Biomedical subjects
M Hoelscher
Publications and source records attributed to M Hoelscher.
[Malaria--diagnosis].
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Sensitivity and specificity of ELISA and immunoblot for diagnosing neurocysticercosis.
In patients with neurocysticercosis (NCC), clinical manifestations and the results of neuroimaging procedures vary widely and often do not facilitate a definite diagnosis. In order to determine the value of immunodiagnosis for NCC, 222 serum and cerebrospinal fluid samples from patients with NCC and healthy subjects were examined. The samples represented patients from various endemic regions, those with other neurological disorders from an endemic area (Mexico), persons with various helminth infections other than NCC, and a group of healthy volunteers. All specimens were tested by enzyme-linked immunosorbent assay and immunoblot for the presence of Taenia solium-specific antibodies. The sensitivities of the enzyme-linked immunosorbent assay and the immunoblot test in NCC patients were almost identical (80% and 81.7%, respectively). For both tests, the sensitivity was higher when cerebrospinal fluid (86%) was tested compared with serum (75%). The overall specificity of enzyme-linked immunosorbent assay was only 75.3% because of frequent false-positive results in patients with other helminth infections, especially in those with echinococcosis. The specificity (99.4%) of the immunoblot test was clearly superior. It is concluded that enzyme-linked immunosorbent assay as a screening method and immunoblot as a confirmatory test contribute considerably to the diagnosis of NCC.
Anti-saccharomyces cerevisiae antibodies in patients with inflammatory bowel disease and their first-degree relatives: potential clinical value.
Anti-Saccharomyces cerevisiae antibodies (ASCA) have been described as specific markers in Crohn's disease and their healthy first-degree relatives. 171 patients with Crohn's disease, their 105 first-degree relatives, 145 patients with ulcerative colitis and 101 first-degree relatives of patients with ulcerative colitis, 50 patients with infectious enterocolitis and 100 healthy controls were tested for ASCA employing the ELISA technique. When compared with the healthy controls (p < 0.0001) and patients with infectious enterocolitis (p < 0.0001) the prevalence of ASCA was significantly increased in patients with Crohn's disease and their first-degree relatives (p < 0.01). Further significant differences concerning the frequency of ASCA within the different groups of our study population were not observed. In particular, ASCA were not found in increased prevalence in infectious enterocolitis. These observations are compatible with a role of ASCA as a marker of genetic predisposition to Crohn's disease.
High proportion of unrelated HIV-1 intersubtype recombinants in the Mbeya region of southwest Tanzania.
BACKGROUND: In Mbeya, a rural region of southwest Tanzania, HIV-1 subtypes A, C and D have been co-circulating since the early 1990s. OBJECTIVE: To define to what extent the co-existence of subtypes has led to recombinant HIV-1 strains and whether there is evidence for epidemic spread of any circulating recombinant form. METHODS: Nine HIV-1-seropositive young adults from Mbeya Town with no evident high-risk behaviour contributed peripheral blood mononuclear cells for this study. Nine virtually full-length-genome-sequences were amplified from this DNA and phylogenetically analysed. RESULTS: Out of the nine samples, two were subtype A (22%), two were subtype C (22%) and five were recombinants (56%): four A/C recombinants and one C/D recombinant. None of the recombinants were related to each other; all of them had different mosaic structures. Most of the genome in the recombinants was subtype C. CONCLUSION: A high proportion of unrelated intersubtype recombinants, none of them apparently spreading in the population, may be present in southwest Tanzania.
Endothelial cell autoantibodies are a marker of disease susceptibility in inflammatory bowel disease but apparently not linked to persistent measles virus infection.
Intestinal vasculitis caused by persistent measles virus infection of intestinal endothelial cells was described in Crohn's disease. Furthermore, endothelial cell autoantibodies have been demonstrated in inflammatory bowel disease (IBD). Autoantibodies against intestinal endothelial cells were visualized by indirect immunofluorescence in patients with IBD, in their healthy first-degree relatives, in patients with infectious enterocolitis, and in healthy, unrelated controls. In intestinal tissue specimens of 22 antibody-positive IBD patients a search for the measles virus genome was performed. Endothelial cell autoantibodies were significantly more frequent in patients with IBD, in both groups of first-degree relatives, and in patients with infectious enterocolitis than in the healthy controls (P = 0.0002 or less). The measles virus genome was found in none of the intestinal biopsies. Endothelial cell autoantibodies are not a genetic but rather an epigenetic (infectious) marker of disease susceptibility. The expression of these autoantibodies is unlikely to be triggered by a persistent measles virus infection.
[Multiple muscle abscesses in a Tibetan woman].
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HIV type 1 V3 serotyping of Tanzanian samples: probable reasons for mismatching with genetic subtyping.
HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.
Estimating the number of HIV transmissions through reused syringes and needles in the Mbeya Region, Tanzania.
OBJECTIVE: HIV infection attributable to medical injections is suspected to be low, although case-control studies have not provided definite results. This study aims to determine the number of HIV infections caused by the reuse of syringes and needles in the Mbeya Region, Tanzania. METHODS: The direct identification or detection of HIV in syringes and needles under field conditions was not appropriate, therefore a surrogate marker consisting of two components for possible HIV transmission was used: insufficient sterilization, and blood remaining from a previous patient. The assumption was that HIV infection can only occur if both markers are positive. Samples were collected in nine health-care facilities. All syringes and needles prepared for use in these facilities were collected without prior notification. The samples were rinsed and the resulting fluid was cultured for bacteria. Traces of blood were detected by urine stick test for haemoglobin volumes > 0.0015 microliters. RESULTS: Bacterial contamination was found in 32.8% of the total 1219 syringes and needles; 67% was caused by improper handling of the equipment after sterilization. Blood was detected in 12.5% of the samples. In the following three sampling strata, both contamination criteria were positive either on the syringe or the needle: wards/outpatient departments (OPD), 1.39%; laboratories, 7.45%; expanded programme on immunization (EPI), < 0.1%. We calculated that from 1.1 million patients injected in wards/OPD in any 1 year, fewer than 13 become infected, in laboratories fewer than 12 (160,000 blood-taking procedures), and less than one child in the EPI (850,000 vaccinations). CONCLUSION: With an established AIDS intervention programme supporting the health system, less than 0.4% of the total annual incidence of 4500-8500 is attributable to medical injections in the Mbeya Region.
A comparison of early function between kidney grafts protected with HTK solution versus Euro-Collins solution.
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Biologic assessment of cyclosporine in serum of kidney transplant patients.
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Fungus infections after liver transplantation.
The problem of fungus infections after liver transplantation was studied. In 100 consecutive recipients of orthotopic liver homografts there were 10 and 8 examples, respectively, of localized and disseminated infections caused by Candida species. Candidemia was demonstrated in 8 of these 18 patients. One patient who had a localized Candida infection also had disseminated cryptococcosis. An additional 31 patients were infested in that Candida could be cultured from sites where it is not normally found, such as the blood (8 examples), urine (8), ascitic fluid (8), and wounds (22). This exorbitant incidence of monilial infections and infestations was associated with a high frequency of complications involving the homograft as well as the hosts' gastrointestinal tract during the post-transplantation period. The yeasts found in blood, urine, ascitic fluid and elsewhere were thought to have originated from the gut. Ten of the 100 patients had aspergillosis which was localized in 7 instances and disseminated in 3. The lung was the most frequently affected organ. The fungus infections played a contributory role in the downhill course of our patients but in the event of death more fundamental and more frequent causes of failure were technical complications involving the homografts, difficulties in controlling rejection with reasonable immunosuppressive doses and bacterial sepsis. Suggestions have been made for the better control of fungal infections in liver recipients.
Infections complicating orthotopic liver transplantation: a study emphasizing graft-related septicemia.
In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant.
Orthotopic liver transplantation in ninety-three patients.
During the 11 1/2 year period ending 13 months ago, 93 consecutive patients were treated with orthotopic liver transplantation. Fifty-six of the recipients were 18 years old or younger, and the other 37 were adults. The most common indications for operation were biliary atresia, primary hepatic malignant tumor, chronic aggressive hepatitis and alcoholic cirrhosis. There has been a gradual improvement in results throughout the period of study, although to a satisfactory level. Twenty-seven of the 93 patients survived for at least one year after liver replacement with a maximum of six years, and 16 are still alive after 13 to 71 months. The 11 late deaths after one to six years were caused by chronic rejection, biliary obstruction, recurrence of hepatoma, systemic infection or hepatitis of the homograft. Rejection of the liver as judged by classical histopathologic criteria played a surprisingly small role in the heavy over-all mortality, accounting for less than 10 per cent of the deaths. Technical or mechanical problems, especially those of biliary duct reconstruction, were a far greater cause of failure, as were systemic infections. Six of the 37 adult recipients had lethal cerebrovascular accidents during, or just after, operation. When abnormalities of liver function developed in the postoperative period, the nearly automatic diagnosis of homograft rejection, in retrospect, proved to have been wrong in most instances. Further development of liver transplantation depends upon two kinds of progress. There must be reduction of operative and early postoperative accidents and complications by more discriminating patient selection, purely technical improvement and better standardization of biliary duct reconstruction. The second area will be in sharpening the criteria for the differnetial diagnosis of postoperative hepatic malfunction, including the liberal use of transhepatic cholangiography and needle biopsy. Only then can better decisions be made about changes in medication or about the need for secondary corrective surgical procedures.
Pharacological prolongation of ischemic tolerance of rat-kidneys by Na-Cu-chlorophyllin.
This experimental study demonstrated that the warm ischemic tolerance of a rat kidney is about 60 mins, in this model. If the warm ischemic time is 60 mins or longer, in unilateral nephrectomized rats, the animals die of renal insufficiency. After pre-operative treatment with Na-Cu-chlorophyllin we observed a significantly lower increase of serum urea and creatinine levels, caused by a pharmacological effect on the kidneys. The prolongation of warm ischemic tolerance of rat kidneys is about 30 mins in this model; that means 50% more than the normal ischemic tolerance. From our results and from the literature we conclude that Na-Cu-chlorophyllin has a membrane stablilizing and an inhibiting effect on autolytic enzymes. The drug Na-Cu-chlorophyllin has indeed 2 positive effects: the immunosuppressive and organ preseving effect. These effects may play a role in donor and recipient pretreatment and treatment after grafting.