Structural differences between the chromatin of procyclic Trypanosoma brucei brucei and of higher eukaryotes as probed by immobilized trypsin.

Soluble chromatin of Trypanosoma brucei brucei procyclic culture forms was submitted to digestion with free or immobilized trypsin. Digestion with trypsin in salt solutions of low and high ionic strengths generated characteristic sets of limit histone peptides. After incubation of chromatin with immobilized trypsin in a solution of low ionic strength, histones were not degraded, whereas a selective proteolysis occurred at 50 mM NaCl. Histones a and d, which correspond to H3 and H4 of higher eukaryotes, were rapidly attacked. Histones b and c, the counterparts of H2A and H2B, were more resistant. The results indicated that probably the basic N-terminal tails of the proteins a and d are located on the surface of the core particle. The location of d on the surface differs from the internal one proposed for histone H4. The salt-induced increase of susceptibility of histones to proteolysis reflects structural changes of T.b. brucei chromatin, which may result in partial chromatin compaction.     

Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden

Left ventricular (LV) diastolic dysfunction is prevalent in the community. Current assessment of diastolic function can be complex, involving Doppler evaluation of an array of hemodynamic data. The relation between left atrial (LA) volume and diastolic function, and between LA volume and cardiovascular risk and disease burden are not well known. In the present prospective study of 140 adults, mean age 58 ± 19 years, referred for a clinically-indicated echocardiogram and in sinus rhythm, with no history of atrial arrhythmias or valvular heart disease, we determined the LA volume, LV diastolic function status, cardiovascular risk score (based on age, gender, history of systemic hypertension, diabetes mellitus, hyperlipidemia, and smoking), and cardiovascular disease burden (based on confirmed vascular disease, congestive heart failure, and transient ischemic attack or stroke). LA volume was found to correlate positively with age, body surface area, cardiovascular risk score, LV end-diastolic and end-systolic dimensions, LV mass, diastolic function grade, tissue Doppler E/E′, tricuspid regurgitation velocity, and negatively with LV ejection fraction (all p <0.006). In a multivariate clinical model, LA volume indexed to body surface area (indexed LA volume) was independently associated with cardiovascular risk score (p <0.001), congestive heart failure (p = 0.014), vascular disease (p = 0.012), transient ischemic attack or stroke (p = 0.021), and history of smoking (p = 0.008). In a clinical and echocardiographic model, indexed LA volume was strongly associated with diastolic function grade (p <0.001), independent of LV ejection fraction, age, gender, and cardiovascular risk score. In patients without a history of atrial arrhythmias or valvular heart disease, LA volume expressed the severity of diastolic dysfunction and provided an index of cardiovascular risk and disease burden.     

Previous creatinine levels safely predict amantadine dose for influenza A outbreak control

BACKGROUND:

Amantadine, an antiviral agent, is the only drug currently approved in Canada for prophylaxis of influenza A virus infection. To minimize side effects, the amantadine dose is adjusted for age and estimated creatinine clearance (CrCl) based on plasma creatinine (Cr) levels. As amantadine is used more frequently for influenza A outbreak control in care facilities for elderly people, physicians are increasingly called on to prescribe it for residents and to consider the necessity of requesting plasma Cr levels.

OBJECTIVE:

To determine whether previous Cr levels are predictive in estimating current CrCl and safe amantadine dose determination.

DESIGN AND SETTING:

Residents'' charts were reviewed in two facilities in Vancouver, British Columbia. CrCl estimated using previous or current Cr results, current weight and age, as well as recommended amantadine doses based on Canadian National Advisory Committee on Immunization guidelines, were studied.

RESULTS:

165 charts with Cr results in March 1998 were included; 122 had results before March 1998, and 103 had Cr results after March 1998. Pearson''s correlation coefficient for CrCl estimated from current and previous Cr values was 0.929 for results less than six months previously, 0.974 for six to 12 months previously and 0.952 for 12 to 18 months previously. The same or a more conservative dose of amantadine was predicted in 92% of cases when using a Cr result taken within the previous year and in 76% of cases when using a Cr result taken 12 to 18 months previously.

CONCLUSION:

In long term care facilities, Cr levels measured up to 12 months previously can usually safely be used to estimate CrCl. Using previous Cr results permits advance preparation of doctor''s orders for amantadine prophylaxis and avoids repeating Cr testing on every resident when an outbreak occurs, reducing related staff time and cost.Key Words: Amantadine hydrochloride, Care facilities, Creatinine clearance, Influenza, Plasma creatinine, ProphylaxisInfluenza is a major infectious cause of death in the elderly, with institutionalized seniors particularly at high risk. Amantadine hydrochloride is the only drug approved in Canada for prophylaxis of influenza A virus infection. Because amantadine is used more frequently for influenza A outbreak control in long term care facilities (LTCFs), physicians are increasingly called on to prescribe it for residents and to consider the necessity of requesting plasma creatinine (Cr) levels to determine the appropriate amantadine dose.Amantadine is 70% to 90% effective in preventing illness caused by influenza A viruses (1), and reduces the severity and duration of influenza A illness if administered within 48 h of onset. About 5% to 10% of healthy young adults taking amantadine for prophylaxis report difficulty concentrating, insomnia, light-headedness and irritability. These side effects are usually mild and cease shortly after the prophylaxis is stopped but may be more frequent in the older population unless a reduced dosage is used. Serious side effects (eg, marked behavioural changes, delerium, hallucinations, agitation and seizures) have been associated with high plasma drug concentrations. Amantadine is excreted by the kidney unmetabolized. To avoid toxic levels, persons with impaired renal function should receive a lower dose. Creatinine clearance (CrCl) is used to reflect renal function and is estimated from Cr levels using the following formulas (2):Male CrCl (mL/min) = [(140 - age) x weight (kg)] / [serum creatinine (µmol/L) x 0.81]Female CrCl (mL/min) = 0.85 x male CrCl

The Role of Colonic Microbiota in Lactose Intolerance

In a previous study we observed a clear difference in lactose intolerance symptoms after a 25-g lactose load in two groups of persons with lactase nonpersistence and similar small intestinal lactase activity. From this observation we hypothesized a colon resistance factor. To identify this factor, the microbial composition of fecal samples of the two lactose intolerant groups (one with mild symptoms, n = 16, and one with diarrhea-predominant symptoms, n = 11) was compared using the fluorescent in situ hybridization technique. Large interindividual differences were found in the numbers of total bacteria and main groups of bacteria (CV: 0.65 and 0.64-0.82 respectively). The bacterial numbers were not significantly different between the two groups. A significant negative correlation, however, was found between the individual symptom scores of the intolerant persons and the numbers of total hybridizable bacteria (r(s) = -0.42, P = 0.03). The results suggest that an increased number of bacteria might contribute--by means of a higher fermentative capacity--to the reduction of lactose intolerance symptoms.     

A national survey of U.S. internists’ experiences with ethical dilemmas and ethics consultation

OBJECTIVE: To identify the ethical dilemmas that internists encounter, the strategies they use to address them, and the usefulness of ethics consultation. DESIGN: National telephone survey. SETTING: Doctors' offices. PARTICIPANTS: General internists, oncologists, and critical care/pulmonologists (N = 344, 64% response rate). MEASUREMENTS: Types of ethical dilemmas recently encountered and likelihood of requesting ethics consultation; satisfaction with resolution of ethical dilemmas with and without ethics consultation. RESULTS: Internists most commonly reported dilemmas regarding end-of-life decision making, patient autonomy, justice, and conflict resolution. General internists, oncologists, and critical care specialists reported participating in an average of 1.4, 1.3, and 4.1 consultations in the preceding 2 years, respectively (P <.0001). Physicians with the least ethics training had the least access to and participated in the fewest ethics consultations; 19% reported consultation was unavailable at their predominant practice site. Dilemmas about end-of-life decisions and patient autonomy were often referred for consultation, while dilemmas about justice, such as lack of insurance or limited resources, were rarely referred. While most physicians thought consultations yielded information that would be useful in dealing with future ethical dilemmas (72%), some hesitated to seek ethics consultation because they believed it was too time consuming (29%), might make the situation worse (15%), or that consultants were unqualified (11%). CONCLUSIONS: While most internists recall recent ethical dilemmas in their practices, those with the least preparation and experience have the least access to ethics consultation. Health care organizations should emphasize ethics educational activities to prepare physicians for handling ethical dilemmas on their own and should improve the accessibility and responsiveness of ethics consultation when needed.     

Molecular biology in transfusion medicine: current applications and future practice

Alloantibodies to blood group antigens are produced because there are differences between the blood group antigens on recipient and donor (or mother and fetus) red blood cells. Historically and currently, blood group antibodies and antigens are detected by hemagglutination, which can require considerable skill. Over the past 2 decades, there has been an astounding pace of growth in the field of molecular biology techniques and even more recently in the understanding of the basis of many blood group antigens and phenotypes. Thus, we are now able to consider identification of blood group antigens in genetic terms and identification of blood group antibodies using molecular approaches. Indeed, this knowledge is being applied to help resolve some long-standing clinical problems that cannot be resolved by classic hemagglutination. This article reviews our current knowledge of molecular approaches for identifying blood group antigens and antibodies as applied to transfusion medicine.     

Nutritional supplementation of very old people at hospital discharge increases muscle strength: a randomised controlled trial

BACKGROUND: Undernutrition is common in older people admitted to hospital, but little is known about how nutritional state changes after discharge. OBJECTIVE: This randomised controlled trial was designed to examine the effect of oral nutritional supplementation of undernourished very old people prepared to take supplements after hospital discharge following acute illness. METHODS: Participants aged>or=75 years with a BMIor=5% during an acute hospital stay were allocated at random to either oral nutritional supplementation for 8 weeks from hospital discharge or to usual care. Primary outcome was change in weight, secondary outcomes were handgrip strength and anthropometry. RESULTS: Of 198 patients eligible to participate, 136 patients (mean age 85 years) were randomised and 76/136 (56%) completed the study. Twenty percent (13/66) of the intervention group withdrew after only 2 weeks, citing intolerance of the supplements. Using intention-to-treat analysis, body weight increased by a mean of 1.6 and 2.2% in the control and intervention groups, respectively, but this between-group difference was not significant (p = 0.188). However, handgrip strength increased more (p=0.055) in the intervention group (13.9%) than in the control group (7.2%). CONCLUSIONS: Oral nutritional supplementation was associated with a greater increase in handgrip strength than in non-supplemented controls and this observation merits further study.