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Biomedical subjects

J H Brämswig

Publications and source records attributed to J H Brämswig.

At least 19 recordsLinked to original sources
PubMed2002

Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

OBJECTIVE: In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. DESIGN AND PATIENTS: Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. RESULTS: The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3.4--7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) SURGERY: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6.3 to +9.5 years, leading to severely reduced final height of 137 to 150 cm in adult patients. Patients tended to follow height percentiles of genetic females. One pubertal patient was suicidal due to short stature. (4) Central precocious puberty (CPP): prolonged exposition to adrenal androgens led to CPP in one patient. He was treated with GnRH analogues until gonadectomy. CONCLUSIONS: Patients with CAH and complete virilization have a high risk of being diagnosed late. There are major problems and uncertainties of the patients' families and the treating physicians concerning gender assignment. Gender identity is disturbed in some patients. In addition, multiple surgical procedures are necessary and short stature as well as central precocious puberty might be important to avoid late sequelae. While some surgical interventions are probably unavoidable, most of these issues could be resolved with an early diagnosis. Thus, especially for these patients, a neonatal screening programme for CAH would be of paramount importance.

Adolescent↗
PubMed2000

Prediction of growth response in prepubertal children treated with growth hormone for idiopathic growth hormone deficiency.

Several multiple regression models have been developed to predict the first-year growth response to human growth hormone (hGH) in children with growth hormone deficiency (GHD). It was the aim of this study to analyse the significance of various growth parameters for a height prediction model. Data from 148 prepubertal children with idiopathic GHD were evaluated. The prediction model was developed by means of univariate and stepwise linear regression analysis and an "all possible" regression approach using Mallow's C(p) statistics. Six out of eight selected variables had a significant influence on the first-year growth rate. The most important parameter was the difference between target height SDS and height SDS at the start of therapy (THSDS-HSDSCO), accounting for 23.95% and 25.74% of the variability. No other single variable or combination of variables was more informative than the variable THSDS-HSDSCO alone. From these data, growth velocity for the first year of hGH treatment was estimated as 1.106 (THSDS-HSDSCO) + 6.8 cm/y +/- 2.2 cm (SE), allowing a prediction for different intervals between THSDS and HSDSCO. This equation was validated in a small group of 18 GHD patients demonstrating a predicted vs. observed first-year growth rate of 9.4 +/- 1.1 vs. 9.5 +/- 2.6 cm/y. We conclude that the difference between THSDS and height SDS at the start of therapy is an important predictor of the first-year growth response in children treated with hGH for idiopathic GHD. Unlike in previous studies, additional parameters did not increase predictability.

Age Factors↗
PubMed1998

The effects of etoposide on testicular function in boys treated for Hodgkin's disease.

BACKGROUND: Testicular dysfunction with elevated follicle-stimulating hormone (FSH) levels (indicating oligospermia and/or azoospermia) is a major late sequelae after treatment for Hodgkin's disease (HD) with high cumulative doses of procarbazine, cyclophosphamide, or chlorambucil. Etoposide is a newer antineoplastic agent that is effective in the treatment of HD. However, little is known regarding its testicular toxicity, especially in the pediatric age group. METHODS: The authors evaluated testicular function in 46 young adults in first continuous complete remission after stage-dependent treatment for HD with the vincristine, etoposide, prednisone, and doxorubicin (OEPA) or OEPA/cyclophosphamide, vincristine, procarbazine, and prednisone [COPP] chemotherapy regimens and involved field irradiation, excluding patients with ilioinguinal radiotherapy. Pubertal development was documented and a standardized intravenous gonadotropin-releasing hormone test was performed measuring testosterone and basal and stimulated levels of FSH and luteinizing hormone (LH). RESULTS: Testicular volumes, Tanner stages of pubic hair, and genital development were found to be appropriate or slightly delayed for the patients' chronologic age. All 27 patients had normal basal levels of FSH and LH after treatment of Ann Arbor Stage I-IIA HD with 2 courses of OEPA. Stimulated FSH and LH levels were found to be elevated only in rare patients, thus indicating normal endocrine function and spermatogenesis. However, basal and stimulated FSH levels were outside the +2 standard deviation range in 37.5% and 83.3% of patients receiving 2 cycles of OEPA and 2 cycles of COPP chemotherapy, and in 36.4% and 66.7% of patients receiving 2 cycles of OEPA and 4 cycles of COPP chemotherapy, demonstrating a high risk of oligospermia or azoospermia with these regimens. Basal LH levels essentially were normal, whereas stimulated LH levels frequently were elevated. CONCLUSIONS: Testicular function was found to be normal in patients with Stage I-IIA HD when etoposide was used in combination with vincristine, prednisone, and doxorubicin (2 cycles of OEPA). Additional chemotherapy with cyclophosphamide and procarbazine (2 cycles of OEPA and 2 or 4 cycles of COPP) negatively affected spermatogenesis and possibly Leydig cell function in a considerable number of patients. This major gonadotoxic effect most likely is due to procarbazine, although an additional effect of etoposide and cyclophosphamide cannot be excluded.

Adolescent↗
PubMed1995

Final height in children with growth hormone deficiency.

Forty-six patients (28 boys, 18 girls) were treated with growth hormone (GH) for short stature. Twenty-eight patients had total growth hormone deficiency (GHD), 12 partial GHD and 6 patients had short stature without GHD. Brain tumours were the cause of GHD in 8 patients and multiple pituitary hormone deficiency was present in 9 children. All patients received GH with subcutaneous injections only, 6-7 times/week. Mean final height for all patients was -1.11 SDS and was similar in boys (-1.09 SDS) and girls (-1.13 SDS). Target height SDS was -0.80 SDS in 42 patients, comparing favourably with a final height SDS of -1.05. Similar results were obtained in all patient sub-groups. Height velocity during the last year of therapy was between 2.1 and 9.9 cm/year in 34 patients and below 2 cm in 12 patients. As further growth is to be expected, target height will probably be reached by most patients.

Adolescent↗
PubMed1994

Hodgkin's disease in children: combined modality treatment for stages IA, IB, and IIA. Results in 356 patients of the German/Austrian Pediatric Study Group.

UNLABELLED: 356 children below 16 yrs of age with CS/PS IA, IB, and IIA were treated in the studies HD-78, HD-82, HD-85, HD-87, and OEPA-pilot 87 between June 1978 and Sept 1990. All patients received combined modality treatment (CMT) with 2 courses of chemotherapy (CT). In HD-78 and HD-82, the MOPP-derived drug combination OPPA (ADR instead of mechlorethamine) was applied. Extended-field radiotherapy (RT) was given in HD-78 using 36-40 Gy to involved-fields (IF) and 36-40 Gy vs. 18-20 Gy to adjacent fields. In HD-82 only IF-RT was applied using 35 Gy. When gonadotoxic effects of procarbazine (PC) in boys was detected in follow-up examinations, this drug was eliminated in studies HD-85 and HD-87 (OPA). Dosages of IF-RT were 35 Gy in HD-85 and 30 Gy in HD-87. With HD-87 a simultaneous pilot study was initiated to test the new combination OEPA (E = etoposide) together with 25 Gy IF-RT. RESULTS: (May 1993): Rates for event-free survival and survival are HD-78 (73 patients): 0.90 and 0.97 at 10 yrs; HD-82 (100 patients): 0.98 and 1.0 at 10 yrs; HD-85 (53 patients): 0.85 and 0.98 at 8 yrs; HD-87 (104 patients): 0.85 and 0.99 at 6 yrs; OEPA-pilot (26 patients): 0.96 and 0.96 at 5 yrs. No secondary leukemias, MDS, or solid tumors were observed in 14-yr observation time. After 2 OPPA, elevated FSH levels indicating impaired spermatogenesis were found in 29% of male patients. In contrast, after 2 OPA (without PC) only normal FSH levels were observed. In female patients, no gonadal dysfunction was found. Subclinical hypothyroidism was seen only after RT doses of > 30 Gy to the neck. Cardiomyopathies were not observed. CONCLUSION: 2 OPPA plus IF-RT using < 30 Gy can presently be considered optimal therapy for girls with localized HD. 2 OEPA plus 25 Gy IF-RT are being evaluated for boys in a phase III study (HD-90). In summary, there are good reasons to use CMT in early stages of HD in children, provided a highly effective CT of short duration and low long-term toxicity with low-dose IFI is applied.

Adolescent↗
PubMed1992

Treatment of children with Hodgkin's disease--results of the German Pediatric Oncology Group.

Six hundred sixty-seven children under age 16 were enrolled in 4 consecutive studies in West Germany between 1978 and 1990. These trials were mainly designed to reduce the long-term sequelae of high dose extended-field irradiation as well as the late effects of chemotherapy, in the context of combined modality treatment for all stages. Treatment concepts and results of studies HD-82, HD-85 and HD-87 are presented here. Patients with stages IA/B and IIA were treated with 2 cycles of OPPA (HD-82, n = 100) or OPA without procarbazine (HD-85, n = 53; HD-87, n = 104), followed by involved field irradiation (IFI) using 35 Gy (HD-82, HD-85) or 30 Gy (HD-87). Kaplan-Meier estimates (KME) for event-free survival (survival) at 4.5 years are 99% (100%) in HD-82, 85% (98%) in HD-85 and 88% (100%) in HD-87. Thus, 2 x OPPA is a highly effective chemotherapy eradicating occult microfoci in the non-irradiated adjacent fields, whereas 2 x OPA is less efficacious. Reduction of the radiation dose to 30 Gy (IFI) within the combined modality concept does not affect treatment outcome. About 30% of the boys treated with 2 x OPPA, but none of the girls and none of the boys treated without procarbazine (PC) showed elevated FSH-levels indicating gonadal dysfunction. No secondary leukemias and preleukemias were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence.

Testicular function was evaluated in 75 boys after treatment for Hodgkin's disease with involved-field or extended-field irradiation and stage-dependent chemotherapy (vincristine, prednisone, procarbazine, Adriamycin [doxorubicin], and cyclophosphamide [OPPA/COPP]). Although pubertal development and testosterone levels were normal in all patients, 18 of 75 (24.0%) had elevated basal and 65/74 (87.8%) elevated stimulated luteinizing hormone (LH) levels, demonstrating chemotherapy-induced Leydig cell damage. In addition, there was a 40.5% and 53.4% incidence of elevated basal and stimulated FSH values, respectively, indicating severe impairment of spermatogenesis as confirmed by azoospermia in four patients. Testicular dysfunction was observed in patients treated before as well as during puberty. The incidence of elevated basal follicle stimulating hormone (FSH) and LH values was significantly higher in patients who had received higher cumulative doses of chemotherapy, i.e., 28.9% and 13.2% with two OPPA, 45.5% and 36.4% with two OPPA/two COPP, and 62.5% and 43.8% with two OPPA/four to six COPP, respectively. Chemotherapy for Hodgkin's disease causes a high and apparently dose-related incidence of testicular dysfunction in prepubertal as well as in pubertal boys affecting Leydig cell function as well as spermatogenesis. Circumstantial evidence indicates that procarbazine is the major gonadotoxic agent involved.

Adolescent↗
PubMed1990

Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction.

To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche-Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height.

Adolescent↗
PubMed1989

The effect of the number of fractions of cranial irradiation on growth in children with acute lymphoblastic leukaemia.

Growth was documented over a period of 7 years in all long-term survivors treated for acute lymphoblastic leukaemia (ALL) with the DAL-70- (n = 15) and BFM-70-protocol (n = 27). Normal growth was documented in patients of the DAL-70-protocol during and after therapy. In contrast, in children treated with the BFM-70-protocol the mean height standard deviation score (SDS) decreased significantly from 1.21 SDS prior to therapy to 0.80 SDS at the end of therapy (p less than 0.001) and remained unchanged thereafter. Prophylactic cranial irradiation was given in total doses of 15 to 30 Gy. Ten children of the DAL-70- and 20 children of the BFM-70-protocol received 24 Gy of cranial irradiation. No significant change in height-SDS was observed in any patients of the DAL-70- and in 8 patients of the BFM-70- group, who received 24 Gy of cranial irradiation in 16-26 fractions. Adult height in 7 girls and 6 boys was normal and 3.15 cm and 5.06 cm above target height. In the remaining 12 patients of the BFM-70-protocol the total dose of 24 Gy of cranial irradiation was applied in 11-14 fractions. Their height-SDS had fallen significantly from 1.24 SDS before to 0.66 SDS (p less than 0.001) at the end of therapy. Adult height in 4 girls and 6 boys was also normal, but the height increase was comparatively smaller, -2.20 cm below target height in the girls and 1.91 cm above in the boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

The results of short-term (6 months) high-dose testosterone treatment on bone age and adult height in boys of excessively tall stature.

Forty-nine pubertal tall boys with a mean height prediction of 203.59 cm according to the Bayley-Pinneau (BP) method were treated prospectively with 500 mg testosterone-oenanthate every 2 weeks for a period of 6 months. Before therapy chronological age (CA) was 14.14 years and bone age (BA) 13.88 years using the Greulich-Pyle (GP) method. During therapy BA advanced by 1.37 years. It continued to accelerate during the 6 months following therapy with a mean delta BA/delta CA being 3.01 at 3 months and 2.24 at 6 months after therapy. The 6 months value was only slightly less than the delta BA/delta CA of 2.47 obtained during therapy. The reduction in adult height was 7.26 cm or 50.8% of the predicted further growth in 12 boys with a long-term follow up of 2.5 years. This is similar to the 51.6% or 9.63 cm observed in 50 boys with a long-term follow up after 14.25 month treatment until a BA of 17 years or more. It is concluded that in the majority of cases high-dose testosterone therapy in boys of tall stature can be limited to a 6-month treatment period. Reassessment of the height prediction after a 6-month interval without therapy should define those patients who have to resume treatment because of their remaining excessive growth potential.

Adolescent↗
PubMed1988

An approach to reduce treatment and invasive staging in childhood Hodgkin's disease: the sequence of the German DAL multicenter studies.

UNLABELLED: From June 1978 through March 1987, 506 children under the age of 16, representing approximatively 70% of the children with Hodgkin's disease in West-Germany entered 3 consecutive multicenter studies at 68 centers. The general objective of these study sequence is to maximize the chance of cure while minimizing radiotherapy and chemotherapy as much as possible in a combined modality treatment concept. The purpose was also to reappraise the need for splenectomy and laparotomy and to define a staging policy which provides adequate evaluation of intraabdominal disease. Study II (HD-82) is described in detail. 203 protocol patients were enrolled between Dec. 1981 and Dec. 1984. Laparotomy was performed in 202 patients, but splenectomy only in 78 (38.4%) using an intraoperative decisional strategy, developed in Study I (HD-78). Patients were stratified according to stage into 3 groups (PS I/IIA, IIB/IIIA and IIIB/IV) receiving 2, 4 or 6 cycles of OPPA/COPP-chemotherapy. Radiotherapy was given only to the involved fields, the dose depending on the extent of chemotherapy (35, 30 or 25 Gy). RESULTS AND CONCLUSIONS: The event-free survival rates after 5 years are 96% (entire group), 99% (stage I/IIA), 96% (stage IIB/IIIA) and 90% (stage IIIB/IV). Thus, only involved field radiotherapy with reduced doses is needed, if a stage-dependent chemotherapy with 2, 4 or 6 cycles of OPPA/COPP is given. The strategy of selective splenectomy has proven very useful. Based on statistical analyses concerning abdominal involvement a clinical decisional strategy for selective laparotomy was developed. Further efforts are needed to reach a stepwise cautious and controlled narrowing-in on the therapy combining the lowest long-term toxicity with the highest chance of cure.

Adolescent↗