SAR user guide to the rectal MR synoptic report (primary staging).

Rectal MR is the key diagnostic exam at initial presentation for rectal cancer patients. It is the primary determinant in establishing clinical stage for the patient and greatly impacts the clinical decision-making process. Consequently, structured reporting for MR is critically important to ensure that all required information is provided to the clinical care team. The SAR initial staging reporting template has been constructed to address these important items, including locoregional extent and factors impacting the surgical approach and management of the patient. Potential outputs to each item are defined, requiring the radiologist to commit to a result. This provides essential information to the surgeon or oncologist to make specific treatment deisions for the patient. The SAR Initial Staging MR reporting template has now been officially adopted by the NAPRC (National Accreditation Program for Rectal Cancer) under the American College of Surgery. With the recent revisions to the reporting template, this user guide has been revamped to improve its practicality and support to the radiologist to complete the structured report. Each line item of the report is supplemented with clinical perspectives, images, and illustrations to help the radiologist understand the potential implications for a given finding. Common errors and pitfalls to avoid are highlighted. Ideally, rectal MR interpretation should not occur in a vacuum but in the context of a multi-disciplinary tumor board to ensure that healthcare providers use common terminology and share a solid understanding of the strengths and weaknesses of MR.

The functional significance of microRNA-145 in prostate cancer.

BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in numerous cellular processes. Recent studies have shown aberrant expression of miRNAs in prostate cancer tissues and cell lines. On the basis of miRNA microarray data, we found that miR-145 is significantly downregulated in prostate cancer. METHODS AND RESULTS: We investigated the expression and functional significance of miR-145 in prostate cancer. The expression of miR-145 was low in all the prostate cell lines tested (PC3, LNCaP and DU145) compared with the normal cell line, PWR-1E, and in cancerous regions of human prostate tissue when compared with the matched adjacent normal. Overexpression of miR-145 in PC3-transfected cells resulted in increased apoptosis and an increase in cells in the G2/M phase, as detected by flow cytometry. Investigation of the mechanisms of inactivation of miR-145 through epigenetic pathways revealed significant DNA methylation of the miR-145 promoter region in prostate cancer cell lines. Microarray analyses of miR-145-overexpressing PC3 cells showed upregulation of the pro-apoptotic gene TNFSF10, which was confirmed by real-time PCR and western analysis. CONCLUSION: One of the genes significantly upregulated by miR-145 overexpression is the proapoptotic gene TNFSF10. Therefore, modulation of miR-145 may be an important therapeutic approach for the management of prostate cancer.

Controlling tuberculosis in India.

BACKGROUND: Tuberculosis kills nearly 500,000 people in India each year. Until recently, less than half of patients with tuberculosis received an accurate diagnosis, and less than half of those received effective treatment. METHODS: We analyzed the effects of new policies introduced in 1993 that have resulted in increased resources, improved laboratory-based diagnosis, direct observation of treatment, and the use of standardized antituberculosis regimens and reporting methods. RESULTS: By September 2001, more than 200,000 health workers had been trained, and 436 million people (more than 40 percent of the entire population) had access to services. About 3.4 million patients had been evaluated for tuberculosis, and nearly 800,000 had received treatment, with a success rate greater than 80 percent. More than half of all those treated in the past 8 years were treated in the past 12 months. CONCLUSIONS: India's tuberculosis-control program has been successful in improving access to care, the quality of diagnosis, and the likelihood of successful treatment. We estimate that the improved program has prevented 200,000 deaths, with indirect savings of more than $400 million--more than eight times the cost of implementation. It will be a substantial challenge to sustain and expand the program, given the country's level of economic development, limited primary health care system, and large and mostly unregulated private health care system, as well as the dual threats of the human immunodeficiency virus and multidrug-resistant tuberculosis.

Effect of bone biopsy in guiding antimicrobial therapy for osteomyelitis complicating open wounds.

BACKGROUND: Osteomyelitis associated with infected overlying wounds represents a difficult diagnostic and therapeutic problem; bone biopsies can be done during debridement of the overlying wounds, but it is unclear how often the results of these bone cultures actually affect subsequent antibiotic decisions. The present study was undertaken to evaluate the usefulness of bone biopsies in guiding antibiotic therapy for this type of osteomyelitis. METHODS: Culture results of 44 bone biopsies taken during surgical debridement in 41 patients over the period from June 1994 to August 1998 were compared with those from the overlying wounds to determine whether the data affected the subsequent choice of antibiotics. The study design was that of a retrospective chart review in which the standard operative and microbiological procedures in place at the Milwaukee Veterans Affairs Medical Center were used. RESULTS: Sixty-one wound and 55 bone isolates were obtained during this study. Thirty-one isolates were found in bone, but not the overlying wound; diphtheroids were the most common organism obtained in this fashion. Correlation between wound and bone isolates was generally poor. Antibiotics were subsequently changed in 20 of the 44 cases after results of the bone biopsy became known, with the bone isolates already being covered in 10 cases and the bone biopsy results ignored in 14 cases. CONCLUSION: Because bone biopsy results seem to aid in tailoring antibiotic therapy in almost half the cases when bone is sampled during wound debridement surgery, this technique may be very helpful in certain cases and should be regularly undertaken when these procedures are carried out.

National tuberculosis control programme.

PIP: In 1962, the government of India launched a National Tuberculosis Control Program to detect as many tuberculosis cases as possible, provide effective treatment, establish district tuberculosis centers, extend short-course chemotherapy, and strengthen existing state tuberculosis training and demonstration centers. To date, district tuberculosis centers have been established in 454 of India's 496 districts and a total of 330 tuberculosis clinics are in operation. The tuberculosis mortality rate dropped from 80/100,000 population in 1970 to 53/100,000 in 1993. However, a 1992 review of the national program revealed inadequate budgetary outlays and drug shortages, an overemphasis on clinical and radiologic diagnosis, insufficient utilization of sputum microscopy facilities, an emphasis on case detection rather than cure, and a lack of consensus on treatment regimens. On the basis of these findings, the national strategy has been revised to achieve an 85% cure rate through administration of short-course (6-8 months) chemotherapy and to detect 70% of estimated cases. Strategies for achieving these objectives include use of sputum testing as the primary diagnostic method among self-referred cases, a standardized treatment regimen, an uninterrupted supply of drugs at all levels of the health system, increased budgetary outlays, creation of a sub-district supervisory unit, and greater emphasis on training and operations research. A pilot project testing this approach in five areas in 1993 resulted in significant improvements in the pulmonary smear positive to negative ratios and cure rates. As a result, the government of India will expand the project strategy to 17 sites covering a population of 15.83 million.^ieng

The replication terminator protein of E. coli is a DNA sequence-specific contra-helicase.

We have cloned the tus gene that encodes the replication terminator protein of Escherichia coli and have efficiently expressed its gene product. The overproducer strain has been used to purify the terminator (ter) protein in high yield to near homogeneity. The protein is a single 36 kd polypeptide. Using the ter protein and highly purified dnaB helicase, we show that the terminator protein is a DNA sequence-specific contra-helicase, i.e., the protein when bound to its recognition sequence (tau) strongly impedes the ATP-dependent unwinding of double-stranded DNA. This contra-helicase activity is polar, i.e., the impedance to unwinding takes place in only one orientation of the tau sequence. The results illuminate the mechanism of replication termination specifically at tau.