Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan. © 1993 Wiley-Liss, Inc.     

An influenza A(H3) reassortant was epidemic in Australia and New Zealand in 2003

During 2003, Australia and New Zealand experienced substantial outbreaks of influenza. The strain responsible was an A(H3N2) influenza virus described as A/Fujian/411/2002-like, which had circulated as a minor variant in the previous Northern Hemisphere (NH) winter, mainly in Korea and Japan. Early in the year the isolates were very similar to those that had been previously isolated in the NH, however, a reassortant strain emerged early in the New Zealand winter, followed by the appearance of similar viruses in Australia and other regional areas. While the hemagglutinin HA1 sequence of these viruses demonstrated only minor differences from the A/Fujian/411/2002 reference strain, the neuraminidase gene was clearly different from that of other recently circulating H3 viruses and most closely matched an earlier reference strain A/Chile/6416/2001. Three internal genes (NS, NP, M) in the reassortant viruses were also more closely related to the A/Chile/6416/2001 lineage. This reassortant A(H3) virus predominated in Australia and New Zealand in 2003 was also seen in Brazil and Malaysia during 2003 and was widespread in the United States and Europe during their 2003-04 winter. Interestingly most of the strains of A(H3) that were isolated at the beginning of the 2004 winter in Australia, did not have this earlier A/Chile/6416/2001-like neuraminidase but had a neuraminidase that was similar to that of the reference strain A/Fujian/411/2002. This was suggestive of the re-introduction of influenza A(H3) from other countries, however, there was still low level circulation of the reassortant virus in 2004 with isolates detected in Australia and Singapore.     

Echo- and electrocardiographic findings in relation to autopsy in myocardial infarction

Summary: Left ventricular (LV) wall motion studied by echocardiography (Echo) may give additional information of site and extension of myocardial damage in myocardial infarction (MI) compared to conventional ECG. We have therefore investigated patients with apparent poor short-term prognosis in the acute phase of an MI. Adequate autopsy data were available in 17 patients who died within a stipulated 2-month period. The left ventricle was divided into 16 segments and concomitant evaluation with ECG and Echo was possible in 164 (56%) of 272 (16 × 17) segments. The Echo parameter mean systolic wall velocity (V) was used with its percent deviation (PD-V) from that obtained in a healthy group. A reduction in PD-V by 30% was used for separating healthy from infarcted segments. This limit gives the method a sensitivity (S) of 92%, specificity (SP) 66%, and predictive accuracy (PA) of 79% with highest PA for anterior and posteroseptal segments (78–87%) in contrast to inferior and lateral segments (73%). Sensitivity for single ECG leads is lower (76%) with SP and PA of 76 and 75%, respectively. PA was highest for an-teroseptal and lateral segments (83%) as compared to 60% for inferoposterior segments. In 11 patients the MI was predominantly anterior which was adequately reflected by both Echo and ECG. Extension beyond this site was better evidenced by Echo than ECG. ECG was nondiagnostic in true posterior extension in contrast to Echo which was correct in all. In 6 patients the MI was predominantly inferior. Echo correctly identified this in 82% of segments and ECG in 71%. Again extensions beyond this site were better evidenced by Echo. Extensions to the true posterior and anterolateral walls were indicated in 79–100% by Echo, while ECG indicated MI in two posterior segments only. We conclude that Echo mapping provides useful information of segmental LV wall function in MI. In comparison to ECG additional information is obtained of MI involvement of especially the basal segments as well as the apical-posteroseptal segments and also of extension beyond the conventional anterior and inferior locations.     

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid

We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml.Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent.While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations.     

Synthesis and biological activity of a series of diaryl-substituted alpha-cyano-beta-hydroxypropenamides, a new class of anthelmintic agents

A series of alpha-cyano-beta-hydroxypropenamides was prepared and tested for anthelmintic activity. alpha-Cyano-beta-hydroxy-N-[4- (trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana. In sheep trials, 1 caused 100% reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta. Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated. Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.     

Pain characteristics and treatment outcome for advanced cancer patients during the first week of specialized palliative care

To examine pain in cancer patients referred for specialized palliative care, we described pain characteristics and medication on admission, examined changes in pain during the first week, and searched for predictors of initial pain intensity and treatment outcome. On arrival in the department (T0) and after one week (T1), pain was evaluated with the Edmonton Symptom Assessment System (ESAS) and EORTC QLQ-C30. Analgesics were recorded. We investigated the associations between initial pain scores as well as differences from T0 to T1, and clinical and sociodemographic parameters, initial medication, and medical interventions. Of 267 eligible patients, initial pain scores were obtained from 175. Initial pain scores were high, although 81% of patients received opioid treatment at T0. Bone metastases, neuropathic pain, mixed pain pathophysiology, and breakthrough pain were associated with higher initial pain scores. Pain scores decreased during the first week. No single parameter convincingly predicted a better or worse outcome of pain treatment.     

Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia

BACKGROUND: The role of various proteases in the pathogenesis of Alzheimer's disease is well documented. Recently, many members of the human tissue kallikrein family, a group of 15 secreted serine proteases, were found to be highly expressed in the central nervous system (CNS). Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies. METHODS: We quantified various kallikreins in CSF of 20 patients with Alzheimer's disease (AD), 16 patients with frontotemporal dementia (FTD), and 15 controls. We then correlated the levels of various kallikreins with presence of AD or FTD. Among all kallikreins measured, detectable levels in CSF were identified for kallikreins hK6, hK7, and hK10. Other tested kallikreins (hK5, hK8, hK11, and hK13) were unmeasurable. The most notable differences between kallikrein levels in CSF and the three groups of subjects were seen between controls and FTD patients for hK6 (decrease in FTD; P = 0.017), controls and FTD patients for hK7 (decrease in FTD; P < 0.001), and controls and AD patients for hK7 (decrease in AD; P = 0.019). In addition, significant differences were seen between FTD patients or control subjects and patients with AD patients for hK10 (increase in AD; P < 0.02). Approximately half of the AD patients had CSF hK10 levels that were higher than all patients with FTD except one and all control subjects except two. Various kallikrein concentrations in CSF were correlated, the strongest correlation seen between hK6 and hK7 (r(s) = 0.58). We also observed a statistically significant association between decreasing hK7 concentration in CSF and possession of one or two ApoE4 alleles (P = 0.014). CONCLUSIONS: We demonstrate for the first time significant alterations of hK6, hK7, and hK10 concentration in CSF of patients with AD and FTD. Notably, all three kallikreins (hK6, hK7, and hK10) are decreased in CSF of FTD patients and hK10 is increased in CSF of AD patients, in comparison to control subjects. The possible connection between these enzymes and the pathogenesis and progression of AD and FTD needs to be further investigated.