[Pharmacist rounds on geriatric wards : Assessment of 1 year of pharmaceutical counseling]. / Pharmazeutische Visite auf geriatrischen Stationen : Auswertung der pharmazeutischen Empfehlungen eines Jahres.

BACKGROUND: Older patients suffer more often from drug-induced complications. OBJECTIVE: What are the precise recommendations pharmacists can give to geriatricians? MATERIAL AND METHODS: Two pharmacists conducted clinical rounds on 2 geriatric wards over a period of 54 weeks. Protocols of conspicuous medications for geriatric patients were analyzed and suggestions were made. RESULTS: Particularly frequent were the questionable medical indications for proton pump inhibitors, allopurinol, pregabalin and gabapentin. Adjustment of the dosage of heparin and its analogs to impaired renal function of patients was often lacking. This was also occasionally the case for metformin, some antibiotics and simvastatin. There were several interactions of drug combinations with a high risk for QT prolongation. The inhibition of resorption of bisphosphonates and L­thyroxin by the simultaneous intake of magnesium and calcium seemed to be probable. Furthermore, it was noticed that for some medications for patients treated by percutaneous endoscopic gastrostomy (PRG) administration by feeding tubes was not possible and combinations of different eye drops which should not be applied simultaneously but at delayed time intervals. CONCLUSION: An additional medication-related visit provides an interventional option for avoidance of medication errors.

[Operative risk of geriatric patients in cardiac surgery]. / Operatives Risiko geriatrischer Patienten in der Herzchirurgie.

BACKGROUND: Despite substantial progress in interventional cardiology, there are still many geriatric patients who require cardiac surgery. Estimation of the operative risk is therefore of great importance. OBJECTIVE: The prognostic value of the geriatric assessment for estimation of the operative risk was evaluated. MATERIAL AND METHODS: Between 2008 and 2009 a geriatric assessment was carried out on 500 patients before an urgent or elective cardiac surgery intervention. The primary endpoints were in-hospital death, death within 30 days after the intervention and stroke. A secondary endpoint was the combination of death, stroke and in-hospital complications. RESULTS: The average age of the patients was 77.1 ± 4.6 years and 44.3% of the particpants were women. Aortic stenosis was the primary reason for surgery in 49.2% of patients and coronary artery disease in 38.8% of patients. Half of the patients (56.5%) showed functional impairments in one or more evaluated domains. Significant limitations in cognitive function were present in 11.8% and in mobility in 2.4% of the patients. The 30-day mortality was 2.9% and stroke occurred in 1.4% of the patients. After multivariate analysis cognitive impairment remained independently associated with the operative mortality (odds ratio OR 3.8, 95% confidence interval CI 1.2-12.7). CONCLUSION: The perioperative mortality of older patients in cardiac surgery is low. A limited functional status detected in the geriatric assessment is associated with an increased mortality. Impaired cognitive function is an independent predictor of postoperative mortality.

[Special care units for acutely ill patients with cognitive impairment in Germany. Position paper]. / Spezialstation für akut erkrankte, kognitiv eingeschränkte Patienten in Deutschland. Positionspapier.

BACKGROUND: Dementia is an increasing challenge for care providers in nursing homes and hospitals. Since the 1980s, special acute care units in nursing homes have developed rapidly. In Germany, the first unit in a hospital opened in 1990. In 2013, there were 22 units. MATERIALS AND METHODS: In the following paper, the German Geriatric Society ("Deutsche Gesellschaft für Geriatrie e. V.") recommends basic standards for these wards. RESULTS: The basic standards for these wards include the following: a maximum of 20 beds, an area physically separated from the geriatric hospital department, their own dayroom and therapy room, a structured daily routine suitable for patients with dementia, the selection of permanent staff on a voluntary basis, specialized training, extended geriatric assessment, and special consideration of the background and social situation of the patients.

Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.

Autosomal recessive pseudohypoaldosteronism type I is a rare life-threatening disease characterized by severe neonatal salt wasting, hyperkalaemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormones. Investigation of affected offspring of consanguineous union reveals mutations in either the alpha or beta subunits of the amiloride-sensitive epithelial sodium channel in five kindreds. These mutations are homozygous in affected subjects, co-segregate with the disease, and introduce frameshift, premature termination or missense mutations that result in loss of channel activity. These findings demonstrate the molecular basis and explain the pathophysiology of this disease.

[Dementia: diagnosis and therapy]. / Demenz: Diagnostik und Therapie.

Dementia is a clinical syndrome characterized by progressive memory loss. Alzheimer's disease, a neurodegenerative disorder, accounts for the majority of clinical cases. The differential diagnosis comprises other neurodegenerative disease entities and vascular dementia, but also secondary and potentially reversible disturbances of cognitive function such as delirium or depression. Diagnostic work-up consists of standardized cognitive testing, neuroimaging, and a basic laboratory test battery. Pharmacological treatment of cognitive symptoms is accompanied by pharmacological and nonpharmacological treatment of psychiatric and behavioral symptoms, establishment of a supportive social network, as well as prevention and treatment of medical complications of dementia. This article summarizes current clinical knowledge on dementia and has a special interest in treatment and prophylaxis of complications in the field of internal medicine.

Adrenergic modulation of sharp wave-ripple activity in rat hippocampal slices.

Norepinephrine (NE) has been shown to facilitate learning and memory by modulating synaptic plasticity in the hippocampus in vivo. During memory consolidation, transiently stored information is transferred from the hippocampus into the cortical mantle. This process is believed to depend on the generation of sharp wave-ripple complexes (SPW-Rs), during which previously stored information might be replayed. Here, we used rat hippocampal slices to investigate neuromodulatory effects of NE on SPW-Rs, induced by a standard long-term potentiation (LTP) protocol, in the CA3 and CA1. NE (10-50 µM) dose-dependently and reversibly suppressed the generation of SPW-Rs via activation of α1 adrenoreceptors, as indicated by the similar effects of phenylephrine (100 µM). In contrast, the unspecific ß adrenoreceptor agonist isoproterenol (2 µM) significantly increased the incidence of SPW-Rs. Furthermore, ß adrenoreceptor activation significantly facilitated induction of both LTP and SPW-Rs within the CA3 network. Suppression of SPW-Rs by NE was associated with a moderate hyperpolarization in the majority of CA3 pyramidal cells and with a reduction of presynaptic Ca(2+) uptake in the stratum radiatum. This was indicated by activity-dependent changes in [Ca(2+) ](o) and Ca(2+) fluorescence signals, by changes in the paired pulse ratio of evoked EPSPs and by analysis of the coefficient of variance. In the presence of NE, repeated high frequency stimulation (high-frequency stimulation (HFS)) failed to induce SPW-Rs, although SPW-Rs appeared following washout of NE. Together, our data indicate that the NE-mediated suppression of hippocampal SPW-Rs depends on α1 adrenoreceptor activation, while their expression and activity-dependent induction is facilitated via ß1-adrenoreceptors.

Treatment of dementia patients with fracture of the proximal femur in a specialized geriatric care unit compared to conventional geriatric care.

To prove the efficiency of a specialized geriatric ward (cognitive geriatric unit, CGU) for patients with a fracture of the proximal femur and additional dementia, we conducted a matched-pair analysis comparing 96 patients with fracture of the proximal femur and additional dementia matched for age, sex, surgical treatment and the degree of cognitive impairment by MMSE score. A total of 48 patients were treated in the CGU, offering extended geriatric assessment, special education of staff, and architecture appropriate for patients with cognitive decline. Target criteria were a gain in the Barthel index and Tinetti score, the length of stay, new admissions to nursing home, the frequency of neuroleptic, antidepressant, and antidementive medication, and the number of specified clinical diagnoses for the dementia syndrome. Length of stay was significantly longer in the CGU. The increase of the Tinetti score was significantly higher in the patients in the CGU, regardless of the length of stay (analysis of covariance: treatment (CGU/non-CGU): F(1/93) = 9.421, p = 0.003; covariate (length of stay): F(1/93) = 3.452, p = 0.066, η(2) = 3.6%). In the intervention group, the number of definite diagnoses concerning the dementia syndrome was also higher. Comparison of drug treatment and the percentage of new admission to a nursing home did not differ between groups. Treatment in a specialized, "cognitive geriatric unit" seems to result in better mobility of demented patients with proximal fractures of the femur.

[Special care units for the treatment of acutely ill, cognitively impaired geriatric patients in Germany]. / Spezialisierte Stationen zur Behandlung von akut erkrankten geriatrischen Patienten mit zusätzlichen kognitiven Beeinträchtigungen in Deutschland.

During recent years, specialized wards have been established in geriatric hospital departments as a consequence of the growing need of special care for acutely ill older patients, who are also cognitively impaired. However, there are neither established standards nor any commonly agreed concept of care. A written survey among 12 specialized wards in Germany revealed some characteristics of these wards: extended geriatric assessment, special education of staff including validation and gerontopsychiatric issues, and particular equipment/architecture, such as hidden doors and group rooms, and in some cases loop tracks for walking, therapeutic facilities, and 'living rooms' on the wards. There is a wide variability with respect to the designation of these wards, the number of beds, length of stay, and admission criteria. It appears from this survey that there should be an exchange of empirical experience made on these wards, and there is a need of collaborative research on its usefulness.

A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin.

Steroid 11 beta-hydroxylase (P450c11) deficiency (failure to convert 11-deoxycortisol to cortisol) causes less than 10% of cases of congenital adrenal hyperplasia in most populations, but it is relatively frequent in Jews of Moroccan origin. P450c11 is encoded by the CYP11B1 gene which is located on chromosome 8q22 along with a homologous gene of unknown function, CYP11B2. To identify mutations in CYP11B1 associated with 11 beta-hydroxylase deficiency in Moroccan Jews, oligonucleotides were used that selectively amplified portions of CYP11B1 in polymerase chain reactions without amplifying CYP11B2. Sequence analysis of amplified fragments from one patient revealed a single base substitution in exon 8, codon 448 from CGC (arginine) to CAC (histidine). This residue is within the "heme binding" peptide that contains a cysteine that is a ligand to the heme group. The equivalent of Arg-448 is found in every known eukaryotic P450, and therefore it seems likely that a mutation of this residue would adversely affect enzymatic activity. 11 of 12 affected alleles from six Moroccan Jewish families carried the mutation in codon 448. This mutation is not normally present in CYP11B2 and thus appears to have arisen in CYP11B1 as a true point mutation rather than a gene conversion.

Prospectively randomized comparison of different mechanical aortic valves.

BACKGROUND: The aim of this prospectively randomized study was to evaluate the hemodynamic and functional outcomes after aortic valve replacement with 3 different bileaflet mechanical valves. METHODS AND RESULTS: Three hundred consecutive patients were randomly assigned to receive ATS (n=100), Carbomedics (n=100), or St Jude Medical Hemodynamic Plus (n=100) mechanical aortic valve replacement. There were no significant differences regarding patient age (average 61+/-8 years), body surface area (1.9+/-0.2 m(2)), left ventricular function (ejection fraction 0.59+/-0.17), and presence of aortic stenosis (90%, 89%, and 91%), respectively. All patients had postoperative as well as 6-month and 1-year follow-ups that included transthoracic echocardiography. Multivariate statistical analysis was performed. Implanted valve sizes were comparable at 24+/-2 (ATS), 23.7+/-1.6 (CM), and 23.6+/-1.9 (SJMHP) mm (NS). At 1-year follow-up, the following incidence of events was noted: death 3/1/1, all non-valve related; stroke 0/1/1; trivial transvalvular incompetence 3/3/2; paravalvular leak 2/3/2; and reoperation 0/1/1, respectively (NS). Transvalvular flow velocities were 2.5/2.6/2.4 m/s postoperatively (P:=0.03) and 2.4/2.4/2.3 m/s at 6-month follow-up, respectively (NS). There was a significant decrease in left ventricular mass for all patients but no significant differences among the groups. CONCLUSIONS: There are no clinically relevant differences among the tested bileaflet aortic valves. Regardless of valve type, there was a low complication rate. On the basis of these findings, all 3 bileaflet prostheses are well suited for aortic valve replacement.

Effects of arousing emotional scenes on the distribution of visuospatial attention: changes with aging and early subcortical vascular dementia.

BACKGROUND: The modulation of attention by emotionally arousing stimuli is highly important for each individual's social function. Disturbances of emotional processing are a supportive feature for the diagnosis of subcortical vascular dementia (SVD). We address here whether these disturbances might be useful as an early disease marker. METHODS: In order to examine the modulation of visual attention by emotionally arousing stimuli of different valence, 12 elderly patients with early SVD, 12 age-comparable healthy adults and 12 young healthy subjects were studied while looking at pairs of pictures from the International Affective Picture Battery that were either neutral-neutral, neutral-positive or neutral-negative in terms of emotional content. Eye movements were recorded with an infrared eye-tracking system. The direction of the first saccade and the dwell time during the 10 s of presentation were measured and compared among groups with parametric tests. RESULTS: All subjects showed a modulation of initial attentional orienting as well as a higher percentage of dwell time towards the pictures containing emotional material. Patients with SVD and old controls did not differ in either experimental measure. Young patients showed a stronger bias towards emotionally negative material than both groups of older individuals. CONCLUSIONS: Modulation of visuospatial attention is preserved in early SVD. This might have implications for therapeutic interventional approaches. A weakened sustained attention towards negative but not positive emotional pictures in the elderly is in accordance with the socioemotional selectivity theory, describing a relative selection of positive stimuli with aging.

Familial hyperkalemia, hypertension, and hyporeninemia with normal aldosterone levels. A tubular defect in potassium handling.

A 52-year-old man had hypertension, persistent hyperkalemia, and hyperchloremic metabolic acidosis; renal and adrenal functions were normal. Four other members of the family have the same findings. The patient's plasma aldosterone (PA) level was within normal range, though plasma renin activity (PRA) was undetectable. The ability to conserve sodium with increased endogenous aldosterone levels, and the inability to increase potassium excretion while exogenous mineralocorticoid (fludrocortisone acetate) was administered, indicated a distal tubular defect in potassium handling. Effective reduction of the hyperkalemia by K+ -Na+ exchange resin also corrected the acidosis and the hyperchloremia, suggesting that hyperkalemia may cause metabolic acidosis.

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers.

Amphiphilic block copolymers are well established as building blocks for the preparation of micellar drug carriers. Over the past decade, the effectiveness of such self-assembled drug delivery devices has been demonstrated numerous times. This review will discuss two approaches that can be used to further improve the effectiveness of amphiphilic block copolymer-based drug delivery systems. The first approach involves the chemical modification of the block copolymer building blocks. Several examples will be discussed of amphiphilic block copolymers modified with crosslinkable groups in order to increase the stability of the micellar drug carriers, or of block copolymers containing specific ligands that could ultimately allow targeted drug delivery. The second approach to improve the performance of micellar drug carriers is the addition of auxiliary agents. To illustrate this approach, the feasibility of channel proteins and metal (nano)particles to improve temporal control over the drug release process is discussed.

Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small-vessel disease.

BACKGROUND AND PURPOSE: Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. METHODS: In 16 patients (mean age 68+/-10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. RESULTS: Relative CBFV increase was significantly greater after pravastatin treatment (41.9+/-23.7% versus 55.7+/-18.3%, P=0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences. There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (beta=-0.64, P=0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. CONCLUSIONS: This pilot study provides the first evidence for a significant improvement of cerebral vasomotor reactivity by statin therapy in patients with cerebral small-vessel disease. The results may help to elucidate the preventive effect of statins and provide insights into the pathophysiology of cerebral small-vessel disease.

The natural history of salt-wasting disorders of adrenal and renal origin.

Twenty one patients with selective aldosterone deficiency due to type 2 corticosterone methyl-oxidase defect [hypoaldosteronism (HA)] and 7 with pseudohypoaldosteronism (PHA) were studied longitudinally for up to 18 yr. All individuals had spontaneous and progressive normalization of sodium and fluid balance with age. The severity of the clinical manifestations varied from acute salt-wasting crisis in infancy and unexplained short stature in childhood to an asymptomatic state in adults detectable only by biochemical studies. Infants with HA had extremely elevated plasma renin activity (PRA; 70-650 ng angiotensin 1/ml X h), which gradually decreased with age, and PRA was normal in adults. Cortisol followed a similar pattern, but marked elevations of plasma deoxycorticosterone (DOC; 28-553 ng/dl) and 18-hydroxycorticosterone (18-OHB; 650-6500 ng/dl) relative to aldosterone (3-29 ng/dl) persisted throughout life in all untreated patients. The plasma 18-OHB/aldosterone ratio, normally 6.2 +/- 3.5 (SD), ranged between 160-760. In contrast, patients with PHA had PRA (70-685 ng angiotensin 1/ml X h), DOC (56-1201 ng/dl), 18-OHB (650-6800 ng/dl), and aldosterone (150-2000 ng/dl) levels which all remained very elevated, but had normal 18-OHB/aldosterone ratios (6.9 +/- 5.1). Comparative studies in 14 untreated patients with 11 beta-hydroxylase deficiency, who had moderate to severe manifestations of mineralocorticoid excess, revealed DOC levels (38-1384 ng/dl) that were remarkably similar to those of patients with HA and PHA. PRA, DOC, and 18-OHB correlated significantly with each other during all variations in sodium balance (P less than 0.001). Sodium repletion partially suppressed these parameters in both disorders, but complete normalization was achieved only in HA when a mineralocorticoid was given. Although the degree of DOC and 18-OHB suppression was similar in all age groups, the changes in PRA were more marked in children than in adults since these were directly proportional to the initial elevations of PRA. Although angiotensin II and potassium increased plasma DOC and 18-OHB, dexamethasone failed to suppress them, indicating that these steroids originated predominantly from the zona glomerulosa. The spontaneous normalization of sodium balance is not due to quantitative differences in hormone secretion with age since the basic steroid abnormalities remain unchanged from infancy to adulthood.(ABSTRACT TRUNCATED AT 400 WORDS)

Absence of steroid biosynthetic defects in heterozygote individuals for classic 11 beta-hydroxylase deficiency due to a R448H mutation in the CYP11B1 gene.

Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxy-cortisol to cortisol) is responsible for less than 5% of cases of classic congenital adrenal hyperplasia, but it is relatively frequent in Israel, among Jews of Moroccan origin. Affected individuals have a single base substitution in exon 8 of CYP11B1 gene, codon 448, from CGC (arginine) to CAC (histidine) (R448H), a mutation that abolishes enzyme activity completely. We studied the hormonal response to ACTH stimulation in individuals genotyped to have the R448H mutation in one allele only (heterozygotes), and who were therefore assumed to have 50% of 11 beta-hydroxylase activity. No demonstrable hormonal abnormalities were found in the 6 adults (3 mothers and 3 fathers) and 2 sons studied, suggesting that a quantitatively reduced 11 beta-hydroxylase is still enough for normal adrenal biosynthesis.

A (R80Q) mutation in 17 beta-hydroxysteroid dehydrogenase type 3 gene among Arabs of Israel is associated with pseudohermaphroditism in males and normal asymptomatic females.

Four isozymes of steroid 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) encoded by different loci catalyze the reversible conversion of androstenedione to testosterone and that of estrone to estradiol. The 17 beta HSD type 3 (17 beta HSD3) isozyme is encoded by the 17 beta HSD3 gene on chromosome 9q22 and expressed only in testes. Inherited defects in the 17 beta HSD3 isozyme cause a form of male pseudohermaphroditism that is rare within the general population, but frequent among a highly inbred Arab population in the Gaza strip. A point mutation in exon 3, codon 80 of the 17 beta HSD3 gene, R80Q, caused by a single base substitution from CGG to CAG was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem, and Lod-Ramle. Twenty-one homozygotes were male pseudohermaphrodites (46,XY) with testicular 17 beta HSD3 deficiency, born with either female-looking external genitalia or various degrees of genital ambiguity. If not reassigned in infancy, they were reared as females until puberty, when marked virilization occurred, often leading to the spontaneous adoption of a male gender role. In contrast, the 3 homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia and normal sexual development, and revealed no biochemical evidence of 17 beta HSD3 deficiency. The molecular pattern in these families is compatible with an autosomal recessive mode of inheritance that is sex dependent.

Mechanisms of androgen production in male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency.

17 beta-Hydroxysteroid dehydrogenase (17 beta HSD) deficiency is a rare cause of male pseudohermaphroditism, but is a frequent disorder among a highly inbred Arab population in the Gaza strip. Affected individuals are born and reared as females until puberty, when marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender role. To investigate the mechanisms and site(s) of androgen production, we determined the gonadal and extragonadal steroid patterns in two postpubertal male pseudohermaphroditism patients, who were castrated and reared as females. Before castration, both patients had very high plasma levels of androstenedione (delta 4-A), normal or moderately low levels of testosterone (T), and significantly elevated delta 4-A/T ratios (P less than 0.01). Dihydrotestosterone (DHT) levels were normal or high, while the DHT/T ratios were lower than normal (P less than 0.01), suggesting enhanced 5 alpha-reductase activity. These abnormalities were much more severe in spermatic venous blood. 17 beta HSD deficiency was also found in the delta 5-pathway, by high dehydroepiandrosterone (DHEA) levels and very high dehydroxyepiandrosterone/delta 5-androstenediol (DHEA/delta 5-diol) ratios, and in peripheral tissue metabolites, by very high androsterone glucuronide/3 alpha-androstanediol glucuronide ratios (P less than 0.01). The estrogen pathway was also impaired (P less than 0.01), even though both estrone and estradiol levels were elevated. Gonadectomy significantly reduced all androgens and estrogens (P less than 0.01), but when compared to 42 castrated controls, both patients had lower delta 4-A and higher T levels. The delta 4-A/T ratio was lower than that in controls, indicating normal to enhanced extragonadal 17 beta HSD activity. A similar pattern was observed in the delta 5- and estrogen pathways. DHT levels were within normal limits, and 3 alpha-diol was moderately decreased. These data suggest that testicular 17 beta HSD activity is under a different genetic control from that in extragonadal tissues. Affected males lack the testicular enzyme, but their extragonadal 17 beta HSD activity is normal or enhanced. Together with enhanced 5 alpha-reductase activity, this represents a highly efficient compensatory mechanism for androgen and estrogen production after puberty.

A nonchromatographic radioimmunoassay for 17alpha-hydroxyprogesterone.

A radioimmunoassay is described for the measurement of 17alpha-hydroxyprogesterone in human plasma. We have employed the principle of "immunologic purification." 17-OHP and related steroids are bound to an excess of antiserum. Steroids with a low affinity for the antibody are extracted by ether. The 17-OHP is subsequently freed from antibody by acid hydrolysis and this extract is assayed by radioimmunoassay.

The nature of the defect in familial male pseudohermaphroditism in Arabs of Gaza.

Studies in six Arab individuals from Gaza with familial male pseudohermaphroditism (MPH) due to 17-ketoreductase deficiency revealed several metabolic aberrations associated with the disorder. Plasma LH, FSH, testosterone, and androstenedione concentrations were low in the two prepubertal patients. After hCG administration plasma androstenedione increased markedly. The four postpubertal MPH patients had very high plasma gonadotropin and androstenedione concentrations, the latter increasing further after hCG administration. Plasma testosterone concentrations in all six patients were moderately low or normal for age and increased little after hCG administration. Spermatic venous testosterone concentrations, measured in three adults, were within the normal range in two and low in one, while androstenedione concentrations were markedly elevated (15- to 32-fold) in all three patients. Kinetic analyses of progesterone and androstenedione metabolism were performed in testicular tissue of these patients and compared to the results in two control subjects. While testicular tissue from the two prepubertal patients metabolized progesterone only to androstenedione, and that to a limited extent, the tissue from the four postpubertal patients metabolized progesterone to 16 alpha- and 16 beta-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, androstenedione, and testosterone and metabolized androstenedione to testosterone. The Michaelis constants of these reactions were similar in the tissue from the MPH and the control subjects. The production of 16 alpha- plus 16 beta-hydroxyprogesterone was 5.4- to 10.3-fold greater, and 17-hydroxylase activity was 5.8- to 8.1-fold lower in the testes of the postpubertal MPH patients compared to values in the control subjects. The preference of androstenedione production through the delta 4- or delta 5-pathways was examined in the testes of two adult MPH patients using an equimolar concentration of [14C]progesterone and [3H]pregnenolone as substrates. While the flow of substrates in the control testes was equal or slightly greater through the delta 4-pathway, the delta 5-pathway predominated in the testes of the MPH patients. A large amount of dehydroepiandrosterone accumulated when NAD, the cofactor for 3 beta-hydroxysteroid dehydrogenase-isomerase, was omitted, supporting the contention that androstenedione was produced in the testes of the MPH patients mainly through the delta 5-pathway. Additional support for this suggestion was the finding that the 3H/14C ratio in androstenedione and testosterone produced from both substrates was 8 times higher in the testes from MPH patients than in those from the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)