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Biomedical subjects

B J Clark

Publications and source records attributed to B J Clark.

At least 37 records · Page 2Linked to original sources
PubMed2001

Steroidogenic acute regulatory protein expression is dependent upon post-translational effects of cAMP-dependent protein kinase A.

Tropic hormones acutely stimulate adrenal and gonadal steroidogenesis by activation of the cAMP-dependent protein kinase A (PKA) signaling pathway and subsequent induction of Steroidogenic Acute Regulatory (StAR) protein (StAR) expression. We present a comparative study of StAR regulation in mouse adrenocortical Y1 and the derived PKA mutant Kin-8 cell lines to evaluate the PKA requirement for StAR expression. A parallel increase in StAR steady-state mRNA and protein was observed in Y1 cells. StAR mRNA was induced in 8-Br-cAMP-treated Kin-8 cells with maximal expression levels approx. 50% of that observed in Y1 cells. However, a corresponding increase in StAR protein, as detected by Western analysis, was absent in the Kin-8 cells. A similar distribution of StAR mRNA in active polysome fractions was observed for both 8-Br-cAMP-treated Y1 and Kin-8 cells, as well as a 2-fold increase in incorporation of [35S]methionine into StAR, which indicated translation was not blocked in Kin-8 cells. Together these data indicate that PKA functions at the post-translational level to regulate StAR expression and we propose that phosphorylation of StAR by PKA contributes to protein stability

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

High-speed microemulsion electrokinetic chromatography.

In previous reports of microemulsion electrokinetic chromatography (MEEKC), analysis times were typically in the order of 10 min as high-ionic strength buffers were used. These buffers produced high currents which limit the voltages which can be applied, therefore, analysis times could not be reduced. The primary cause of the high-ionic strength is the relatively high concentrations of surfactants required to form the microemulsion. The surfactant concentration can be lower when using an oil with a smaller surface tension. This preliminary study showed that migration times in MEEKC can be reduced to below 1 min by using a combination of an optimum microemulsion composition, high voltage, high temperature, short capillaries by injecting via the "short end", or by simultaneously applying pressure and voltage. Long injection sequences and quantitation were found to be possible with minimum buffer depletion effects.

Benzoates↗
PubMed2001

Unexpected death after reconstructive surgery for hypoplastic left heart syndrome.

BACKGROUND: Although operative mortality for reconstructive surgery for hypoplastic left heart syndrome continues to improve, nonoperative mortality, especially in the first year of life, remains relatively high. A number of patients who are thought to be clinically well at hospital discharge die unexpectedly. The goal of the present study was to determine the incidence of and risk factors for unexpected death in patients with hypoplastic left heart syndrome. METHODS: Retrospectively, we determined the incidence of unexpected death among 536 patients with hypoplastic left heart syndrome who were discharged to home after stage I surgical procedure. To identify potential risk factors, a nested case-control analysis was undertaken. RESULTS: Unexpected death occurred in 22 of 536 patients (4.1%) discharged to home after stage I surgical procedure. The median age at unexpected death was 79 days (range, 25 to 227 days). Seizures preceded cardiac arrest in 2 patients, and ventricular arrhythmias were documented in 3 additional patients during attempted resuscitation. Autopsy studies were performed in 12 patients and identified residual lesions that may have contributed to death in 2 patients. In multivariate analysis documented perioperative arrhythmia and earlier year of stage I surgical procedure were associated with an increased risk for unexpected death (p = 0.03 and p = 0.04, respectively). There were 4 additional patients who had unexpected death after subsequent cavopulmonary operation at a median age of 1.6 years (range, 0.9 to 3.8 years). CONCLUSIONS: Unexpected death occurred in more than 4% of patients with hypoplastic left heart syndrome who were discharged to home after stage I surgical procedure and was most common in the first several months of life. Factors that may contribute to unexpected death include residual lesions, arrhythmias, and neurologic events, although in the majority of cases the cause remains largely unknown.

Cardiac Surgical Procedures↗
PubMed2001

Sarcoma of the mitral valve causing coronary arterial occlusion in children.

Primary tumors of the cardiac valves are rare. One of the most common reasons that left-sided cardiac tumors come to clinical attention is embolization to the systemic circulation. We present two children who suffered left coronary arterial occlusion due to embolization of a sarcoma of the mitral valve. A 6-year-old female who had been admitted to the hospital after cerebrovascular embolization of a fragment of sarcoma of the mitral valve experienced sudden cardiovascular collapse due to occlusion of the left coronary artery. She was placed on extracorporeal membrane oxygenation, and underwent coronary embolectomy and resection of the tumor from the mitral valve and its tendinous cords. Left ventricular function did not improve, and she underwent orthotopic heart transplantation. On follow-up 32 months after transplant, the patient is well, with no evidence of recurrence of or metastasis from the tumor. The tumor arose from the leaflets and tendinous cords of the mitral valve, and was composed grossly of multiple white nodules. Histopathologic evaluation disclosed fragments composed predominantly of peripheral spindle cells in an extensive fibromyxoid stroma. The mildly pleomorphic cells of the tumor gradually blended with adjacent pieces of the mitral valvar leaflet and tendinous cords. Immunohistochemical studies revealed strong staining for vimentin, smooth muscle actin, muscle specific actin, and myoglobin, suggesting myogenic differentiation. The other patient was a 2 1/2-year-old female who died suddenly at home. Grossly and histologically, the tumor was essentially identical to the first case, and there was a 3 cm string-like extension passing into the orifice of the left coronary artery. To put the cases in context, we compare them with other descriptions of this rare type of tumor.

Child↗
PubMed2001

Calculation of the electrophoretic mobility of amines in methanol-aqueous electrolyte systems.

An equation for calculating the electrophoretic mobility of an analyte with respect to the concentration of organic modifier in mixed aqueous-organic modifier running buffer was derived from mixture response surface methodology. In order to assess the accuracy and predictability of the proposed model, the electrophoretic mobilities of four aliphatic amines and imidazole (background absorber) were measured in mixed water-methanol running buffer containing 0-100% v/v methanol by capillary zone electrophoresis with indirect UV detection. The accuracy of the proposed model was examined by fitting all the experimental data points. The predictability of the model was then evaluated by employing six training data points to compute the model constants, and the mobility at the other data points was predicted by the trained model. The proposed model gave accurate results for the correlation and prediction, with mean percentage errors for the amines studied of 0.6% to 0.5% and 1.5% to 1.1%, respectively.

Amines↗
PubMed2001

Design and baseline characteristics for the ACE Inhibitor After Anthracycline (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors.

PURPOSE: The ACE Inhibitor After Anthracycline (AAA) study is a randomized, double-blind, controlled clinical trial comparing enalapril with placebo to determine whether treatment can slow the progression of cardiac decline in patients who screen positive for anthracycline cardiotoxicity. METHODS: The primary outcome measure is the rate of decline, over time, in maximal cardiac index (in liters per minute per meters squared) at peak exercise; the secondary outcome measure is the rate of increase in left ventricular end systolic wall stress (in grams per centimeters squared). Patients >2 years off therapy and <4 years from diagnosis, aged 8 years and older, were eligible if they had received anthracyclines and had at least one cardiac abnormality identified at any time after anthracycline exposure. RESULTS: A total of 135 patients were randomized to enalapril or placebo. Baseline characteristics were similar across treatment groups. CONCLUSIONS: The AAA study will provide important information concerning the efficacy of using angiotensin-converting enzyme inhibitors to offset the effects of late anthracycline cardiotoxicity.

Adolescent↗
PubMed2001

Palisaded encapsulated neuroma (solitary circumscribed neuroma of skin) of the eyelid: report of two cases and review of the literature.

BACKGROUND/AIMS: Palisaded encapsulated neuroma of the skin (PEN) is an uncommon benign neural tumour that occurs on the head and neck, including the eyelid, but is unfamiliar to many ophthalmic clinicians. For the first time in the ophthalmic literature, the clinical and histopathological features of two patients with PEN of the eyelid are described. METHODS: Two cases of PEN were identified in the archives of the Department of Pathology, Institute of Ophthalmology, London. Clinical details were derived by a case note review and the histopathological features defined using standard methods including immunohistochemistry. RESULTS: Two cases of PEN are described, from the eyelids of patients aged 43 and 70 years. The tumours were virtually identical in nature, being painless solid masses composed of a mixture of S100 positive Schwann cells and scattered neurofilament positive nerve fibres. An incomplete thin fibrous capsule, which contains EMA positive perineural cells, partially surrounded each lesion. The lesions were distinguishable from other more common eyelid lesions only on histopathological examination. Both tumours were completely excised with no evidence of recurrence. Neither patient had signs of any associated systemic disease. CONCLUSION: PENs are usually solitary, firm, non-pigmented, dome-shaped lesions that are found on the face of patients usually over the age of 40 years. Most often these lesions are diagnosed clinically as basal cell carcinomas, dermal naevi, or skin adnexal tumours. Histologically, PENs must be differentiated from other neural tumours that may be associated with systemic syndromes, such as neurofibromas or mucosal neuromas.

Adult↗
PubMed2001

Impact of prenatal diagnosis on survival and early neurologic morbidity in neonates with the hypoplastic left heart syndrome.

BACKGROUND: Prenatal echocardiography can identify the fetus that has complex congenital heart disease and may improve early management and surgical outcome. Prenatal diagnosis may be particularly beneficial to patients who have hypoplastic left heart syndrome (HLHS) and who are at risk for hypoxic-ischemic insult at presentation. OBJECTIVES: We sought to determine whether prenatal diagnosis reduces neurologic morbidity and operative mortality in patients who undergo palliative surgery for the HLHS. METHODS: Data from all patients who had HLHS, except for those with lethal genetic anomalies, and who were admitted to our institution between July 1992 and September 1997 were analyzed to assess the impact of prenatal diagnosis on preoperative management, neurologic morbidity, and surgical mortality. The primary outcome measures were hospital mortality and the incidence of adverse neurologic events (seizure or coma). RESULTS: There were 216 patients who had HLHS and were referred for surgical palliation, 79 (36.6%) of whom had been diagnosed prenatally. All patients who had been diagnosed prenatally were delivered in an advanced nursery and were started on prostaglandin E(1) on the first day of life. Patients whose HLHS was diagnosed postnatally were begun on prostaglandin E(1) later in life (median = day 2 [range = 1-28 days]). There were 4 preoperative deaths and 53 operative or postoperative deaths. Overall hospital mortality was 26.4% and did not differ between patients whose HLHS had been diagnosed prenatally and those whose HLHS had been diagnosed postnatally. With the use of multivariable analysis, prenatal diagnosis was associated with fewer adverse perioperative neurologic events in the patients whose HLHS had been diagnosed prenatally than in those whose HLHS had been diagnosed postnatally (odds ratio = 0.46). CONCLUSIONS: These data suggest that prenatal diagnosis has a favorable impact on treatment of patients who have HLHS and are undergoing staged palliation and reduces early neurologic morbidity. Prenatal diagnosis was not associated with reduced hospital mortality. It is possible that prenatal diagnosis may improve long-term neurologic outcome.

Coma↗
PubMed2001

Point prevalence of cardiac abnormalities in children with systemic lupus erythematosus.

OBJECTIVE: To determine the point prevalence and pattern of silent cardiac abnormalities and associations with suspected risk factors in a sample of children with systemic lupus erythematosus (SLE). METHODS: Cross-sectional analysis of 19 children with SLE from a referral-based rheumatology clinic at an urban children's hospital. Patients were eligible if they were 20 years of age or younger and classified with SLE using the revised criteria of the American College of Rheumatology. Each patient completed a survey, physical examination, standard 12-lead electrocardiogram (ECG), echocardiogram, and had laboratory determinations of complement, triglyceride, and cholesterol levels. RESULTS: Six patients (32%) had cardiac abnormalities on ECG or echocardiogram. In 3, the abnormalities were mild and considered within the normal range. In 5, the abnormalities were considered silent. These abnormalities included ischemic changes (3 patients), valvular insufficiency (3 patients), ventricular repolarization defects (2 patients), cardiac enlargement (1 patient), and ventricular dysfunction (1 patient). Only a recent history of palpitations was significantly associated with the presence of cardiac abnormalities (p = 0.04). CONCLUSIONS: Silent cardiac abnormalities can occur in children with SLE. A recent history of palpitations may be associated with cardiac abnormalities. Routine evaluation of children with SLE using ECG and echocardiogram may help screen for these abnormalities. However, future studies comprising larger sample sizes and longitudinal followup will be required to determine the natural history of cardiac abnormalities in children with SLE and to identify risk factors.

Adolescent↗
PubMed2000

Survival after reconstructive surgery for hypoplastic left heart syndrome: A 15-year experience from a single institution.

BACKGROUND: There are limited data regarding the long-term survival of patients who have undergone reconstructive surgery for hypoplastic left heart syndrome (HLHS). We reviewed the 15-year experience at our institution to examine survival in the context of continued improvements in early operative results. METHODS AND RESULTS: Between 1984 and 1999, 840 patients underwent stage I surgery for HLHS. From review of medical records and direct patient contact, survival status was determined. The 1-, 2-, 5-, 10-, and 15-year survival for the entire cohort was 51%, 43%, 40%, 39%, and 39%, respectively. Late death occurred in 14 of the 291 patients discharged to home after the Fontan procedure, although only 1 patient has died beyond 5 years of age. Heart transplantation after stage I reconstruction was performed in 5 patients. Later era of stage I surgery was associated with significantly improved survival (P:<0.001). Three-year survival for patients undergoing stage I reconstruction from 1995 to 1998 was 66% versus 28% for those patients undergoing surgery from 1984 to 1988. Age >14 days at stage I and weight <2.5 kg at stage I were also associated with higher mortality (P:=0.004 and P:=0.01, respectively). Other variables, including anatomic subtype, heterotaxia, and age at subsequent staging procedures, were not associated with survival. CONCLUSIONS: Over the 15-year course of this study, early- and intermediate-term survival for patients with HLHS undergoing staged palliation increased significantly. Late death and the need for cardiac transplantation were uncommon.

Body Weight↗
PubMed2000

Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma.

The forkhead transcription factor gene FOXC1 (formerly FKHL7) is responsible for a number of glaucoma phenotypes in families in which the disease maps to 6p25, although mutations have not been found in all families in which the disease maps to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to 6p25 (peak LOD score 6.20 [recombination fraction 0] at D6S967), no FOXC1 mutations were detected by direct sequencing. However, genotyping with microsatellite repeat markers suggested the presence of a chromosomal duplication that segregated with the disease phenotype. The duplication was confirmed in affected individuals by FISH with markers encompassing FOXC1. These results provide evidence of gene duplication causing developmental disease in humans, with increased gene dosage of either FOXC1 or other, as yet unknown genes within the duplicated segment being the probable mechanism responsible for the phenotype.

Chromosomes, Human, Pair 6↗
PubMed2000

Calculation of electrophoretic mobilities in water-organic modifier mixtures in capillary electrophoresis.

In order to correlate/predict electrophoretic mobility data in the mixture of water+organic modifier four equations have been presented and examined. The experimental mobilities of five analytes were determined in a water-methanol mixture. These data have been used to assess the accuracy and predictability of the models. Also, some previously published mobility data in water-organic modifier mixtures has been employed for further evaluation of the models. The models produced accurate results and the means of percentage deviations were in the range of 0.66-1.30.

Electrophoresis, Capillary↗
PubMed2000

Bilateral sequential lung transplant for ectodermal dysplasia.

A case of bilateral sequential lung transplantation for anhidrotic ectodermal dysplasia is presented. The patient was a 16-year-old male with end-stage lung disease secondary to chronic severe respiratory infection. Although a relatively rare disease, the common association of fatal pulmonary compromise in those affected with this disorder warrants consideration of lung transplantation as a viable therapeutic option.

Adolescent↗
PubMed2000

Prolonged extracorporeal membrane oxygenation as a bridge to cardiac transplantation.

Cardiac transplantation provides the best option for neonates with congenital heart disease that is not amenable to surgical repair or palliation. The scarcity of suitable organs for this group has resulted in prolonged waiting times; many infants die awaiting transplantation. We present the case of a newborn with severe Ebstein's anomaly and low cardiac output who was supported with extracorporeal membrane oxygenation for 1,126 hours, until an appropriate organ became available.

Cardiac Output, Low↗
PubMed2000

Survival after acute graft failure in pediatric thoracic organ transplant recipients.

Survival among recipients of repeat thoracic organ transplantation, particularly in the setting of acute graft failure (AGF), is lower than survival after a primary transplant. This has created controversy over the fair allocation of scarce organs. We reviewed our experience to assess the effectiveness of aggressive therapy and retransplantation in pediatric patients with AGF. Between November 1994 and March 1998, 52 patients aged 49 days to 16.9 years (median age 4.7 years) underwent thoracic organ transplantation (32 primary and 4 repeat heart, 16 primary and 4 repeat lung, and 3 primary heart-lung transplants). Acute graft failure occurred in nine (4 heart, 3 lung, 2 heart-lung transplants), six of whom were supported with extracorporeal membrane oxygenation (ECMO), and four of whom underwent repeat transplant. Six of the nine survived, including all of those who were retransplanted, and five of the nine were alive 1 year later. The average postoperative hospital stay after receiving a second organ was 46.5 days vs. a postoperative 22-day stay in recipients without AGF (p = 0.07). We conclude that the decision to allocate institutional and professional resources to the aggressive support of patients with AGF must be made at the level of the individual transplant center. However, we feel that the outcome of aggressive support and retransplantation justifies the allocation of organs to these patients and suggests that the current policies governing organ allocation for patients with early graft failure should be re-examined.

Acute Disease↗