Reduction of Blood Pressure Retards the Progression of Chronic Renal Failure in Man

The effect of blood pressure reduction on the progression rateof chronic renal failure (CRF) was studied in 28 patients withCRF of diverse aetiology entering a prospective study (observationtime 7–24 months, mean 16 months). Endogenous creatinineclearance was 12–66 ml/mm (mean 30±3 ml/mm). Weaimed to keep the blood pressure below 160/90 mmlHg. Dietaryprotein was not restricted. The progression rate of CRF wasassessed from the regression coefficients of the regressionsof creatinine clearance and the inverse of s-creatinine, respectively,on time. Progression rate and the means of all recordings ofmean arterial blood pressure (MAP) and urinary protein excretion,respectively, in each patient during the prospective phase werecompared with retro spective data from the proceeding period(observation time 4–25 months, mean 19 months). The patientsreceived various combinations of antihypertensive drugs includingdiuretics, beta-blockers and vasodilatory drugs. In 19 patientsMAP decreased from 109±2 to 102±2 mmHg (groupI), whereas MAP increased from 105±2 to l08±2mmHgin nine patients (group II). In group I proteinuria was significantlylower (P<0.05) and the progression of CRF was approximately50% slower (P.<0.01) in the prospective phase than in theretrospective phase; no changes were observed in group II. Calculatedfor all patients, significant correlations were observed betweenthe change in MAP and the change in progression rate and proteinexcretion, respectively. These results indicate that loweringof blood pressure results in decreased proteinuria and retardationof the progression of CRF irrespective of the aetiology.     

Diphtheria-tetanus toxoids-pertussis vaccination does not increase the risk of hospitalization with an infectious illness.

The purpose of this study was to determine whether children hospitalized with a primary diagnosis of infection were more likely than matched controls to have had a diphtheria-tetanus toxoids-pertussis immunization in the 30 days before hospitalization of the case. Cases were less likely than controls to have received an immunization (P = 0.003). They were also less likely to have been breast-fed (P < 0.001) and to have had a well-child care clinic visit (P = 0.01). Cases were significantly more likely to be preterm (< 38 weeks gestation), low birth weight (< 2500 g) and attending day care than their matched nonhospitalized controls (P = 0.003, 0.03 and 0.002, respectively). This study demonstrates no association between receipt of diphtheria-tetanus toxoids-pertussis immunization and subsequent hospitalization for an infectious illness.     

Pre-Implantation Multiple Cytokine mRNA Expression Analysis of Donor Lung Grafts Predicts Survival After Lung Transplantation in Humans

While current donor selection with clinical findings is generally effective, the imprecise nature of the assessment forces clinicians to remain on the conservative side. A reliable biological marker would assist donor selection and would improve donor organ utilization. We collected biopsies from 169 donor lungs before implantation. Expression levels of IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and IL-1beta were measured by quantitative real-time RT-PCR (qRT-PCR). Seventeen cases died within 30 days after transplantation. No donor factor was significantly associated with 30-day mortality. Univariate analysis of the 84 cases for development of the prediction model showed that IL-6, IL-8, TNF-alpha and IL-1beta were risk factors for mortality and IL-10 and IFN-gamma were protective factors. We analyzed the cytokine expression ratios of risk to protective cytokines. A stepwise logistic regression for 30-day mortality demonstrated that a model containing the ratio of IL-6/IL-10 was the most predictive (p = 0.0013). When applied to the remaining 85 cases for validation, the test of model fit was significant (p = 0.039). Using the cytokine ratio, we were able to define three risk groups with striking differences in survival (p = 0.0003). Multi-cytokine analysis of the donor lung graft with qRT-PCR shows significant promise as a strategy to biologically evaluate the donor lung prior to implantation.     

Underutilization of β-Adrenoceptor Antagonists Post-Myocardial Infarction

Coronary artery disease continues to be the leading cause of death in the US. Several classes of drugs available today have shown benefit in decreasing the progression of coronary artery disease and its associated symptoms. When a patient experiences an acute coronary syndrome, beta-adrenoceptor antagonists are considered one of the cornerstones of medical therapy.Over the past 25 years, trials have demonstrated morbidity and mortality benefit when this class of drugs was given early in the post-myocardial infarction period. Subsequent substantial data have confirmed their beneficial effect on outcomes in other high-risk populations such as the elderly, those with left ventricular dysfunction, peripheral vascular disease, diabetic patients, and selected patients with reactive airway disease.Several reviews of hospital discharge data revealed that beta-adrenoceptor antagonists remain significantly underutilized in patients with acute, as well as chronic coronary artery disease. Misconceptions about the adverse effects and who would benefit probably account for physician reluctance to prescribe these medications. With rare exception, the overwhelming evidence currently supports the practice of prescribing beta-adrenoceptor antagonists to all patients immediately post-myocardial infarction and therapy to be continued indefinitely.     

Defining the Role of Surgery for Primary Gastrointestinal Tract Melanoma

Objective The objective of the study was to determine the outcomes for primary gastrointestinal melanomas (PGIM). Material and methods The Surveillance, Epidemiology, and End Results database (1973–2004) was queried. Results Overall, 659 cases of PGIM were identified. The annual incidence of PGIM was approximately 0.47 cases per million in 2000. Overall median survival time was 17 months. Tumors were identified in the oral–nasopharynx (32.8%), anal canal (31.4%), rectum (22.2%), esophagus (5.9%), stomach (2.7%), small bowel (2.3%), gallbladder (1.4%), and large bowel (0.9%). Univariate analysis demonstrated age, tumor location, stage, surgery, and lymph node status were significant predictors of improved survival. MST has not been reached for tumors located in the large bowel, while tumors located in the stomach demonstrated the shortest median survival (5 months). Improvement in MST was observed for those patients undergoing surgical resection. The presence of lymph node involvement conferred a poorer prognosis. Multivariate analysis of the cohort identified that location, advanced tumor stage, failure to undertake surgical resection, positive lymph node status, and age were all independent predictors of poorer outcome. Conclusion PGIM occurs most often in the oral–nasopharynx and anal canal. Surgical extirpation is the only identifiable treatment modality that significantly improves survival.     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Becoming a mother — an analysis of women's experience of early motherhood

This paper presents the results of a qualitative study conducted by midwife researchers into women's experience of new motherhood. Data were collected using focus groups involving 55 first-time mothers and analysed using grounded theory method. The analysis produced six categories: 'realizing', 'unready', 'drained', 'aloneness', 'loss' and 'working it out'. The core category, 'becoming a mother', integrates all other categories and encapsulates the process of change experienced by women. Also explained are factors mediating the often distressing experience of becoming a mother. The analysis provides a conceptualization of early motherhood enabling the development of strategies for midwives, nurses and others helping women negotiate this challenge.