Adequacy of hormone replacement therapy for osteoporosis prevention assessed by serum oestradiol measurement, and the degree of association with menopausal symptoms.

BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis prevention rather than menopausal symptom control may be asymptomatic, despite inadequate replacement and low serum oestradiol (E2) levels. In the primary health care setting, therapeutic monitoring of HRT is not carried out routinely so that patients with serum E2 levels inadequate to protect bone may be missed. AIM: To determine the proportion of women on transdermal E2 preparations with serum E2 levels insufficient to protect bone and to assess the value of a questionnaire-derived menopausal symptom score (MSS) for detecting these patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years using transdermal E2 preparations obtained from a computer register of 14500 patients in a suburban practice. One blood sample was obtained from each patient at the time the MSS questionnaire was completed. Serum E2 concentration was measured using a fluoroimmunoassay and compared with the MSS. Levels below 150 pmol/l were considered to be insufficient to protect bone. The diagnostic accuracy of the MSS in screening for levels below 150 pmol/l was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95% CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in 24 out of 45 patients. There was no difference in the MSS (median, 95% CI) between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half the women were inadequately replaced to protect against osteoporosis. Furthermore, the MSS was of no value in screening for those with low serum E2 levels. Serum E2 levels should be monitored in women on HRT for osteoporosis prevention and the E2 dosage adjusted accordingly.     

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.     

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner.

A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized.     

An approach to haemorrhoids

OBJECTIVE: Many patients with haemorrhoids are investigated because of the fear of missing colorectal cancer (CRC). The aim of this study was to determine whether a primarily clinical approach regarding the need for investigation was safe and did not miss patients with CRC. PATIENTS AND METHODS: Data was collected prospectively on 589 consecutive patients with the principle diagnosis of haemorrhoids at first clinic visit. All had clinical assessment including rigid sigmoidoscopy and were treated by phenol injection or banding. They were categorized for (1) no review unless symptoms persisted -'One Stop SOS' (2) outpatient review or (3) investigation. To check for the development of CRC they were contacted by postal questionnaire or telephone interview with a minimum of one year from diagnosis and treatment. All 589 patients were cross-referenced with the Pathology database and the Hospital Information Services System. RESULTS: Four hundred and sixty-nine (80%) answered the questionnaire; 352 patients (60% of the total group) fell in the 'one stop SOS' outpatient category; 95 (16%) patients were followed up to review response to treatment for large haemorrhoids; 105 (18%) were investigated with barium enema (12%), flexible sigmoidoscopy (4%), colonoscopy (1%) and miscellaneous (1%); 37 (6%) patients were either given a haemorrhoidectomy date or referred on with a different diagnosis. No patients selected for 'one-stop' treatment developed CRC. Five (0.8%) patients were diagnosed with CRC after appropriate investigation was instituted for suspicious symptoms. One patient with distal transverse colon cancer had a delayed diagnosis as she was investigated initially by flexible sigmoidoscopy. CONCLUSION: Most patients with the primary diagnosis of symptomatic haemorrhoids do not need investigation.     

12-month outcome of patients with major depression and comorbid psychiatric or medical illness (compound depression)

OBJECTIVE: Inpatients with major depressive illness often have coexistent nonaffective psychiatric and/or medical conditions. The authors' objective is to address the following questions: 1) What is the effect of comorbid illness on the severity of major depression and associated psychosocial factors? 2) How does the course of depression differ for patients with and without concurrent illness? 3) Do patients with compound depression differ in rate of recovery and time to recovery from patients with pure depression? METHOD: The subjects were 78 patients with a DSM-III diagnosis of major depression who were consecutively admitted to an acute care university-affiliated psychiatric hospital; 37 of these patients had major depression only and 41 had major depression compounded by a coexisting axis I, II, or III condition. The patients were studied while hospitalized and for 12 months after hospital discharge. Instruments used included the Modified Hamilton Rating Scale for Depression, the Global Assessment Scale, and the Social Readjustment Rating Scale. RESULTS: Patients with compound depression reported significantly poorer functioning over the 12-month follow-up period and had lower recovery rates than the patients with pure depression. There were no differences in recovery rates between men and women with compound depression, but significantly more men than women with pure depression recovered. CONCLUSIONS: Compound depression is a common clinical occurrence, the course of illness is more difficult for patients with compound depression than for patients with pure depression, and the recovery rate of patients with compound depression is lower than that of patients with pure depression.     

Supratentorial hemangioblastoma associated with Von Hippel Lindau disease: case report and review of the literature

Multiple vascular lesions in the brain were identified by angiography in a 45-year-old woman with Von Hippel Lindau disease. One of these lesions was a histologically-proven hemangioblastoma. The occurrence of such lesions in a cerebral hemisphere is exceedingly rare and is usually related to Von Hippel Lindau disease.     

A new approach to chemotherapy based on molecular biology and nucleic acid chemistry: Matagen (masking tape for gene expression)

The nucleotide sequences of genes contain information which can potentially be used to understand gene function and thus the biological properties of living organisms. This information can also be used to develop innovative new strategies for chemotherapy employing sequence-specific non-ionic oligonucleoside methylphosphonates. These oligonucleotide analogs, termed Matagen (an acronym for masking tape for gene expression), have the following properties: (1) the negatively charged phosphodiester linkage normally found in nucleic acids is replaced with a non-charged methylphosphonate group which confers increased lipophilicity to the oligomer; (2) the oligomers form stable hydrogen-bonded complexes with complementary nucleic acid sequences and retain the fidelity of Watson-Crick base pairing; (3) the lipophilic oligomers cross the cell membrane and also enter various organs of the body; and (4) the methylphosphonate backbone is inherently resistant to nuclease hydrolysis and thus oligomers are taken up intact from cell culture media and remain stable within the cellular environment. Two general strategies are used to block gene expression by Matagens at the mRNA level in mammalian cells. In the first approach, Matagens complementary to specific sites such as the initiation codon region are used to block translation of mRNA. Thus Matagens specifically inhibit translation of rabbit globin mRNA in cell-free systems and rabbit reticulocytes, and vesicular stomatitis virus protein synthesis, but not cellular protein synthesis, in virus-infected cells. In the second approach, Matagens complementary to splice junctions of precursor mRNAs are used to inhibit splicing. For example, a Matagen complementary to the donor splice junction of simian virus 40 (SV40) large T-antigen mRNA inhibits T-antigen synthesis in SV40-infected cells, and a Matagen complementary to the acceptor splice junction of herpes simplex virus (HSV) immediate early pre-mRNA 4 + 5 inhibits HSV replication in virus-infected cells. Two new types of Matagen, one derivatized with the photoactivatable cross-linking group psoralen and the other derivatized with a hydroxyl radical-producing group, EDTA-Fe(II), have been designed to improve the efficacy of Matagen and to overcome some of the problems inherent in physical binding of Matagens to complementary nucleic acids. The Matagen approach provides a new way to design antiviral and chemotherapeutic agents in a rational manner. It combines nucleic acid chemistry and chemotherapy to form a common basis for drug development as well as to provide fundamental knowledge about organisms and humans.     

Standards of care for area mental health services

A provisional set of standards of care was derived from a quality assurance strand of a wider research project, which reported the development of evaluation strategies for area integrated mental health services (AIMHS). In contrast to most published standards, they apply to all facets of care in a comprehensive catchment area mental health service, whether clinical or functional, community or hospital based, urban or rural, or managed by the public, private or voluntary sectors. We review briefly existing sets of standards of mental health services and report the process of development of standards of care, each with sub-sets of performance indicators and examples. While the AIMHS standards and a companion quality assurance manual are still undergoing refinement, they offer a guide for mental health professionals to the provision of services, and a checklist to service-users of services that should be available to them at every stage of care in a mental health system.     

Escherichia coli tryptophan repressor binds multiple sites within the aroH and trp operators

DNase I footprinting and methylation protection studies have been used to analyze the binding of Escherichia coli Trp repressor to the trpR, aroH, and trp operators. The methylation protection assay shows that Trp repressor binds in two successive major grooves of the trpR operator, three successive major grooves of the aroH operator, and four successive major grooves of the trp operator. The simplest model that explains the difference in Trp repressor interaction at the three operators is that the aroH and trp operators are composed of multiple, helically stacked binding sites. When viewed in three dimensions, each site is positioned on a different face of the DNA, and together process up the surface of the DNA helix. Analysis of a deletion derivative of the trp operator supports this model.