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Biomedical subjects

M Fowler

Publications and source records attributed to M Fowler.

At least 19 recordsLinked to original sources
PubMed2006

Intraspinal synovial cysts: a retrospective study.

BACKGROUND: We report the clinical presentation, radiographic studies, intraoperative findings, histopathological analysis, and post-treatment outcome in 26 patients diagnosed with spinal synovial cysts (SSCs). AIMS: To describe the clinical presentation, radiographic studies, operative findings, and postoperative follow-up in 26 patients with SSCs. SETTINGS AND DESIGN: The study was retrospective in design, involving chart review. Individual patient data was tabulated and patterns were recognized. MATERIALS AND METHODS: The charts for 26 patients who underwent surgical extirpation of SSC between April 1993 and October 2002 were retrospectively reviewed. Specifically, initial clinical presentation, pertinent radiographs (X-rays, magnetic resonance imaging, computed tomography), intraoperative findings, histopathology, and postoperative follow-up were noted. STATISTICAL ANALYSIS USED: Patient data was tabulated and analyzed for patterns in demographics, symptoms and histopathology. RESULTS: SSCs were more common in females than males (17:9 ratio). Presenting symptoms were back pain with radiculopathy in 13 (50%), radicular pain in the absence of back pain in 10 (38%), and back pain without radicular pain in three (11%). In addition, 17 patients (65%) had sensory deficit, and 9 (35%) had motor deficit. Most SSCs occurred at the lumbar (19/26) or lumbosacral (5/26) regions, with only 2 (2/26) in the thoracic region. One patient had bilateral SSC at the L4-5 level. Intraoperatively, each cyst was located adjacent to a degenerated facet joint. These lesions could grossly be identified intraoperatively and histopathological confirmation was achieved in all the cases. CONCLUSIONS: SSCs are important lesions to consider in the differential diagnosis of lumbar epidural masses and surgical resection leads to significant improvement in the majority of cases.

Humans↗
PubMed2003

Human neuroepithelial cells express NMDA receptors.

L-glutamate, an excitatory neurotransmitter, binds to both ionotropic and metabotropic glutamate receptors. In certain parts of the brain the BBB contains two normally impermeable barriers: 1) cerebral endothelial barrier and 2) cerebral epithelial barrier. Human cerebral endothelial cells express NMDA receptors; however, to date, human cerebral epithelial cells (neuroepithelial cells) have not been shown to express NMDA receptor message or protein. In this study, human hypothalamic sections were examined for NMDA receptors (NMDAR) expression via immunohistochemistry and murine neuroepithelial cell line (V1) were examined for NMDAR via RT-PCR and Western analysis. We found that human cerebral epithelium express protein and cultured mouse neuroepithelial cells express both mRNA and protein for the NMDA receptor. These findings may have important consequences for neuroepithelial responses during excitotoxicity and in disease.

Animals↗
PubMed2001

Membrane cross-talk in the early distal tubule segment of frog kidney: role of calcium stores and chloride.

The activities of transport mechanisms in epithelial cells are generally coordinated in order to minimise disturbances in cellular ion content and volume. Furosemide, a potent inhibitor of transport in the renal diluting segment, up-regulates apical K+ channel activity following the release of calcium from intracellular stores. The signal pathway between furosemide application and this calcium release is not known. Single early distal tubule segments from frog kidney were permeabilised with saponin in order to monitor calcium levels within cytoplasmic stores using the calcium-sensitive dye, mag-fura. The uptake (or release) of calcium to (or from) stores was initiated by adding agents to the bath solution, which is in direct contact with the intracellular organelles. ATP promoted calcium uptake into stores, whereas ATP removal led to a slower, spontaneous calcium release. Following loading, calcium stores could be rapidly depleted by inositol 1,4,5-trisphosphate (IP3), but not ryanodine. Calcium release was evident upon lowering the "intracellular" chloride concentration from 12 to 4 mM, equivalent to the fall in chloride induced by furosemide in intact cells. These results suggest that intracellular chloride may function as a second messenger, mediating cross-talk between the apical membrane and intracellular calcium stores.

Adenosine Triphosphate↗
PubMed2001

The ultrastructural and immunohistochemical heterogeneity of CD-30-positive neoplasms: so-called anaplastic large cell Ki-1 lymphomas.

Anaplastic large cell lymphoma (ALCL), also referred to as Ki-1 lymphomas, was first recognized as an entity with characteristic light microscopic appearance in 1985. This tumor is composed of variably cohesive cells, often with large, markedly atypical, and multinucleated cellular forms. The recognition of ALCL resulted from the development of a monoclonal antibody in Kiel, Germany, named Ki-1, which was initially believed to be a putative marker for Reed-Sternberg cells. This antibody was later found to be specific against the epitope CD-30. Attempts to create strict criteria to preserve this neoplasm as a specific entity have undergone evolution. However, it is now clear that included in this group are a variety of pleomorphic neoplasms with CD-30 immunoreactivity. Some of these neoplasms are nonlymphoid and show marked heterogeneity in their immunohistochemical and ultrastructural profiles. This article aims to highlight the ultrastructural spectrum of neoplasms exhibiting CD-30 positivity that are within the spectrum of ALCL. It remains to be determined if there are subgroups of these CD-30-positive neoplasms that can be segregated on the basis of ultrastructural and immunohistochemical criteria with corresponding clinical correlates that may impact on their management, treatment, and prognosis. We review here the heterogeneity of CD-30-positive neoplasms (so-called anaplastic large cell Ki-1 lymphomas).

Abdominal Neoplasms↗
PubMed2000

Outpatient cervical ripening with intravaginal misoprostol.

OBJECTIVE: To determine if outpatient cervical ripening using misoprostol can initiate labor within 48 hours of medication administration and to determine if time from medication administration to time of delivery is decreased using outpatient cervical ripening. METHODS: Uncomplicated singleton, vertex pregnancies at 41 weeks' gestation or later with Bishop score of 4 or less were eligible for enrollment. Other inclusion criteria included intact membranes, less than eight uterine contractions per hour, a reactive nonstress test, and amniotic fluid index (AFI) over 5 cm. After randomization, 25 micro(cg) of misoprostol or placebo was placed within the posterior vaginal fornix. Patients were continuously monitored for 4 hours, then discharged if not in active labor. Patients returned in 24 hours for a repeat administration of the respective medication. Patients not delivered within 48 hours were admitted for inpatient induction of labor. Statistical analysis was performed with the Fisher, Student t, chi(2), and Mann-Whitney U tests, with P <.05 considered statistically significant. RESULTS: Among the 60 patients enrolled, 27 (45%) received misoprostol and 33 (55%) received placebo. The majority (24 of 27, 88.9%) of study group patients entered active labor within 48 hours after dosing, compared with 16.7% (five of 33) of placebo group patients (P <.001). The time from initial dose to delivery was significantly shorter in the misoprostol group (36.9 +/- 3.8 compared with 61.3 +/- 3.8 hours, P <.001). CONCLUSION: Intravaginal misoprostol is effective for outpatient cervical ripening. No adverse effects were encountered, although further study is required to determine the safety of this treatment regimen.

Administration, Intravaginal↗
PubMed2000

Rationale, design, and methods for a Coreg (carvedilol) Heart Failure Registry (COHERE). COHERE Participant Physicians.

BACKGROUND: The success of beta-blocking agents in clinical trials of heart failure (HF) has led to a widespread call for their increased use, which assumes these agents will perform as well in the usual care setting. Given the traditional contraindication of the use of beta-blocking agents in HF, and their perception as difficult to use in HF, observing how they perform in the usual care setting could be critical in accelerating their widespread application. Carvedilol is the only beta-blocking agent currently approved in the United States for use in HF. METHODS: The Coreg (brand of carvedilol; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) Heart Failure Registry (COHERE) is intended to collect data on outcomes and other clinical variables in a typical HF population and to observe experience with carvedilol in the hands of community practitioners. COHERE does not include any specific patient selection or exclusion criteria. The decision to use carvedilol is entirely at the discretion of the participant physician, based on evidence of HF as judged by assessments the practitioner usually uses. All patients will be followed for 1 year, with information on outcomes and other clinical variables collected and analyzed at baseline, the end of titration, and at 6 and 12 months after reaching the maximum tolerated dose. About 600 participant physicians selected to be as representative as possible of the community practice setting will enroll approximately 6,000 patients. CONCLUSIONS: COHERE will be the first and largest prospective observational experience with a new treatment, ie, carvedilol, in patients with HF managed in the usual care setting and should provide valuable information about this new treatment in this environment compared with the more rigid clinical trials setting.

Adrenergic beta-Antagonists↗
PubMed2000

Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children < or = 5 years of age, Pediatric Spectrum of HIV Disease project (PSD), USA.

BACKGROUND: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. METHODS: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. RESULTS: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. CONCLUSION: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Glioblastoma multiforme in a case of acquired immunodeficiency syndrome: investigation a possible oncogenic influence of human immunodeficiency virus on glial cells. Case report and review of the literature.

Malignant glioma is the most common primary brain neoplasm, but generally it is not included in the differential diagnosis of enhancing lesions of the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome. We report a case of glioblastoma multiforme (GBM) in a 29-year-old man with human immunodeficiency virus (HIV). Primary CNS lymphoma was suspected, making a definitive histological diagnosis crucial. An initial stereotactic biopsy sample was insufficient to establish a diagnosis and a second biopsy of the lesion was obtained. The histopathological investigation confirmed GBM and adjuvant external radiation treatment was given to the patient, who survived for 4 months after the initial biopsy. A decline in the rate of Toxoplasma infection and the changing diseases observed in HIV infection indicate the importance of obtaining a biopsy in cases of CNS mass lesions.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies.

BACKGROUND: To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. METHODS: North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. RESULTS: The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. CONCLUSIONS: The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine.

Anti-HIV Agents↗
PubMed1999

Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams.

CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. DESIGN: Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES: Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. RESULTS: Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.

Anti-HIV Agents↗
PubMed1999

Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure.

OBJECTIVES: We examined the effect of long-term treatment with two doses of the angiotensin converting enzyme (ACE) inhibitor enalapril on various immunological variables in patients with chronic congestive heart failure (CHF). BACKGROUND: Immunological mediators are increasingly recognized to play a pathogenic role in the pathophysiology of CHF. Whether ACE inhibitor therapy modifies immunological variables has not previously been investigated. METHODS: Seventy-five patients (mean age 52 +/- 11 years) with CHF were randomized between low-(5 m g daily) and high-dose (40 mg daily) enalapril in a double-blind trial. Circulating levels of immunological parameters (i.e., proinflammatory cytokines, chemokines and adhesion molecules) were measured at baseline, at 10 weeks and at the end of the study (34 weeks). RESULTS: All immunological parameters, except soluble interleukin (IL)-6 receptor, were increased in CHF compared with 21 healthy controls. During the study immunoreactive IL-6 levels decreased (p < 0.05) and soluble IL-6 receptor increased (p < 0.05) during high-dose but not during low-dose enalapril therapy. Furthermore, IL-6 bioactivity decreased only during the high-dose (p < 0.001), resulting in a significant difference in change during treatment between the two dosage groups (p < 0.001). This decrease in IL-6 bioactivity was significantly associated with decreased interventricular septum thickness as assessed by echocardiography (r = 0.56, p = 0.013). No other variables changed during treatment. CONCLUSIONS: In patients with severe CHF, high-dose enalapril therapy is associated with a significant decrease in IL-6 activity. However, despite treatment with a high-dose ACE inhibitor, a persistent immune activation exists in these patients which may be of importance for the progression of CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Immunohistochemical localization of NMDA- and AMPA-type glutamate receptor subunits in the basal ganglia of red-eared turtles.

Corticostriatal and thalamostriatal projection systems have been shown to utilize glutamate as a neurotransmitter in mammals and birds. Although corticostriatal and thalamostriatal projection systems have been demonstrated in turtles, it is uncertain whether they too use glutamate as their neurotransmitter. Immunohistochemical localization of glutamate and of NMDA- and AMPA-type ionotropic glutamate receptor subunits (NMDAR2A/B, GluR1, GluR2/3, and GluR4) were used to address this issue. Numerous medium-sized neurons that were rich in NMDAR2A/B and GluR2/3 were observed in the striatal part of the basal ganglia of red-eared turtles. Smaller numbers of medium-sized neurons and some large neurons rich in the GluR1 and GluR4 subunits were also observed in the striatum. The striatal neuropil was notably rich in GluR1, GluR2/3 and NMDAR2A/B subunits. The pallidal region was specifically rich in large neurons possessing GluR4 subunits. Consistent with the glutamate receptors on striatal and pallidal neurons, sources of input to the striatum and pallidum in turtle such as the dorsomedial and dorsolateral thalamic nuclei (which appear to correspond to intralaminar thalamic nuclei), telencephalic pallial cell groups, and the apparent subthalamic nucleus homologue were rich in glutamatergic neurons. The results show that the thalamostriatal, corticostriatal and subthalamo-pallidal projection systems of turtles are glutamatergic and that similar basal ganglia cell types in turtles and mammals have largely similar glutamate receptor characteristics.

Animals↗
PubMed1998

Neuropeptide Y receptor 1 (NPY-Y1) expression in human heart failure and heart transplantation.

Neuropeptide Y (NPY) is a neurotransmitter released from cardiac sympathetic nerve terminals along with catecholamines. It influences vascular tone and cardiac function, probably through the receptor subtype Y1. The present study examined the expression of Y1 in patients with end-stage heart failure and in heart transplant recipients. Y1 mRNA was analyzed in right ventricular endomyocardial biopsies taken from 12 donor hearts prior to implantation (controls), 15 patients with end stage heart failure at time of transplantation, and 16 patients more than 1 year after transplantation. RT-PCR (reverse transcription polymerase chain reaction) was used to detect mRNA for the Y1 receptor, the beta1-adrenergic-receptor, and beta-actin. Y1 mRNA was present in biopsies of all donor hearts, but was observed significantly less frequently in the two patient groups; only 5 out of 15 (P < 0.01) heart failure and 9 out of 16 (P < 0.05) transplant recipients demonstrated visible PCR product. In contrast, mRNA for the beta1-adrenergic receptor and beta-actin were detected by RT-PCR in all samples. Our results provide the first evidence for altered regulation of the neuropeptide Y1 receptor in heart failure and transplant patients, and suggests that loss of signal transduction by this receptor may be adaptive in both groups.

Actins↗
PubMed1998

Serial exercise testing and prognosis in selected patients considered for cardiac transplantation.

OBJECTIVES: This study sought to examine the predictive value of variables obtained from serial maximal exercise testing, echocardiography, and ejection fraction in patients referred as potential heart transplant candidates. BACKGROUND: Variables such as peak VO2, left ventricular dimensions, ejection fraction, and hemodynamic measurements are known to predict prognosis in heart failure, but there are few data on the impact of serial measurements of these variables on subsequent mortality. METHODS AND RESULTS: Two hundred sixty-three ambulatory patients with severe heart failure referred as potential candidates for heart transplantation who underwent two exercise tests (mean 7.8 months apart) after optimal medical treatment were identified. At the same two time points, echocardiography was performed in 106 (37%) and ejection fraction was measured in 84 (30%). During a mean follow-up period of 3.9+/-0.1 years, 70 (25%) died and 45 (19%) underwent heart transplantation. Exercise capacity, peak exercise heart rate, and peak exercise systolic blood pressure achieved were all significantly higher among survivors compared with nonsurvivors. Among the survivors a slight increase in peak VO2 and ejection fraction were observed, but there were no significant differences in the changes of any of the measured variables between survivors and nonsurvivors. There were no significant differences in survival between patients with increased versus those with decreased peak VO2, left ventricular dimensions, or ejection fraction. CONCLUSION: Although peak VO2, left ventricular dimensions, and ejection fraction predict survival, changes in these parameters do not add any prognostic information in patients with severe heart failure who have been stabilized with optimal medical treatment. Routine use of these procedures therefore does not seem to be warranted and should be performed only in the context of a specific clinical situation. Serial measurements of these parameters do not appear to be useful in the risk stratification of patients referred for heart transplantation.

Case-Control Studies↗
PubMed1998

Angiotensin II receptor subtype AT1 and AT2 expression after heart transplantation.

OBJECTIVE: Cardiac hypertrophy appears early after heart transplantation, and may represent a myocardial response to injury. Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes. We therefore asked whether hypertrophy after heart transplantation is characterized by alterations in Ang II receptor gene expression. METHODS: The expression of Ang II receptor subtypes. AT1 and AT2, was analyzed in right ventricular endomyocardial biopsies taken from 10 human donor hearts prior to implantation (controls) and from 17 heart transplant recipients, 11 studied during annual evaluation (> 1 year after transplantation) and 6 one week after transplantation. Competitive reverse transcription polymerase chain reaction (RT-PCR) was performed using synthetic RNA internal standards for both receptor subtypes. RESULTS: AT1 and AT2 receptor mRNAs were detected in all samples. AT1 receptor mRNA decreased 4.5 fold (p < 0.01) and AT2 receptor mRNA 4.2 fold (p < 0.001) in transplant patients compared with controls. In the subgroup of patients examined one week after surgery AT1 was reduced relative to AT2 receptor mRNA, resulting in an altered ratio of AT1 to AT2 early after transplantation. There was no correlation between Ang II receptor levels and left ventricular wall thickness, and the decrease in receptor level did not correlate with any hemodynamic parameters, cyclosporine blood levels, or plasma renin, Ang II or pANP, except for a negative correlation between AT2 mRNA and plasma renin (r = -0.49, p = 0.05). CONCLUSIONS: Contrary to our expectations, mRNA for both Ang II receptors was downregulated after heart transplantation. The cause of myocardial hypertrophy after heart transplantation is still unclear, but the hypertrophy does not appear to be driven by increased transcription of the AT1 receptor.

Adult↗