Immunohistochemically Detected p53 Mutations in Epithelial Tumors and Results of Treatment with Chemotherapy and Radiotherapy A Treatment-Specific Overview of the Clinical Data

BACKGROUND: The aim was to ascertain whether many hundreds of clinical reports over the last decade are consistent with the prediction of a poorer outcome in cancer patients with p53 abnormalities treated with cytotoxic drugs and radiation. MATERIAL AND METHOD: There are 301 studies on the influence of p53 overexpression published through summer 2000, in which chemotherapy or radiotherapy was used alone or in combination with surgery. From 45 reports meeting stringent selection rules, comparison groups are identified in whom the same measure of outcome was reported for the same treatment applied to the same tumor, with results corrected for important prognostic factors. Metaanalysis techniques are then applied to the comparison groups. Attention was limited to reports using immunohistochemical techniques, to form comparison groups of sufficient size. RESULTS: Four comparison groups were identified by treatment and endpoint: 1) Stage I-III breast cancer (surgery and chemotherapy, disease-free survival, seven studies); 2) stage I-III breast cancer (surgery and chemotherapy, overall survival, six studies); 3) stage II-IV head and neck cancer (radiotherapy and chemotherapy, overall survival, five studies); 4) FIGO I-IV ovarian cancer (surgery and chemotherapy, overall survival, six studies). In the breast (disease-free survival) and ovarian (overall survival) comparison groups, the hazard ratio for a deleterious effect of p53 overexpression was significant or marginally significant, depending on assumed ranges for unreported hazard ratios in non-significant studies. CONCLUSIONS: Despite the many caveats related to metaanalysis applied to retrospective data, high variability of immunohistochemical technique, etc., a nearly significant negative effect of p53 overexpression on outcome of treatment with cytotoxic drugs and radiation emerges in the few studies where heterogeneity can be sufficiently reduced or accounted for.     

Diverticulite solitaire du c?lon droit

Diverticula of the right colon are a rare clinical entity. Diverticulitis can occur with these lesions, but the diagnosis is frequently missed as the presentation is similar to that of acute appendicitis and can mimic other acute intraabdominal infections such as cholecystitis. The authors report a case of solitary diverticulitis of the right colon in a young woman, an incidental discovery during surgery for suspected appendicitis, with emphasis on the diagnostic and therapeutic modalities.     

Do topical antibiotics reduce exit site infection rates and peritonitis episodes in peritoneal dialysis patients? The Pan Thames Renal Audit

Background and objectives: Peritonitis is the major cause of peritoneal dialysis (PD) technique failure. Prophylactic topical antibiotics have been reported to reduce peritoneal dialysis catheter exit site infections (ESI) and peritonitis rates. Methods: We audited the effect of different exit site practices in the 12 Pan Thames and South East England PD centres, on ESIs and peritonitis between 2005 and 2008. Results: PD patients used prophylactic mupirocin (n=1,270), gentamicin (n=502) and no prophylactic antibiotics (n=1,203); annualised ESI rates were reduced with mupirocin (median 0.18, interquartile range [IQR] 0.13-0.23, patient episodes per year, vs. median 0.32, IQR 0.24-0.69, for no antibiotic prophylaxis, p<0.01). Gentamicin treatment was not significantly lower (median 0.29, IQR 0.21-0.47). Staphylococcal ESIs accounted for 39.6% in the no antibiotic group and fell to 25.7% with mupirocin and 28.2% with gentamicin. Despite the reduction in ESIs, there was no significant reduction in peritonitis rates (no antibiotics: median 0.56, IQR 0.5-0.65; mupirocin: median 0.55, IQR 0.53-0.75; and gentamicin: median 0.47, IQR 0.32-0.65). In particular, mupirocin did not reduce Staphylococcus aureus peritonitis rates. Conclusions: Topical antibiotics have been reported to reduce both ESI and peritonitis rates in controlled trials, and although in this audit of routine clinical practice, topical mupirocin did reduce overall ESI rates and both mupirocin and gentamicin reduced S. aureus ESIs, neither reduced overall peritonitis rates.     

Calmodulin antagonists inhibit and phorbol esters enhance transferrin endocytosis and iron uptake by immature erythroid cells

Seven antagonists of the calcium-binding protein calmodulin were found to inhibit iron and transferrin uptake by reticulocytes. This inhibition could be completely accounted for by inhibition of the endocytosis and exocytosis of transferrin. When four of the antagonists were tested with the nucleated erythroid cells from the liver of the fetal rat, inhibition of iron uptake was also observed but at higher concentrations than required for the same degree of inhibition with reticulocytes. The tumor promoters phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB) were shown to increase the rates of iron and transferrin uptake by reticulocytes and fetal liver erythroid cells by accelerating the rates of transferrin endocytosis and exocytosis. Since these substances are known to stimulate the calcium-activated enzyme protein kinase C while calmodulin antagonists are inhibitory, it is concluded that this enzyme plays an important role in the endocytosis and intracellular cycling of transferrin, and iron uptake by immature erythroid cells. However, the possibilities that calmodulin is also involved or that the inhibitory effects of the calmodulin antagonists are due to nonspecific actions on the cell membrane cannot be excluded.     

Control of sympathetic nerve activity by vagal mechanoreflexes is blunted in heart failure.

BACKGROUND. Previous studies have documented abnormalities of arterial baroreflexes in animals and patients with congestive heart failure. This study determined whether cardiopulmonary reflex control of sympathetic nerve activity was abnormal in a canine model of low-output heart failure induced by rapid ventricular pacing. METHODS AND RESULTS. We stimulated mechanoreceptors throughout the cardiopulmonary region by volume expansion and left atrial mechanoreceptors selectively by inflating small balloons at the junctions of the pulmonary veins and left atrium. Responses of renal sympathetic nerve activity and left atrial and systemic arterial pressures were recorded. In the control group, 15% volume expansion raised left atrial pressure 3.5 +/- 0.8 mm Hg and resulted in a 70 +/- 8% reduction in renal nerve activity. In the heart failure group, 15% volume expansion resulted in a 6.8 +/- 3.0 mm Hg rise in left atrial pressure with only a 16 +/- 20% reduction in renal nerve activity (p < 0.01). When volume expansion was performed after pretreatment with hemorrhage to lower left atrial pressure to the normal range in the heart failure group, the markedly attenuated response in the heart failure group persisted. After vagotomy, volume expansion elicited no change in renal nerve activity. Inflation of the atrial balloons caused a 28 +/- 9% reduction in renal sympathetic nerve activity and a 13 +/- 4 mm Hg decrease in arterial pressure in the control group. Renal nerve activity (-5 +/- 3%) and mean arterial pressure (-1 +/- 1 mm Hg) did not change with balloon inflation in the heart failure group. CONCLUSIONS. We conclude that dogs with low-output heart failure exhibit marked attenuation of cardiopulmonary mechanoreflex control of sympathetic nerve activity. This attenuated response is mediated via cardiac vagal afferent fibers and is due to either abnormalities in cardiopulmonary baroreceptors or abnormalities in the central nervous system.     

Responses of sympathetic nerves to programmed ventricular stimulation

Ventricular arrhythmias generally result in a decrease in arterial pressure and increases in atrial and ventricular filling pressures which would be expected to induce reflex changes in efferent sympathetic nerve activity to the heart and peripheral circulation. Experiments were performed in 14 anesthetized dogs in order to determine whether programmed ventricular stimulation produces changes in renal sympathetic nerve activity; quantitate these changes; and determine the cardiovascular reflexes that mediate these changes. Arterial and right atrial pressures and renal sympathetic nerve activity were recorded in dogs before and after administration of single and double programmed ventricular stimuli. In a group of 10 dogs after single extrastimuli, diastolic arterial pressure decreased by 18 +/- 2 mm Hg (mean +/- SEM) while renal sympathetic nerve activity increased by 39 +/- 15 impulses/s. These changes were directly related to degree of stimulus prematurity. After double extrastimuli, diastolic arterial pressure decreased by 22 +/- 2 mm Hg whereas renal sympathetic activity increased by 55 +/- 8 impulses/s. In an additional four dogs, double extrastimuli decreased arterial pressure (-34 +/- 1 mm Hg) and increased cardiac (86 +/- 16%) and renal (82 +/- 12%) sympathetic traffic. After sinoaortic denervation, neither single nor double programmed ventricular stimuli resulted in alterations in cardiac or renal sympathetic nerve activity. It is concluded that the decreased arterial pressure caused by single and double programmed ventricular stimuli leads to increases in cardiac and renal sympathetic nerve activity that are mediated by sinoaortic baroreflexes.     

Afferent reinnervation of the autotransplanted heart in dogs

Patients have been observed with a chest pain syndrome after cardiac transplantation. For this pain to be cardiac in origin the afferent nerves carrying sensory information from the heart would have to reinnervate the heart. A previous study in dogs indicated that afferent reinnervation is uncommon during the first 2 years after transplantation. The purpose of this study was to determine whether afferent reinnervation of the heart occurs in the long term. The decreases in arterial pressure and renal nerve activity resulting from chemical stimulation of left ventricular sensory receptors with vagal afferents with cryptenamine (veratrum alkaloid) were assessed in three dogs 8 to 12 years and in four dogs 6 to 8 weeks after cardiac autotransplantation and in six sham-operated dogs (thoracotomy-pericardiotomy 6 to 8 weeks before study). Responses of renal nerve activity to physiologic stimulation of cardiac receptors by volume expansion were also determined. Left ventricular cryptenamine inhibited renal nerve activity by 72 +/- 8% in dogs with long-term and by 10 +/- 6% in dogs with short-term autotransplantation and by 92 +/- 5% in sham-operated dogs. Decreases in mean arterial pressure in these groups were 34 +/- 4, 11 +/- 3 and 67 +/- 16 mm Hg, respectively. Volume expansion inhibited renal nerve activity in long-term autotransplant (43%) and sham-operated (48%) groups but less in the short-term transplant group (33%) for comparable increases in cardiac filling pressure. It is concluded that in dogs there is extensive afferent reinnervation of the long-term autotransplanted heart that results in relatively normal cardiopulmonary baroreflex responses to volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laparoscopic cholecystectomy: a multicenter study

Laparoscopic cholecystectomy has been developed as an alternative to open cholecystectomy for the treatment of symptomatic cholelithiasis. A collaborative study of 261 patients undergoing laparoscopic cholecystectomy at three Texas institutions was performed to determine the effectiveness and safety of this technique. There were 65 males and 196 females with a mean age of 49 years (range 17-94 years). Acute cholecystitis was present in 38 patients and chronic cholecystitis in 223 patients. Mean length of surgery was 80 minutes (20 min to 4 hr). Fifteen patients were converted to the open technique intraoperatively due to bleeding, adhesions, or difficulty of dissection. There were no perioperative deaths and morbidity was 3% including urinary retention, small bowel obstruction, arrhythmia, wound infection, and bile leakage. There were no common duct injuries. Hospitalization ranged from outpatient surgery to 7 postoperative days with a mean of 1.2 days. We conclude that laparoscopic cholecystectomy can be performed safely and with low morbidity and offers shorter hospitalization and postoperative recovery.