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Biomedical subjects

S E Holm

Publications and source records attributed to S E Holm.

At least 19 recordsLinked to original sources

The prevalence of potentially pathogenic bacteria in nasopharyngeal samples from individuals with a long-standing cough-clinical value of a nasopharyngeal sample.

BACKGROUND: A long-standing cough is a common cause for visits to a GP. If the patient also has a respiratory tract infection, one of the concerns of the doctor is to decide if the cough is caused by an underlying bacterial infection. OBJECTIVES: Our aim was to investigate whether a nasopharyngeal sample, obtained in routine medical practice, could yield information about the aetiology of a long-standing cough in patients with a respiratory tract infection. METHODS: The prevalence of potentially pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) in nasopharyngeal swab samples from 618 healthy individuals was compared with that from 236 patients with a respiratory tract infection and long-standing cough (>9 days) of the same age in a defined geographical area. RESULTS: The proportion of cultures with potentially pathogenic bacteria decreased with age and was 44% among healthy individuals of pre-school age, 13% in schoolchildren and 6% in adults. The corresponding figures for patients with a long-standing cough were 83, 35 and 36%, respectively. All types of potentially pathogenic bacteria were found more frequently in pre-school children and in adults with a long-standing cough compared with healthy individuals of the same age. CONCLUSIONS: In patients with a respiratory tract infection and a long-standing cough, where a bacterial infection is suspected on clinical grounds, a nasopharyngeal culture could yield information about the aetiology. If M.catarrhalis is found in pre-school children, or if H.influenzae is found in adults, they are likely to be the aetiological agent.

Adolescent

Bacterial contamination and sperm recovery after semen preparation by density gradient centrifugation using silane-coated silica particles at different g forces.

The effects of density gradient centrifugation through silane-coated silica particles (PureSperm) using 100, 200, 300 and 500 g on bacterial contamination of sperm samples and recovery of motile spermatozoa from sperm samples were investigated with conventional culturing techniques and microscopic visual assessment. The recovery of motile spermatozoa was variable and was not improved using 500 g compared to the recommended 300 g. The bacterial contamination was highly decreased by gradient centrifugation through PureSperm and was almost abolished when strict aseptic techniques were used, with changes to sterile Pasteur pipettes and tubes prior to washing procedures.

Adult

Allele substitution of the streptokinase gene reduces the nephritogenic capacity of group A streptococcal strain NZ131.

To investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strain Streptococcus equisimilis H46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131. The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN. The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain. The mutant and the wild-type strains produced equivalent amounts of streptokinase. Complementation of the ska deletion derivative with the original ska allele reconstituted the nephritogenicity of wild-type NZ131. The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.

Alleles

In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis by alpha-hemolytic streptococci from healthy children.

The present study aimed to investigate the inhibitory activity of the normal epipharyngeal flora against the three most common acute otitis media (AOM) pathogens in healthy children, and to study if the inhibitory activity differs between alpha-hemolytic streptococci (AHS) sampled from the tubal orifice and from those sampled from the adenoid. A total number of ten isolates of AHS were collected from the tubal orifice and the adenoid, respectively, in ten children undergoing adenoidectomy or tonsillectomy. None of the children had a history of otitis media, neither secretory otitis media (SOM) nor AOM. The method used to test the bacterial interference in vitro was a modified agar overlay method. The results showed that the AHS from nasopharynx were able to inhibit the majority of the S. pneumoniae, nontypable Haemophilus influenzae and Moraxella catharralis isolates tested. The AHS isolates from the tubal orifice inhibited growth of 93% of S. pneumoniae, 79% of H. influenzae and 84% of M. catharralis isolates. The corresponding figures among isolates from the adenoid were 76, 48 and 62%. This difference in the inhibitory capacity between the AHS isolates collected from the adenoid, compared with the AHS collected from the tubal orifice, is statistically significant (P<0.01) and implies that it is important to know the exact sampling locality before conclusions are made concerning the significance of bacterial interference in the upper airways.

Adenoids

Tolerance and efficacy of interfering alpha-streptococci in recurrence of streptococcal pharyngotonsillitis: a placebo-controlled study.

A total of 342 patients with clinical signs of tonsillitis and suspected group A beta-haemolytic streptococci (GAS) aetiology, verified with rapid test and GAS culture, were enrolled in a randomized, placebo-controlled, double-blind, multicentre study. They received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococcal or placebo spray treatment in the ratio of 2 : 1. Pharyngeal status, throat culture and adverse events were investigated up to 75 days after treatment. The frequency of bacteriologically verified clinical recurrence was 13% in the alpha-streptococcal group and 15% in the placebo group at the follow-up on day 22. The corresponding figures at the last valid visit after 45-75 days were 19% and 30%, respectively, a statistically significant difference (p = 0.037). Furthermore, at the last valid visit 5% of subjects in the alpha-streptococcal and 12% in the placebo group were healthy carriers, bacteriological treatment failures, of GAS (p = 0.029). Treatment with alpha-streptococci and placebo spray were equally well tolerated. Thus, re-colonization with alpha-streptococci seem to hinder late recurrences of GAS pharyngotonsillitis.

Adolescent

Pathogenic mechanism of acute post-streptococcal glomerulonephritis.

Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease.

Acute Disease

Perianal streptococcal dermatitis. The possible protective role of alpha-streptococci against spread and recurrence of group A streptococcal throat infection.

OBJECTIVE: To follow the spread of beta-haemolytic streptococci group A (GAS) within a family and examine the protective activity of normally occurring alpha-streptococci against GAS tonsillitis. DESIGN: Follow up of recurrent GAS throat infection within a family. SETTING: Intra familial spread of GAS. PATIENTS: A family of four, the mother suffering from recurrent streptococcal tonsillitis and a son with perianal streptococcal dermatitis. RESULTS: The strain of the GAS found in the perianal region of the boy was identical with that found in the throat of his mother. She had recurrent streptococcal tonsillitis, while the boy remained healthy in the throat. She lacked interfering alpha-streptococci in the throat, while the boy had a massive growth of alpha-streptococci in his throat with capacity to inhibit the growth of the streptococcal isolate. MAIN OUTCOME MEASURES: Infection with GAS within a family correlated with the growth-inhibiting activity of the alpha-streptococci in vitro. CONCLUSIONS: The study demonstrated the spread of GAS from a patient with streptococcal dermatitis to the throat of another person within the family, and the hindrance of induction of infection in patients carrying interfering alpha-streptococci.

Anus Diseases

Invasive group A streptococcal infections: T1M1 isolates expressing pyrogenic exotoxins A and B in combination with selective lack of toxin-neutralizing antibodies are associated with increased risk of streptococcal toxic shock syndrome.

Analysis of 132 group A streptococcal (GAS) isolates from 151 invasive episodes, including streptococcal toxic shock syndrome (STSS), from 1983 to 1995 showed great genetic variation by use of T serotyping in combination with restriction fragment length polymorphism. In contrast, genetically homogenous T1M1 isolates appeared in epidemic patterns with significantly increased risk of STSS. The speA gene, with the allelic variants speA2 and speA3 carried by the T1M1 and T3M3 serotypes, respectively, was strongly associated with STSS. Infection with a GAS isolate carrying speA, alcohol abuse, and malignancy recently treated with cytostatic drugs were factors independently related to STSS. Neutralization of SpeA lymphocyte mitogenicity was totally absent in sera from patients with STSS and low in sera from persons with uncomplicated bacteremia compared with levels in sera from uncomplicated erysipelas. Neutralization of SpeB was significantly lower in sera of patients with STSS than in sera from persons with bacteremia or erysipelas.

Adult

The role of fiberoptic endoscopy in dysphagia rehabilitation.

The clinical bedside swallow evaluation and videofluoroscopy routinely have been used for dysphagia management. This article explores clinical issues for dysphagia management in the population with brain injury in the acute rehabilitation setting. Citing the dysphagia, cognitive, and other relevant issues present in the population with brain injury, the use of fiberoptic endoscopy to address dysphagia assessment and intervention is presented. Factors for decision making, a retrospective review of recent studies, and relevant cases are discussed.

Acute Disease

Synchronous occurrence of carcinoid tumour of the appendix and T-cell lymphoma of the ileum. A case report with review of the literature.

Carcinoid tumours of the gastrointestinal tract are often associated with other tumour types at various sites. However, only rarely has a lymphoma constituted the second tumour. In the present paper, we report the case of a 62-year-old woman who was operated on for a perforated T-cell lymphoma of the ileum and in whom an appendicular carcinoid tumour was incidentally discovered at surgery. It was possible to completely remove both tumours and postoperatively the patient underwent CHOP treatment. Ten months after surgery the patient is well, with no tumour manifestations. We also discuss problems concerning classification of the lymphoma on account of loss of the T-cell antigen CD45RO (UCHL-1).

Appendiceal Neoplasms

Streptococcal DNase B is immunologically identical to superantigen SpeF but involves separate domains.

The previous suggestion that streptococcal superantigen SpeF might be identical to DNase B was confirmed in this study. Polyclonal SpeF-specific antisera were able to inhibit depolymerization of methyl-green DNA by DNase B. However, T-cell mitogenicity and nuclease activity appear to involve separate immune epitopes on SpeF, since sera with the capacity to neutralize the mitogenic activity of SpeF did not always inhibit the DNase activity.

Animals

Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF).

A series of 11 synthetic peptides of 30 amino acids, each with 10 amino acids overlap which spanned the entire sequence of streptococcal pyrogenic exotoxin F (SpeF), were employed in proliferation studies on human peripheral blood mononuclear cells (PBMCs). Regions 41-70, 141-170 and 181-210 were identified as important for SpeF-induced lymphocyte activation. Secondary structure predictions of these peptides showed similarities to regions in other superantigens known to be important for T cell mitogenicity. Furthermore, antisera specific to peptides covering amino acids 1-70 and 181-228 were able to inhibit SpeF-induced mitogenicity by 25% when pre-incubated with SpeF prior to PBMC activation.

Adjuvants, Immunologic

The prevalence of potential pathogenic bacteria in nasopharyngeal samples from healthy children and adults.

OBJECTIVE: To elucidate the prevalence of potential pathogenic bacteria in nasopharyngeal samples from healthy individuals, and the influence on the carrier rate of age, season of the year, and type of child day care. DESIGN: Nasopharyngeal swab samples obtained in routine medical care from individuals with no sign of infection were studied in 159 pre-school children aged below 7 years, 198 schoolchildren aged 7-15 years, and 261 adults (.16 years). RESULTS: The prevalence of pathogenic bacteria in healthy individuals decreased with age. The overall isolation frequencies for pre-schoolchildren, schoolchildren, and adults, respectively, were: Moraxella catarrhalis (27%, 4% and 2%); Streptococcus pneumoniae (19%, 6% and 0.8%); Haemophilus influenzae (13%, 6% and 3%). The prevalence of S. pneumoniae in children 7-15 years was higher during the summer than in the winter. We could not confirm any variation in the carrier rate due to the type of child day care. CONCLUSION: Potentially pathogenic bacteria are often present in nasopharyngeal samples taken from healthy pre-school children, but rarely from people > or = 16 years of age. This means that the use of nasopharyngeal samples to discriminate between bacterial and viral respiratory tract infection needs to be evaluated further in patients < 16 years. The importance of the seasonal variation in the prevalence of potential pathogenic bacteria in the nasopharynx needs further study.

Adolescent

Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome.

In a retrospective study of invasive infections due to group A Streptococcus (GAS) in Stockholm during 1987 to 1995, the average incidence per 100,000 residents per year was 2.3, varying between 3.7 per 100,000 (in 1988) and 1.3 per 100,000 (in 1993). Incidence was 1.8 in the age group of 0-4 years but otherwise increased by age, from 0.48 in the age group of 5-14 years to 6.1 among those over 65 years of age. A review of 151 invasive episodes occurring in 1983-1995 showed cyclic increases of infections due to T1M1-serotype strains during 1986-1990 and 1993-1995. The T1M1 serotype accounted for 27 (20%) of 135 available GAS strains. Streptococcal toxic shock syndrome (STSS) developed in 19 (13%) of the 151 episodes. The case fatality rate was 11% overall but 47% among patients with STSS. In a multivariate logistic regression model, STSS was associated with a history of alcohol abuse (odds ratio [OR], 6.3; P = .004) and infection with a T1M1 strain (OR, 6.7; P = .007). Case fatality was associated with age (OR, 14.5; P = .08), immunosuppression (OR, 4.7; P = .02), and STSS (OR, 21.5; P < .0001) but not with T1M1 infection. Hypotension was significantly associated with a fatal outcome, regardless of whether STSS developed (P < .0001).

Adolescent

Estimation of type-specific anti-streptococcal M-protein antibodies with biotinylated peptides in human sera.

The design of a novel enzyme-linked immunosorbent assay for the estimation of antibodies directed against the N-terminus of the M-protein of Streptococcus pyogenes is described. The ELISA employs biotinylated peptide antigens of the types 1, 4, 12 and 19 immobilized by (strept-)avidin on the surface of polystyrene microtiter wells. In rabbit hyperimmune sera and in human serum samples, antibodies against the corresponding serotype could be detected with high sensitivity and specificity.

Adult

Streptokinase as a mediator of acute post-streptococcal glomerulonephritis in an experimental mouse model.

Group A streptococcal infections are sometimes followed by the inflammatory kidney disease acute post-streptococcal glomerulonephritis (APSGN). To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associated ska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice. In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains. After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed. Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection. These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade. Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity. Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition.

Animals

Chloroform mode of action: implications for cancer risk assessment.

Risk assessment methodology, particularly pertaining to potential human carcinogenic risks from exposures to environmental chemicals, is undergoing intense scrutiny from scientists, regulators, and legislators. The current practice of estimating human cancer risk is based almost exclusively on extrapolating the results of chronic, high-dose studies in rodents to estimate potential risk in humans. However, many scientists are questioning whether the logic used in this current risk assessment methodology is the best way to safeguard public health. A major tool of human cancer risk assessment is the linearized multistage (LMS) model. The LMS model has been identified as an aspect of risk assessment that could be improved. One way to facilitate this improvement is by developing a way to incorporate a carefully derived, more biologically relevant mechanism of action data on carcinogenesis. Recent data on chloroform indicate that the dose-response relationship for chloroform-induced tumors in rats and mice is nonlinear, based upon events secondary to cell necrosis and subsequent regeneration as the likely mode of action for the carcinogenic effects of chloroform. In light of these data, there is a sound scientific basis for removing some of the uncertainty that accompanies current cancer risk assessments of chloroform. The following points summarize the critical data: (1) a substantial body of data demonstrates a lack of direct in vivo or in vitro genotoxicity of chloroform; (2) chloroform induces liver and kidney tumors in long-term rodent cancer bioassays only at doses that induce frank toxicity at these target sites; (3) the chloroform doses required to produce tumors in susceptible species exceed the MTD, often by a considerable margin; (4) cytotoxicity and compensatory cell proliferation are associated with the chloroform doses required to induce liver or kidney tumors in susceptible rodent species; (5) there are no instances of chloroform-induced tumors that are not preceded by this pattern of dose-dependent toxic responses; (6) it is biologically plausible that cytolethality leads to chronically stimulated cell proliferation and related events such as inflammation and growth stimulation which act to initiate and promote the carcinogenic process; and (7) the consistently linked cellular events of cytolethality and subsequent cell proliferation, for which doses of no adverse effect have been clearly shown to exist, are one of the biological prerequisites for chloroform-induced tumors in animals. Based on these data, it is inappropriate to extrapolate cancer risk from high doses that produce necrosis and regenerative cell proliferation to low doses that do not with a model that presumes genotoxicity and a linear dose-response relationship. The weight of the scientific evidence concerning chloroform-induced tumors in rodents is consistent with and supports a cancer risk assessment methodology based on mode of action as the basis for establishing regulatory standards for this compound.

Administration, Inhalation