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Biomedical subjects

E Olding-Stenkvist

Publications and source records attributed to E Olding-Stenkvist.

At least 19 recordsLinked to original sources

Diagnosis of pulmonary infections in immunocompromised patients by fiber-optic bronchoscopy with bronchoalveolar lavage and serology.

Fiber-optic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) were performed on 67 occasions in 57 immunocompromised patients with symptoms consistent with pulmonary infection. Diagnosis was achieved more often in renal transplant patients than in patients with hematological malignancies (85% versus 28%). Culture (bacteria, virus, fungi), staining and microscopy (bacteria, fungi, Pneumocystis carinii (PC)) and antigen detection by indirect immunofluorescence (cytomegalovirus (CMV), respiratory viruses, PC, Legionella) were used for diagnosis. On 20 occasions transbronchial biopsies with histopathologic examination were performed. In addition, serology comprising the herpes group (HHV-6) and respiratory viruses was done. A microbial diagnosis was obtained on 45% of occasions. The most common pathogens found were CMV (31%) and PC (25%). On 22 (33%) occasions a rapid diagnosis of 1 or more microbial agents was obtained within 24 h by conventional staining or indirect immunofluorescence. The clinical relevance of findings of CMV, HHV-6, and Epstein-Barr virus in BAL by polymerase chain detection on 18, 6 and 3 occasions is discussed. On 4 occasions pathogenic bacteria were found. It was not possible to relate findings of coagulase-negative staphylococci, alpha-streptococci and Candida albicans to the pulmonary infection.

Adolescent↗

Diagnostic markers and risk factors of cytomegalovirus infection and disease in renal allograft recipients.

In a prospective study, the incidences of CMV infection and disease were 56 and 23%, respectively, during the first 6 months following kidney transplantation. Viremia was found in all patients with CMV disease and arthralgia was present in 71% prior to the development of CMV disease. The positive predictive value for CMV disease reached up to 90% for viremia and arthralgia in combination. Viruria was poorly correlated to viremia and hence CMV disease. The majority of patients (93%) who developed CMV disease had a seropositive donor, and viremia was significantly more common in patients who received CMV-seropositive kidneys. CMV disease was more common in CMV-seronegative recipients than in seropositive recipients. The 1-year graft survival rate was 75% in the entire study group. In patients with CMV viremia and disease, the rates were 78 and 73%, respectively. Antiviral treatment was initiated within 3 weeks of viremia detection in the 6 patients with CMV disease who survived. We found that the combination of arthralgia and viremia was a useful predictor of CMV disease and that recipients of CMV-seropositive allografts were at a greater risk of developing CMV disease. To obtain an early diagnosis and commence an early treatment of CMV disease, patients prone to develop CMV disease should be identified and clinical examination and viremia surveillance should be performed regularly.

Adolescent↗

Diagnosis of cytomegalovirus in bronchoalveolar lavage by polymerase chain reaction, in comparison with virus isolation and detection of viral antigen.

Bronchoalveolar lavage (BAL) products from 52 immunocompromised patients with symptoms of pulmonary infection was examined for cytomegalovirus (CMV) by virus isolation, polymerase chain reaction (PCR) and detection of CMV antigen by immunofluorescence or immunoperoxidase staining after short-term incubation in tissue culture and directly in BAL cells. We found that PCR detected all cases positive by virus isolation (15/52 samples) and the result was obtained within 5 h. PCR detected more cases of CMV than did virus isolation (22/52 samples). Positive PCR and negative virus isolation were consistent with probable CMV infection in 3/7 patients when other clinical and laboratory parameters of CMV infection were considered. The negative predictive value of PCR was high; none of 30 patients negative by PCR developed CMV pneumonia within the subsequent 2 months. Detection of CMV antigen after short-term incubation was rapid enough to be used in clinical practice, specific (100%) and with a sensitivity of 60%. Demonstration of CMV antigen in alveolar cells was highly specific (100%) but had too low a sensitivity (26.7%) to be used as the only rapid method. Our conclusion is that a combination of PCR and detection of CMV antigen after short-term incubation and directly in alveolar cells is optimal for rapid identification of CMV.

Adolescent↗

Early detection of cytomegalovirus in cell culture by a new monoclonal antibody, CCH2.

A CMV monoclonal antibody, CCH2, produced in this laboratory was evaluated for rapid detection of CMV. Two staining procedures, immunofluorescence and an immunoenzymatic technique using biotin-streptavidin peroxidase, were compared. The CCH2 monoclonal antibody was used to demonstrate early CMV antigen in cell culture 24 h after inoculation of 598 urine samples from kidney transplanted patients by indirect immunofluorescence in comparison with virus isolation. One hundred and sixty of the specimens were stained additionally by an immunoenzymatic technique and the results were compared. CMV was isolated from 170 out of 598 specimens within 6 weeks. Early CMV antigen was demonstrated in 114 of these specimens by immunofluorescence giving a sensitivity of 67% and a specificity of 95%. In the comparison with the immunoenzymatic staining procedure the results for all three tests agreed for 81% (130/160) of the specimens. After resolving discordant results into true positives and true negatives, the sensitivity was 87, 85 and 70%, respectively for virus isolation, immunoenzymatic staining and immunofluorescence and the specificity 100, 96 and 99%. The CCH2 monoclonal antibody proved to be useful for rapid detection of CMV in urine specimens and using immunoenzymatic staining with biotin-streptavidin a sensitivity comparable to that of virus isolation was found.

Antibodies, Monoclonal↗

Cytological and DNA characteristics of hyperplasia/inflammation and cancer of the prostate.

A study has been made of the correlation between objectively measured nuclear DNA content (by image analysis cytometry) and visual pathologic/cytologic diagnoses in hyperplasia/inflammation and well, moderately and poorly differentiated carcinomas of the prostate. The DNA measurement data were described by four statistical description methods--namely mean deviation from 2C, percentage greater than 4.25 C, DNA index and entropy. In 36% (5/14) of well differentiated and 13% (1/8) of moderately differentiated cancer it was not possible by objective measurement methods to demonstrate any difference between hyperplasia/inflammation and cancer. On the other hand one or more of the statistical descriptors was significantly different from hyperplasia/inflammation in all of those cancers visually diagnosed as poorly differentiated. The results underline the need for improvement of diagnostic criteria of prostate cancer--in particular well differentiated--in order to correctly understand the epidemiology (true incidence), survival and effects of treatment on the disease.

DNA↗

Specific in vitro IgG subclass synthesis and lymphocyte proliferation responses in herpes virus encephalitis.

Cerebrospinal fluid, peripheral blood lymphocytes (PBL) and sera from 5 patients with herpes simplex encephalitis (HSVE), 3 with varicellae zoster (VZV) meningoencephalitis and 5 with encephalitis of unknown origin (NUD) were analyzed. Lymphocytes from both blood and CSF were shown to synthesize anti-VZV IgG subclasses in VZV meningoencephalitis and anti-HSV IgG subclasses in HSVE. The subclass patterns of CSF and in vitro synthesized anti-viral IgG were similar, suggesting that a considerable portion of the antiviral IgG subclasses detected are synthesized in the CNS compartment. Antigen presentation in vitro seemed to produce a heterologous IgG4 and/or 3 response in 3 patients. Lymphocyte proliferation was detectable in response to HSV and VZV, respectively.

Antibodies, Viral↗

Antibodies against varicella-zoster virus and herpes simplex virus deoxythymidine kinase in heterologous infections.

Antibody responses to varicella-zoster virus (VZV) deoxythymidine kinase (dTK) and herpes simplex virus (HSV) dTK in homologous and heterologous infections were studied. Antibodies blocking the enzymatic activity of VZV-dTK appeared late after varicella and decreased more or less in parallel with the decreasing complement fixing [CF] titre. In herpes zoster, on the other hand, antibodies to VZV-dTK appeared soon after infection. Antibodies against HSV dTKs appeared long after primary infection, but they were subsequently present in all other HSV-CF positive sera. In recurrent HSV, all acute sera were already HSV-dTK antibody positive, and three of nine persons showed an increase in titer between their acute and convalescent sera. Blocking antibodies to VZV-dTK appeared rapidly in specimens from three of 18 individuals positive by an immunofluorescence VZV-immunity test during HSV infection, whereas all other specimens remained devoid of blocking antibodies against VZV-dTK. A rise in antibody titre against HSV-dTK during VZV infections was observed in serum specimens from three of 13 HSV-CF positive patients, whereas an antibody response against HSV-dTK was not found in HSV-CF negative individuals in connection with VZV infections. The relevance of the sporadic increase in the titres of antibodies against heterologous viral dTKs is discussed.

Adolescent↗

Antiviral IgM and IgG subclasses in varicella zoster associated neurological syndromes.

The varicella zoster virus (VZV) and herpes simplex virus (HSV) IgGl-4 subclasses were compared in serum and cerebrospinal fluid (CSF) of 22 patients with VZV-associated neurological symptoms, 12 patients with HSV-associated neurological symptoms and 14 controls. The clinical syndromes of the VZV-associated diseases comprised meningo-encephalitis, myelitis, myelopathies and polyneuropathies, mostly with a favourable outcome. A characteristic finding was an intrathecal synthesis of VZV IgG1 and HSV-3. Commonly also IgG2 and 4 were seen in CSF of VZV patients. Their intrathecally synthesised HSV IgG was restricted to IgG1. VZV IgG3 occurred in serum and/or CFS together with VZV IgM in 14 cases and may be a marker of recent VZV replication. In patients with HSV-associated neurological disease, a multi-IgG subclass HSV response and concomitant VZV antibodies restricted to IgG1 was found. Intrathecal synthesis of both HSV and VZV IgG occurred in 20 patients. Detection of two or more VZV or HSV specific IgG subclasses synthesised intrathecally identified the aetiological agent in 19 of these 20 cases.

Adult↗

Varicella zoster virus deoxythymidine kinase is present in serum before the onset of varicella.

A sensitive enzyme assay with 125I-iododeoxyuridine as substrate and cytidine triphosphate as phosphate donor was used for the direct detection of varicella zoster virus (VZV) deoxythymidine kinase (TK) in human serum. Sera sampled during the incubation period of varicella from 2 patients, a 42-year-old man and his 11-year-old son, have been analysed for TK activity. A simultaneous increase in cellular and VZV TK activity, starting 5 to 3 days before the onset of clinical varicella, was observed.

Adult↗

Detection of giardia antigen in stool samples by a semi-quantitative enzyme immunoassay (EIA) test.

A semi-quantitative enzyme immunoassay (EIA) test for the detection of Giardia intestinalis antigen in faeces was developed. In order to avoid unspecific reactions due to anticalf serum activity, IgG fractions of anti-giardia rabbit and sheep sera were purified from antibovine antibodies by immunoadsorption. Faecal specimens tested in the assay were mixed with normal horse serum to avoid unspecific and proteolytic effects of stool components. Out of a range of bacterial and parasitic antigens tested, only high concentrations of Ascaris suum egg antigen and Shigella sonnei gave slight unspecific reactions. During an outbreak of waterborne giardia infection faecal samples from 49 individuals were tested. Giardia cysts were found by microscopy in 22 individuals and specimens from 24 persons were positive by EIA. The estimated amount of antigen found in the positive samples ranged from 50 to 5,000 ng giardia protein/ml. After filtration through a 0.45 microns filter antigenic activity was found in the filtrate of 10 samples. In 3/6 samples with no cysts detected by microscopy, mainly soluble giardia antigen was found.

Adolescent↗

Specific IgG subclass reactivity in herpes simplex encephalitis.

Serum and cerebrospinal fluid (CSF) samples from 19 patients with a previous diagnosis of herpes simplex virus encephalitis (HSVE), from 14 patients with a previous diagnosis of non HSVE encephalitis and from 21 healthy subjects were examined to detect IgG subclasses 1-4 reactive with herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV). Antibodies to HSV were detected in CSF and serum from the 14 HSVE-patients with a reactivated HSV infection and from 3 of the 5 patients with a primary HSV infection. The predominant subclass pattern was an early HSV-specific IgG1 rise, followed by IgG3 and, more seldom, IgG4; HSV IgG2 was rarely seen. In HSVE patients, HSV IgG3 was absent in early samples and usually appeared 10-20 days after onset of disease. In 14 out of 16 seropositive healthy controls, on the other hand, HSV IgG3 was present in the CSF. Rising VZV IgG levels in serum and CSF were found in 11 HSVE patients. Eight of them showed signs of intrathecal VZV IgG1 synthesis. The VZV IgG reactivity was restricted to IgG1 in 7 of these whereas the HSV IgG subclass response also included IgG3 or 4. The appearance of several HSV IgG subclasses appeared to serve as a marker of HSV infection in spite of the serological VZV reaction, usually restricted to VZV IgG1. Intrathecal synthesis of the quantitatively minor HSV IgG3 and 4 subclasses was detected earlier than intrathecal synthesis of total HSV IgG, dominated by IgG1 in 4 patients with HSVE.

Encephalitis↗

Detection of viral antigens in cerebrospinal fluid of patients with herpes simplex virus encephalitis.

Thirty-two cerebrospinal fluid (CSF) samples from eighteen patients with confirmed herpes simplex encephalitis (HSE) were assayed by an indirect enzyme-linked immunosorbent assay (ELISA) for the presence of viral antigens. The results are expressed as an antigen ratio distinguishing between herpes simplex virus (HSV) antigens containing samples and negative samples. Judged by this criterion a positive result was obtained in 33% of the patients. Overall, 25% of the CSF samples from HSE patients were positive. In one out of 33 control patients with other neurological disorders a positive antigen ratio was found. Two or more CSF samples were available from eleven patients. In six of these, the second or later samples showed a decreased antigen ratio when compared to the first CSF sample. An increase of the anti-HSV antibody titer was seen in the CSF of five of these six patients. Five out of six patients with a decreasing antigen ratio had an unfavorable outcome of their encephalitis, while a favorable outcome was seen in four of the five patients with an increasing or steady antigen ratio. A decrease of the antigen ratio in the course of HSE can be explained by the presence of immune complexes in CSF and may indicate a poor prognosis.

Antibodies, Viral↗

Aetiology and epidemiology of acute gastro-enteritis in Swedish children.

In a prospective 1-year study, 144 children attending or admitted to hospital and 272 children outside hospital with acute gastro-enteritis and 200 controls were investigated by a broad panel of diagnostic methods for enteropathogenic agents in the faeces and for related antibody responses. Enteropathogens were identified in 77% of the inpatients, 63% of the outpatients and 8% of the controls. Rotavirus and Yersinia enterocolitica were detected significantly more often among inpatients. Altogether, viral, bacterial and parasitic agents were found in 58%, 14% and 1% of diarrhoeal patients, respectively. The isolation of more than one pathogenic agent was uncommon (6.5%). Rotavirus (45%) and enteric adenoviruses 40 and 41 (7.9%) predominated among the viruses, while Campylobacter jejuni (4.8%) was most common among the bacteria. Clostridium difficile and/or its cytotoxin, which were found in 14% of the children with gastroenteritis and in 15% of the controls, were significantly associated with antibiotic therapy but not with gastro-intestinal illness. Diarrhoeal infections of unknown aetiology exhibited a seasonal peak in the autumn. The duration of excretion of enteropathogens was investigated. Rotavirus particles were detectable by solid-phase immune electron microscopy for 14-25 days after the diarrhoea had ceased. Transmission of rotavirus and bacterial pathogens within families was studied also.

Acute Disease↗

Clinical features of acute gastroenteritis associated with rotavirus, enteric adenoviruses, and bacteria.

In a prospective one year study, comprising children with acute gastroenteritis admitted to hospital or treated as outpatients, the clinical and laboratory features of rotavirus diarrhoea (168 cases) were compared with those of enteric adenovirus (32 cases), bacterial (42), mixed (16), and non-specific (135) infections. The rotavirus disease was remarkably consistent, with a sudden onset of vomiting, a high frequency of fever and dehydration, and a mean duration of diarrhoea of 5.9 days. Outpatients excreting rotavirus had a similar but milder illness, mainly on account of less pronounced vomiting. The predominant symptom of enteric adenoviruses was long lasting diarrhoea (mean 10.8 days). Abdominal pain, bloody stools, prolonged diarrhoea (mean 14.1 days), leucocytosis, and a raised erythrocyte sedimentation rate strongly suggested a bacterial aetiology. Mixed infections caused longer lasting diarrhoea (mean 8.0 days) than rotavirus alone, but the severity of the illness was not increased. The clinical features of infection with unidentified pathogens most resembled those of bacterial infections. Respiratory symptoms were not significantly associated with any particular pathogen. Hypernatraemia and complications were uncommon. This study showed that the clinical features of gastroenteritis with rotavirus, enteric adenoviruses, and bacteria each exhibited patterns that could guide the experienced clinician to a presumptive diagnosis.

Adenoviridae Infections↗