Impact of Pelvic Radiotherapy on Morbidity and Durability of Sphincter Preservation After Coloanal Anastomosis for Rectal Cancers

Purpose This study was designed to assess the impact of pelvic radiotherapy on the incidence of complications and colostomy-free survival of patients after a coloanal anastomosis for rectal cancer. Methods A total of 192 patients underwent a coloanal anastomosis between 1982 and 2001: 87 patients did not receive pelvic radiotherapy; 105 patients received pelvic radiotherapy (39 preoperative and 66 postoperative). Early and late complications requiring surgical intervention and the colostomy-free survival rate were assessed by retrospective review of patient records. Results After a median follow-up of 62 months, 151 patients were alive. The most frequent complication was development of an anastomotic stricture (5-year rate of a stricture, 16 percent; 95 percent confidence interval, 10–21). Patients receiving pelvic radiotherapy had a higher rate of complications other than anastomotic strictures, including fecal incontinence, fistulas, abscesses, and bowel obstructions compared with patients not receiving pelvic radiotherapy (5-year rate: 20 percent (95 percent confidence interval, 10–29) vs. 5 percent (95 percent confidence interval, 0–10); P = 0.001). Patients receiving pelvic radiotherapy had a lower colostomy-free survival than did patients not receiving pelvic radiotherapy (5-year colostomy-free rate: 72 percent (95 percent confidence interval, 62–84) vs. 92 percent (95 percent confidence interval, 86–98); P < 0.001). There was no significant difference in the colostomy-free survival of patients receiving preoperative and postoperative pelvic radiotherapy. Conclusions After coloanal anastomosis, a significant number of patients will have complications requiring surgical intervention, and some will require a permanent colostomy. Pelvic radiotherapy, whether it is administered preoperatively or postoperatively, significantly increases the need for a permanent colostomy.     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V

Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid- dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506- FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC.     

Exotic and indigenous problem plants species used,by the Bapedi,to treat sexually transmitted infections in Limpopo Province,South Africa

Background

The ethnic usage of exotics and indigenous problem plants is a highly debated topic, as legislative requirements over-shadow their potential medicinal value, particularly to treat sexually transmitted infections (STIs). Limited information exists regarding their medicinal value among the Bapedi.

Objectives

To ascertain the importance of exotics and indigenous problem plants in the treatment of STIs, a major global primary health care challenge.

Methods

A field observation and semi-structured questionnaire focussing on species diversity, types of STIs treated and medicinal preparation as well as application was used to collect data from 34 traditional healers.

Results

Seven exotics and three indigenous problem species were identified. These species were used to treat four STIs; with Catharanthus roseus illustrating its dominance in the treatment of gonorrhoea. Some medicinal species used by Bapedi traditional healers have been validated through scientific research or through their extensive use by various cultures in South Africa and other parts of Africa. To the best of our knowledge Alternanthera pungens, Caesalpinia decapetala, Cinnamomum verum, and Citrullus lanatus are reported for the first time in the treatment of the investigated STIs.

Conclusions

Exotic and indigenous problem species constitute an important component of the STIs treatment protocol. Their utilization by Bapedi cautions against the narrow-minded approach of indiscriminate eradication, as these species can play a significant role in the primary health care needs of socio-economic vulnerable people.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.     

Risk of Neoplastic Change in Ileal Pouches in Familial Adenomatous Polyposis

Introduction

Neoplastic change in ileal reservoirs after proctocolectomy has been reported in patients with familial adenomatous polyposis. We aim to determine the incidence and progression of neoplastic change in the ileal pouch of familial adenomatous polyposis patients at our institution.

Methods

A retrospective review of all patients who underwent proctocolectomy for familial adenomatous polyposis with construction of an ileal pouch from 1972 to 2007 was performed. Data and status at follow-up were retrieved from the Mayo Clinic Colorectal Surgery Pouch database.

Results

One hundred seventeen patients were identified with a median age of 26, 52 were male. Ileal reservoirs included J-pouch (a?=?104), Kock pouch (n?=?9), S-pouch (n?=?3), and W-pouch (n?=?1). Median follow-up was 125 months. Polyps were biopsied in 33 patients: non-dysplastic polyps (n?=?2), low-grade dysplasia (n?=?30), and adenocarcinoma (n?=?1). No patients had high-grade dysplasia. Median time to development of dysplasia was 149 months. Adenocarcinoma developed in one patient after 284 months. Risk of dysplasia at 10, 20, and 25 years was 17, 45, and 69 %, respectively.

Conclusion

Though there is a high incidence of low-grade dysplasia in the ileal reservoir in familial adenomatous polyposis patients, high-grade dysplasia and cancer occur rarely. Patients with low-grade dysplasia may still necessitate regular follow-up.