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Biomedical subjects

S C Winter

Publications and source records attributed to S C Winter.

13 recordsLinked to original sources
PubMed2000

Cardiomyopathy in childhood, mitochondrial dysfunction, and the role of L-carnitine.

Cardiomyopathy in childhood is associated with high morbidity and mortality rates. Many metabolic causes have been identified, including genetic or acquired defects in mitochondrial energy production affecting beta-oxidation, carnitine transport, and the electron transport chain. Combining conventional inotropic and antiarrhythmic therapy with metabolic interventions has improved overall outcome. L-carnitine, a natural substance involved in mitochondrial transport of fatty acids, is one such therapy and plays a central role in the regulation of the inner mitochondrial supply of free coenzyme A. Carnitine deficiency can be caused by both genetic and environmental causes with resultant signs and symptoms of metabolic disease, including cardiomyopathy. Administration of L-carnitine can result in improvement or resolution of the cardiomyopathy.

Cardiomyopathies↗
PubMed2000

Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy.

OBJECTIVES: A multicenter retrospective study was conducted to investigate the possible metabolic causes of pediatric cardiomyopathy and evaluate the outcome of patients treated with L-carnitine. METHODS: Seventy-six patients diagnosed with cardiomyopathy were treated with L-carnitine in addition to conventional cardiac treatment, and 145 patients were treated with conventional treatment only. There were 101 males and 120 females between 1 day and 18 years old. Cardiomyopathy diagnoses included dilated (148 patients), hypertrophic (42 patients), restrictive (16 patients), mixed diagnosis (11 patients), and 4 with an unknown type. Of 76 L-carnitine-treated patients, 29 (38%) had evidence to suggest a disorder of metabolism, and of 145 control patients, 15 (10%) were suspected to have a disorder of metabolism. These metabolic disorders were thought to be the cause for the cardiomyopathy of the patients. The duration of L-carnitine treatment ranged from 2 weeks to >1 year. Information was collected on length of survival (time-to-event), clinical outcome, echocardiogram parameters, and clinical assessments. Data were collected at intervals from baseline to study endpoint, death, transplant, or last known follow-up visit. RESULTS: L-Carnitine-treated patients were younger than control patients and had poorer clinical functioning at baseline, yet they demonstrated lower mortality and a level of clinical functioning and clinical severity comparable to control patients on conventional therapy by the end of the study. An analysis of the interaction between clinical outcome and concomitant medications unexpectedly revealed that the population of patients treated with angiotensin-converting enzyme (ACE) inhibitors (40% of patients) had significantly poorer survival (although their greater likelihood for poor survival may possibly have made them more likely to receive ACE inhibitors). CONCLUSION: Results suggest that L-carnitine provides clinical benefit in treating pediatric cardiomyopathy. There is a need for further exploration of potential explanatory factors for the higher mortality observed in the population of patients treated with ACE inhibitors.

Cardiomyopathies↗
PubMed1999

HELLP syndrome.

Explore the source record for details and available documents.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

Inborn errors of metabolism: medical and administrative "orphans".

CONTEXT: Inborn errors of metabolism are genetic conditions that affect the normal biochemical functions of the body in any organ and at any age. More than 500 metabolic diseases are known; almost all are classified as orphan diseases under the US Food and Drug Administration guidelines (incidence < 200,000 persons) and each has its own requirements for diagnosis and treatment. Management of these complex, lifelong, multisystem disorders often requires a coordinated, multidisciplinary approach involving several subspecialists and which may include complex laboratory evaluations, genetic counseling, nutritional therapy, and unusual therapeutic approaches that have been used in only a small number of cases. RESULTS: Not infrequently, inborn errors of metabolism fall outside current standard diagnostic and treatment guidelines of managed care plans. This results in delays in diagnosis and appropriate management, with increased costs to patients and to society. CONCLUSIONS: Patients with inborn errors of metabolism should not be discriminated against and all health plans should specify that access to specialists and metabolic centers are a covered benefit of the plan. The acceptance of treatment guidelines, the development of international disease classification codes for the disorders, and the performance of cost-benefit analyses would all greatly facilitate this process. However, without recognition that these disorders require such services, and steps to provide them by the insurance industry, the care of children with metabolic disorders and other chronic diseases will continue to be a source of frustration and anger among the caregivers and the families they serve.

Cost-Benefit Analysis↗
PubMed1993

Primary sequence analysis and representation techniques in carbohydrates.

Sequence similarity calculations of carbohydrates present several problems which must be addressed if a computer implementation is to be achieved. These problems range from the computational representation of the complex carbohydrate structure to the method by which the comparison of residue and linkage is to be made. This paper therefore discusses the form of this representation and how two or more carbohydrates can be meaningful compared. An example set of results using this approach is presented and discussed to illustrate how similarity comparison can show relationships between carbohydrates, features that are otherwise hidden by the sheer volume of data which must be considered.

Algorithms↗
PubMed1992

Plasma carnitine in fasting neonatal and adult northern elephant seals.

Maintenance of adequate body carnitine stores is a requisite for fasting mammals, whose energy is derived mainly from free fatty acid oxidation. The impact of longterm fasting on carnitine status is unclear, and there have been no reports of carnitine during naturally occurring fasts. Total (TC), free (FC), and acylated (AC) plasma carnitine levels were determined in 10 weaned and 11 adult northern elephant seals (Mirounga angustirostris) during natural fasts lasting from 1 to 3 mo. In pups, TC declined little and AC increased only slightly [P greater than 0.05, analysis of variance (ANOVA)] through 11 wk of fasting. Plasma FC dropped by 53 and 26% from week 1 values at 10 and 11 wk fasting, respectively (P = 0.014, ANOVA). The AC/FC ratio did not approach 1.0 until 7 wk of fasting. TC was 38.6 +/- 1.4 microM and 47.6 +/- 4.1 microM in adult females and males, respectively. Adult AC/FC ratios were 0.71 +/- 0.10 (females) and 0.08 +/- 0.04 (males). Plasma TC status is not negatively affected by extended fasting in adult and weaned northern elephant seals. These data support the hypothesis that fasting northern elephant seals defend plasma TC and maintain an attenuated AC/FC ratio well into their prolonged natural fast.

Acylation↗
PubMed1991

Urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate and tiglylglycine after isoleucine loading in the diagnosis of 2-methylacetoacetyl-CoA thiolase deficiency.

The concentrations of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate and tiglylglycine were determined by gas chromatography-mass spectrometry in urine collected before and for 8 h after loading with 100 mg of isoleucine per kg of body weight. The sum of 2-methylacetoacetate and 2-butanone, a decarboxylation product, was determined as the 2-butanone dinitrophenylhydrazone derivative. Substantial increases in each compound were encountered in a patient with a documented defect of 2-methylacetoacetyl-CoA thiolase. Increased quantities of 2-methyl-3-hydroxybutyrate and tiglylglycine were also found in four children with clinical symptoms similar to those associated with 2-methylacetoacetyl-CoA thiolase deficiency but in whom the activity of the enzyme was found to be normal. The concentration of 2-methylacetoacetate plus 2-butanone in the urine increased after an isoleucine load only in the patient with 2-methylacetoacetyl-CoA thiolase deficiency.

Acetoacetates↗
PubMed1989

Relative carnitine insufficiency in children with type I diabetes mellitus.

Recognizing the similarity of type I diabetes mellitus to inborn errors of metabolism that have responded to carnitine therapy, we initiated a study of 54 children with type I diabetes mellitus. Examining a fasting blood sample for levels of carnitine, glucose, and glycosylated hemoglobin A1c, and a urine sample for levels of ketones and glucose, we found 13 children were deficient of free carnitine (less than 20 mumol/L) and 30 had elevated acyl carnitine levels (greater than 11 mumol/L). Statistical tests confirmed a significant difference between the diabetic population and normal population for reduced free carnitine, elevated acyl carnitine, and an elevated ratio of acyl carnitine to free carnitine. Also, a significant correlation was found between the levels of urine glucose and ketones and the level of acyl carnitine. Our data indicate that carnitine deficiency and relative insufficiency may be an overlooked component in the management of diabetes.

Adolescent↗
PubMed1988

Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness.

Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55% vs. control of less than 10%). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. control of 14 +/- 2 nmol/mg protein) and was 75% esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50% of control levels of acyl-CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 muM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50% of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect.

Acyl-CoA Dehydrogenase↗
PubMed1987

Plasma carnitine deficiency. Clinical observations in 51 pediatric patients.

We studied the clinical spectrum associated with secondary plasma carnitine deficiency in 51 pediatric patients. Forty-three patients had total plasma carnitine values below 20 mumol/L and an additional eight patients had total values above 20 mumol/L but had low free plasma carnitine levels. The clinical presentation in the patients with total plasma carnitine deficiency included hypotonia (34 of 43), failure to thrive (27 of 43), recurrent infections (27 of 43), encephalopathy (six of 43), nonketotic hypoglycemia (seven of 43), and cardiomyopathy (nine of 43). Of the eight patients with low free and elevated esterified carnitine levels, the signs and symptoms at presentation included hypotonia (six of eight), recurrent infections (six of eight), failure to thrive (six of eight), encephalopathy (three of eight), nonketotic hypoglycemia (one of eight), and cardiomyopathy (one of eight). All patients were treated with L-carnitine. Treatment time varied from one month to 24 months (average, four months). A subjective improvement in muscle tone was seen in 24 of 38 patients, 22 of 33 patients showed acceleration of incremental growth, and infection frequency appeared to decrease in 18 of 33 patients. After therapy, the echocardiograms of all patients with cardiomyopathy normalized. There were no further hypoglycemic episodes. Of the nine patients with encephalopathy, eight showed improvement in their mental status. Three patients died of complications of their primary disorder. In our experience, secondary plasma carnitine deficiency is a common pediatric finding. The presence of failure to thrive, recurrent infections, hypotonia, encephalopathy, cardiomyopathy, or nonketotic hypoglycemia requires investigation of carnitine status.

Adolescent↗
PubMed1986

Prenatal diagnosis of the Beckwith-Wiedemann syndrome.

We report on the prenatal diagnosis of Beckwith-Wiedemann syndrome (BWS) in a pregnancy monitored because of a previously affected child. The proposita had classical stigmata of BWS including macroglossia, omphalocele, and typical ear creases. Chromosomes were 46,XX. Both parents and the extended maternal family were clinically normal. In a subsequent pregnancy by another father, the mother had serial ultrasound monitoring at 13.5, 18, and 19 weeks gestation which showed an enlarged abdominal circumference and a 2-cm omphalocele. At termination the female fetus weighed more than two times the expected weight, had striking hypertrophy of skeletal muscles, a protuberant abdomen, and a 2-cm omphalocele and characteristic facial appearance. Autopsy confirmed generalized organomegaly. This is the first report of the prenatal diagnosis of BWS prior to 20 weeks in an at-risk family. The recurrence in this family emphasizes the difficulty in providing accurate genetic recurrence risks in BWS and suggests that ultrasonographic prenatal diagnosis should be offered to families even when the case appears to be "sporadic."

Abortion, Induced↗