

Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee.

Studies have shown a positive association between obesity and knee osteoarthritis. Studies evaluating hand or hip osteoarthritis and weight, however, have assessed x-ray osteoarthritis or been cross-sectional, or both, and results of these have been inconsistent. We assessed the association between body weight, body mass index, and incident symptomatic osteoarthritis in 134 matched case-control pairs of women who were part of a case-control study on estrogen replacement therapy and osteoarthritis. We identified incident symptomatic osteoarthritis cases of the hand, hip, and knee in women ages 20-89 years who were members of a health plan between January 1, 1990 and December 31, 1993. For each case we selected a control woman who was matched by closest date of birth to the case. Medical records were reviewed to obtain weight and height information for the period before disease onset. After controlling for estrogen use, smoking status, height, and health care use, we found that body weight was a predictor of incident osteoarthritis of the hand, hip, and knee. Odds ratios ranged from 3.0 to 10.5 for women in the upper tertiles of weight compared with women in the lowest tertile. Similar associations were observed for body mass index. Our results suggest that obesity is associated with the development of incident osteoarthritis at all joints studied.

Adult↗
PubMed1999

Post-traumatic stress responses following liver transplantation in older children.

Eighteen children aged between 7 and 16 years who had undergone a liver transplantation were interviewed using the Child Post-Traumatic Stress Reaction Index (CPTS-RI) to discover if they had post-traumatic stress symptoms. A case control design was used to define which factors were important for the development of post-traumatic stress. Results of a one-way analysis of variance (ANOVA), with post-traumatic stress symptom intensity as measured on the CPTS-RI as the dependent variable, revealed a significant difference between the liver transplantation group compared with children who had a chronic life-threatening illness or had undergone a routine surgical operation. A post hoc (Tukey's HSD test) statistical analysis was performed and significance at the .05 level was found between the liver transplantation group and both the chronic illness group and the routine surgical operation group. Our results indicate that the acute life-threat involved in the liver transplantation contributed to the development of post-traumatic stress. It was thought that dissociation may be important in preventing the resolution of the trauma. Additional investigations are needed with larger numbers in a longitudinal study beginning before the transplant to determine the course of the PTSD symptoms and the appropriate timing of interventions to reduce the harmful effects of these symptoms.

Adolescent↗