Biomedical subjects
Publications and source records attributed to M Borkenstein.
Sexual behavior has changed during the last decades. Teenage fertility rate, and the number of gonococcal infections are both extremely high; the incidence of HIV-infections is increasing. Preventive measures include sex education. Sex education may help the adolescents to identify their own goals for sexual behavior, to avoid unintended and unwanted pregnancy, and to avoid sexually transmitted diseases.
A now 10 month old female infant suffered from persistent non ketotic neonatal hypoglycemia despite continuous intravenous application of glucose (greater than 10 mg/kg/min). There was only a transient response of blood glucose after intravenous administration of glucagon and prednisolon. Biochemical findings indicated hyperinsulinismus (insulin level of 26 mE/ml during hypoglycemia). Oral diazoxid treatment in high doses (22 mg/kg) stopped hypoglycemia episodes for several days but the newborn remained glucose infusion depended. Finally the treatment had to be interrupted because of vomiting. At the age of 4 1/2 weeks a subtotal pancreatectomy was performed. The histological examination of the pancreas confirmed the clinically suspected diagnosis of nesidioblastosis. After pancreatectomy the infant required insulin therapy. Since six months the girl is without insulin in a good condition. Despite periods of arrested head growth before pancreatectomy the psychomotoric development is normal.
Using a recently described technique for expanding of human T lymphocyte populations from cerebrospinal fluid (CSF), we investigated the local cellular immune response in a patient with chronic rubella panencephalitis. A total of 328 T cell lines (TCLs) was established by seeding CSF cells at limiting dilution into histoplates in the presence of irradiated feeder cells and phytohemagglutinin (PHA)-containing conditioned medium. 80% of TCLs expressed the CD4+CD8-, 5% the CD4-CD8+ phenotype and 15% of TCLs contained different proportions of CD4+ and CD8+ cells. Of 191 TCLs analyzed, 85 were cytotoxic, as shown by their lectin-dependent cytotoxicity against allogeneic uninfected target cells. Eight of them demonstrated specificity for the autologous, rubella virus-infected target cells. When tested for antigen-specific proliferative activity, 26 TCLs responded to rubella antigen, 16 TCLs reacted to myelin basic protein (MBP), four TCLs to proteolipid protein (PLP), four to galactocerebrosides and two to actin. Fourteen out of 16 MBP-specific TCLs also responded, to a minor degree, to rubella antigen and/or actin. The results showed that the persisting rubella infection had given rise to autoreactive T cells. Virus-induced autoreactivity to brain antigens may be an important pathogenetic mechanism in other chronic inflammatory disorders of the CNS.
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During the Annual Meeting of the Austrian Diabetes Association various diabetic centres presented their success and failure rates with respect to metabolic control and prevention of late complications in diabetic patients on a country-wide basis. The analysis revealed that only 30% of all type I diabetic patients are adequately controlled. Intensive education in diabetes self-management, capable of leading to optimal metabolic control in up to 50% of the instructed patients, is however available only to a small minority of the diabetic patients to date. Despite the enormous improvement which has been achieved in the management of pregnant diabetic women, intensive specialized care is often commenced far too late. In rural areas, in particular, even conventional therapy is not fully implemented and late complications are, thus, inevitable.
Ten children who underwent allogeneic (n = 5) or autologous (n = 5) bone marrow transplantation (BMT) for chronic myelogenous leukaemia (n = 2), acute lymphoblastic leukaemia (n = 1), acute myelogenous leukaemia (n = 2), severe aplastic anaemia (n = 2), malignant histiocytosis (n = 1), neuroblastoma (n = 1) and teratoma (n = 1) were assessed for endocrinological function. Transplant preparative regimens consisted of high-dose cyclophosphamide, high-dose cyclophosphamide in combination with high-dose busulphan, high-dose melphalan as well as BACT (BCNU, cytarabine, cyclophosphamide and 6-thioguanine) chemotherapy. None of the patients received total body irradiation (TBI). Median survival following BMT was 37 months (range 7-115). Growth hormone deficiency was present in only one patient; none of the patients had abnormal thyroid or adrenocortical function. This is in contrast to previous reports in which growth hormone deficiency and abnormal thyroid and adrenocortical function occurred in a much higher percentage of patients after BMT conditioned with TBI.
A multiple injection regimen using a pen-injector (Novo Pen) was applied to 34 diabetic adolescents (age: 15.4 +/- 2.4 years). During the observation-period of 6 months HbA1c fell significantly from 8.98 +/- 0.31 to 7.82 +/- 0.25 rel%. At the end of the study all patients wanted to continue this regimen considering the advantage of improved life quality compensating for the inconvenience of multiple injections.
Fifty-three prepubertal boys with unilateral (n = 38) or bilateral (n = 15) cryptorchidism were treated for 4 weeks with synthetic LH-RH (Cryptocur, Hoechst) 1.2 mg daily, divided into 3 X 400 micrograms and administered intranasally. Complete descent was observed in 54% of testes--37% in the boys with unilateral cryptorchidism and 77% in the boys with bilateral cryptorchidism. Follow-up examination 6 months after therapy showed relapse in 30%, and a second therapeutic trial with intranasal LH-RH was effective in all these cases. Treatment of cryptorchidism with intranasal synthetic LH-RH, 3 X 400 micrograms/day, seems to be very effective, painless and without major side effects. However, follow-up is mandatory.
Hypercalciuria is a major cause of urolithiasis in adults and has reached increasing attendance in childhood. Traditionally urinary excretion of calcium is evaluated by 24-hour urine collection. Previous reports proposed the urinary calcium/urinary creatinine ratio (Ca/Cr-ratio) to diagnose hypercalciuric states. In 10 children with normocalciuria and 8 children with hypercalciuria the values of calcium excretion and Ca/Cr-ratio in a 24-hour urine collection were compared. 40 analyses showed a significant correlation (p = 0.001, r = 0.91) and hypercalciuria (urinary calcium greater than 4 mg/kg/day) is present if the Ca/Cr-ratio exceeds 0.23 (mg/mg). In 10 of the 18 patients the Ca/Cr-ratio of the 24-hour collection was compared with the Ca/Cr-ratio of a random urine sample collected 3 hours after breakfast. No significant difference was present. In 9 of 10 patients the correct diagnosis (normocalciuria or hypercalciuria) was possible by evaluation of this random urine sample. Our studies indicate that the evaluation of Ca/Cr-ratio in a random urine sample is a simple and reliable method to detect hypercalciuria and should be performed in all children with urolithiasis or unexplained hematuria. It is also a simple test for early detection of hypercalciuria in patients with long-term administration of vitamin D metabolites.
The effects of intranasal insufflation of the synthetic growth hormone releasing factor GRF 1-29-NH2 on serum growth hormone (GH) were investigated in five healthy prepubertal children with short stature. 100 micrograms/kg/body weight of synthetic GRF 1-29-NH2, 500 micrograms in 100 microliters water, were insufflated intranasally after careful cleaning of the nose. GRF 1-29-NH2 induced a prompt rise of serum GH levels with peak values at 15 minutes in all children investigated. Peak serum GH values were 28.3 +/- 12.0 ng/ml (mean +/- SD), range 17.1 - 47.6 ng/ml; delta GH was 27.0 +/- 12.2 ng/ml (mean +/- SD). Serum GH levels were still significantly raised 120 minutes after the insufflation of GRF 1-29-NH2 (p less than 0.05). No side effects, except for burning of the nasal mucosa in one patient, were observed. The results of this study demonstrate that intranasal insufflation of synthetic GRF 1-29-NH2 induces a prompt release of GH in otherwise normal children with short stature. Pulsatile intranasal insufflation of GRF 1-29-NH2 probably could be used for the treatment of some children with GH deficiency due to a defect at a suprapituitary level.
To evaluate the role of Coxsackie B viruses in the pathogenesis of insulin-dependent (juvenile-onset, type 1) diabetes mellitus (IDDM), attempts were made to correlate virus-specific IgM responses with HLA genes, autoimmune responses, and C-peptide secretion. HLA DR3, DR4, or both were present in 73 of 90 (81%) diabetic patients; 22 of 23 (96%) with Coxsackie-B-virus-specific IgM had at least one of these HLA types, compared with 51 of 67 (76%) without virus-specific IgM. There was no correlation between HLA A, B, or C types or immunoglobulin allotypes and virus-specific IgM responses. 16 of 22 (64%) patients with Coxsackie-B-virus-specific IgM compared with 26 of 72 (36%) without had complement-fixing islet-cell antibodies; no relation was found between virus-specific IgM and antibodies against thyroid or adrenal tissue or parietal cells. C-peptide secretion was significantly lower in patients with Coxsackie-B-virus-specific IgM.
Patients from England, Austria, and Australia with recently diagnosed juvenile-onset insulin-dependent diabetes (type 1) mellitus (IDDM) and matched controls were tested for specific IgM responses to Coxsackie B1-5 viruses. 37 of 122 (30%) patients aged less than 15, but only 15 of 204 (6%) controls, were positive (p less than 0.005). Differences in Coxsackie B virus specific IgM responses between patients and controls were statistically significant for patients in England and Austria (p less than 0.005). Coxsackie B virus specific IgM responses were detected in only 3 of 31 patients aged greater than 16. Virus-specific IgM responses were directed against a single serotype, usually Coxsackie B4 or 5, in 23 of 37 (62.5%) children aged less than 15; 10 of 13 (77%) of children aged less than 7 had monotypic responses. Among families of Austrian patients with IDDM, 8 of 79 (10%) siblings had Coxsackie B virus specific IgM responses, 1 of whom subsequently had IDDM, but none of the 80 parents was positive. In contrast, there was no evidence of recent infection by mumps, rubella, or cytomegalovirus (CMV), since mumps-virus specific IgM was present in only 2 of 100 children with IDDM and 5 of 139 controls; no rubella or CMV specific IgM responses were detected in 60 sera from patients with IDDM.
53 prepubertal boys with untreated cryptorchidism were investigated in this study. 38 boys had unilateral, and 15 boys had bilateral cryptorchidism. 200 micrograms synthetic LHRH in a 0.2% aqueous solution (Cryptocur) were sprayed 3 times daily into each nostril (total dosage: 1.2 mg/d). The duration of therapy was 4 weeks. The boys were examined by palpation before, and then 2, 4 weeks and 6 months after commencement of treatment. Descent was achieved in 67.6% of testes; in the boys with unilateral cryptorchidism descent was achieved in 57.9% and in the boys with bilateral cryptorchidism in 80.0%. Follow-up control 6 months later showed relapse in 14 cases (30.4%). Treatment of cryptorchidism by intranasal application of LHRH, 3 times 400 micrograms/d is very effective. Administration is simple, painless and well tolerated. Follow-up is recommended, however, in view of the relatively high relapse rate.
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The association of optic nerve hypoplasia and deficiency of the septum pellucidum and hypopituitarism is known as the De Morsier syndrome or septo-optic dysplasia. Four children with blindness and growth retardation due to growth hormone deficiency are described. Frequent recurrent episodes of severe hypoglycaemia, starting in the newborn period, were observed in three of them. Although visual impairment was noted during the first year and growth failure was detected between the first and sixth year of life in all four patients, the diagnosis of septo-optic dysplasia was delayed for two to six years. Early diagnosis and treatment with growth hormone should prevent attacks of hypoglycaemia and their sequelae and bring about normal growth.
Factor VIII activity (VIII C), factor VIII coagulant antigen (VIII C:Ag), factor VIII-related antigen (VIII R:Ag), Ristocetin cofactor (R:Cof), and growth hormone were studied in eight children with growth hormone deficiency prior to, and 60, 120, and 180 minutes after administration of human growth hormone (Crescormone, Kabi), 4 U/m2. Growth hormone has been administered for 1.0 to 6.8 years but was stopped one week prior to this investigation. Basal levels of VIII C, VIII C:Ag, VIII R:Ag, and R:Cof were within the normal limits. After administration of human growth hormone, VIII C, VIII C:Ag, VIII R:Ag, and R:Cof showed a significant rise. Our study shows that growth hormone is not necessary to maintain the basal levels of the factor VIII complex within the normal limits. However, out data suggest that growth hormone has some influences on the levels of the factor VIII complex. The mechanisms for the rise of the factor VIII complex--whether this is a direct effect of growth hormone or not--are not clear at this point.
Measurements of T4, T3, rT3, and TSH were done in 27 children with newly diagnosed type I diabetes mellitus prior to institution of treatment. Serum T4 concentrations were low in 18%, serum T3 concentrations were low in 37%. Serum rT3 concentrations were elevated in 59%; the ratio rT3/T3 was elevated in 78%. The ratio rT3/T3 was significantly higher in the group of patients with the low pH, the low bicarbonate levels, the high blood glucose, and the high serum osmolality values than in the group of patients with the high pH, the high bicarbonate levels, the low blood glucose, and the low serum osmolality values.