Applicability of the SHBG androgen sensitivity test in the differential diagnosis of 46,XY gonadal dysgenesis, true hermaphroditism, and androgen insensitivity syndrome.

The sex hormone-binding globulin (SHBG) androgen sensitivity test has been used as a simple method to assess androgen receptor function in vivo. After a short term oral administration of the anabolic-androgenic steroid stanozolol the mean nadir serum concentration of SHBG is used as a measure of androgen response. We performed this test in order to evaluate its applicability in 16 patients with intersexual genital status: eleven with 46,XY gonadal dysgenesis and three with true hermaphroditism (group I), and in two patients with androgen insensitivity syndrome (AIS, group II). Ten healthy adult volunteers served as controls. In the two patients with AIS (group II) we found a diminished decrease of serum SHBG to 80.1 % and 80.7 %, respectively, indicating slight residual androgen responsiveness. In eleven patients of group I who were not on hormone replacement therapy, a mean nadir level of 51.7 +/- 8.7 % was found. In the controls the mean nadir serum SHBG level was significantly higher (62.7 +/- 5.2 %), probably due to interference of endogenous androgens and contraceptive medication with the stanozolol-induced SHBG decrease. In three gonadectomised patients who were on hormone replacement therapy the initial SHBG concentration was increased (513.5 +/- 239.1 nmol/l); the mean nadir SHBG concentration of 45.6 +/- 9.8 % of the initial level indicates an increased sensitivity of the test in patients in whom the counteracting ovarian androgens are absent. Our findings confirm that under standard test conditions the SHBG androgen sensitivity test is a simple diagnostic tool for the detection of androgen receptor malfunction.     

Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with onset in childhood and rapid progression. There is no causative and insufficient symptomatic drug therapy. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been reported to improve motor function. Most case reports, however, are limited to short observational periods. The impact of DBS on the progression and life expectancy in PKAN is unknown. We present a 5-year outcome and video documentation of bilateral GPi-DBS of an adolescent patient suffering from genetically defined PKAN.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Quantitative whole-body autoradiographic analysis of the tissue distribution of orally-administered [14C]cholesterol in hypercholesterolemic rats

The cholesterol-fed rat model has been used to examine the distribution of radiolabeled cholesterol by whole-body autoradiographic and quantitative videodensitometric methods. Animals were fed a hypercholesterolemic diet for 7 days, and were subsequently killed at 3, 6, 12, 24, or 72 h following a single oral dose of [14C]cholesterol. Maximum blood and tissue levels were observed at 12 h, while liver and adrenals were the most intensely labeled tissues. Liver maintained consistently high levels over the course of the study, while activity in other tissues declined moderately by 72 h, indicating the long half-life of cholesterol radioequivalents in tissue. The results of these experiments suggest that autoradiographic examination of cholesterol distribution in animals treated with pharmaceutical agents designed to modify cholesterol absorption or clearance will be useful in providing supplemental or confirmatory information on the drugs' mode of action.     

Multiple cutaneous granular cell tumors in childhood

We have described two children with multiple cutaneous granular cell tumors (GCT) and have reviewed the literature. Multiple tumors of the skin are relatively rare, especially in children, with only 18 pediatric cases previously reported. Surgical excision of rapidly growing or symptomatic lesions is the treatment of choice. In these two children with multiple GCT, three lesions were excised. Specific stains for enolase and S-100 protein clearly demarcated tumor margins after surgical excision. Despite intensive investigation, the histogenesis of this tumor is still in dispute. The most tenable theory at this time is that these tumors are derived either directly from Schwann cells or from undifferentiated cells developing neural characteristics.     

Effect of labor and delivery on neonatal polymorphonuclear leukocyte number and function.

The ability of the neonate to mount an adequate polymorphonuclear leukocyte (PMN) response, either quantitatively or functionally, is impaired. To assess whether neonatal PMN number and function are altered by labor and delivery, three groups of infants were studied: cesarean section without labor (10), cesarean section after labor (10), and vaginal delivery (11). PMN counts were higher in the groups undergoing labor (p less than 0.01) compared with the cesarean section without labor group. Similarly, the labor groups had evidence of complement activation (increased C3a desarg) compared with the cesarean section without labor group. No differences were noted between the groups in measures of PMN motility (chemokinesis or chemotaxis) or PMN degranulation (plasma lysozyme), suggesting that normal labor and delivery does not contribute to the general PMN dysfunction of the neonate.     

Percutaneous transluminal coronary angioplasty. A growing surgical problem

The incidence of prior percutaneous transluminal coronary angioplasty in surgical cases is nearly doubling yearly. In 1985, 11.4% of our bypass patients had one or more prior angioplasties. One hundred thirty-five patients with prior angioplasty are compared to 2,205 patients without angioplasty undergoing surgical revascularization. The mortality is 3.2 times higher in the angioplasty patients than in the control patients and the perioperative infarction rate is 2.5 times higher. Forty-four patients were taken directly to the operating room from the catheterization laboratory, 50 were operated on within 10 days, and 41 underwent operation more than 10 days after angioplasty. All of these late failures were of the lesion previously dilated. The infarction rate was less in patients taken immediately to the operating room on an emergency basis than in those whose operation was delayed up to 10 days (30% versus 70%). All patients who died had angioplasty of the anterior descending coronary artery. Angioplasty of this artery increases operative mortality should surgical treatment become necessary acutely. Patients should be informed before angioplasty of the increased surgical risks after a failed angioplasty procedure.     

What is the visual field?]

Eye movements were recorded in the course of visual field determination. The behaviour of the eye is various in different persons, defying any rule, except, contrary to the definition of the visual field, it does not remain immobile but executes one or more saccades. Discussing the results the authors present a new concept of the visual field.     

Granulomatous interstitial nephritis after nonsteroidal anti-inflammatory drugs

Electrolyte and renal hemodynamic imbalance, acute interstitial nephritis with nephrotic-range proteinuria, papillary necrosis, tubular necrosis, and vasculitis are complications after intake of nonsteroidal anti-inflammatory drugs (NSAID). We report on 2 cases of biopsy-proven granulomatous interstitial nephritis with rapidly progressing renal insufficiency. Patient 1 was on ketoprofen for 7 months and indomethacin for 10 weeks before admission to hospital. The medication was not discontinued and renal insufficiency progressed to end-stage renal failure. Renal function did not respond to steroid and tuberculostatic treatment. Patient 2 was on diclofenac for 6 months and indomethacin for 7 weeks before admission to hospital. These drugs were withdrawn at diagnosis and renal function rapidly improved. We conclude that granulomatous interstitial nephritis may be a complication of NSAID medication indicating a cell-mediated immunologic disorder. False diagnosis (sarcoidosis, tuberculosis) may lead to end-stage renal disease (case 1). Discontinuation of medication obviates further therapy (case 2).