Biomedical subjects
Publications and source records attributed to E Sandström.
Between March 1978 and October 1980 seven patients with beta-lactamase-producing gonococci in the pharynx were treated wit spectinomycin of cefuroxime or both. One-day treatment with spectinomycin was effective in only one of six patients and with cefuroxime in only one of four patients. Prolonged treatment with cefuroxime was successful in all five cases so treated.
The rate of reinfection after treatment was studied in four groups of patients. The first group of 100 patients were evaluated retrospectively after treatment with 1.0 g ampicillin twice followed by two re-examinations over a 2-week period during which time intercourse was prohibited. The second and third prospectively groups consisted of 100 and 200 patients respectively, treated with 1 g ampicillin twice and 1.4 g pivampicillin + probenecid respectively, with re-examinations at intervals of 1 week and 4 weeks after treatment. In these two groups sexual intercourse was allowed during the last 10 days of the follow-up period. The fourth study group consisted of all patients infected with gonococci having MIC greater than or equal to 0.3 micrograms/ml for ampicillin and/or benzylpenicillin, who were treated with 1 g ampicillin twice during the period of 1973-76. In the first group no positive cultures were obtained at re-examination. In groups two and three, 35 out of 300 (12%) were found to have positive cultures at re-examination. Some of these were probably treatment failures. The failure rate in group four was found to be 20%, indicating that the treatment regimen used left a narrow therapeutic margin. However, the risk of re-infection, in this urban clinic, seems to be higher than the risk of treatment failure which would have remained undetected had sexual intercourse been forbidden.
Gonococcal strains, isolated in two different geographical areas of central Sweden (Stockholm and Orebro County) during two corresponding time periods, were subjected to serogrouping by the co-agglutination method with reagents covering the previously described serogroups W I, W II and W III. All strains tested could be grouped. Significant differences were found between the two geographical areas studied. Isolates from different sites on one and the same patient and strains from contact pairs gave identical results. The test results were reproducible, when the strains were exchanged between the two participating laboratories. The reagents distinguished Neisseria gonorrhoeae from other Neisseria species and other oxidase-positive bacteria. The potential of serogrouping gonococci for epidemiological studies by means of the co-agglutination method is discussed.
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The co-agglutination (COA) and line-rocket immunoelectrophoresis (L-RIE) techniques were investigated for the serological classification of Neisseria gonorrhoeae. COA with absorbed sera was found to demonstrate "strain-specific" as well as cross-reacting antigens. The results were dependent on the immunizing, absorbing and agglutinating properties of a particular strain. Heated (100 degrees C) whole cells were found to be more reactive in the COA tests than untreated or formalin-fixed organisms. It was possible by L-RIE to compare the antigenic relationship between at least 20 strains in a single test run. This technique was applied on the 16 major outer membrane protein (MOMP) reference strains, which could then be divided into two separate groups with regard to cross-reacting antigens. Based on the findings by the L-RIE tests, selective absorptions of antibodies were performed for use in preparation of COA reagents. It was found that the reactions of these reagents with the MOMP reference strains could be assigned to three different antigenic classes. Reagents prepared for these classes are proposed as a basis for serological classification of Neisseria gonorrhoeae.
The co-agglutination (COA) method has been adapted for serological classification of Neisseria gonorrhoeae. COA reagents were prepared with selectively absorbed rabbit hyperimmune antibodies against gonoccal (GC) major outer membrane protein (MOMP) serotype strains. Using these reagents, the 16 MOMP reference strains could be referred to at least three antigen classes, tentatively named W, J and M. The GC antigens of class W were divided into three groups I, II and III, and they were in part sensitive to pronase. The antigens of class J reflected strain specific or serotype reactions, some sensitive and others resistant to proteolytic enzymes. The antigens of class M were sensitive to periodate and resistant to pronase. Strains used in serological studies by other authors were tested. The properties of class W correlated well with those of the so-called micro-immunofluorescence and immunotype systems, and class M with those of the so-called endotoxin and acid polysaccharide systems. Strains from three different laboratories could all be grouped by class W and M reagents. Identical strains obtained independently from different laboratories gave very similar reaction patterns with the reagents available. Repeated GC-isolates from patients infected with beta-lactamase producing strains showed stable reactions with class W and J reagents, while there was a time-related variation of the class M pattern. We have found that the COA method is rapid, easy and reproducible in the serological classification of Neisseria gonorrhoeae and all the 117 GC-strains tested could be classified.
Serological classification of Neisseria gonorrhoeae by co-agglutination (COA) into previously described antigen classes W and J was confirmed in the present work. Immunization of rabbits with classified organisms gave antibodies which produced the expected results when used in the preparation of COA reagents. Colour/opacity colonial variants of isogenic strains, characterized by stereomicroscopy as opaque and transparent, respectively, were found to influence immunization, absorption, co-agglutination and precipitation in immunoelectrophoresis (IE). It was shown by COA and IE that organisms of opaque colonies often contained an extra antigenic factor(s) which resisted heating at 100 degrees C but was sensitive to treatment with pronase. They were extracted by heating the organisms in saline or lithium chloride solution. Serological classification with COA in clinical isolates was reproducible with reagents for antigen classes W and J. Colony morphology dependent reactions, mostly due to organisms of opaque colonies, occurred in 7% with reagents for antigen class W and in 20% for antigen class J.
In a systematic study of dose-response relationship 883 patients with uncomplicated gonorrhoea were given single oral doses of 400, 800 or 1600 mg bacampicillin, with 1 g probenecid. A single dose of bacampicillin 800 mg plus probenecid was the minimum effective dose in patients with fully ampicillin-sensitive strains. In patients with gonococci showing reduced sensitivity to ampicillin, 1600 mg bacampicillin was required to reach a cure rate above 95%. Bacampicillin was well tolerated in all treatment groups. Side-effects were reported in 4.6% of the courses of treatment. The most frequent adverse reaction was loose stools (1.9%), which was noted more often after the 1600 mg dose but was considered to be of no or very little clinical importance.
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Among a group of four selected strains of Neisseria gonorrhaeae, common and strain-specific antigens were demonstrated by immunoelectrophoresis, indirect immunofluorescence (IFL) and co-agglutination (COA). In preparations of ultrasonically-disrupted organisms, the strain-specific antigens appeared in crossed-line immunoelectrophoresis (C-LIE) with antigen containing intermediate agar gel as a two-peak precipitin line, one peak close to the antigen well, the other towards the anode. A similar pattern was found for each of the four strains studied. These strain-specific precipitin lines were also identified in rocket-line immunoelectrophoresis (R-LIE) tests, which were found useful for comparative studies. Using whole cells, strain-specific antigens were also demonstrated by COA and IFL tests with the use of cross-absorbed antibodies. The results corresponded to those obtained with C-LIE and R-LIE. Immunosorption experiments indicated identity between the strain-specific antigens shown by COA tests and those demonstrated by C-LIE and R-LIE tests.
Lymphocyte reactivity to virulent gonococcal antigen T2 and the non-pathogenic Neisseria pharyngis (NPN) has been studied by using the 14C-thymidine uptake in cell cultures from 42 patients with gonococcal urethritis and from 18 controls. The DNA synthesis in cell cultures with T2 antigen was higher in 21 female patients than in the 18 controls. No differences in DNA synthesis were observed in antigen-stimulated cell cultures from patients with single or multiple infections, from patients with urogenital complication, or from controls. Gonococcal antibodies in the serum were detected by the gonococcal complement-fixation test (GCFT). A study of the possible correlation between the outcome of the serological test and the cellular response to gonococcal antigen showed that 14C-thymidine uptake in lymphocyte cultures from male patients with negative GCFT, stimulated with T2 antigen, was much lower than the thymidine uptake in stimulated cell cultures from all the other male and female patients (P less than 0.001). The DNA synthesis was higher in cell cultures from seronegative women than from seronegative men (P less than 0.01). A significant difference (P less than 0.01) was also noted in the lymphocyte reactivity to gonococcal antigen between controls and all patients, except in those men who gave negative results to the serological tests. There were no differences between these two groups with respect to the thymidine uptake in NPN-stimulated cell cultures.
The efficiency of a commercial kit--Kvadricult--intended for the culture diagnosis of gonorrhoea and specially designed to simplify "bedside" inoculation, was compared in two laboratories with their standard laboratory gonococcal (GC) culture methods. The yields of specimens inoculated "bedside" were compared with those inoculated after transport for 4-18 hrs in a modified Stuart transport medium. The highest positive yield was obtained by "bedside" inoculation with approximately equal results for the conventional methods and the Kvadricult system. Compared with "bedside" inoculation, the loss of positive specimens after transport was less than 10% in one laboratory but more than 17% in the other, which was found to be due to inferiority of the GC medium used in this laboratory, the reasons for which are discussed. Prolonged transportation of specimens for 2 days increased the loss of positive specimens, rising to as much as 55% even at the laboratory with the more efficient GC medium. These losses can obviously be avoided by transport for less than 24 hours--or better still, by "bedside" inoculation. From this point of view we have found the Kvadricult system efficient and easy to handle.
The gonococcal complement fixation test (GCFT) was investigated with regard to its sensitivity and specificity by testing serum specimens from (a) female patients attending a VD out-patient clinic because of suspected gonorrhoea, (b) patients with a proven, uncomplicated, urogenital gonococcal, infection, (c) patients with disseminated gonococcal infection (DGI). Three different pools of gonococcal (GC) antigens were used which were comprised of GC strains from two different geographical areas. It was found that 39% of the females with culture-proven uncomplicated gonorrhoea had a positive GCFT whereas 10% of the females with negative GC cultures had a positive GCFT. The latter were found to have either a history of gonorrhoea or strong clinical suspicion of recent GC infection. One of the GC antigen pools gave a much lower diagnostic yield than the other two pools in the GCFTs with serum specimens from patients with uncomplicated gonorrhoea. However, no differences were found between the antigen pools in the tests with serum specimens from patients with DGI. These findings indicate the presence of various strain antigens participating in the immune response to complicated as well as uncomplicated GC infections. The results are presented in detail and discussed.
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An eight-year-old child from Zaire died in Sweden in 1982 after a clinical course compatible with the acquired immunodeficiency syndrome (AIDS). In 1975, at the age of 5 months, the infant had an acute viral infection with a rash; this illness was followed by a chronic cough. During the course of the disease he had recurrent septicemia, fever (frequently with miliary lung infiltrates), disseminated lymphadenopathy, hepatosplenomegaly, candidiasis, and diarrhea. Late in the illness the child developed lethal disseminated disturbances of the central nervous system. Immunologic investigations revealed a pronounced hypergammaglobulinemia, normal C3 but low C4 values, decreased number of T-lymphocytes, and decreased lymphocyte stimulation with T-cell and B-cell mitogens. Samples of serum taken in 1981 and 1982 were analyzed and found to be positive for antibodies to HTLV-III virus. The course of the disease in this child was more prolonged than most of the pediatric cases described earlier. It is likely that this child developed AIDS early in 1975, long before the AIDS epidemic was apparent in the United States.
The S-100 family of proteins are acidic calcium and zinc binding low molecular weight proteins mainly present in astrocytes and in a population of oligodendrocytes of the CNS. S100b, an acidic low weight and zinc binding protein, has attracted considerable interest due to its release into the cerebrospinal fluid and blood from brain tissue following brain damage and from malignant melanomas. A new simple two-step incubation assay has now been elaborated in which two catcher and one tracer monoclonal antibodies are used. The specificity of this assay is high because all the MAbs used bind exclusively to S-100B, as shown by real-time biospecific interaction analyses. Moreover, the working range of the assay is 0.2-60 micrograms/L with a CV of less than 10%; the resulting high sensitivity has been confirmed by clinical studies. Time dependence, shaking conditions, lower limit of detection limits, effects of dilution, hook effect, recovery, impression as intra- and interassay variations, and crossreactivities with S-100A1 were tested in order to obtain a highly reproducible assay. Sera from healthy blood donors and patients undergoing cardiopulmonary bypass operations were tested with the assay. Several of the patients undergoing open heart surgery presented measurable values in this IRMA S-100 assay, indicating cerebral effects of open heart surgery. The test may be used for postoperative monitoring of these patients.
Clinical diagnosis of STDs is unreliable and therefore constitutes a poor basis for choice of treatment. A syndromic approach has been suggested to increase effectiveness of treatment in resource poor settings. Algorithms for the treatment of STD syndromes were evaluated. A total of 436 patients were followed; cure rates were defined and estimated for genital ulcer disease (GUD), urethral and vaginal discharge. Cure rates for the discharge syndromes were high, 97-98%, for both sexes. The cure rate for GUD was 83% for female and 69% for male patients. A higher prevalence of syphilis in the female study population probably contributed to this. It is likely that a large proportion of the treatment failures were due to decreased susceptibility of Haemophilus ducreyi to trimethoprim-sulpha. The determination of cure rates met with a number of methodological problems. This makes it difficult to evaluate the algorithms as part of routine activities, as suggested earlier by WHO.
Isotope technique and determination of the intramitochondrial concentration of GSH were used with the aim of studying the uptake of alloxan in isolated mouse mitochondria. A significantly decreased concentration of GSH was observed in mitochondria from liver and pancreas incubated with alloxan. This effect was significantly more marked in mitochondria depleted of Pi. Increased radioactivity was found in isolated mitochondria from liver, exocrine pancreas and endocrine pancreas incubated with 14C-2-alloxan. Even this effect was significantly more marked in Pi depleted mitochondria. Isolated liver mitochondria of the KsJ-strain of C57BL-mice possessed a significantly lower concentration of endogenous Pi than those of the 6J-strain. The findings support the view that alloxan can pass across the inner mitochondrial membrane, and suggest that the intramitochondrial concentration of Pi is one of the factors which has an influence on the uptake of alloxan in isolated mouse mitochondria.