MGB1 Poor Adherence to Hypertension Treatment Guidelines: An Analysis of Therapeutic Choices

The recent Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) reiterated long-standing recommendations that Stage 1 hypertension (BP ≥ 140/90 mm Hg) without comorbidity should be treated initially with diuretics (DI) or beta blockers (BB). Yet market research suggests that many physicians prefer to use other drug classes, such as calcium channel blockers and ACE inhibitors.
OBJECTIVES: To explore the determinants of therapeutic choice in hypertension.
METHODS: We surveyed by mail a stratified random sample of 10,000 U.S. cardiologists, internists, and family/general practitioners. Physicians were queried about their practice environment and their knowledge, attitudes, and practices regarding antihypertensive therapy, including their choice of drugs to treat patients with specified clinical profiles. The probability that physicians would follow JNC guidelines Stage 1 hypertension was analyzed using multiple logistic regression with stepwise backward elimination to select variable with p < 0.001.
RESULTS: Completed surveys were received from 1,023 physicians. 86.7% prescribe drug therapy for Stage 1 hypertension, and 19.5% (22.5% of drug prescribers) limit their choices to DI and BB. Guideline conformity was higher among physicians who: practice in academic medical centrers; are older; are general practitioners (versus general internists); have smaller caseloads; have fewer hypertensive patients; have higher proportions of HMO, Medicaid, and uninsured patients; and experience more formulary restrictions. Cardiologists and family practitioners were less likely than internists to follow guidelines.
CONCLUSION: JNC guidelines are better accepted by academic physicians, older physicians who have more expenence using DI and BB, physicians with smaller caseloads and hence more time for follow-up and therapy adjustment, and physicians who face drug reimbursement constraints.     

Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan

Introduction: A dramatic increase in incidence of adenocarcinoma of the esophagogastric junction (EGJ) over the past two decades has been reported in the West. However, epidemiological data from Asian countries have not shown a similar trend. The aim of this study was to determine the incidence of adenocarcinoma of the EGJ in a cohort of consecutive patients operated on for gastric adenocarcinoma at a major cancer referral center in Japan. Method: We reviewed pathological reports of all patients who underwent surgery for advanced gastric adenocarcinoma between 1962 and 2005 at the National Cancer Centre Hospital in Tokyo. Adenocarcinoma of the EGJ was defined from images recorded for each patient, in accordance with the classification of Siewert and Stein. The proportion of adenocarcinoma at the EGJ among operated gastric adenocarcinoma patients was compiled at five‐year intervals and serial comparison made. Results: A total of 6953 patients with advanced gastric adenocarcinoma were operated on; adenocarcinoma of EGJ was found in 520 patients. The overall proportion of adenocarcinoma of the EGJ increased from 2.3% (1962–1965) to 10.0% (2001–2005). The proportion of Siewert Type II rose from 28.5% (1962–1965) to 57.3% (2001–2005), while that of Type I remained at around 1%. Conclusion: An increasing trend of adenocarcinoma of EGJ is observed in this study of patients operated on for gastric adenocarcinoma from 1962 to 2005 in a large tertiary referral center in Japan.     

An Audit of the Activities of the Pediatric Dermatology Nurse Specialist (PDNS)

Abstract:   In the current financial climate where resources in the National Health Service are becoming increasingly limited, it is essential that the role of the pediatric dermatology nurse specialist remains appreciated and supported. Our pediatric dermatology nurse specialist was first employed in September 2002 having had 6 years experience nursing children with a wide variety of dermatologic conditions prior to her employment. She achieved her pediatric community nursing degree in 2003 undertaking the nurse prescribing extended formulary course in 2006, her training history representative of many nurse specialists. We present the results of an audit highlighting how the employment of our pediatric dermatology nurse specialist has led to a decrease in hospital admissions as well as providing a significant positive impact on waiting lists.     

New agents for treatment of advanced transitional cell carcinoma

The prognosis for any patient with progressive or recurrentinvasive transitional cell carcinoma remains poor. In this context,the focus of clinical research in these invasive cancers concentrateson identifying systemic treatment options and new agents inorder to improve survival of patients. Cisplatin-based chemotherapyis standard treatment of patients with metastatic urothelialcancer; however, despite regimens as the cisplatin–gemcitabinecombination, the overall response rates vary between 40% and65%, with complete response in 15%–25% with survivalsup to 16 months. This survival is frequently achieved with severeand life-threatening side effects. None the less, almost allresponding patients relapse within the first year; therefore,the need for development of new and tolerable agents is urgent.This review highlights some new active chemotherapeutic as newplatinum compounds (oxaliplatin, lobaplatin), gallium nitrate,ifosfamide, the antifolates piritrexim and pemetrexed (Alimta®,LY231514), vinflunine and molecular targeting agents such asfarnesyltransferase inhibitors (lonafarnib, R115777, SCH66336),ribozyme (RPI.4610), histone deacetylase inhibitor (CI-994)and monoclonal antibodies (epidermal growth factor receptor,Her 2/neu). Key words: transitional cell carcinoma, gallium nitrate, vinflunine, platinum compounds, antifolates, molecular targeting agents Received for publication February 8, 2006. Revision received August 4, 2006. Accepted for publication August 10, 2006.     

Recombinant interferon-gamma and chemotherapy with isoniazid and rifampicin in experimental murine tuberculosis.

Viable bacterial counts in the lungs and spleens of mice infected intravenously with Mycobacterium tuberculosis, strain H37Rv were reduced by intravenous recombinant murine interferon-gamma (IFN-gamma) 1000-5000 u, but not by 200 u. Reduction in counts was greatest when IFN-gamma was given 1 day before infection and was not increased by additional doses in the preceding 2 days. The effect was complete in 1 day and was not increased by successive doses during the next week. Giving IFN-gamma in multilamellar liposomes further reduced the spleen viable counts, but this appeared due to the liposomes themselves and not to encapsulation of IFN-gamma within them. Only a minimal reduction in organ viable counts, not statistically significant, occurred when IFN-gamma was given 5 days after infection. Although IFN-gamma alone and isoniazid 25 mg/kg alone reduced the organ viable counts, combined treatment with IFN-gamma and isoniazid was no more bactericidal than isoniazid alone. Similarly, the bactericidal activity of rifampicin 25 mg/kg was not increased by simultaneous administration of IFN-gamma. There seems little likelihood that IFN-gamma would increase the efficacy of the early stages of the chemotherapy of tuberculosis.     

Fluid shift and protein leakage corrections in protein binding equilibrium dialysis experiments

Conventional equilibrium dialysis methods used in the estimation of ligand-macromolecule binding parameters (affinities, capacities. unbound ligand fractions, etc.) tacitly assume and require that no ligand-macromolecule binding occurs on the buffer side of the dialysis chamber. Unfortunately, this is almost never a valid assumption, as small amounts of plasma proteins are invariably detected in the buffer chamber. Provided the extent of protein leakage is in the usual region (about 0.1%) and the extent of ligand binding does not exceed approximately 99%. errors associated with conventional free fraction estimations obtained from calculations ignoring the effect of protein leakage are usually small (about 1–10% error). As ligand binding exceeds 99%, significant errors may ensue. A generalized theoretical equilibrium dialysis method is developed which permits the estimation of association constants, the number of binding sites and free fraction determinations for a model employing any number of classes of binding sites. Application of the method requires a minimum of two experimental runs for each class of binding sites; volume shifts are automatically adjusted for by the method.     

Activated human monocytes inhibit the intracellular multiplication of legionnaires’ disease bacteria

We have examined the interaction between virulent egg yolk-grown L. pneumophila, Philadelphia 1 strain, and in vitro-activated human monocytes, under antibiotic-free conditions. Freshly explanted human monocytes activated by incubation with concanavalin A (Con A) and human lymphocytes inhibited the intracellular multiplication of L. pneumophila. Both Con A and lymphocytes were required for activation. Con A was consistently maximally effective at greater than or equal to 4 μg/ml. Monocytes activated by incubation with cell-free filtered supernatant from Con A-sensitized mononuclear cell cultures also inhibited the intracellular multiplication of L. pneumophil a. The most potent supernatant was obtained from mononuclear cell cultures incubated with greater than or equal to 15 μg/ml Con A for 48 h. The degree of monocyte inhibition of L. pneumophila multiplication was proportional to the length of time monocytes were preincubated with supernatant (48 {greater than} 24 {greater than} 12 h) and to the concentration of supernatant added (40 percent {greater than} 20 percent {greater than} 10 percent {greater than} 5 percent). Monocytes treated with supernatant daily were more inhibitory than monocytes treated initially only. With time in culture, monocytes progressively lost a limited degree of spontaneous inhibitory capacity and also lost their capacity to respond to supernatant with inhibition of L. pneumophila multiplication. Supernatant-activated monocytes inhibited L. pneumophila multiplication in two ways. They phagocytosed fewer bacteria, and they slowed the rate of intracellular multiplication of bacteria that were internalized. As was the case with nonactivated monocytes, antibody had no effect on the rate of intracellular multiplication in supernatant-activated monocytes. Neither supernatant-activated nor nonactivated monocytes killed L. pneumophila in the absence of antibody. Both killed a limited proportion of these bacteria in the presence of antibody and complement. We have previously reported that anti-L, pneumophila antibody and complement neither promote effective killing of L. pneumophila by human polymorphonuclear leukocytes and monocytes nor inhibit the rate of L. pneumophila multiplication in monocytes. These findings and our present report that activated monocytes do inhibit L. pneumophila multiplication indicate that cell-mediated immunity plays a major role in host defense against Legionnaires’ disease.