Multi-atmosphere picosecond CO2 amplifier optically pumped at 4.3 µm.

The possibility of the amplification of picosecond 10 µm pulses to gigawatt powers in an optically pumped 20 atmosphere CO2 laser is shown using numerical simulations. Multi-millijoule 4.3 µm pulses generated by a tunable Fe:ZnSe laser are considered for pumping.

Early Doppler echocardiographic dysfunction is associated with an increased mortality after orthotopic cardiac transplantation.

BACKGROUND: Doppler echocardiographic (DE) diastolic dysfunction has been correlated with rejection after orthotopic cardiac transplantation (Tx). However, the relationship of early diastolic dysfunction to late outcome is unknown. The purpose of this study was to assess the correlation between early DE diastolic dysfunction and outcome after heart Tx. METHODS AND RESULTS: Of 133 patients undergoing heart Tx between October 1990 and April 1994, 83 were identified with > or = 4 routine DE performed during the first 6 months. Assessment of diastolic function included measurement of isovolumic relaxation time (IVRT), pressure half-time (PHT), and peak early mitral inflow velocity (M1). Diastolic dysfunction was defined as a decrease of 15% from baseline (IVRT and PHT) or an increase of 20% (M1). A mean dysfunction score (MDS) was calculated for each patient (number of episodes of dysfunction by Doppler total number of echocardiograms performed). The population diastole MDS was determined and two groups established (group 1, MDS < mean; group 2, MDS > mean). Actuarial survival, rejection, and transplant coronary artery disease (TxCAD) were compared between groups. Actuarial survival was significantly reduced in patients with greater early diastolic dysfunction (P < .05). There were 17 deaths overall: 5 in group 1 (mean, 786 days) and 12 in group 2 (mean, 384 days). There were no significant differences in treated rejection episodes, actuarial freedom from rejection or TxCAD, immunosuppression, sex, donor age, donor ischemic time, or cytomegalovirus between the two groups. CONCLUSIONS: Diastolic dysfunction within 6 months of transplant was associated with an increased late mortality.

Detection and identification of gastrointestinal microsporidia using non-invasive techniques.

AIMS: To detect enteric microsporidia in faecal specimens from patients with the acquired immunodeficiency syndrome (AIDS), and to identify the spores to species level without using invasive procedures. METHODS: Formalised faecal preparations were examined using a modification of the strong trichrome staining method to demonstrate microsporidian spores. Six positive specimens were prepared for electron microscopy by emulsification and separation using a 9% Ficoll gradient. RESULTS: The modified staining technique readily identified microsporidian spores. Spores of different species showed variation in size. Identification using electron microscopy was successful for five of the six positive specimens examined. It was unsuccessful for one specimen in which spores were less abundant on initial staining. CONCLUSIONS: The modified strong trichrome staining method is a useful way of detecting spores of intestinal microsporidia in faecal specimens. Variation in spore size may permit provisional identification by light microscopy. Electron microscopic examination of faecal preparations is useful for identifying spores to species level.

Treatment of intestinal microsporidiosis with albendazole in patients with AIDS.

OBJECTIVE: To determine the clinical and parasitological response to treatment of intestinal microsporidiosis with albendazole. DESIGN: Open prospective study. SETTING: Hospital-based HIV/genito-urinary medicine unit. PATIENTS, PARTICIPANTS: Six consecutive AIDS patients with small intestinal microsporidiosis as the only identified cause of diarrhoea after intensive gastrointestinal investigations. RESULTS: Diarrhoea resolved completely in all patients within 1 week of starting treatment, and body weight stabilized or increased. Four patients who relapsed at 19-31 days after the cessation of treatment responded to a second course of albendazole. Degenerative changes occurred in the parasites after treatment, which had not been seen either in pre-treatment biopsies or, in four patients, following therapy with other drugs. CONCLUSIONS: Albenazole is a useful palliative treatment for microsporidial diarrhoea.

Simultaneous infection with two types of intestinal microsporidia in a patient with AIDS.

We report the first case of a non-Enterocytozoon bieneusi microsporidial infection in the small intestine of a European AIDS patient with diarrhoea. It is also the first case in which a double infection with two different types of microsporidia has been encountered.

Histological diagnosis of intestinal microsporidiosis in patients with AIDS.

Fifty nine patients seropositive for human immunodeficiency virus (HIV) and diarrhoea and 20 with weight loss were investigated for microsporidiosis using light and electron microscopical examination of duodenal and jejunal biopsy specimens. Eight cases of microsporidiosis were found, in five of whom it was the sole pathogen. In all eight cases the organism was identified at light microscopy without prior knowledge of the electron microscopical findings. All stages of the life cycle are best seen in resin sections cut at 1 micron and stained with Giemsa, but spores could easily be identified in paraffin sections cut at 5 microns and stained with haematoxylin and eosin. In all cases the parasite was identified both in duodenal pinch and jejunal "Crosby" capsule biopsy specimens. All cases of microsporidiosis occurred in patients with diarrhoea. Both electron and light microscopical examination suggested that the pathogenic mechanism involves the shedding of infected enterocytes containing large numbers of spores. It is suggested that the optimal way to diagnose microsporidiosis is by light microscopical examination of duodenal pinch biopsy specimens.

The chemotherapy of rodent malaria. XLIV. Studies on the mode of action of CM 6606, an indolo (3,2-c) quinoline N-oxide.

CM 6606 differs in its mode of action from chloroquine but studies on its activity against parasites resistant to other antimalarials suggest that it may have some features in common with aminoalcohols. Similarities in drug-induced pigment changes are especially striking. Only halofantrine shows a reduced activity, however, against parasites that are highly resistant to CM 6606, while such parasites are slightly hypersensitive to sulfadoxine and clindamycin. Evidence suggesting that CM 6606 may function through an active metabolite, possibly CM 6609 in which the N-oxide is reduced, is discussed.

Morphogenesis of yellow fever virus 17D in infected cell cultures.

The morphogenesis of yellow fever virus replication was examined in infected Vero cell cultures. Penetration and uncoating occurred by endocytosis with the formation of coated vesicles, similar to that demonstrated for other enveloped and unenveloped viruses. Inclusion bodies associated with newly formed nucleocapsids were evident in the perinuclear region during the growth cycle. No evidence of RNA synthesis in the vicinity of the inclusion bodies was obtained by autoradiography, suggesting that genome replication and assembly of viral nucleocapsids occur at separate cytoplasmic sites. An excessive proliferation of membrane-bound organelles involving both vacuoles and endoplasmic reticula was the most striking feature of virus-infected cells late in infection. No morphological changes in the appearance of nuclei or mitochondria were detected. Virus release appeared to occur by movement of nascent virions through the proliferated endoplasmic reticula followed by exocytic fusion of virus-containing vesicles with the plasmalemma. A possible mechanism whereby the internal nucleocapsid acquires an outer envelope is discussed.

Progression of aortic stenosis in adult men. Detection by noninvasive methods.

One hundred seventy-one patients with aortic stenosis (AS) who had hemodynamic studies were evaluated by a scoring system of the seven following noninvasive variables which our laboratory had developed to estimate the severity of AS: left ventricular hypertrophy (LVH) by ECG; visible aortic valve calcification by chest x-ray examination; loudness of A2; Q to peak of systolic murmur; T-time of the carotid pulse; LV ejection time; and LVH by M-mode echocardiography. The range of the severity score is 0 to 16, and a score greater than or equal to 5 has been shown correctly to identify 93 percent of patients with severe AS (valve area less than or equal to 1.0 cm2). The present study has applied this method to the detection of progression of AS. Eleven patients (mean age, 60.4 years) were studied who had hemodynamic studies performed two to nine years apart (mean, three years). Progression of stenosis occurred in all, with an increase in mean aortic valve gradient from 23 +/- 4.7 mm Hg to 46 +/- 6.5 mm Hg (p less than 0.005). Aortic valve area decreased from 1.5 +/- 0.18 cm2 to 0.88 +/- 0.10 cm2 (p less than 0.005). Noninvasive scores increased in these patients from 0.7 +/- 0.5 to 7.1 +/- 2.3 (p less than 0.005). Thirty-five patients (mean age, 62.4 years) had repeat noninvasive studies one to six years apart (mean 3 years). Twenty-two (63 percent) had an increase in the noninvasive score of greater than or equal to 3 points, and 20 (57 percent) attained a score of greater than or equal to 5, indicating probable severe AS. The mean initial severity score was 2.2 +/- 0.3, and at the end of a mean follow-up of three years, the score was 8.3 +/- 0.6 (p less than 0.005). It is concluded that in the elderly male, progression of AS over a three-year period occurs in about 60 percent of patients, and progression can be detected by simple, noninvasive methods.

Localization of covalent immune complexes on the epithelial side of the glomerular basement membrane in mice.

The site of immune complex localization in human glomerulonephritis is important in determining the kind of disease that may develop. Immune complex deposits found on the subepithelial side of the glomerular basement membrane are characteristic of membranous nephropathy, a common and often severe form of human renal disease. The pathogenesis of this disease remains controversial and arguments have recently been put forward that the subepithelial deposits arise from an in situ mechanism. This mechanism involves the initial localization of antigen allowing the antibody to subsequently combine, i.e. the immune complex is formed locally. This mechanism is thus in contrast to that in which immune complexes formed in the circulation are localized in the glomeruli. Covalent immune complexes do not dissociate and hence are ideal tools for studies to investigate whether complexes are able to cross the glomerular basement membrane. Covalent immune complexes of defined size and antigen-antibody ratio were prepared with a monoclonal antibody and photoaffinity labelling antigen, 4-azido-2-nitro-phenylated bovine serum albumin. When these complexes were injected into mice, complexes of 550,000 MW molecular weight (but not those of 800,000 MW) were shown by electron microscopic autoradiography to localize on the subepithelial side of the glomerular basement membrane. It is thus proposed that small circulating immune complexes may be important in the pathogenesis of subepithelial deposits and there is a need for devising reliable tests for measuring small immune complexes.

Pilot study for large-scale plasma procurement using automated plasmapheresis.

A pilot study for large-scale automated plasmapheresis using the Haemonetics Model 50 machine was undertaken in the Yorkshire Region of the United Kingdom to determine the viability of such a programme for national self-sufficiency in fresh plasma procurement for factor VIII concentrate production. The study was designed to resolve three areas of concern: donor safety and recruitment; a cost analysis, and the choice of anticoagulant for optimum factor VIII yields. The results show that large-scale automated plasmapheresis could safely and economically produce high-quality source plasma necessary for national self-sufficiency.