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.     

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).     

Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females.

Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease.     

N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis, increases blood pressure in rats and reverses the pregnancy-induced refractoriness to vasopressor agents.

OBJECTIVE: With N omega-nitro-L-arginine, a potent inhibitor of nitric oxide synthesis, we tested the hypothesis that nitric oxide plays a functional role in the blunted pressor responsiveness seen during pregnancy. STUDY DESIGN: A group of six pregnant rats were instrumented on the fourteenth day of gestation and studied on days 19 and 20, as well as 7 days post partum. Another group of six virgin rats were similarly prepared and used 5 days after surgery. Blood pressure and heart rate were monitored in conscious freely moving animals before and during the administration of drugs or placebo. Results were analyzed, by one-way repeated-measures analysis of variance, with Dunnett's t test, or by paired t test where applicable. RESULTS: Basal mean arterial pressure and heart rate were 90.8 +/- 3.0 mm Hg and 330 +/- 6 beats/min in pregnant animals and 107.1 +/- 3.2 mm Hg and 315 +/- 7 beats/min in nonpregnant animals. Pressor responses to angiotensin II, vasopressin, and norepinephrine were attenuated in gravid animals. Infusion of N omega-nitro-L-arginine significantly and in a dose-dependent manner increased mean arterial pressure and reduced heart rate. These effects could be completely reversed by L-arginine administration. Changes in mean arterial pressure were higher during pregnancy as compared with postpartum values. N omega-nitro-L-arginine infusion potentiated pressor responses to all three vasopressors, resulting in dose-response curves that were significantly shifted to the left, making them virtually identical in pregnant and postpartum rats. CONCLUSION: Our data support the emerging view that nitric oxide plays a key role in the regulation of blood pressure during pregnancy.     

Cholinesterases and peanut agglutinin binding related to cell proliferation and axonal growth in embryonic chick limbs

Embryonic cholinesterases are assigned important functions during morphogenesis. Here we describe the expression of butyrylcholinesterase and acetylcholinesterase, and the binding of peanut agglutinin, and relate the results to mitotic activity in chick wing and leg buds from embryonic day 4 to embryonic day 9. During early stages, butyrylcholinesterase is elevated in cells under the apical ectodermal ridge and around invading motoraxons, while acetylcholinesterase is found in the chondrogenic core, on motoraxons and along the ectoderm. Peanut agglutinin binds to the apical ectodermal ridge and most prominently to the chondrogenic core. Measurements of thymidine incorporation and enzyme activities were consistent with our histological findings. Butyrylcholinesterase is concentrated near proliferative zones and periods, while acetylcholinesterase is associated with low proliferative activity. At late stages of limb development, acetylcholinesterase is concentrated in muscles and nonexistent within bones, while butyrylcholinesterase shows an inverse pattern. Thus, as in other systems, in limb formation butyrylcholinesterase is a transmitotic marker preceding differentiation, acetylcholinesterase is found on navigating axons, while peanut agglutinin appears in non-invaded regions. These data suggest roles for cholinesterases as positive regulators and peanut-agglutinin-binding proteins as negative regulators of neural differentiation.