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Biomedical subjects

M S Kappy

Publications and source records attributed to M S Kappy.

At least 19 recordsLinked to original sources
PubMed1994

Advances in the treatment of precocious puberty.

The development of immunoassay techniques for accurately measuring serum gonadotropins and gonadal steroids allows distinction between central (GnRH-dependent) and peripheral (GnRH-independent) precocious puberty in children. Previously (see case 3) it was not possible to do this, and a rational approach to therapy could not be designed. Significant advances in the synthesis of superagonists of gonadotropin-releasing hormone have allowed effective treatment for children with CPP. Such treatment has only been possible for the past 10 to 15 years, and GnRHa have been approved for use in the United States for this indication only since 1992. Long-term studies are still needed to determine what effect, if any, such treatment has on fertility, because only a few patients, even from the earliest studies, have reached child-bearing age. All indications, however, suggest that treatment with GnRHa is reversible, as well as safe and efficacious. More challenging is the effective treatment of PPP, for which innovative approaches involving inhibition of gonadal steroid synthesis or action have met with some success. Again, long-term studies or efficacy and safety are needed.

Adolescent↗
PubMed1993

Cerebral salt wasting in children. The need for recognition and treatment.

OBJECTIVES: To describe a salt-wasting syndrome in children with central nervous system (CNS) insults and to differentiate it from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and diabetes insipidus so that it may be more readily diagnosed and treated. DESIGN: Case reports. SETTING: Community teaching hospital. PATIENTS: Two inpatients with CNS insults (closed head trauma in one and seizure disorder, spastic diplegia, mental retardation, and hydrocephalus in the other). SELECTION CRITERIA: Evidence of hyponatremia accompanied by elevated urine sodium concentration and excessive urine output. INTERVENTIONS: Volume-for-volume urine replacement with 0.9% and/or 3% sodium chloride. Oral salt supplementation was required for brief periods to maintain normal plasma sodium concentration after discharge from the hospital. MEASUREMENTS AND MAIN RESULTS: Both patients had hyponatremia, high urine sodium concentrations, hypovolemia, and excessive urine output while receiving maintenance fluids. They also had elevated plasma atrial natriuretic hormone (ANH) concentrations, decreased aldosterone concentrations, and decreased [corrected] plasma renin activity for their degree of hyponatremia and negative fluid balance. Both patients maintained normal serum electrolyte concentrations with appropriate treatment. CONCLUSIONS: These patients showed true salt wasting associated with acute or chronic CNS injury, with hormonal patterns consistent with "inappropriate" ANH secretion and distinct from the SIADH. It is important to distinguish cerebral salt wasting (CSW) from the two other major disturbances of water metabolism seen following CNS injury (ie, SIADH and diabetes insipidus), because incorrect diagnosis and treatment could greatly increase morbidity in CSW. The etiologic roles of ANH or brain natriuretic peptide in CSW need to be further elucidated.

Atrial Natriuretic Factor↗
PubMed1993

Long-term effectiveness of depot gonadotropin-releasing hormone analogue in the treatment of children with central precocious puberty.

OBJECTIVE: To assess the efficacy and safety of a long-acting gonadotropin-releasing hormone analogue (GnRHa), leuprolide acetate for depot suspension (Lupron Depot), in the treatment of central precocious puberty in children, and to determine the reversibility of GnRHa therapy after it has been discontinued. RESEARCH DESIGN: Children with documented central precocious puberty were treated with Lupron Depot for 1.6 to 3.5 years. Their course of pubertal development, growth rate, skeletal maturation, and response to gonadorelin hydrochloride testing were compared before and during treatment. For those girls who finished treatment, an assessment of the reversibility of the GnRHa was performed by documenting a return to pubertal responses to gonadorelin testing, and by documenting menarche at an appropriately mature bone age. SETTING: Community teaching hospital. PATIENTS: Ten girls with central precocious puberty defined as pubertal maturation statistically advanced for age combined with a pubertal gonadotropin response to gonadorelin testing. Children who had been treated for less than 1.5 years were excluded, as were those with congenital adrenal hyperplasia. Patients who finished treatment have been followed up for up to 5 years, and will continue in follow-up throughout their reproductive life. SELECTION SAMPLE: A consecutive group of children with documented central precocious puberty was studied. INTERVENTIONS: Lupron Depot was administered as a single monthly subcutaneous injection to each patient. Treatment was usually discontinued by 10 to 11 years of age, at which time pubertal progression was allowed to resume. MEASUREMENT AND RESULTS: Mean peak serum concentrations of follicle-stimulating and luteinizing hormone responses to gonadorelin testing decreased significantly after the initial dose (from 21.8 +/- 4.5 [+/- SEM] to 2.4 +/- 0.2 IU/L for follicle-stimulating hormone and from 50.1 +/- 11.2 to 5.0 +/- 0.8 IU/L for luteinizing hormone) and remained suppressed for the duration of treatment. The progression of puberty slowed or reversed in all patients. Mean growth rate for chronologic age was significantly increased initially by 3.9 SDs and decreased to 0.9 SDs during treatment. The mean rates of skeletal maturation divided by the change in chronologic and height age changes over time were advanced (1.4 +/- 0.1 and 1.1 +/- 0.15, respectively) at the onset of therapy and decreased significantly to 0.7 +/- 0.1 and 0.8 +/- 0.1, respectively, on treatment. There was an increase in mean predicted height of 3.4 cm for all patients, and this was statistically significant. Thus, treatment with Lupron Depot at least maintained the predicted height at the onset of therapy. Girls who completed their course of treatment had pubertal gonadotropin responses to gonadorelin testing within 2 to 6 months, and menarche within the first year if skeletal maturation reached 13.0 to 13.5 years. No significant side effects of therapy were noted. CONCLUSIONS: Treatment of central precocious puberty in children using Lupron Depot is safe and efficacious. Its effects are readily reversible after treatment is discontinued, and menarche occurs at a normal bone age. Measurement of serum luteinizing hormone concentrations using an assay that is specific for the beta-subunit is necessary to monitor chemical suppression of luteinizing hormone during treatment. Longer-term studies, including reproductive history, will be needed before the potential effects of treatment on fertility can be assessed.

Age Determination by Skeleton↗
PubMed1993

Developing therapeutic relationships in multicultural settings.

The expertise of native peoples as well as resources drawn from humanities, education, and arts organizations in Arizona contributed to an educational program to heighten the cultural sensitivity of health care professionals at the Children's Health Center of St. Joseph's Hospital. The sentiment expressed by Kraut that "respect for the cultural preferences and taboos of more traditional medical systems thus renders American physicians more effective and in the long run more efficient" is supported by our experience with this program.

Black or African American↗
PubMed1993

Mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene in a patient with classic salt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia.

Inherited adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency is most likely caused by a mutation of the type II 3 beta-HSD gene. Cloning and sequencing of exons I-II, III, and IV and portions of the adjacent introns, amplified by polymerase chain reaction using primers specific for the type II gene, in one male pseudohermaphrodite with salt-wasting classic 3 beta-HSD deficiency congenital adrenal hyperplasia revealed the same mutation in all nine clones of exon IV consisting of a missense mutation at codon 248 [GTC(Val)-->AAC(Asn)] followed by a frameshift mutation at codon 249 [CGA (Arg)-->TA], resulting in a stop codon TAG, and normal sequences of exon I-II and III and the adjacent portions of introns. The same codon 248 and 249 mutations were found on one clone of his mother's DNA, but two other clones revealed normal sequences. These data indicate a homozygous combined missense/frameshift mutation in exon IV of the type II 3 beta-HSD gene resulting in severe salt-wasting adrenal and gonadal 3 beta-HSD deficiency in the patient.

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

Diabetes in pregnancy: rationale and guidelines for care.

The management of pregnancy in a woman with diabetes is directed toward insuring a normal outcome for the mother and her newborn baby. There is ample evidence from studies in both humans and animals that maintenance of a normal maternal metabolic environment, particularly blood glucose concentrations, can avoid or ameliorate the complications of pregnancy responsible for increased morbidity and mortality in the mother and her baby. It is essential that this metabolic normalcy be achieved preconceptionally if congenital malformations, the leading cause of death in IDMs, are to be avoided. Thus, preconceptional care, intensive regulation of maternal glucose metabolism and fetal surveillance throughout pregnancy are critical. The use of the multidisciplinary team to optimize care has led to significant reductions in maternal and perinatal morbidity/mortality in IDMs, and is thus essential to successful outcomes in pregnancies complicated by diabetes.

Clinical Protocols↗
PubMed1988

Efficacy of leuprolide therapy in children with central precocious puberty.

Eight girls with central precocious puberty were treated with the long-acting gonadotropin releasing hormone analogue leuprolide acetate (Lupron) for a period of six to 18 months. Suppression of gonadotropin and estradiol secretion and regression of secondary sexual characteristics and menses were observed while patients received a subcutaneous dose of 35 to 40 micrograms/kg/d. Growth velocity was slowed in all but one patient, and the rate of skeletal maturation was slowed even more, resulting in a stabilization or improvement in predicted adult height. There were no major side effects. Although the long-term effects of leuprolide therapy cannot be determined with this study, it appears to be efficacious in the treatment of central precocious puberty.

Age Determination by Skeleton↗
PubMed1987

Maturity-onset diabetes of youth in black Americans.

Twelve of 129 black patients with youth-onset diabetes were identified as having an unusual clinical course, with apparent insulin dependence at the time of presentation followed by absence of dependence months to years later. This atypical form of diabetes was found in at least two generations in 9 of the 12 families of the propositi. Fourteen of the diabetic relatives, as well as the 12 propositi, were studied. Islet-cell autoantibodies were not found in any of the patients, and thyroid microsomal auto-antibodies were found in only one. The frequencies of the insulin-dependent-diabetes-associated antigens HLA-DR3 and DR4 were not increased among the propositi, and diabetes did not cosegregate with HLA haplotypes in the informative families. Insulin secretion, as measured by C-peptide responses to a liquid mixed meal (Sustacal), was intermediate between secretion in nondiabetic controls and that in patients with classic insulin-dependent diabetes. Peripheral-blood monocytes expressed increased numbers of insulin receptors as well as decreased empty-site affinities. The atypical form of diabetes in black Americans can be distinguished from classically defined insulin-dependent diabetes and may be best classified as a form of maturity-onset diabetes of youth.

Adult↗
PubMed1987

Sublingual administration of desmopressin. Effectiveness in an infant with holoprosencephaly and central diabetes insipidus.

A 3-month-old child with bilateral cleft lip and palate and holoprosencephaly was hospitalized after he developed diabetes insipidus presumably due to hypothalamic dysfunction. He was initially treated with subcutaneous vasopressin injection but was switched to therapy with desmopressin acetate (DDAVP) before discharge. Because of his abnormal nasopharyngeal anatomy, we decided to administer the desmopressin acetate sublingually, and this was effective. A single daily dose of 2 micrograms (0.4 microgram/kg) resulted in a prompt antidiuresis, and the effect gradually lessened over a 24-hour period. Serum electrolyte values were restored to normal and have remained normal after three months of treatment. After additional study, the sublingual route might be considered for the administration of small-polypeptide therapeutic agents when other routes are impractical.

Abnormalities, Multiple↗
PubMed1987

Regulation of growth in children with chronic illness. Therapeutic implications for the year 2000.

Children with chronic illness often have poor growth and short stature. The causes are multiple and are related to the organ systems involved, malnutrition, superimposed infections, and the effects of specific therapy, eg, steroids. The impairment of growth contributes to poor body image in these children and may result in problems complying with the treatment regimen and poorer long-term outcome, eg, in diabetes. The somatomedin system or net circulating somatomedin activity in the blood has been shown to mediate growth in children. In addition, many authors have now documented reduced somatomedin generation by the liver and an increase in plasma factors that inhibit the effects of somatomedin on growth in children with chronic illness. Recognition of these phenomena may lead to the use of somatomedin to promote growth in certain of these children in the future.

Child↗
PubMed1986

Insulin is a growth-promoter of the developing brain: possible implications for the infant of the diabetic mother.

The combination of diabetes mellitus and pregnancy was once associated with significantly increased morbidity and mortality for mother and baby. Advances in the obstetric management of the mother with diabetes and parallel advances in the management of the infant of the diabetic mother (IDM) have lowered the morbidity and mortality in many centers to near those for pregnancies in the non-diabetic woman. A significant increase still exists in the prevalence of congenital malformations in IDMs. Recent animal studies have shown that these malformations are related to maternal hyperglycemia early in the pregnancy, and that if it is controlled with insulin during the critical period of embryologic development, then the malformations may be prevented.

Animals↗