Comparing hospital and telephone follow-up for patients treated for stage-I endometrial cancer (ENDCAT trial): a randomised, multicentre, non-inferiority trial.

OBJECTIVE: To evaluate the effectiveness of nurse-led telephone follow-up (TFU) for patients with stage-I endometrial cancer. DESIGN: Multicentre, randomised, non-inferiority trial. SETTING: Five centres in the North West of England. SAMPLE: A cohort of 259 women treated for stage-I endometrial cancer attending hospital outpatient clinics for routine follow-up. METHODS: Participants were randomly allocated to receive traditional hospital based follow-up (HFU) or nurse-led TFU. MAIN OUTCOME MEASURES: Primary outcomes were psychological morbidity (State Trait Anxiety Inventory, STAI-S) and patient satisfaction with the information provided. Secondary outcomes included patient satisfaction with service, quality of life, and time to detection of recurrence. RESULTS: The STAI-S scores post-randomisation were similar between groups [mean (SD): TFU 33.0 (11.0); HFU 35.5 (13.0)]. The estimated between-group difference in STAI-S was 0.7 (95% confidence interval, 95% CI -1.9 to 3.3); the confidence interval lies above the non-inferiority limit (-3.5), indicating the non-inferiority of TFU. There was no significant difference between groups in reported satisfaction with information (odds ratio, OR 0.9; 95% CI 0.4-2.1; P = 0.83). Women in the HFU group were more likely to report being kept waiting for their appointment (P = 0.001), that they did not need any information (P = 0.003), and were less likely to report that the nurse knew about their particular case and situation (P = 0.005). CONCLUSIONS: The TFU provides an effective alternative to HFU for patients with stage-I endometrial cancer, with no reported physical or psychological detriment. Patient satisfaction with information was high, with similar levels between groups. TWEETABLE ABSTRACT: ENDCAT trial shows effectiveness of nurse-led telephone follow-up for patients with stage-I endometrial cancer.

PSMB7 is associated with anthracycline resistance and is a prognostic biomarker in breast cancer.

BACKGROUND: To date individual markers have failed to correctly predict resistance against anticancer agents in breast cancer. We used gene expression patterns attributable to chemotherapy-resistant cells to detect potential new biomarkers related to anthracycline resistance. One of the genes, PSMB7, was selected for further functional studies and clinical validation. METHODS: We contrasted the expression profiles of four pairs of different human tumour cell lines and of their counterparts resistant to doxorubicin. Observed overexpression of PSMB7 in resistant cell lines was validated by immunohistochemistry. To examine its function in chemoresistance, we silenced the gene by RNA interference (RNAi) in doxorubicin-resistant MCF-7 breast cancer cells, then cell vitality was measured after doxorubicin treatment. Microarray gene expression from GEO raw microarray samples with available progression-free survival data was downloaded, and expression of PSMB7 was used for grouping samples. RESULTS: After doxorubicin treatment, 79.8+/-13.3% of resistant cells survived. Silencing of PSMB7 in resistant cells decreased survival to 31.8+/-6.4% (P>0.001). A similar effect was observed after paclitaxel treatment. In 1592 microarray samples, the patients with high PSMB7 expression had a significantly shorter survival than the patients with low expression (P<0.001). CONCLUSION: Our findings suggest that high PSMB7 expression is an unfavourable prognostic marker in breast cancer.

Molecular genetics of beta-thalassaemia syndrome in Pakistan.

This molecular genetics study was conducted in Karachi, Pakistan from 2004 to 2006 to provide guidelines for prenatal diagnosis programmes in the country. Blood samples of patients with beta-thalassaemia minor (n=200) and beta-thalassaemia major (n=150) were collected from hospitals, transfusion centres and diagnostic laboratories from different districts of Karachi, representing 5 major ethnic groups. Molecular analysis revealed 11 genetic mutations of the beta-thalassaemia gene, among which 5 mutations accounted for 88% of the total beta-thalassaemia genes identified [IVS-1-5 (G-C), Fr 8/9 (+G), Fr 41/42 (-TTCT), IVS-1-1 (G-T) and Del 619]. Other mutations identified were: CAP+1 IVS-II-1 (G-A), Cd 5 (-CT), Cd 15 (G-A). Cd 16 and Cd 30.

Transobturator tension free vaginal tapes and bladder injury.

INTRODUCTION: Tension free vaginal tapes have transformed the surgical management of female urodynamic stress incontinence (USI). Transobturator approach of tension free vaginal tapes are emerging as one of the surgical options for USI. MATERIALS AND METHODS: A literature search to answer question of routine cystoscopy during transobturator tape procedures. CONCLUSION: Though, both TOT and TVT-O has been shown not to enter pelvis on anatomical dissection on female cadavers, many cases of bladder injury have been reported. Delorome and De Leval strongly suggest avoiding routine cystoscopy during insertion. Avoidance of cystoscopy means shorter operating time as well as less costly for patients. We recommend that routine cystoscopy at least need to be considered in selected group patients. In cases of associated pelvic surgery or presence of prolapse, previous retropubic surgery or difficult insertion of the tapes, cystoscopy could be considered. Further, large randomised clinical trials are needed to asses TVT, TOT and TVT-O in-order to conclude the question of routine cystoscopy or not.

Detection of DNA by scraping the formalin-fixed paraffin-embedded tissue.

BACKGROUND: Pakistan is a developing country and most of the research laboratories have limited required infrastructures for the diagnosis of cancer at molecular level. The polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded tissues is becoming a popular procedure in the research centres. The study was conducted to introduce two new methods of DNA extraction for the PCR from formalin-fixed paraffin-embedded sections of surgical pathology specimens. MATERIALS AND METHODS: Two methods of DNA detection were used. In method A the formalin-fixed tissues were grossed, proper sections were taken, processed in an automatic tissue processor, embedded in paraffin blocks, and microtomic sections were made. In method B, the procedure was the same until embedding in the paraffin blocks, after which the selected paraffin blocks were set on a black card paper (4 cm x 4 cm) and 1 mg of pure scraped tissue was obtained using a scalpel, manually without using microtone. RESULTS: DNA was successfully extracted but point mutation of p53 gene was not seen in SCP while it was determined in 96 and 93.75 per cent cases of SCC by method A and method B respectively. There was no statistical difference in the results by both methods (P = 0.359). CONCLUSION: Scraping of the tissue for DNA detection was a simple method and may be performed in any laboratory. The reliability, reproducibility, and quality assurance of the present results are consistent with the already established techniques of DNA extraction for PCR.

The PI3K inhibitor LY294002 blocks drug export from resistant colon carcinoma cells overexpressing MRP1.

Multidrug resistance may be achieved by the activation of membrane transporters, detoxification, alterations in DNA repair or failure in apoptotic pathways. Recent data have suggested an involvement of mitogenic signalling pathways mediated by Ras and phosphoinositol-3-kinase (PI3K/Akt) in controlling multidrug resistance. Since these pathways are important targets for therapeutic interference, we sought to investigate whether blocking effectors kinases by specific inhibitors would result in a sensitization toward cytotoxic drugs. We found that cotreatment of drug-resistant HT29RDB colon cancer cells with the topoisomerase inhibitor doxorubicin and the PI3K-inhibitor LY294002 resulted in massive apoptosis, while cotreatment with the Mek inhibitors PD98059 or U0126 had no effect. This suggested that the PI3K-pathways controls cell survival and drug resistance in these cells. Besides blocking Akt phosphorylation, the PI3K-inibitor increased the intracellular doxorubicin concentration threefold. LY294002 inhibits drug export in a competitive manner as revealed by measuring drug efflux in the presence and the absence of inhibitor. The efficacy of drug efflux inhibition by LY294002 was similar to that achieved by the MRP1 inhibitors MK571 and genistein. We conclude that the PI3K inhibitor LY294002 may have therapeutic potential when combined with doxorubicin in the treatment of MRP1-mediated drug resistance.

Oscillating saw injuries during removal of plaster.

The aim of this study was to assess the incidence of injuries to patients who have had a plaster cast removed by oscillating circular saw at the Alexandra Hospital, Redditch, and to recommend measures to avoid such injuries. The record of each patient who had his/her plaster removed was kept in the plaster room and later studied. Over a 12-month period (1995-96), 3875 plaster casts were removed; 28 patients (0.72%) sustained abrasions or burns over the skin. Recently there has been a sudden rise in the number of cases who sustained injury or burns by oscillating saw following plaster cast removal and a few patients have demanded compensation from the hospital. These incidences prompted the start of this study. The identified cause of injury was the removal of a plaster cast by an inexperienced, ill-trained user or blunt saw blade. Strict protocols were required and have been introduced at the Alexandra Hospital to avoid litigation.

Pyogenic liver abscesses in children.

Five children with pyogenic liver abscess were admitted to Institute of Child Health, Kabul during the period 1978 to 1980. All patients were males, and their ages ranged from 4 to 10 years. The clinical picture was characterized by fever, upper abdominal pain, enlarged tender liver with raised right dome of the diaphragm. The abscesses were located in the right lobe of liver in all cases, and they were solitary in three cases. Staphylococcus aureus was the etiologic agent in four cases and Escherichia coli in one. Open surgical drainage coupled with prompt parenteral antibiotic therapy in all cases seem to have favorably influenced the outcome. With a high index of suspicion pyogenic liver abscess in children can be diagnosed clinically without the aid of hepatic radionuclide scanning.

The influence of fasting insulin level in post-gestational diabetes mellitus women receiving low-glycaemic-index diets.

Post-gestational diabetes mellitus (GDM) women are recommended weight loss to manage increased cardio-metabolic risks. We investigated the effects of lowering diet glycaemic index (GI) on fasting blood glucose (FBG), serum lipids, body weight and composition of post-GDM women with varying fasting insulin levels (INS). Seventy-seven Asian, non-diabetic women with previous GDM (aged 20-40 years, mean BMI: 26.4±4.6 kg m(-2)) were recruited. At baseline, 20 subjects with INS <2 µIU ml(-1) and 18 with INS 2 µIU ml(-1) received conventional dietary recommendations (CHDR) only. CHDR emphasised energy and fat intake restriction and encouraged increase in dietary fibre intakes. Twenty-four subjects with INS <2 µIU ml(-1) and 15 with INS 2 µIU ml(-1), in addition to CHDR, received low-GI education (LGI). Changes in FBG, serum lipids, body weight and body composition were evaluated. Subjects with INS <2 µIU ml(-1) had similar outcomes with both diets. After 1 year, subjects with INS 2 µIU ml(-1) who received LGI education had reductions in FBG and triglycerides. Subjects who received CHDR observed increase in both FBG and triglycerides (P<0.05). Among all subjects, diet GI was lower and dietary fibre intakes were higher in LGI compared with CHDR subjects (all P<0.05). Thus, in Asian post-GDM women with normal/higher INS, adding low-GI education to CHDR improved management of FBG and triglycerides.

Inhibitory effect of asiatic acid on acetylcholinesterase, excitatory post synaptic potential and locomotor activity.

The asiatic acid, a triterpenoids isolated from Centella asiatica was used to delineate its inhibitory effect on acetylcholinesterase (AChE) properties, excitatory post synaptic potential (EPSP) and locomotor activity. This study is consistent with asiatic acid having an effect on AChE, a selective GABA(B) receptor agonist and no sedative effect on locomotor.

Acute renal failure following the use of rosiglitazone in a chronic kidney disease patient.

Drug-induced acute interstitial nephritis is a well-recognised and important reversible cause of acute renal failure. Peroxisome-proliferator activated receptor-gamma agonists, such as rosiglitazone, have been proven to be safe in chronic kidney disease patients. We describe a 65-year-old man with long-standing diabetes mellitus and hypertension, presenting with a five-day history of fluid overload and uraemic symptoms. There was no ingestion of analgesics, alternative medicine and other nephrotoxic drugs, the only new prescription being rosiglitazone, which was commenced during his last clinic follow-up two weeks prior to presentation. He required haemodialysis with minimal improvement in renal profile, despite cessation of the offending drug. Renal biopsy revealed findings consistent with acute interstitial nephritis. An episode of upper gastrointestinal bleeding with bleeding duodenal ulcer limited the use of steroids. He was treated with a course of mycophenolate mofetil which showed good gradual response and he remained stable with residual renal impairment.

Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Afghanistan.

Twenty children (18 boys and 2 girls) with a proven or presumptive diagnosis of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency developed intravascular haemolysis following administration of antimalarials in 9, chloroquine and chloramphenicol in 1, chloroquine, chloramphenicol and aspirin in 1, chloramphenicol and aspirin in 3, and aspirin alone in 4. Eleven of these children developed acute renal insufficiency. All were managed with supportive care, including blood transfusion, forced diuresis and peritoneal dialysis wherever indicated. Only 16 children recovered completely. The occurrence of G-6-PD deficiency is being reported for the first time in Afghanistan.

Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells.

Telomerase (hTER and hTERT) plays a crucial role in cellular immortalization and carcinogenesis. Telomerase activity can be detected in about 85% of different malignant tumors, but is absent in most normal cells. In situ hybridization analysis showed that high levels of hTER and hTERT expression are present in bladder cancer, while no signal was detected in normal tissue. Therefore, in this work we propose to use hTER and hTERT transcriptional regulatory sequences to control the expression of a cytotoxic gene in bladder tumor cells, resulting in the selective destruction of this cell population. Expression vectors containing the diphtheria toxin A-chain (DT-A) gene were linked to hTER and hTERT transcriptional regulatory sequences, respectively. Inhibition of protein synthesis occurred in bladder and hepatocellular carcinoma cells transfected with the plasmids containing the DT-A gene under the control of the hTER or hTERT promoters in correlation with their activity. These studies support the feasibility of using hTER and hTERT transcriptional regulatory sequences for targeted patient-oriented gene therapy of human cancer.