Patterns of allele losses suggest the existence of five distinct regions of loh on chromosome 17 in breast cancer

Chromosome 17 is a frequent target during breast-cancer formation and progression. It has been shown to be affected by allele losses at multiple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of breast tumors. To this end we analyzed 151 pairs of tumor and cognate lymphocyte DNAs by Southern blotting with 5 RFLP or VNTR probes and by PCR at 8 CA repeat polymorphic loci for LOHs. Moreover, we studied DNA amplification of the evi2, erbB2, thra1, gcsf and rara genes. Data presented here point strongly to the existence of 5 distinct regions of allele losses on chromosome 17:2 on 17p, 3 on 17q. Of the 2 regions on 17p, one involves tp53 while the second is located more distally toward the telomere. LOH was found in 45.9% and 58.8% respectively. The 3 regions on 17q are located: (i) on the proximal portion of the long arm band q21, corresponding to the brcal region; (ii) in a central region defined by the marker D17S74; (iii) on the distal part of 17q (band q25) characterized by losses of the marker D17S24. Each of these regions presented respectively allele losses in 47.5%, 33.3% and 40.8% of the informative tumors. Whereas some tumors presented patterns of LOH consistent with the loss of a complete chromosomal arm or of large portions of the chromosome, a high proportion of the analyzed tumors showed interstitial losses. Amplifications were found in 15% of the tumors and were centered around erbB2. An altered chromosome 17 (bearing an LOH or a DNA amplification) was found in more than 80% of the breast tumor set analyzed here and multiple anomalies affecting this chromosome were often detected in the same sample.     

Trancranial Doppler Monitoring of Response to Therapy for Meningovascular Syphilis

Meningovascular syphilis is now quite uncommon, but there have been increasing reports in patients immunocompromised with human immunodeficiency virus. The response of syphilis affecting the central nervous system to antibiotic therapy remains a challenge. This is an even greater challenge in patients who have underlying compromise of the immune system. The authors present a 46-year-old male with recurrent stroke who was found to have cerebrospinal fluid compatible with syphilitic involvement of the central nervous system and a cerebral arteriogram, which revealed focal narrowing of the right middle cerebral artery. The baseline transcranial Doppler study demonstrated increased mean and peak flow velocity within the right middle cerebral artery. Despite a 10-day course of intravenous penicillin, with substantial improvement in the cerebrospinal fluid results, this flow velocity elevation persisted, in a remarkably consistent pattern, over a 4-month follow-up period. Thus, the involved vessel remained patent following treatment, but no clear resolution of the stenotic lesion was observed.     

Carcinosarcoma (malignant mixed tumor) of the parotid: Report of a case with a pure rhabdomyosarcoma component

Background. Carcinosarcoma or true malignant mixed tumor of the parotid gland is extremely rare, accounting for <1% of all salivary gland malignancies. Methods. A 63-year-old woman presented with a 5-cm right parotid mass which was resected with a radical parotidectomy and infratemporal fossa dissection. Results. The tumor contained two distinctive histologic patterns, that of a poorly differentiated ductal carcinoma and a pleomorphic rhabdomyosarcoma. Additionally, a residual focus of pleomorphic adenoma was present peripherally, Immunohistochemical and electron microscopic studies confirmed the skeletal muscle differentiation. Conclusions. The pattern of combined rhabdomyosarcoma and ductal carcinoma has not been previously reported and adds further evidence to the myoepithelial derivation of these tumors. © 1994 John Wiley & Sons, Inc.     

Mediating effects of social support on firefighters' sense of community and perceptions of care

This study examined the relationship between psychological sense of community, social‐support networks, and care‐giver stress and satisfaction among firefighters. No significant gender differences were obtained, but zero‐order correlates demonstrated significant relationships among all four variables. In examining the mediating effects of social‐support satisfaction, partial mediation for psychological sense of community on care‐giver satisfaction was determined, as well as full mediation for psychological sense of community on care‐giver stress. Therefore, firefighters who are satisfied with the support they receive may experience less stress with their care giving than those who experience low levels of support satisfaction. Future studies should assess these relationships more extensively in other areas of civic responsibility among public‐service employees to delineate effective support avenues. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 121–126, 2004.     

Chronic Progressive Autonomic Dysfunction in a Dog

A 3.5‐year‐old intact male American Pit Bull was presented because of urinary incontinence and dysuria. Constipation, followed by diarrhoea, ocular disturbances and finally regurgitation developed over the next 4 years. Autonomic dysfunction was evidenced by clinical presentation, as well as positive ophthalmic pilocarpine test and subnormal Schirmer tear test. Diagnosis, however, was established through histopathological and immunohistochemical examination. Lesions attributable to inflammatory degenerative neuropathy of the autonomic ganglia, which represents one of the various types of human autonomic failure, were detected.     

Monitoring of Neuromuscular Blockade at the P6 Acupuncture Point Reduces the Incidence of Postoperative Nausea and Vomiting

Background: Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.

Methods: In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.

Results: No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).     

Inzidentalome der Nebenniere

Adrenal incidentalomas are clinically inapparent masses detected incidentally with imaging studies conducted for other reasons. They are relatively common and require structured diagnostic workup. In many cases surveillance is warranted. The diagnostic workflow has to reveal whether the mass is hormonally functioning and/or if there is evidence of malignancy. If the tumor is functionally silent and not larger than 4 cm, surveillance is warranted. Functioning tumors and masses larger than 6 cm have to be resected. Fine-needle aspiration biopsy is indicated in very rare cases, but pheochromocytoma has to be ruled out first.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.