Variations in helminth faecal egg counts in Kato-Katz thick smears and their implications in assessing infection status with Schistosoma mansoni

Examination of stool specimens by Kato-Katz (K-K) thick smears is the standard method recommended by the WHO for field diagnosis of intestinal schistosomiasis. However, there is increasing concern that this technique has low diagnostic sensitivity. In 326 study subjects, we compared the diagnostic yield of examining one, three or five Kato-Katz thick smears prepared from one stool specimen using 41.7 mg templates. In a subset of 169 subjects who had no demonstrable Schistosoma mansoni eggs in their first three Kato-Katz thick smears, we assessed the comparative advantage of examining an additional three Kato-Katz thick smears from another stool specimen, taken four weeks later, to that of cumulative yield obtained by examining all five Kato-Katz thick smears derived from the first stool specimen. For all helminth infections, single Kato-Katz thick smear-based prevalence estimates were significantly lower than those obtained from triplet or quintet Kato-Katz thick smears. Prevalence of S. mansoni infection based on single, triplet and quintet Kato-Katz thick smears from one stool specimen were 31.3%, 45.7% and 52.1%, respectively. Prevalence estimate of S. mansoni based on quintet Kato-Katz thick smears from the first day stool specimens was not different from cumulative estimate obtained with two triplet Kato-Katz thick smears from two stool specimens, 52.1% and 52.8%, respectively. In conclusion, either examination of quintet Kato-Katz thick smears from one stool specimen using 41.7 mg template or initial triplet Kato-Katz thick smears from one stool specimen, and if these are negative, followed by examination of additional triplet Kato-Katz thick smears from subsequent day stool specimen can adequately assess individuals for infection status with S. mansoni.     

Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects

OBJECTIVE: Studies to prove a relationship between fatigue and immunological, inflammatory, or other disease characteristics of systemic lupus erythematosus (SLE) have shown no consistent findings. To further elucidate the basis for fatigue in SLE, we examined the affective states, personality traits, and mental health status in an unselected group of patients with SLE. METHODS: Fifty-seven Caucasian patients with SLE were examined. Fatigue was measured by the Fatigue Severity Scale. Personality traits and psychological function were evaluated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the affective states by Beck Depression Inventory, and mental health status by the General Health Questionnaire version 30 (GHQ-30). RESULTS: Fatigue was closely associated with high scores on subscales Depression (D-2) and Hysteria (Hy-3) on MMPI-2 (R2 = 0.31; p = 0.0002), as well as with high scores on BDI (R2 = 0.22; p = 0.0006) and GHQ (R2 = 0.33; p < 0.0001). CONCLUSION: Fatigue does not seem to be caused by any easily recognizable single or multiple factor(s) of an inflammatory or immunological state. Our results point to fatigue being a multifaceted phenomenon where several psychosocial factors are strongly related, and indicate that fatigue is part of a complex response to chronic disease.     

Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in autoimmune Addison's disease are mainly immunoglobulin G1

OBJECTIVE: Immunoglobulin G (IgG) antibodies to the steroidogenic enzymes 21-hydroxylase (21OH) and side-chain cleavage enzyme (SCC) are important diagnostic markers for autoimmune Addison's disease and autoimmune polyendocrine syndromes (APS) types I and II. The characterization of autoantibody (IgG) subclasses may reveal information on how tIssue destruction takes place; therefore, IgG subtypes of anti-21OH and anti-SCC antibodies from sera of patients with Addison's disease, APS I and APS II were determined using recombinant 21OH and SCC. METHODS: SCC(51-521) and his-SCC(51-521) were expressed by pET-scc in the Escherichia coli strain BL21 Star (DE3) and inclusion bodies were purified. Full-length, human 21OH fused to an N-terminal 6x histidine affinity tag was expressed in insect cells by using the baculovirus expression system bac-to-bac. Western blots were used to investigate the IgG subtype(s) of the autoantibodies against 21OH and SCC in patients and healthy blood donors. RESULTS: All anti-SCC positive sera (n=10) contained autoantibodies of the IgG1 subclass, while four out of ten also contained IgG3. All anti-21OH positive sera (n=16) had autoantibodies exclusively against IgG1. Sera from 20 healthy subjects did not show any reactivity against 21OH or SCC. CONCLUSIONS: The finding of a predominating IgG1 response against 21OH and SCC may suggest that T helper (Th) cells of the Th1 subclass are involved in destruction of the adrenal cortex in patients with autoimmune Addison's disease.     

Early response predicts thalidomide efficiency in patients with advanced multiple myeloma

Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0.200/h, 0.140/h, 0.886 l/kg, 0.126 l/h/kg and 4.98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.     

Long-term risk of adverse cardiovascular outcomes associated with cutaneous lupus erythematosus: a nationwide cohort study

Clinical Rheumatology - Autoimmune diseases, including systemic lupus erythematosus, have been associated with a substantial risk of cardiovascular morbidity and mortality. However, data on the...     

Interface connections of a transmembrane voltage sensor

Voltage-sensitive ion channels open and close in response to changes in transmembrane (TM) potential caused by the motion of the S4 voltage sensors. These sensors are alpha-helices that include four or more positively charged amino acids, most commonly arginine. The so-called paddle model, based on the high-resolution structure of the KvAP K+ channel [Jiang, et al. (2003) Nature 423, 33-41], posits that the S4 sensors move within the membrane bilayer in response to TM voltage changes. Direct exposure of S4 sensors to lipid is contrary to the classical expectation that the dielectric contrast between the membrane hydrocarbon core and water presents an insurmountable energetic penalty to burial of electric charges. Nevertheless, recent experiments have shown that a helix with the sequence of KvAP S4 can be inserted across the endoplasmic reticulum membrane. To reconcile this result with the classical energetics argument, we have carried out a molecular dynamics simulation of an isolated TM S4 helix in a lipid bilayer. The simulation reveals a stabilizing hydrogen-bonded network of water and lipid phosphates around the arginines that reduces the effective thickness of the bilayer hydrocarbon core to approximately 10 A in the vicinity of the helix. It suggests that bilayer phospholipids can adapt locally to strongly perturbing protein elements, causing the phospholipids to become a structural extension of the protein.     

Double-blind crossover randomized trial of intravenously administered verapamil. Its use for atrial fibrillation and flutter following open heart surgery

Fourteen patients with onset of atrial fibrillation (11) or flutter (three) and ventricular rate over 120 beats per minute following cardiac surgery were treated with intravenous (IV) doses of verapamil hydrochloride or placebo in a double-blind crossover protocol. Patients with poor left ventricular function, hypotension, atrioventricular block, and taking beta-blockers and disopyramide were excluded. The dosages were 0.075 mg/kg and 0.15 mg/kg given 15 minutes apart, with termination of study on achieving an end point (conversion to sinus rhythm or slowing of ventricular rate to below 100 beats per minute). None reached the end point with placebo but all with verapamil. Baseline ventricular rate was 144 +/- 20 beats per minute, after placebo 143 +/- 16 beats per minute, and after verapamil 89 +/- 7 beats per minute (mean +/- SD). Thus, IV verapamil briefly slows the ventricular rate of atrial tachyarrhythmias following cardiac surgery.     

Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium

Muscarinic acetylcholine receptors (mAChRs) mediate their main cardiac effects via pertussis toxin-sensitive G-proteins. Physiological effects differ considerably between atrium and ventricle, and it is unknown to which extent these differences derive from selective receptor-G-protein coupling or further downstream events. We have characterized specific coupling between mAChRs and Gi/Go-protein isoforms in atrial and ventricular myocardium by agonist-dependent photoaffinity labeling with [(32)P]azidoanilido GTP (aaGTP) and immunoprecipitation in sarcolemmal membranes from terminally failing human hearts. The total amount of mAChRs, as determined by specific binding of [(3)H]QNB, was significantly higher in right-atrial (RA +/- SEM, 959 +/- 68 fmol/mg, n = 4) than in left-ventricular membranes (LV, 582 +/- 53 fmol/mg, n = 6). Standardized immunoblots revealed that Gialpha-2 was the predominant subtype in both regions. A 40-kDa splice variant of Goalpha (Goalpha-1 and/or Goalpha-3) was almost exclusively detectable in RA. Levels of Gialpha-3 and a 39-kDa splice variant of Goalpha (Goalpha-2) were also higher in RA. Basal aaGTP binding was higher in RA than in LV for all Gialpha/Goalpha subtypes. The carbachol (10 micromol/l)-induced increase in aaGTP binding was significantly higher in RA than in LV for Goalpha-1/3 (336 +/- 95% of LV, n = 4) and for Gialpha-3 (211 +/- 83%), lower for Gialpha-2 (42 +/- 5%), and was similar in both regions for Goalpha-2 (130 +/- 62%). The differential coupling of mAChRs in human RA and LV suggests that the initiation of different physiological responses to mAChR stimulation starts with signal sorting at the receptor-G-protein level.