Postprandial acid reflux is reduced by delayed gastric emptying.

The aim of this study was to investigate influence of delayed gastric emptying on postprandial reflux in esophageal pH. Sixty-nine consecutive patients underwent 24 hour (h) esophageal pH monitoring and gastric emptying. In 24 h esophageal pH monitoring, % postprandial reflux pH<4 for 2 h after each meal (% PRT) was extracted from the 24 h pH profile. After solid test meal (1 mCi, Tc99m) was given, gastric emptying was measured with a gamma detector placed transnasally 5 cm below lower esophageal sphincter. % PRT was similar among the 34 normal, 26 delayed and 9 rapid gastric emptying rate patients. Thirty-five with a positive pH study and 34 with a negative had a similar prevalence of gastric emptying disorder. In the positive pH study group, patients with normal gastric emptying had significantly higher % PRT than those with delayed gastric emptying (22.0 vs 12.1%, P<0.05). In the same population, patients with a normal %PRT had a significantly higher prevalence of delayed gastric emptying compared with those with a positive % PRT (6/8 vs 9/27, P<0.05). In patient with abnormal acid exposure but normal % PRT on 24 h esophageal pH monitoring, gastric emptying may be delayed.     

The primary motor and premotor areas of the human cerebral cortex.

Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.     

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death

OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.     

Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data.

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.     

Use of the silver nucleolar organizer region (AgNOR) technique in the differential diagnosis of central nervous system neoplasia.

Because the distinction between gliosis and low-grade astrocytoma may prove difficult by routine light microscopy, we evaluated the silver nucleolar organizer region (AgNOR) technique in making this distinction. The AgNOR impregnation was performed on formalin-fixed, paraffin-embedded tissue from 49 central nervous system (CNS) biopsies: eight normal brain, 14 gliosis, 14 grade 2 astrocytoma (Daumas-Duport scale), two grade 4 astrocytoma, nine medulloblastoma, one metastatic carcinoma, and one choroid plexus papilloma. Quantitative and qualitative differences were found between gliosis and low-grade astrocytomas. In gliosis, AgNOR counts averaged 1.18 +/- 0.11 (SD) AgNOR/nucleus, while in low-grade astrocytomas AgNOR counts averaged 2.22 +/- 0.39 (p less than 0.001). Compound AgNOR were frequent in 9/14 grade 2 astrocytomas and in both grade 4 astrocytomas, whereas compound AgNOR were extremely rare in cases of gliosis. Quantitative and qualitative differences were also found between normal cerebellar internal granular cells and medulloblastoma cells. Cerebellar granular cells averaged 0.90 +/- 0.10 AgNOR/nucleus whereas medulloblastoma cells had an average of 4.52 +/- 0.95 (p less than 0.001). Compound AgNOR were seen in all medulloblastomas but not in internal granular cells. These findings suggest that the AgNOR technique may be a useful adjunct in the diagnosis of CNS neoplasia.     

Giving patients an audiotape of their GP consultation: a randomised controlled trial.

BACKGROUND: Providing patients with an audiotape of their medical consultation has been a relatively common practice in oncology clinics for some years. However, broader generalisability of the technique has yet to be examined. AIMS: To investigate the efficacy of providing patients with an audiotape of their consultation in a general practice setting. DESIGN OF STUDY: Randomised controlled trial: 95 experimental participants, 85 controls. SETTING: Routine surgeries run by two general practitioners (GPs) in two different health centres. METHOD: All patients attending GP appointments were eligible for inclusion. Patients were followed up by telephone 7-10 days later. RESULTS: More than half (61%) of the patients who received a tape listened to it. Among listeners, 64% rated the tape useful or very useful; 24% noticed information not heard in the consultation. Half of listeners (46%) said that their understanding of the consultation improved after listening to the tape. Half of the listeners (48%) shared the tape with others, of whom 71% found sharing helpful or very helpful. However, 21% of those who shared the information with others found this unhelpful or very unhelpful, suggesting that patients may need to be briefed on the potential risks of sharing. At follow-up a week later, it emerged that being given a tape had no effect on adherence with GPs' advice, nor on anxiety about conditions. CONCLUSION: Providing patients with an audiotape of their GP consultation was positively rated by many patients. Although there were no detectable clinical effects at follow-up, the technique merits further evaluation in general practice.     

Cardiology

This article describes recent developments in cardiology and cardiovascular disease that are likely to be relevant to primary healthcare professionals and their patients. The following subject areas are covered: Primary prevention: recent developments in pharmaco-logical interventions, drug interactions, and drugs that are likely to cause harm; cardiovascular risk estimation and shared decision making with patients; and new developments in 24-hour ambulatory blood pressure monitoring. Secondary prevention: new models of care, including nurse-led care for the provision of hypertension and secondary prevention clinics; new drugs for the treatment of angina and myocardial infarction; ambulatory electrocardiography for the diagnosis of arrhythmias in primary care; and new developments in the treatment of atrial fibrillation - direct thrombin inhibitors and implantable devices. Tertiary prevention: recent developments in cardiac rehabilitation; recent evidence concerning revascularisation procedures and appropriateness criteria for referral; and implantable defibrillators.     

Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron

The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.