A novel and sensitive method to monitor helminth infections by faecal sampling

The Kato-Katz technique is the method routinely used for diagnosing human schistosomiasis mansoni by estimating faecal egg burdens. To improve the sensitivity of faecal diagnosis, we established and validated a novel separation technique based upon the greater density of viable schistosome eggs relative to faecal material. Subsequently, it was used for faecal examination of 27 schistosomiasis patients in El-Sharkia, Egypt, with Kato-Katz smears as criterion standard. Low intensity infections (<100 eggs/g) were only detected by our technique. Moreover, triple Kato-Katz analysis on consecutive samples still missed 7.4% of all human patients, whereas the new method diagnosed 100% of samples correctly on second analysis. We conclude that in endemic areas many patients are being systematically missed by routine diagnosis. Moreover, the sensitivity of our method allows its use in proposed pre-clinical and clinical vaccine trials in non-human primates and humans, where reliable estimates of faecal egg counts are essential.     

Die Bedeutung des Wirbelkanaldurchmessers im thorakolumbalen und lumbalen Bereich nach Trauma

A relationship between traumatic spinal canal stenosis and the degree of neurological deficit is known for the cervical spine. However, this has not been proven for the thoracolumbar and lumbar spine. During a period of 4 years, from 1996 to 1999, 1168 patients with a spinal injury were treated at our department, 473 of these by operation. Thirty-five were examined in a separate group.They showed a single fracture of the thoracolumbar and lumbar spine with stenosis of the spinal canal. All fractures were single burst fractures after blunt trauma. All patients were conscious and fully oriented at the time of admission and a thorough neurological examination could be performed. The fractures were diagnosed by conventional X-ray in two views and computed tomography (CT). Using the transverse CT scans in horizontal view, the sagittal diameter was measured and the degree of stenosis calculated in percent at the level of the fracture and one below and above. The group included 25 male and 10 female patients, with a mean age of 38 years (range: 17-61 years). Of the 35 patients, 19 (54.3%) showed neurological deficits after spinal cord injury,and 16 (45.7%) were without any neurological complications at the time of first admission to the hospital. There was no correlation between the extent of spinal canal stenosis and the degree of the neurological deficit. One patient with stenosis of 20% suffered from neurological dysfunction, others with stenosis up to 80% were without spinal cord injury. The average stenosis of the spinal canal was 49.6% in cases with cord injury and 46.3% in patients without neurological dysfunction. No correlation and no predisposing anatomical structures could be found between stenosis and neurological deficit.     

Die postoperative Kontroll-CT nach Acetabulumfraktur

Fractures of the acetabulum are severe injuries of the hip joint. Exact preoperative management is necessary to make possible an anatomical reconstruction. Postoperative quality control is done best with computed tomography. Is the higher radiation exposure caused by this routine examination justified? During the 5 years from 1995 to 1999, a total of 154 patients with fractures of the acetabulum were examined postoperatively at our clinic using CT to control reconstruction, implant position and the remaining free fragments in the joint. Thirteen of these patients (8.4%) had to be re-operated after postoperative CT control. The causes of the re-operation were four cases of an intra-articular implant position, three of free fragments remaining in the joint, and in 6 patients showed inadequate reconstruction. The mean radiation exposure was 25 mGy per patient. The low mean age of the patients and the long lasting consequences of a probably unrecognised complication, justify routine, postoperative CT control, even though the radiation exposure is about 10 mGy higher than the conventional radiological diagnosis. The use of CT diagnosis as a routine postoperative measure is an appropriate control procedure that allows an objective assessment of the quality of the result for the patient as well as for the surgeon.     

The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis

Study objective: To investigate the acute effect of mannitol on the clearance of mucus, and (1) the 24-h mucus retention, and (2) the mucus clearance rate and lung function 24 h after inhalation of a single dose of mannitol. DESIGN: Clearance of mucus was measured on 3 consecutive days using (99m)Tc-sulfur colloid radioaerosol and a gamma camera. INTERVENTIONS: Mannitol, 330 +/- 68 mg (mean+/- SD), was inhaled using a dry powder inhaler only on day 2. PATIENTS: Eight patients with bronchiectasis (age range, 29 to 70 years). Measurements and results: On each day, lung images were collected over 2 h and at 24 h. Key findings of the study are as follows: (1) the 24-h retention of mucus was reduced the day after mannitol had been inhaled, compared to the day without mannitol (day 1) in the whole right lung (57.6 +/- 6.2% vs 68.1 +/- 5.9%), central (47.5 +/- 6.7% vs 56.9 +/- 6.5%), intermediate (61.7 +/- 5.6% vs 73.8 +/- 5.5%), and peripheral regions (70.9 +/- 4.3% vs 86.6 +/- 4.6%)(p < 0.02); and (2) mannitol helped patients clear mucus within 2 h that might otherwise take up to 24 h, from the whole right lung and defined regions. However, clearance over 60 min measured 24 h after mannitol inhalation was not significantly different to baseline clearance without mannitol (8.7 +/- 1.9% on day 1 vs 9.7 +/- 3.7% 24 h after mannitol; p > 0.8). The patients maintained the same lung function the day before and after mannitol had been inhaled: FEV(1) (percent predicted), 79 +/- 5 on day 1 vs 80 +/- 5 on day 3; and forced expiratory flow, midexpiratory phase (percent predicted), 50 +/- 6 on day 1 vs 51 +/- 6 on day 3; p > 0.6). CONCLUSIONS: Mannitol inhalation acutely increases clearance of mucus, and this effect extends beyond the acute study period, resulting in decreased mucus retention at 24 h.     

Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and Oseltamivir by suppressing the expression of Carboxylesterases HCE1 and HCE2

Carboxylesterases constitute a class of enzymes that play important roles in the hydrolytic metabolism of drugs and other xenobiotics, patients with liver conditions such as cirrhosis show increased secretion of proinflammatory cytokines [e. g., interleukin-6 （IL- 6）] and decreased capacity of hydrolysis. In this sfudy, we provide a molecular explanation linking cytokine secretion directly to the decreased capacity of hydrolytic biotransformation. In both primary hepatocytes and HepG2 cells, treatment with IL-6 decreased the expression of human carboxylesterases HCE1 and HCE2 by as much as 60%. The decreased expression occurred at both mRNA and protein levels, and it was confirmed .by enzymatic assay. In cotransfection experiments, both HCE1 and HCE2 promoters were significantly repressed, and the repression was comparable with the decrease in HCE1 and HCE2 mRNA, suggesting that transrepression is responsible for the suppressed expression. In addition, pretreatment with IL-6 altered the cellular responsiveness in an opposite manner of overexpression of HCE1 and HCE2 toward various ester therapeutic agents （ e. g., clopidogrel）. Transfection of HCE1, for example, decreased the cytotoxicity induced by antithrombogenic agent clopidogrel, whereas pretreatment with IL-6 increased the cytotoxicity. Such a reversal was observed with other ester drugs, including anticancer agent irinotecan and anti-influenza agent oseltamivir. The altered cellular responsiveness was observed when drugs were assayed at sub-and low-micromolar concentrations, suggesting that suppressed expression of carboxylesterases by IL-6 has profound pharmacological consequences, particularly with those that are hvdrolvzed in an isoform-specific manner.     

白三烯抑制剂在哮喘治疗中的进展

目的：介绍白三烯抑制剂治疗哮喘的进展。方法：综述近年来国外有关文献,介绍和评价白三烯抑制剂的临床疗效,不良反应和用法用量。结果：白三烯抑制剂有效地治疗哮喘发作,且副作用较少。结论：白三烯抑制剂临床使用安全有效,是一类新的哮喘治疗药物。     

Obstetric and nonmalignant gynecologic bleeding: treatment with angiographic embolization

Eight patients (seven post partum, one post abortion) with massive pelvic hemorrhage related to pregnancy and one patient with uncontrollable bleeding following a cervical biopsy underwent angiography to facilitate the identification and treatment of bleeding sites. In all nine patients pelvic hemorrhage was successfully controlled with embolization under angiographic guidance. Angiographic embolization allowed preservation of the uterus in six patients referred prior to hysterectomy, and one patient subsequently became pregnant. When conservative measures and minor surgical repairs have failed, embolization should be the next step in the treatment of postpartum hemorrhage to avoid major surgery in an unstable patient and to maintain reproductive function.     

Ultrastructural changes of human amniotic cells induced by natural human interferon-alpha

Human interferon-alpha (Hu-IFN alpha) and phorbol myristate acetate (PMA), a direct activator of protein kinase C (PK-C), induce the translocation of protein kinase C from the cytosol to the membrane fraction. By the use of transmission (TEM) and scanning (SEM) electron microscopy we have shown that treatment of human amniotic cells (UAC) with Hu-IFN alpha resulted in profound changes in the shape, volume and ultrastructure of the cells. Most treated cells had enlarged nuclei with marginal condensation of chromatin. Nucleolar segregation, disintegration and clumping of nucleolar components were also observed. The number of interdigitating cell processes decreased and the cell surface microvilli became shortened. Similar ultrastructural alterations were induced by PMA also. All these functional and morphological data strongly support the hypothesis that protein kinase C is a key factor in IFN-mediated cell reactions.     

Prevalence of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum isolates from southern Mauritania

The increasing resistance of Plasmodium falciparum in the treatment of uncomplicated malaria with pyrimethamine/sulphadoxine has been associated in several studies with the occurrence of point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). In this study, the prevalence of these mutations was examined in samples from south-east Mauritania, where atypically strong rainfalls in 1998 and 1999 led to a severe outbreak of falciparum malaria. We analysed 386 samples by polymerase chain reaction (PCR) for infection with P. falciparum, of which 162 (41.97%) were positive. These isolates were examined for point mutations in the genes of DHFR (codons 16, 51, 59, 108 and 164) and DHPS (codons 436, 437, 540, 581 and 613) by nested PCR and subsequent mutation-specific restriction enzyme digest. We found a low overall prevalence of DHFR gene mutations (up to 18.6% of isolates), but a high overall prevalence of DHPS gene mutations (up to 49.1% of isolates). Thus, emerging resistance to antifolate drugs may be expected to develop soon in the investigated area. This study demonstrates the utility of simple, relatively rapid and inexpensive molecular methods and their application in surveillance programmes. Testing for prevalence of point mutations conferring antifolate resistance might help to identify the developing of drug resistance at a very early stage.     

Immunoblotting characterization of neutrophil antigenic targets in autoimmune neutropenia

We characterized neutrophil autoantigens using an immunoblotting technique with antibodies obtained from patients with autoimmune neutropenia. These results were correlated with serologic characterization of the antibodies, using indirect immunofluorescence and leukoagglutination. Of the 17 sera immunoblotted, 16 showed discrete bands in the molecular weight range of 30 to 112. Three patients with Felty's syndrome reacted with an antigenic target of 80 to 84 Kd molecular mass, a finding not seen in any of the other patients studied. By serologic testing, none of the autoimmune sera showed serologic specificity for any known neutrophil-specific alloantigen. Using an anti-NA-1 serum, we identified antigenic targets at 40, 50, and 101 Kd in both NA-1-positive and NA-1-negative neutrophils. Ten of 17 autoimmune sera showed reactivity in this corresponding range. These studies demonstrate that immunoblotting may be used to identify antigenic targets in autoimmune neutropenia and may suggest a specificity of these antibodies not definable by serologic techniques. Correlation of immunoblot reactivity with disease states associated with immune neutropenia may be useful in the study of the pathogenesis of the different forms of autoimmune neutropenia.