Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells

p53 mutation is commonly associated with high-grade, high-stage human urothelial carcinomas. Recent studies suggest that p53 mutation in low- grade, low-stage bladder carcinomas may be correlated with the progression of the disease. In the present study, we used antisense RNA methodology in vitro to evaluate the significance of the loss of p53 function at an early stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA in antisense orientation. The transfection resulted in a significant reduction in p53 mRNA expression and protein synthesis, in stimulation of anchorage- dependent growth, and in acquisition of anchorage-independent growth potential. Three such clones, when tested in athymic nude mice, all formed muscle-invasive, high-grade transitional cell carcinomas at s.c. injection sites. When cells were inoculated into an orthotopic site (urinary bladder), one of two antisense transfectants tested formed bulky tumors in the bladder in all seven nude mice and metastases to lungs in three of the seven mice. Analysis of these cells revealed a decrease in the expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene product. Phosphorylation of Rb protein was not inhibited when the cells were starved. No significant difference was observed in the expression of p16 protein. In cell cycle analysis, all antisense transfectants tested escaped from G1 arrest by starvation. Furthermore, secretion of interleukin (IL)-6 into culture medium was increased significantly. Treatment with anti-IL-6 antibody suppressed anchorage-dependent growth. This study directly demonstrates that the loss of p53 function at an early stage of urothelial carcinogenesis may result in acquisition of a malignant phenotype by regulating IL-6 production as well as cell cycle related genes.      

Interaction of the C-terminal tail region of the metabotropic glutamate receptor 7 with the protein kinase C substrate PICK1

Group III metabotropic glutamate receptors (mGluRs) are highly enriched in the presynaptic terminals of glutamatergic synapses where they mediate feedback inhibition of neurotransmitter release. Here, we used the yeast two-hybrid system to identify a direct interaction of the C-terminal tail region of mGluR7 with the rat homologue of the protein kinase C substrate PICK1. This interaction is specifically mediated by the very C-terminal amino acids of the receptor and can be reconstituted in human embryonic kidney 293 cells by transfection of full-length mGluR7 and PICK1 cDNAs. Quantitative beta-galactosidase assays revealed that among the different group III mGluRs, mGluR7 is the major PICK1 binding partner although other subfamily members can also interact with PICK1. These data indicate that PDZ domain-containing proteins might contribute to the presynaptic localization of group III mGluRs.     

Indirect fluorescence laryngoscopy in the diagnosis of precancerous and cancerous laryngeal lesions

Indirect fluorescence endoscopy of the larynx has proven to facilitate the detection and delineation of precancerous and cancerous lesion. The different methods are easy to handle and can be performed on an outpatient basis. Early diagnosis of laryngeal cancer and its precursor lesions is simplified. The aim of the present study is to compare indirect autofluorescence laryngoscopy to 5-ALA-induced PPIX fluorescence laryngoscopy. In a prospective study, 56 patients with suspected precancerous or cancerous lesions were primarily investigated by indirect autofluorescence laryngoscopy. In a second step 5-ALA-NaCl (0.6%) was topically applied to the larynx by inhalation, and indirect fluorescence laryngoscopy repeated 2 h after application. Autofluorescence as well as 5-ALA-induced fluorescence was induced by filtered light (375–440 nm) of a xenon short arc lamp and processed by a CCD camera system (D-light-AF System, Storz, Tuttlingen, Germany). White-light and fluorescence images were digitally recorded, immediately assessed for diagnosis and finally compared to pathohistological findings. Inconspicuous laryngeal mucosa presented a typical green fluorescence signal in autofluorescence endoscopy, which turned blue during 5-ALA-laryngoscopy. Precancerous and cancerous lesions displayed a loss of autofluorescence in autofluorescence endoscopy whereas increased protoporphyrin IX fluorescence could be observed in 5-ALA laryngoscopy. Both imaging techniques were suitable to distinguish benign from precancerous or cancerous lesions. In contrast PPIX fluorescence was easily recognized in scarred vocal folds. According to our results, both non-invasive fluorescence imaging techniques are useful in the early diagnosis of laryngeal cancer. Moreover autofluorescence can be used immediately without drug application and possible side effects. 5-ALA-induced fluorescence seems to be more suited for diagnostic examination of mucosal lesions in recurrent precancerous and cancerous lesions after surgery.     

Survey of sibling and peer visitation policies in southern California hospitals

A survey of southern California hospitals identified current visitation policies and the rationale for the restrictions of siblings and peers. Questionnaires mailed to the nursing administrators of 212 hospitals having designated pediatric beds indicated that the majority allowed some form of sibling visitation. The rationales for restriction most frequently given were prevention of infection and spread of communicable disease. The results indicate a gap between sibling visitation research and the theoretical rationale given to support restrictive policies.     

Nicht adjustierbare Bänder zur Therapie der männlichen Belastungsharninkontinenz

Even though the artificial sphincter is still the treatment of choice in the surgical therapy of male stress urinary incontinence, recent developments have introduced numerous minimally invasive treatment options with acceptable clinical results. The male slings have been included into the EAU guidelines for treatment of male stress urinary incontinence. A distinct choice of patients and treatment options will lead to the highest chance of success. Besides the adjustable compressive slings, the non-adjustable and non-compressive AdVance® Sling offers a possible option for a functional approach to treatmentratio. A critical assessment of all these methods remains essential and prospective randomized trials are still missing.