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M Klein

Publications and source records attributed to M Klein.

At least 91 records · Page 5Linked to original sources

The ABC-like vacuolar transporter for rye mesophyll flavone glucuronides is not species-specific.

In many cases, the vacuolar uptake of secondary metabolites has been demonstrated to be strictly specific for a given compound and plant species. While most plants contain glycosylated secondary substances, few cases are known where flavonoids may also carry negative charges, e.g. as glucuronide conjugates. Vacuolar transport of glucosylated phenylpropanoid derivatives has been shown to occur by proton substrate antiport mechanisms (Klein, M., Weissenböck. G., Dufaud, A., Gaillard, C., Kreuz, K., Martinoia, E., 1996. Different energization mechanisms drive the vacuolar uptake of a flavonoid glucoside and a herbicide glucoside. J. Biol. Chem. 271, 29,666-29,671). In contrast, flavone glucuronides appearing specifically in rye mesophyll vacuoles are taken up by direct energisation utilising MgATP, strongly arguing for the presence of an ATP-binding cassette (ABC) transporter belonging to the subfamily of multidrug resistance-associated proteins (MRP) on the rye vacuolar membrane (Klein, M., Martinoia, E., Hoffmann-Thoma, G., Weissenböck, G., 2000. A membrane-potential dependent, ubiquitous ABC-like transporter mediates the vacuolar uptake of rye flavone glucuronides regulation of glucturonide uptake by glutathione and its conjugates. Plant Journal 21, 289-304). MRPs are known to transport negatively charged organic anions. Results presented here suggest that the vacuolar directly energised MRP-like glucuronate pump for plant-specific flavone glucuronides is ubiquitously present in diverse plant species since rye flavone glucuronides are taken up into vacuoles isolated from the barley mesophyll or from the broccoli stalk parenchyma representing two species which do not synthesise glucuronidated secondary compounds. According to the transport characteristics and inhibition profile observed we propose the existence of a high-capacity, uncoupler-insensitive vacuolar ABC transporter for flavone glucuronides and possibly other negatively charged organic compounds -- plant-born or xenobiotic -- irrespective of the plant's capability to endogenously produce glucuronidated compounds.

ATP-Binding Cassette Transporters↗

Myocardial revascularization in patients with end-stage renal disease: comparison of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting.

BACKGROUND: Ischemic heart disease is the major cause of death in patients with end-stage renal disease. The high prevalence of coronary artery disease results in a rising number of dialysis patients requiring myocardial revascularisation. OBJECTIVE: The objective of this study was to compare the outcomes of recurrent angina, myocardial infarction, rate of reinterventions and cardiovascular death following percutaneous coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) in patients with end-stage renal disease. PATIENTS AND METHODS: In a retrospective investigation 40 patients with chronic renal failure undergoing primarily PTCA and 65 patients undergoing CABG were included. Both groups were comparable for gender, duration on dialysis and the number of cardiovascular risk factors per patient. Patients undergoing PTCA were younger (53 +/- 12 years vs. 57 + 8 years; p < 0.05) and more often diabetics (30% vs. 14%; p < 0.05). RESULTS: Most patients in both groups had a multi-vessel disease (95% in the CABG group vs. 74% in the PTCA group), in the CABG group there were significantly more patients with a triple-vessel disease (62% with vs. 40% in the PTCA group; p < 0.01), PTCA was primarily successful in 95% of the patients while complete revascularization was achieved in 88% of patients undergoing CABG. The perioperative mortality after CABG was 4.8% as compared to none after interventional revascularisation. The cumulative freedom of angina after 6, 12 and 24 months after intervention was significantly lower after PTCA (54%, 40%, 29%) than after bypass grafting (97%, 94%, 90%, p < 0.001). The frequency of reinterventions following PTCA was significantly higher compared to patients following CABG (p < 0.001). After PTCA 15 patients needed further revascularisations, 8 of them underwent CABG, whereas after CABG only two patients required additional myocardial revascularisation. There was no significant difference in the overall mortality between both groups; the survival rate after 12 and 24 months was 95% and 82% after PTCA and 93% and 86% after CABG, respectively. CONDITION: Although patients receiving CABG had a more severe coronary artery disease the overall mortality was comparable and clinical and functional outcome was improved compared to patients after coronary angioplasty.

Adult↗

Mutation analysis of SYNJ1: a possible candidate gene for chromosome 21q22-linked bipolar disorder.

Genes involved in the regulation of synaptic vesicle function are potential candidates for the development of psychiatric disorders. In addition to experimental and theoretical considerations, a number of genes involved in synaptic vesicle function map to regions of the genome that have been linked to bipolar disorder (BPD) and schizophrenia (SZ). One is synaptojanin 1 (SYNJ1) which maps to 21q22.2, a chromosomal region that has been linked to BPD in a subset of families in several studies. Synaptojanin 1 is an inositol 5-phosphatase that has an important role in synaptic vesicle endocytosis. Mutation screening of 32 exons, intron--exon junctions, and 839 bases of 5'-flanking DNA resulted in the identification of 11 mutations of which four were very common and seven were very rare. Of the 11 mutations identified, several may have functional significance including two coding variants, two that may affect the binding of a transcription factor, and two that involve known splicing regulatory domains. Five bipolar patients out of 149 analyzed were found who have one of the four rare variants that were most likely to have functional significance compared with 0/148 controls. The allele frequencies for three of the four common variants were very similar in bipolar patients and controls. A slight difference in allele frequency was found for an interesting mutation we detected in intron 12 in which two non-adjacent thymidine residues are deleted in a poly-AT tract located near the exon 12 splice donor site (chi(2) = 2.45, P = 0.12, 2-tailed). Although we failed to unequivocally identify a specific SYNJ1 allele that could be responsible for putative chromosome 21q22-linked BPD, several interesting variants were found to be increased in bipolar subjects and should be further investigated.

5' Untranslated Regions↗

The bioavailability of oral fludarabine phosphate is unaffected by food.

INTRODUCTION: A prospective, open and randomized, two-way crossover study was conducted to evaluate the pharmacokinetics and bioavailability of oral fludarabine phosphate when taken on a full versus an empty stomach. The effectiveness of therapy was also assessed after two cycles of treatment, four weeks apart MATERIALS AND METHODS: Patients with chronic lymphocytic leukemia or low-grade non-Hodgkin's lymphoma were randomly assigned to two groups, both of which received two cycles of treatment with 90 mg of oral fludarabine phosphate administered when either fed or fasted. Patients in Group 1 (n = 8) received oral treatment on a full stomach for the first cycle then on a fasted stomach for the second, while those in Group 2 (n = 10) received their treatment in the reverse sequence. Oral fludarabine phosphate was administered on the first day of the two study cycles and intravenous fludarabine phosphate was administered on days 3-6. RESULTS AND CONCLUSION: Of 22 patients recruited, 18 (CLL n = 10; NHL n = 8) were eligible for efficacy and safety evaluation, and 16 for bioavailability and pharmacokinetic analyses. The response to oral 2-F-ara-AMP was rapid: by two treatment cycles, 12 out of 18 patients (66.7%) had achieved partial response. Of the six patients who did not respond, five patients (27.7%) had stable disease. There was no notable difference in the rate of response between patients with B-CLL and lg-NHL. There was a marginal increase in total systemic availability of fludarabine phosphate when administered orally on a fed stomach (2-F-ara-A AUC((0-24 h)) = 3.28 +/- 1.48 microg.h/ml) compared to a fasted stomach (2-F-ara-A AUC((0-24 h)) = 3.05 +/- 1.56 microg.h/ml). Time to peak plasma concentration was slightly extended by the presence of food (2.2 +/- 1.0 versus 1.3 +/- 0.74 h) but the terminal half-life was unaffected. The minor differences in the pharmacokinetics of oral fludarabine phosphate when taken after food were not statistically significantly different and seem unlikely to be clinically relevant. The efficacy and safety data closely paralleled previous experience with the intravenous formulation.

Administration, Oral↗

Bone tunnel remodeling at the site of biodegradable interference screws used for anterior cruciate ligament reconstruction: 5-year follow-up.

PURPOSE: The purpose of this prospective study was to review, using expanded clinical-assessment tools, the long-term results of the local effects of a bioabsorbable interference screw (copolymer 85/15 D,L lactide/glycolide) in anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY: This prospective study was initiated in May 1993. The inclusion criteria for patient selection included rupture of the ACL in athletic patients without involvement of the collateral ligaments, arthroscopic ACL reconstruction using middle third of the ligamentum patella, and magnetic resonance imaging (MRI) and plain radiographic examinations of the knee joint during follow-up. MATERIALS: Between May 1993 and October 1994, 32 patients were enlisted in the study; 48 patients did not fit the inclusion criteria. There were 25 men 7 women. The average age was 29.1 years (range, 19 to 50 years). There were 21 right knees and 11 left knees. The follow-up examinations were performed by an independent examiner. There were 28 patients available for follow-up at a medium of 5.2 years (range, 4.1 to 6.4 years). The evaluation included various testing systems (i.e., OAK, IKDC, Lysholm) as well as MRI and plain radiographic studies to investigate the longevity of the implant and potential adverse effects of this new bioabsorbable material. RESULTS: The clinical results were good. The OAK score (Orthopädische Arbeitsgruppe Knie) showed 93% excellent and good results, and 7% fair results. The IKDC and Lysholm scores were 92% and 96% good and excellent results, respectively. MRI showed bone remodeling and new bone formations at the site of the implant in the femoral as well as in the tibial bone tunnel at follow-up. No cystic or osteolytic changes where seen on MRI or plain radiographs. CONCLUSIONS: This study showed the correlation between histology and MRI: there was minimal surgical-site edema, minimal reaction to this material, and complete replacement by new bone formation of the previous site of this implant. At 5 years, this bioabsorbable interference screw appeared clinically safe and effective for fixation of bone blocks during ACL reconstruction and MRI showed complete absorption and replacement with new bone.

Absorbable Implants↗

Intraoperative computed tomography with the mobile CT Tomoscan M during surgical treatment of orbital fractures.

Up to now it has only been possible to monitor the alignment of orbital floor fractures postoperatively with a computed tomography (CT) examination with coronal sectioning. If this showed an incorrect positioning, renewed surgery and anaesthetics were often required. The purpose of this study was the implementation and definition of the spectrum of indications for intraoperative CT examinations while keeping patient radiation exposure to a minimum. Thirty-two orbital fracture cases were examined pre- and intraoperatively using the mobile computer tomograph Tomoscan M in coronal sectioning. In this patient collective, 12 cases showed an isolated orbital floor fracture and twenty cases an orbital floor fracture associated with a zygomatic fracture. The technical prerequisite for these examinations was the construction of a suitable radiolucent operating table which permitted coronal sections to be made with the CT-Gantry tilted. The authors aimed to reduce radiation exposure by optimizing the technical setting parameters and closely defining the scan region for the operator. In three of 32 cases there were no surgical indications following clinical and preoperative CT examination. In three of the 20 cases with associated zygomatic fracture a closed reduction with a reduction hook was carried out, and no revision was necessary after the intraoperative CT examination. In 26 cases an open reduction was carried out. Of these open reduced fractures, four had to be revised after intraoperative CT monitoring; one of the isolated orbital floor fractures and three of those associated with a zygomatic fracture. Intraoperative CT monitoring of orbital floor fractures is considered a useful surgical aid. Its advantages are immediate monitoring of the surgical reduction, the presence of the surgeon during scanning enabling him to determine directly the relevant sections to scan, and the resulting radiation exposure.

Adult↗

Polymicrobial polyarticular septic arthritis: a rare clinical entity.

Polymicrobial polyarticular septic arthritis is a rare clinical entity, with only a few cases having been reported to date. We report a case due to Streptococcus pyogenes and Staphylococcus aureus in an IVDU, complicated by fatal streptococcal toxic-shock syndrome, and review the current literature. We conclude that whenever polymicrobial polyarticular septic arthritis is diagnosed, a high index of suspicion should be maintained for the detection of locally destructive infectious processes as well as systemic complications, and that a high mortality rate should be expected.

Adult↗

Energy metabolism of cocks and broiler chickens fed on diets with different carbohydrate sources.

Energy balances of cocks and chickens were measured using the nitrogen-carbon-balance method. In Experiment 1 twelve adult White Leghorn cocks were fed alternately on a basal ration or on a supplemental ration composed of 75% basal diet and 25% carbohydrate source as a supplement. In Experiment 2 six groups of 12 male broiler chickens were fed successively on two diets each with different carbohydrate sources (40% of DM) and on two energy levels. The investigated carbohydrate sources were glucose, fructose, sucrose, maize starch, raw and steamed potato starch, dried sugar beet pulp, tapioca, wheat, maize, rye and barley. In both experiments the energy digestibility of the diets with raw potato starch, beet pulp and barley was significantly lower compared to the other diets. Digestibility of those ranged from 88 to 81%. By simple linear regression no significant differences in efficiency of utilisation of ME of the diets between the carbohydrate sources sugars, starches and cereal grains could be proved. The corresponding MEm values agreed very close among the diets (411 to 429 kJ.kg BW-0.75.d-1).

Animal Nutritional Physiological Phenomena↗

The use of external radioactive markers in scintimammography.

In Tc-99m MIBI scintimammography, the exact localization of foci of increased tracer uptake or the exact anatomic correlation of palpated breast masses with a scintigraphic finding is difficult. The authors describe three patients with known or possible malignant breast lesions for whom the use of external radioactive markers successfully helped to provide this information, thus improving the diagnostic accuracy and guiding decision-making in the patients' treatment.

Adult↗

Tc-99m mercaptoacetyltriglycine clearance: comparison of camera-assisted methods.

PURPOSE: To compare the accuracy of three camera-assisted methods for the measurement of Tc-99m mercaptoacetyltriglycine (MAG3) clearance. MATERIALS AND METHODS: MAG3 renal scintigraphy was performed in 21 adults with different degrees of renal function. Posterior views were obtained that included the heart and the kidneys in the camera field of view. The syringe for injection was imaged before and after injection. Blood samples were drawn 24 and 43 minutes after injection and plasma radioactivity was measured. Three camera-assisted techniques to measure MAG3 clearance were tested: 1) Biexponential fitting of the left ventricular curve, normalized to plasma activity at 24 minutes; 2) calculation of clearance by relating the integral of the plasma curve (normalized to plasma activity) to the kidney activity using the Rutland-Patlak space method; and 3) a regression equation measuring clearance from the percentage of the injected dose accumulating in the kidneys during the 1- to 2.5-minute period. The camera-assisted clearances were compared with the single-sample MAG3 clearances calculated using the Russell equation. Linear regression analysis was used to measure the correlation between the camera-based methods and the single-sample techniques. RESULTS: Correlation with r > 0.900 was found for all three techniques. The difference in correlation coefficients between the three methods was not significant; however, the regression line of method 3 was significantly closer to the line of identity (P = 0.005). CONCLUSION: Method 3 most closely fits the line of identity and is probably the most practical because no blood sample is needed.

Adult↗

Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

With the complete human genomic sequence being unraveled, the focus will shift to gene identification and to the functional analysis of gene products. The generation of a set of cDNAs, both sequences and physical clones, which contains the complete and noninterrupted protein coding regions of all human genes will provide the indispensable tools for the systematic and comprehensive analysis of protein function to eventually understand the molecular basis of man. Here we report the sequencing and analysis of 500 novel human cDNAs containing the complete protein coding frame. Assignment to functional categories was possible for 52% (259) of the encoded proteins, the remaining fraction having no similarities with known proteins. By aligning the cDNA sequences with the sequences of the finished chromosomes 21 and 22 we identified a number of genes that either had been completely missed in the analysis of the genomic sequences or had been wrongly predicted. Three of these genes appear to be present in several copies. We conclude that full-length cDNA sequencing continues to be crucial also for the accurate identification of genes. The set of 500 novel cDNAs, and another 1000 full-coding cDNAs of known transcripts we have identified, adds up to cDNA representations covering 2%--5 % of all human genes. We thus substantially contribute to the generation of a gene catalog, consisting of both full-coding cDNA sequences and clones, which should be made freely available and will become an invaluable tool for detailed functional studies.

3' Untranslated Regions↗

Multiple lateral transfers of dissimilatory sulfite reductase genes between major lineages of sulfate-reducing prokaryotes.

A large fragment of the dissimilatory sulfite reductase genes (dsrAB) was PCR amplified and fully sequenced from 30 reference strains representing all recognized lineages of sulfate-reducing bacteria. In addition, the sequence of the dsrAB gene homologs of the sulfite reducer Desulfitobacterium dehalogenans was determined. In contrast to previous reports, comparative analysis of all available DsrAB sequences produced a tree topology partially inconsistent with the corresponding 16S rRNA phylogeny. For example, the DsrAB sequences of several Desulfotomaculum species (low G+C gram-positive division) and two members of the genus Thermodesulfobacterium (a separate bacterial division) were monophyletic with delta-proteobacterial DsrAB sequences. The most parsimonious interpretation of these data is that dsrAB genes from ancestors of as-yet-unrecognized sulfate reducers within the delta-Proteobacteria were laterally transferred across divisions. A number of insertions and deletions in the DsrAB alignment independently support these inferred lateral acquisitions of dsrAB genes. Evidence for a dsrAB lateral gene transfer event also was found within the delta-Proteobacteria, affecting Desulfobacula toluolica. The root of the dsr tree was inferred to be within the Thermodesulfovibrio lineage by paralogous rooting of the alpha and beta subunits. This rooting suggests that the dsrAB genes in Archaeoglobus species also are the result of an ancient lateral transfer from a bacterial donor. Although these findings complicate the use of dsrAB genes to infer phylogenetic relationships among sulfate reducers in molecular diversity studies, they establish a framework to resolve the origins and diversification of this ancient respiratory lifestyle among organisms mediating a key step in the biogeochemical cycling of sulfur.

Amino Acid Sequence↗

Induction of neutralizing antibodies and gag-specific cellular immune responses to an R5 primary isolate of human immunodeficiency virus type 1 in rhesus macaques.

The ability to generate antibodies that cross-neutralize diverse primary isolates is an important goal for human immunodeficiency virus type 1 (HIV-1) vaccine development. Most of the candidate HIV-1 vaccines tested in humans and nonhuman primates have failed in this regard. Past efforts have focused almost entirely on the envelope glycoproteins of a small number of T-cell line-adapted strains of the virus as immunogens. Here we assessed the immunogenicity of noninfectious virus-like particles (VLP) consisting of Gag, Pro (protease), and Env from R5 primary isolate HIV-1(Bx08). Immunogens were delivered to rhesus macaques in the form of either purified VLP, recombinant DNA and canarypox (ALVAC) vectors engineered to express VLP, or a combination of these products. Seroconversion to Gag and Pro was detected in all of the immunized animals. Antibodies that could neutralize HIV-1(Bx08) were detected in animals that received (i) coinoculations with DNA(Bx08) and VLP(Bx08), (ii) DNA(Bx08) followed by ALVAC(Bx08) boosting, and (iii) VLP(Bx08) alone. The neutralizing antibodies were highly strain specific despite the fact that they did not appear to be directed to linear epitopes in the V3 loop. Virus-specific cellular immune responses also were generated, as judged by the presence of Gag-specific gamma interferon (IFN-gamma)-producing cells. These cellular immune responses required the inclusion of DNA(Bx08) in the immunization modality, since few or no IFN-gamma-producing cells were detected in animals that received either VLP(Bx08) or ALVAC(Bx08) alone. The results demonstrate the feasibility of generating neutralizing antibodies and cellular immune responses that target an R5 primary HIV-1 isolate by vaccination in primates.

Animals↗

Changes in fatal and near-fatal asthma in an urban area of South Africa from 1980-1997.

Over the past two decades, changes in the health services designed to improve access to and quality of asthma care have occurred in South Africa. The aim of this study was to investigate the incidence of fatal and near-fatal asthma (NFA) from 1980-1997 in an urban part of South Africa. A retrospective analysis of fatal asthma and NFA in the Cape Town City Council area was performed. Mortality data were obtained from death notification records. Data on NFA were obtained from the records of patients admitted for asthma to intensive care units (ICUs) at major academic hospitals serving the area. There were 1,506 deaths (mean age 56 yrs) from asthma reported; 39 and 3% occurred in people under 55 and 15 yrs, respectively. Average annual asthma mortality rate (8.1 +/- 1.9 per 100,000 population) was highest amongst people of mixed race (10.1 +/- 2.0), followed by Blacks (6.8 +/- 3.1) and Whites (5.0 +/- 1.9, p<0.001). Asthma mortality declined by 0.28 deaths per 100,000 population per year; rates decreased in all ethnic groups. Most deaths (72.3%) were outside a health facility and a higher number of deaths occurred on weekends (223 deaths x day(-1)) than weekdays (207 deaths x day(-1), p=0.014). Paediatric asthma ICU admissions declined by 1.81 children yr(-1). The annual number of adults admitted to ICU for asthma, and the proportion requiring intermittent positive pressure ventilation did not change. These results indicate that the incidence of fatal and near-fatal asthma in this area has declined over the period and this may reflect improved asthma management. However, the relatively high asthma mortality rate in people of mixed race and the predominance of deaths outside health facilities and on weekends suggest problems with access to care.

Adolescent↗

Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma.

Vascular endothelial growth factor (VEGF) is a potent stimulator of endothelial cell proliferation. It has been implicated in tumor growth of human thyroid carcinomas. Using the VEGF immunohistochemistry staining score, we correlated the level of VEGF expression with the metastatic spread of 19 cases of thyroid papillary carcinoma. The VEGF immunostaining score, ranging from 0-9, was determined as the multiplication of a percentage of labeled thyrocytes score (0, no labeling; 1, <30%; 2, 31--60%; 3, >61% of labeled thyrocytes) and an intensity score (0, no staining; 1, weak; 2, mild; 3, strong staining). The mean score +/- SD was 5.74 +/- 2.59 for all carcinomas. The mean score for metastatic papillary carcinoma was 8.25 +/- 1.13 vs. 3.91 +/- 1.5 for nonmetastatic papillary cancers (P < 0.001). By discriminant analysis, we found a threshold value of 6.0, with a sensitivity of 100% and a specificity of 87.5%. There were no statistical differences between metastatic and nonmetastatic carcinomas when age, tumor size, or thyroglobulin levels were considered. The VEGF immunostaining score seems to be a helpful marker for metastasis spread in differentiated thyroid cancers. An increased production of VEGF could assess an aggressive disease and be the hallmark of a trend to produce metastasis. We propose the VEGF immunostaining score as a marker for the prognosis in differentiated thyroid cancers. A value of 6 or more, should be considered as at high risk for metastasis threat, prompting the physician to institute a tight follow up of the patient.

Adolescent↗

Lectin binding patterns of uterine glands in mares with chronic endometrial degeneration.

OBJECTIVE: To evaluate changes of glycoconjugate in uterine glands of endometrial tissues obtained from mares. ANIMALS: adult mares. PROCEDURE: Uterine biopsy samples were collected during the breeding season and analyzed histologically for signs of chronic endometrial degeneration. Stage of the estrous cycle was established, using clinical examination and determination of hormonal status. Uterine tissue samples were analyzed, using lectin histochemical and immunohistochemical techniques (estrogen and progesterone receptors). Connective tissues were stained to determine alterations of ground substance in periglandular fibrosis. RESULTS: Of 50 mares, 30 (60%) were classified as normal or having modest alterations, and 20 (40%) were classified as having moderate or severe endometrial degeneration. In normal equine endometrium, several lectins (Helix pomatia agglutinin, Lotus tetragonolobus agglutinin, Ricinus communis I agglutinin, Ulex europaeus agglutinin, and wheat germ agglutinin) bound to glycoconjugates of the luminal epithelium and openings of uterine glands. Lectin binding patterns of cystic dilated glands or fibrotic glands in endometrial samples were remarkably strong, whereas normal surrounding cells remained unstained. Lotus tetragonolobus lectin was not suitable for detecting endometrial alterations. Connective tissues stained with Alcian blue and results of Hale colloidal-iron binding revealed acidic ground substance in periglandular fibrosis. Estrogen and progesterone receptors were evenly distributed in healthy and affected endometrial samples. CONCLUSIONS AND CLINICAL RELEVANCE: Glycoconjugate patterns of uterine glands were altered in mares with chronic endometrial degeneration. Therefore, uterine secretions are likely to be altered. These changes are not induced by changes in content of estrogen and progesterone receptors in endometrial tissues.

Animals↗

Aetiology and outcome of pneumonia in human immunodeficiency virus-infected children hospitalized in South Africa.

UNLABELLED: To determine the aetiology and outcome of pneumonia in human immunodeficiency virus (HIV)-infected children, we prospectively investigated 250 children hospitalized with pneumonia who were known or clinically suspected to be HIV-positive, or who required intensive care support in Cape Town, South Africa. Blood culture, induced sputum or bronchoalveolar lavage, nasopharyngeal aspirate and gastric lavage were performed. Of the total, 151 children (60.4%) were HIV-infected. Pneumocystis carinii pneumonia (PCP), occurring in 19 (7.6%) children (15 HIV-positive), was the AIDS-defining infection in 20.3%. The incidence and type of bacteraemia (14.3%) were similar in HIV-positive and HIV-negative patients; S. pneumoniae (5%) and S. aureus (2%) were the predominant isolates. Sputum or BAL cultures yielded bacteria in 145 of 243 (60%) specimens; viruses were cultured in 37 (15.2%). Bacterial prevalence (including M. tuberculosis in 8%) and anti-microbial resistance did not differ by HIV status except for S. aureus which was more common in HIV-infected children. Thirty-one (20%) HIV-positive and 8 (8%) HIV-negative children died [RR 1.16 (95% CI 1.05-1.28), p=0.008]; using multiple logistic regression, PCP was the only risk factor for mortality (p = 0.03). CONCLUSION: In South Africa, PCP is an important AIDS-defining infection in children; bacterial pathogens occur commonly and with a similar prevalence in HIV-positive and HIV-negative children hospitalized for pneumonia. HIV-infected children with pneumonia have a worse outcome than HIV-negative patients.

Female↗