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M Jansen

Publications and source records attributed to M Jansen.

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

Structure of the fluorosulfite anion: rotational disorder of SO(2)F(-) in the alkali metal fluorosulfites and crystal structures of alpha- and beta-CsSO(2)F.

19F solid-state NMR spectra of the alkali metal fluorosulfites KSO(2)F, RbSO(2)F, alpha-CsSO(2)F, and beta-CsSO(2)F show that the fluorosulfite anion is subjected to dynamical disorder at room temperature. This disorder can be modeled by 120 degrees rotational jumps with respect to the C(3)-pseudoaxis of the anion. The exchange frequency of this disorder decreases with decreasing temperature. The calculated jump frequencies at room temperature are 5 x 10(5) Hz for KSO(2)F, 2 x 10(5) Hz for RbSO(2)F, 1 x 10(7) Hz for alpha-CsSO(2)F, and 5 x 10(5) Hz for beta-CsSO(2)F, respectively. The crystal structures of alpha- and beta-CsSO(2)F were determined for the first time (alpha: Pnma; Z = 4; a = 790.98(8), b = 666.07(7), c = 798.93(9) pm; T = 293 K. beta: R3m; Z = 3; a = 659.22(6), c = 800.50(4) pm; T = 293 K). X-ray single-crystal data of KSO(2)F, RbSO(2)F, and alpha-CsSO(2)F taken at various temperatures were refined using the disorder model developed from the NMR results. It is shown that it is impossible to obtain reliable structural parameters of the SO(2)F(-) ion by refinement of X-ray data as long as rotational disorder persists. The preference of an ordered structure increases with decreasing temperature. The degree of disorder remaining in alpha-CsSO(2)F at 93 K is small. The structural parameters of the fluorosulfite anion as obtained by a routine refinement of this phase (S-F, 169.0(2) pm; S-O, 147.8(1) pm) are the best lower (S-F) and upper (S-O) limits of the "true" bond lengths determined experimentally. They comply with the values obtained from quantum chemical calculations.

Journal Article↗
PubMed2001

[Lump in the neck: 4 patients with a medullary thyroid carcinoma].

In a 25-year-old man, medullary thyroid carcinoma (probably a solitary sporadic form) was diagnosed following investigation of a small lump in the patient's neck. This was removed and followed up with further treatment. In a 27-year-old man, episodes of headache, palpitations and excessive perspiration (due to a pheochromocytoma) and a positive family history of thyroid problems led to further investigations and the subsequent diagnosis of multiple endocrine neoplasia (MEN) type 2A. The patient died at 48 years of age as the result of liver metastases. A total thyroidectomy had been carried out on a 19-year-old man with familial medullary thyroid carcinoma. The calcitonin levels remained elevated, but no tumour residues could be found. A 16-year-old girl with MEN type 2B had also previously undergone surgery. Her main complaint consisted of persistent constipation. Thyroid carcinomas usually present as a nodule in the neck. In 25% of cases, medullary thyroid carcinoma is part of the MEN2 syndrome. The clinical approach for medullary thyroid carcinoma is based on pathological findings following fine needle aspiration biopsy. The results of DNA tests determine the course of treatment and the need for family testing. In families with a hereditary form, there is a clear genotype-phenotype correlation. Early diagnosis and treatment can improve life expectancy.

Adolescent↗
PubMed2001

Al(22)Cl(20).12L (L = THF, THP): the first polyhedral aluminum chlorides.

Aluminum subhalides of the type Al(22)X(20).12L (X = Cl, Br; L = THF, THP) are the only known representatives of polyhedral aluminum subhalides and exhibit interesting multicenter bonding properties. Herein, we report on the synthesis and structural investigation of the first chlorides of this type. Additional investigations applying solid-state (27)Al NMR (MAS), XPS (of Al(4)Cp(4) and Al(22)X(20).12L), and quantum chemical calculations shed more light upon the structure of the molecules and possible Al modifications.

Journal Article↗
PubMed2001

Activity of human IgG and IgA subclasses in immune defense against Neisseria meningitidis serogroup B.

Both IgG and IgA Abs have been implicated in host defense against bacterial infections, although their relative contributions remain unclear. We generated a unique panel of human chimeric Abs of all human IgG and IgA subclasses with identical V genes against porin A, a major subcapsular protein Ag of Neisseria meningitidis and a vaccine candidate. Chimeric Abs were produced in baby hamster kidney cells, and IgA-producing clones were cotransfected with human J chain and/or human secretory component. Although IgG (isotypes IgG1-3) mediated efficient complement-dependent lysis, IgA was unable to. However, IgA proved equally active to IgG in stimulating polymorphonuclear leukocyte respiratory burst. Remarkably, although porin-specific monomeric, dimeric, and polymeric IgA triggered efficient phagocytosis, secretory IgA did not. These studies reveal unique and nonoverlapping roles for IgG and IgA Abs in defense against meningococcal infections.

Animals↗
PubMed2001

Mono-N-carboxymethyl chitosan (MCC), a polyampholytic chitosan derivative, enhances the intestinal absorption of low molecular weight heparin across intestinal epithelia in vitro and in vivo.

The synthesis and evaluation of mono-N-carboxymethyl chitosan (MCC) as an intestinal permeation enhancer for macromolecular therapeutics is presented. MCCs were synthesized from two different viscosity grade chitosans to yield both high and low viscosity grade products. These MCCs were tested on Caco-2 cells for their efficiency to decrease the transepithelial electrical resistance (TEER) and to increase the paracellular permeability of the anionic macromolecular anticoagulant low molecular weight heparin (LMWH). For in vivo studies, LMWH was administered intraduodenally with or without MCC to rats. Both types of experiments were performed at pH 7.4. Results show that both viscosity grade MCCs managed to significantly decrease the TEER of Caco-2 cell monolayers when they were applied apically at concentrations of 3-5% (w/v). Transport studies with Caco-2 cells revealed substantial increases of LMWH permeation in the presence of both viscosity grade MCCs compared with controls. In rats, 3% (w/v) low viscosity MCC significantly increased the intestinal absorption of LMWH, reaching the therapeutic anticoagulant blood levels of LMWH. Both in vitro and in vivo results indicate that the polyampholytic chitosan modification MCC is a suitable and functional polymer for the delivery and intestinal absorption of anionic macromolecular therapeutics like LMWH.

Animals↗
PubMed2001

[Prognostic factors for development of peritoneal carcinosis in stomach carcinoma].

OBJECTIVE: Several adjuvant therapy concepts have been developed to improve the treatment of gastric cancer patients. Dealing with intraperitoneal chemotherapy, it seems to be useful to determine suitable prognostic factors for the occurrence of peritoneal carcinosis, as it is possible to select patients who may profit from this therapy. METHODS: Between June 1975 and December 1999 resection of gastric cancer was performed in 575 patients. From 1 January 1986 clinical data were recorded prospectively, before that time, retrospectively. The complete data concerning preoperative diagnosis, operation, histology, postoperative course and survival time were documented in an Excel file for statistical analysis. Multivariate analysis was performed using the chi-squared logistic regression test. RESULTS: Significant correlation was found between the occurrence of peritoneal dissemination and tumour stage pT3, pN2, G3, cancer of the whole stomach and cancer at the anastomotic site after partial gastric resection. Lauren classification, signet-ring cell cancer, liver metastasis and tumour localisation in the distal or proximal stomach showed no significant correlation to peritoneal carcinosis in the multivariate analysis. However, only one-third of patients with liver metastasis had simultaneous peritoneal dissemination. CONCLUSION: The results show a clinical correlation of tumour localisation, infiltration of the serosa, lymph node metastasis and grading with peritoneal dissemination. The present data serve as a basis for further histochemical and molecular biological investigations e.g. of the expression of adhesion molecules to determine the risk of peritoneal tumour dissemination after gastric cancer.

Adult↗
PubMed2001

STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas.

Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of some IPMNs.

AMP-Activated Protein Kinase Kinases↗
PubMed2001

Atorvastatin improves blood rheology in patients with familial hypercholesterolemia (FH) on long-term LDL apheresis treatment.

To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH) on regular LDL apheresis, we prospectively studied the rheological variables fibrinogen, plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit and platelet aggregation in 12 patients (two homozygous, ten heterozygous) before and during treatment with atorvastatin. Baseline values of red cell aggregation and whole blood viscosity were increased in FH patients on regular LDL apheresis compared with healthy controls (P<0.05), whereas fibrinogen, plasma viscosity and hematocrit were similar in the two groups. Treatment with atorvastatin reduced red cell aggregation (P<0.01), whole blood viscosity (P<0.01), plasma viscosity (P<0.01) and platelet aggregation (P<0.05), but caused a slight increase in plasma fibrinogen (by 5%; P<0.01). Our findings suggest that atorvastatin improves blood rheology in patients with FH on regular LDL-apheresis. This improvement in blood flow properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.

Adult↗
PubMed2001

Protection of hematopoietic cells from O(6)-alkylation damage by O(6)-methylguanine DNA methyltransferase gene transfer: studies with different O(6)-alkylating agents and retroviral backbones.

Overexpression of O(6)-methylguanine DNA methyltransferase (MGMT) can protect hematopoietic cells from O(6)-alkylation damage. To identify possible clinical applications of this technology we compared the effect of MGMT gene transfer on the hematotoxicity induced by different O(6)-alkylating agents in clinical use: the chloroethylnitrosoureas ACNU, BCNU, CCNU and the tetrazine derivative temozolomide. In addition, various retroviral vectors expressing the MGMT-cDNA were investigated to identify optimal viral backbones for hematoprotection by MGMT expression. Protection from ACNU, BCNU, CCNU or temozolomide toxicity was evaluated utilizing a Moloney murine leukemia virus-based retroviral vector (N2/Zip-PGK-MGMT) to transduce primary murine bone marrow cells. Increased resistance in murine colony-forming units (CFU) was demonstrated for all four drugs. In comparison to mock-transduced controls, after transduction with N2/Zip-PGK-MGMT the IC50 for CFU increased on average 4.7-fold for ACNU, 2.5-fold for BCNU, 6.3-fold for CCNU and 1.5-fold for temozolomide. To study the effect of the retroviral backbone on hematoprotection various vectors expressing the human MGMT-cDNA from a murine embryonic sarcoma virus LTR (MSCV-MGMT) or a hybrid spleen focus-forming/murine embryonic sarcoma virus LTR (SF1-MGMT) were compared with the N2/Zip-PGK-MGMT vector. While all vectors increased resistance of transduced human CFU to ACNU, the SF1-MGMT construct was most efficient especially at high ACNU concentrations (8-12 microg/ml). Similar results were obtained for protection of murine high-proliferative-potential colony-forming cells. These data may help to optimize treatment design and retroviral constructs in future clinical studies aiming at hematoprotection by MGMT gene transfer.

Alkylating Agents↗
PubMed2001

Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb).

Coagulation inhibitors may occur as alloantibodies in patients with congenital factor deficiencies or as autoantibodies in patients with a previously normal coagulation. We treated 10 patients with factor VIII inhibitors (three haemophiliacs and seven patients with acquired factor VIII inhibitors) and one patient with a factor V inhibitor using extracorporeal immunoadsorption to immobilized antibodies against human immunoglobulins (Ig-Therasorb). The initial inhibitor titre was between 18 BU/ml and 540 BU/ml. Nine patients had signs of bleeding. Eighty-nine immunoadsorption sessions were performed in the 11 patients (8.1 +/- 5.1 per patient), each processing 6980 +/- 880 ml of plasma in 3.8 +/- 0.5 h. The mean reduction of the inhibitor titre was 71.9 +/- 19.4% per session. Serum IgG, IgA and IgM levels decreased by 68.7 +/- 10.1%, 55.7 +/- 12.7% and 48.6 +/- 11.1% respectively. In two haemophiliac patients, an initial titre reduction prior to an immune tolerance protocol was performed. Another haemophiliac patient was treated because of acute cerebral bleeding. In six out of eight patients with acquired inhibitors, a durable elimination was achieved within a median of 18 d. Treatment was safe and well-tolerated and seems to be a promising method in the treatment of patients with coagulation inhibitors, especially when a fast inhibitor titre reduction is necessary.

Adult↗
PubMed2001

Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age.

OBJECTIVE: To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age. DESIGN: In a prospective, randomised double-blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)]. PATIENTS: Seventy-eight children with short stature (height SD-score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment. MEASUREMENTS: Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment. RESULTS: Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups. CONCLUSIONS: Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long-term hyperinsulinism during childhood are unknown, careful follow-up of these GH-treated children born small for gestational age is required.

Area Under Curve↗
PubMed2001

Long-term follow-up of percutaneous transhepatic therapy (PTT) in patients with definite benign anastomotic strictures after hepaticojejunostomy.

BACKGROUND AND STUDY AIMS: Percutaneous transhepatic therapy (PTT) is a promising minimally invasive procedure for benign stenosis of the anastomosis after hepaticojejunostomy. In this prospective study, the effectiveness and safety of this technique were investigated. PATIENTS AND METHODS: Between October 1995 and May 2000 34 consecutive patients were referred for treatment of symptomatic cholestasis due to anastomotic strictures after hepaticojejunostomy. In all patients percutaneous transhepatic cholangioscopic (PTCS) drainage and bougienage of the stenosis up to 16 Fr were performed. Associated bile duct stones were fractured using PTCS laser lithotripsy and removed into the jejunum. Afterwards, patients received transhepatic drainage for 3 months initially. The tubes were replaced in case of persistent strictures every 3 months up to 1 year. Patients in whom treatment failed underwent surgery or received biliary metal stents, depending on risk factors and individual anatomy. RESULTS: The procedure was performed in 34 patients (mean age 57 +/- 15) with cholestasis (alkaline phosphatase 691 +/- 485 U/l, bilirubin level mean 3.2 +/- 3.1 mg/dl). The transhepatic tube was successfully positioned into the right hepatic bile duct (n = 25), into the left (n = 3), or into both (n = 3) after 4 +/- 1 sessions, except in two patients in whom an external drainage was used and another patient in whom the procedure had to be stopped due to a bleeding complication. In 14 patients bile duct stones were successfully treated by PTCS laser lithotripsy before the placement of a transhepatic tube. The 30-day morbidity and mortality rates were 23.5% and 0% respectively. In 23 patients, the transhepatic tube could be removed after 212 +/- 122 days, with no evidence of cholestasis during a further follow-up of 736 +/- 479 days. Four patients received metal stents because of persistent strictures after transhepatic intubation. Surgery had to be performed in a total of five patients, because of recurrent bile duct stones or recurrent strictures, in one patient with previous implantation of a metal stent, and in two patients with bile duct disconnection. Two patients died, one 1.5 years after surgery and one 427 days after metal stent implantation. None of these cases was related to the procedure. In two patients, the transhepatic tube is still in situ. CONCLUSIONS: Percutaneous transhepatic treatment of anastomotic strictures after hepaticojejunostomy is safe and highly effective in achieving internal biliary drainage. Temporary transhepatic intubation seems to be a promising minimally invasive alternative to surgery.

Adult↗
PubMed2001

Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin.

BACKGROUND: The autoinducible metabolic transformation of the anticancer agent ifosfamide involves activation through 4-hydroxyifosfamide to the ultimate cytotoxic ifosforamide mustard and deactivation to 2- and 3-dechloroethylifosfamide with concomitant release of the neurotoxic chloroacetaldehyde. Activation is mediated by cytochrome P450 (CYP) 3A4 and deactivation by CYP3A4 and CYP2B6. The aim of this study was to investigate modulation of the CYP-mediated metabolism of ifosfamide with ketoconazole, a potent inhibitor of CYP3A4, and rifampin (INN, rifampicin), an inducer of CYP3A4/CYP2B6. METHODS: In a double-randomized, 2-way crossover study a total of 16 patients received ifosfamide 3 g/m(2) per 24 hours intravenously, either alone or in combination with 200 mg ketoconazole twice daily (1 day before treatment and 3 days of concomitant administration) or 300 mg rifampin twice daily (3 days before treatment and 3 days of concomitant administration). Plasma pharmacokinetics and urinary excretion of ifosfamide, 2- and 3-dechloroethylifosfamide, and 4-hydroxyifosfamide were assessed in both courses. Data analysis was performed with a population pharmacokinetic model with a description of autoinduction of ifosfamide. RESULTS: Rifampin increased the clearance of ifosfamide at the start of therapy at 102%. The fraction of ifosfamide metabolized to the dechloroethylated metabolites was increased, whereas exposure to the metabolites was decreased as a result of increased elimination. The fraction metabolized and the exposure to 4-hydroxyifosfamide were not significantly influenced. Ketoconazole did not affect the fraction metabolized or the exposure to the dechloroethylated metabolites, whereas both parameters were reduced with 4-hydroxyifosfamide. CONCLUSIONS: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes in the pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamide therapy.

Adult↗
PubMed2001

Zinc cyanamide, Zn(CN2).

Single crystals of the title compound have been grown by annealing microcrystalline zinc cyanamide at 843 K in silver crucibles. Zn(CN(2)) crystallizes as colourless prisms. The crystal structure is composed of corner-linked ZnN(4/2) tetrahedra. Carbon and nitrogen form (CN(2))(2-) dumb-bells with the C atom on a twofold axis. Nitrogen is approximately trigonally planar, coordinated by two Zn atoms and one C atom.

Journal Article↗
PubMed2001

Reversible phase transitions in Na2S under pressure: a comparison with the cation array in Na2SO4.

The structural behavior of the antifluorite Na(2)S, disodium sulfide, has been studied under pressure up to 22 GPa by in situ synchrotron X-ray diffraction experiments in a diamond anvil cell at room temperature. At approximately 7 GPa, Na(2)S undergoes a first phase transition to the orthorhombic anticotunnite (PbCl(2)) structure (Pnma, Z = 4). The lattice parameters at 8.2 GPa are a = 6.707 (5), b = 4.120 (3), c = 8.025 (4) A. At approximately 16 GPa, Na(2)S undergoes a second transition adopting the structure of the Ni(2)In-type (P6(3)/mmc, Z = 2). The lattice parameters at 16.6 GPa are a = 4.376 (18), c = 5.856 (9) A. Both pressure-induced phases have been confirmed by full Rietveld refinements. An inspection of the cation array of Na(2)SO(4) reveals that its Na(2)S subarray is also of the Ni(2)In-type. This feature represents a new example of how the cation arrangements in ternary oxides correspond to the topology of the respective binary compounds. We discuss analogies between the insertion of oxygen and the application of pressure.

Journal Article↗
PubMed2001

Non-growth-associated demethylation of dimethylsulfoniopropionate by (homo)acetogenic bacteria.

The demethylation of the algal osmolyte dimethylsulfoniopropionate (DMSP) to methylthiopropionate (MTPA) by (homo)acetogenic bacteria was studied. Five Eubacterium limosum strains (including the type strain), Sporomusa ovata DSM 2662(T), Sporomusa sphaeroides DSM 2875(T), and Acetobacterium woodii DSM 1030(T) were shown to demethylate DMSP stoichiometrically to MTPA. The (homo)acetogenic fermentation based on this demethylation did not result in any significant increase in biomass. The analogous demethylation of glycine betaine to dimethylglycine does support growth of acetogens. In batch cultures of E. limosum PM31 DMSP and glycine betaine were demethylated simultaneously. In mixed substrates experiments with fructose-DMSP or methanol-DMSP, DMSP was used rapidly but only after exhaustion of the fructose or the methanol. In steady-state fructose-limited chemostat cultures (at a dilution rate of 0.03 h(-1)) with DMSP as a second reservoir substrate, DMSP was biotransformed to MTPA but this did not result in higher biomass values than in cultures without DMSP; cells from such cultures demethylated DMSP at rates of approximately 50 nmol min(-1) mg of protein(-1), both after growth in the presence of DMSP and after growth in its absence. In cell extracts of glycine betaine-grown strain PM31, DMSP demethylation activities of 21 to 24 nmol min(-1) mg of protein(-1) were detected with tetrahydrofolate as a methyl acceptor; the activities seen with glycine betaine were approximately 10-fold lower. A speculative explanation for the demethylation of DMSP without an obvious benefit for the organism is that the DMSP-demethylating activity is catalyzed by the glycine betaine-demethylating enzyme and that a transport-related factor, in particular a higher energy demand for DMSP transport across the cytoplasmic membrane than for glycine betaine transport, may reduce the overall ATP yield of the fermentation to virtually zero.

Acetyl Coenzyme A↗
PubMed2001

Dehydroepiandrosterone sulfate treatment for atrichia pubis.

OBJECTIVE: To evaluate the efficacy of oral dehydroepiandrosterone sulfate (DHEAS) treatment for atrichia pubis in female adolescents. STUDY DESIGN: Two XY female adolescents with 17-hydroxylase deficiency and 2 XX females with panhypopituitarism presenting with atrichia pubis were treated with a daily dosage of DHEAS 10 mg/m2 body surface in addition to their regular substitution therapy. The dosage was increased according to clinical response. Pubic hair stages, growth and serum DHEAS were evaluated and in 1 case also serum IGFs and IGFBPs. RESULTS: A dosage of 10 mg/m2 for 1 year led to serum DHEAS levels at the lower limit of the normal range. 15 mg/m2 was needed to achieve pubic hair stage 4-5 and axillary hair in patients with 17-hydroxylase deficiency. In panhypopituitarism, pubic hair developed at a slower pace and reached stage 4 on a dosage of 25-30 mg/m2. Baseline serum IGF-I SDS was -0.67 and did not change on the initial dosage of DHEAS, in combination with submaximal estrogen substitution (10 microg ethinyl estradiol). On the combination of 15 mg/m2 DHEAS and full estrogen substitution, IGF-I SDS increased to an average of -0.15. IGFBP-3 SDS increased from 1.4 to a mean of 2.6 in the first year, and went back to 1.4 in the second year. IGFBP-6 SDS was low at baseline (-2.5) and rose to -1.9 and -1.7 IGF-II and IGFBP-1 showed an irregular pattern. CONCLUSIONS: Oral administration of DHEAS in a dosage of 15 mg/m2 o.d. is an efficacious treatment for atrichia pubis. For females with a panhypopituitarism a higher dosage appears needed. Given this and other biological actions of DHEAS, substitution therapy with DHEAS or DHEA to females with adrenal androgen deficiency appears rational.

Administration, Oral↗