Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease

Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene involved has been localized to chromosome 10q22-23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and, by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein. Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype. In 10 patients no mutation could be detected so far. In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity.      

The predictors of red cell transfusions in total hip arthroplasties

BACKGROUND: Most blood crossmatched in a hospital blood bank is for surgical patients, and the majority is never transfused. The maximal standard blood order schedule is used to promote efficient ordering practices for surgical patients. STUDY DESIGN and METHODS: To ascertain the predictors of red cell transfusions for patients undergoing total hip arthroplasty, the charts of 299 adult patients undergoing primary and revision total hip arthroplasty were reviewed. A surgical blood order equation was developed for calculating the number of units of red cells that should be ordered. Stepwise regression analysis was used to determine which patient-and-case-related variables should be considered in the surgical blood order equation. RESULTS: The significant indicators for allogeneic red cell transfusion to patients on the day of total hip arthroplasty were preoperative hemoglobin concentration, weight, age, estimated blood loss, and aspirin use. The surgical blood order equation would result in a lower crossmatch-to-transfusion ratio than would the maximal standard blood order schedule (1.23 vs. 3.14). Costs were also lower with the surgical blood order equation. CONCLUSION: Incorporation of patient factors resulted in increased efficiency of blood-ordering practices in total hip arthroplasty.     

Chromosomal assignment of the human thrombin receptor gene: localization to region q13 of chromosome 5

A functional thrombin receptor (TR) structurally related to other members of the seven-transmembrane receptor family has been isolated from diverse cellular types intimately involved in the regulation of the thrombotic response. This receptor recapitulates many of the previously identified sequelae of thrombin-mediated cell activation phenomenon, and requires proteolytic cleavage for downstream effector- response coupling events. Using two complementary approaches, we have now completed the chromosomal assignment of the human thrombin receptor gene. Discordancy analysis of polymerase chain reaction products from a human-rodent hybrid cell mapping panel assigned the sequence to human chromosome 5 with no observed discordancies. Cytogenetic localization using fluorescence in situ hybridization on human metaphase chromosomes specifically localized the human TR gene to region q13 of chromosome 5, confirming its presence as a single-locus gene in the human genome. The chromosomal localization of the human TR gene is at or contiguous with the proximal breakpoint site identified in the majority of patients with the 5q- syndrome (dysmegakaryocytopoiesis and refractory anemia).     

Glucocorticoids inhibit apoptosis of human neutrophils

Human neutrophils rapidly undergo apoptotic cell death. Because glucocorticoids are known to modulate an array of neutrophil functional activities as well as induce rapid apoptosis in susceptible lymphocyte populations, we have examined the effects of glucocorticoids on apoptosis in mature human neutrophils. In cultures of neutrophils maintained in vitro, the glucocorticoids, dexamethasone, 6 alpha- methylprednisolone, and hydrocortisone, inhibited the development of apoptotic morphology by 59% to 90% when assessed at 12, 24, and 48 hours. In contrast, corticosteroids lacking anti-inflammatory activity and progesterone failed to affect development of the morphologic features of apoptosis. The concentration of dexamethasone required to reduce apoptosis by 50% at 24 hours was approximately 5 x 10(-8) mol/L, a concentration that is achievable in plasma after dexamethasone treatment. Dexamethasone (10(-6) mol/L), but not progesterone, reduced the percentage of hypodiploid (apoptotic) nuclei by 40% to 90% over this time course. Similarly, dexamethasone reduced the DNA cleavage associated with apoptosis and prolonged the viability of neutrophils maintained in culture for 12 to 48 hours. Glucocorticoid-mediated modulation of neutrophil apoptosis was qualitatively similar, but lesser in magnitude, when compared with the effects of granulocyte colony-stimulating factor (100 ng/mL). Thus, glucocorticoids exert a protective effect on human neutrophil survival by delaying apoptosis.     

Self-expanding metallic stent as a bridge to surgery versus emergency resection for obstructing left-sided colorectal cancer: A case-matched study

This study aimed to compare the outcomes of patients who suffered from obstructing left-sided colorectal cancer, treated with self-expanding metallic stent (SEMS) as a bridge to surgery, with those who underwent emergency operation. Twenty patients who had acute obstruction due to left-sided colorectal cancer underwent surgical resection after insertion of SEMS (group I) were matched to 40 patients with emergency colonic resection (group II). The two groups were compared for the incidence of primary anastomosis, stoma rate, hospital stay, duration of intensive care, postoperative morbidity, and mortality. Both groups had similar preoperative comorbidity and stage of disease, but the tumors in group I were more distally located (P<0.001). In group I, one patient developed colon perforation and required Hartmann’s operation. All the other patients underwent elective operation with primary anastomosis. In group II, primary anastomosis was performed in 29 patients (72.5%; P=0.047). The operative mortality of group I and group II was 5% and 12.5%, respectively (P=0.653). Significantly shorter median postoperative hospital stay and median stay in the intensive care unit (ICU) were observed in group I (9 days [range, 5–39 days] vs. 12 days [range, 8–49 days], P=0.015 and 0 day [range, 0–17 days] vs. 0.5 day [range, 0–18 days], P=0.022, respectively). There were no differences in hospital mortality (P=0.653) or 30-day mortality (P=0.653). Both groups had similar reoperation rates, surgical complications, and medical complications. When compared with emergency resection, insertion of SEMS as a bridge to surgery for obstructing left-sided colorectal cancer is associated with a higher rate of primary anastomosis as well as a better outcome in terms of hospital stay and stay in the ICU. The wider application of this treatment option for obstructing colorectal cancer warranted further studies. Presented at Digestive Disease Week, SSAT/ASCRS Joint Symposium, Forty-Sixth Annual Meeting of the Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005.     

Epigenetic change in e-cardherin and COX-2 to predict chronic periodontitis

Background  

DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2) in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis.     

Intratesticular varicocele

Extratesticular varicocele is a common clinical condition, occurring in up to 20% of the normal adult male population. It is characterized by dilatation of the veins of the spermatic cord and has well‐described sonographic appearances. Intratesticular varicocele is characterized by dilated intratesticular veins and is extremely rare. It usually, but not always, occurs in association with an ipsilateral extratesticular varicocele. We describe the sonographic and colour Doppler appearances of this poorly described entity in a middle‐aged man referred for evaluation of a painful left testicular swelling.