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Biomedical subjects

C Metzger

Publications and source records attributed to C Metzger.

At least 19 recordsLinked to original sources
PubMed2004

Comparison of two sites in Mobile Bay using in vivo biomarkers in largemouth bass, sediment bioassays, and sediment contaminant analysis.

This research addresses whether chemical contaminants are having a biologically measurable effect on largemouth bass (Micropterus salmoides), an important fish species in the Mobile Bay National Estuary. Bass and sediment samples were collected in September 2001 from Big Bateau and D'Olive Bays; the latter has been suggested to be an environmentally impacted site. There was a significant difference in the age distribution of bass collected from the two sites. However, none of the animals showed any evidence of reproductive activity or had mature gametes. The age and gonadosomatic index were greater in animals collected from the Bateau site. Fish liver microsome ethoxyresorufin-O-deethylase (EROD) activities (elevated in the presence of CYP1A-inducing contaminants) were not significantly different between sites but were significantly higher in older bass. Plasma steroid concentrations in younger animals (less than 1 year old) tended to be higher and more variable than the concentrations found in older animals. Once the significant effects of age on plasma steroid concentrations were removed, an analysis of the residual change in steroids revealed no differences in testosterone or estradiol between animals collected at the two sites. Sediments were collected for chemical extraction and analysis in two bioassays: the H4IIE rat hepatoma EROD assay and the yeast estrogen screen (YES assay). The H4IIE bioassay indicated the presence of sediment BaP induction equivalents between 72 and 320 ng/g, whereas the YES assay indicated that potent estrogenic substances were not present in the sediment samples. The H4IIE bioassay results were higher for D'Olive samples, which was consistent with higher PAH concentrations in those sediments. Taken together the biomarkers and chemical analysis suggested generally low organic contamination at these two sites.

Alabama↗
PubMed2002

[The use of rapid tests for individual diagnosis of influenza].

Antiviral therapy against influenza requires the beginning of treatment within 36 to 48 h after the onset of symptoms. With the availability of the neuraminidase inhibitors which are effective against influenza A and B a rapid diagnosis of influenza is of increasing interest. A diagnosis during the first consultation would be ideal for treatment. This can be achieved with clinical diagnosis and with quick tests that can be conducted in the practice (point of care test). The costs of such virological examinations have to be considered in relation to the use of information they create. The cost benefit relation is discussed in relation with different epidemic situations. The benefit and additional information of tests for individual diagnosis is high when the incidence of influenza is low, while in periods with high incidences the clinical diagnosis alone appears sufficient.

Antiviral Agents↗
PubMed2001

First outbreak of callitrichid hepatitis in Germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains.

Callitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were > or =99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains.

Amino Acid Sequence↗
PubMed2001

[Rational and efficient enterovirus diagnosis].

BACKGROUND AND OBJECTIVE: Demonstration of the causative pathogen by isolating the virus in cell culture is taken as the standard in the diagnosis of diseases caused by enterovirus. When diagnosing the virus in cerebrospinal fluid (CSF), isolation of the virus has been largely replaced by the rapid demonstration of the virus using the reverse transcriptase polymerase chain reaction (RT-PCR), because of its greater sensitivity. The serological diagnosis is mostly made with the complement binding reaction (CBR). A new enzyme immunoassay for demonstrating anti-enterovirus IGM antibodies (IgM-EIA) allows a more rapid diagnosis from a single serum sample. It was the aim of this study to compare the diagnostic value of these various tests. METHODS: Several methods for demonstrating virus from faeces, swabs and CSF (virus isolation in cell culture and RT-PCR) and of antibodies in serum (IgM-EIA and CBR) were compared. The clinical material was obtained largely from children under the age of 10 years, many of whom had serous meningitis, flu-like symptoms or enteritis. In one cohort (C1), only stool or throat swabs were available for each of 154 patients. In the other cohort (C2) of 164 patients, CSF and at least one serum sample were available in addition to occasional stool samples. RESULTS: From C1 enteroviruses were isolated from 32 patients. rotavirus twice from stool or throat swab and rotavirus once from stool or throat swab, and herpes simplex once from throat swab. RT-PCR was positive 55 times for enterovirus, five times false-negative when the virus had been isolated. In C2 enterovirus nucleic acid was demonstrated in 43 patients from CSF. Parallel serological tests gave positive IgM values for 15 patients, while CBR titres were raised in nine. CONCLUSIONS: Complementary tests of CSF, stool, swabs and serum samples by all possible combinations of viral isolation, RT-PCR and IgM-EIA improve the diagnosis of enterovirus-associated diseases. RT-PCR is the method of choice. The serological diagnosis should be confirmed by the demonstration of virus in stool or swab.

Adolescent↗
PubMed2000

Evaluation of enterovirus serological tests IgM-EIA and complement fixation in patients with meningitis, confirmed by detection of enteroviral RNA by RT-PCR in cerebrospinal fluid.

An enzyme immunoassay (EIA) for detection of anti-enterovirus IgM antibodies was compared with complement fixation test in 43 patients with confirmed enterovirus meningitis by RT-PCR of cerebrospinal fluids (CSF). In 34% of patients with enterovirus meningitis, IgM antibodies could be found, whereas complement fixation tests were positive in only 20%. The specificity was determined with sera of 105 patients with non-enterovirus meningitis. Specificity of IgM EIA and of complement fixation was 94% and 85%, respectively. In four patients with meningitis but without enterovirus detection in CSF, RT-PCR and virus isolation from stools were positive. In three of these patients, IgM antibodies were detected, giving a strong indication of an enterovirus-associated disease. Because of the high specificity of IgM EIA, diagnosis of enterovirus-associated diseases can be carried out in a single serum sample, whereas by complement fixation tests, only fourfold increases in antibody titres in paired sera indicate an acute infection. The application of IgM EIA is especially important in cases of meningitis when CSF samples are not available and for diagnosis of enterovirus diseases with other clinical symptoms such as fever, enteritis, and hand-foot-and-mouth disease.

Adolescent↗
PubMed2000

A new enzyme immunoassay for the detection of enteroviruses in faecal specimens.

A new enzyme immunoassay (EIA) for direct detection of enteroviruses based on a group-specific monoclonal antibody was evaluated using stool samples from patients with suspected enteroviral infection. The EIA was compared with polymerase chain reaction (PCR) and virus isolation in cell culture. Of 204 samples tested, 20 were positive by EIA, 34 by PCR, and 18 by cell culture. Compared with PCR, the most sensitive method, the sensitivity of EIA was 58% (20/34); the sensitivity of cell culture isolation was 52% (18/34). The results of both assays correlated in only 60% of cases. The combination of EIA and cell culture isolation detected 76% of PCR-positive stool samples. Enterovirus EIA provides results within 3-4 hr and requires only standard EIA equipment. It represents a rapid, reliable, and cost-effective diagnostic tool for enterovirus diagnosis from faecal samples. Negative results must be confirmed by other techniques, such as PCR or virus isolation in cell culture.

Adult↗
PubMed1999

Dehydroepiandrosterone increases the zone [correction of in zone] of glutamine synthetase-positive hepatocytes in female rat liver: a putative androgenic effect.

The adrenal steroid dehydroepiandrosterone (DHEA) is a hepatocarcinogen and peroxisome proliferator in the rat, producing an increase in peroxisomes mainly in perivenular parts of the liver lobule. Glutamine synthetase (GS) is expressed exclusively in hepatocytes that directly surround the central terminal vein in rat liver. The GS-positive zone is wider in males than in females, covering about two to three cell layers in males and one to two cell layers in females. Treatment of rats with DHEA at a concentration of 0.6% in the diet for 4, 20, 32, 70 and 84 weeks resulted in an enlargement of the GS-positive zone in females, whereas no change was observed in males. In females treated for up to 32 weeks with DHEA, the relative mean width (RMW) of the GS-positive zone was as large as that observed in males. The increase in the RMW was paralleled by an increase in the number of GS-positive hepatocytes. Upon longer treatment, the width of GS expression decreased to that observed in untreated controls. The findings suggest an androgenic effect of DHEA. The areas of peroxisome proliferation, identified in haematoxylin and eosin- and periodic acid-Schiff-stained sections, and GS expression were not identical. Furthermore, preneoplastic and neoplastic liver lesions induced by DHEA were all negative for GS, indicating that they do not derive from the perivenular cells which show the most pronounced peroxisomal proliferation.

Androgens↗
PubMed1998

Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone.

Preneoplastic liver foci and neoplasms of different morphological phenotypes were induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7 weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly observed in rats treated with DHEA alone or in combination with NNM. The 2 types of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic lineage and the amphophilic lineage, which are characterized by distinct patterns of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of glucose metabolizing pathways were modified (increase in glucose-6-phosphate dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly demonstrated alterations in mitochondrial enzymes (increase in cytochrome c oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and acyl-CoA oxidase). The alterations in enzyme expression reflect an insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms resulting from APF show a more differentiated phenotype than those arising from GSF. We suggest that the different and in many aspects opposite effects of the 2 carcinogens on key enzymes of distinct pathways of energy metabolism modulate the process of neoplastic liver cell transformation and result in phenotypically different preneoplasias and neoplasias reflecting different cellular lineages.

Animals↗
PubMed1998

A new method for flat-embedding large native cryostat sections for targeting small preneoplastic lesions in comparative ultrastructural and ultracytochemical investigations.

Ultrastructural studies of rare and small cellular lesions in pathologically altered tissue are difficult to perform by applying conventional electron microscopic preparation. The search for lesions, often consisting of only a few cells in randomly obtained small specimen blocks, is time consuming and often without success. The methodological requirements for comparative enzyme cytochemical and morphological studies, i.e., preservation of both enzyme activity and ultrastructure, are divergent. By processing large native cryostat sections for electron microscopy, small preneoplastic focal lesions were successfully targeted in liver and kidney. Glucose-6-phosphatase, alkaline phosphatase, acid phosphatase, catalase, and cytochrome c oxidase activities were distinctly localized to endoplasmic reticulum, canalicular membrane, lysosomes, peroxisomes, and mitochondria, respectively, in the morphologically altered cells. Fixation of serial cryostat sections and enzyme reactions were both carried out through a semipermeable membrane except those for cytochrome c oxidase, which was demonstrated after fixation through the membrane by floating the section in incubation medium containing cytochrome c. Thereafter, the sections were flat embedded and polymerized between epoxy resin disks and aluminum dishes fitting exactly together. The objects of interest were identified in the light microscope, cut out, and reembedded in reversed gelatine capsules. By using this technique an ultrastructural preservation was achieved similar to that seen after immersion fixation. The enzyme activities were clearly localized without diffusion of the reaction product or unspecific deposits. The procedure permits precise targeting and complex studies of rare and small lesions, and opens new perspectives for the use of cryo-preserved tissue.

Animals↗
PubMed1998

Differentiation between acute primary and recurrent human cytomegalovirus infection in pregnancy, using a microneutralization assay.

Acute primary human cytomegalovirus (HCMV) infection in pregnancy, the major cause of congenital symptomatic infection, is often difficult to differentiate from recurrent infection, which presents a considerably smaller risk to the fetus. Therefore, the diagnosis of primary infection in pregnancy is very important, especially if seroconversion is not documented and follow-up sera with declining IgM-titers are not available. To investigate the value of the neutralizing antibody response against HCMV in differentiating acute primary from recurrent and past infection, well-characterized sera from pregnant women were examined. Employing a microneutralization assay, it was found that neutralizing antibodies first appeared approximately 15 weeks after acute infection. However, serum samples of pregnant women with recurrent or past infection consistently displayed neutralizing activity. In conclusion, the neutralization assay can be used as a reliable method for discriminating acute primary from previous or recurrent infection in a single serum sample.

Antibodies, Viral↗
PubMed1997

Enhancement and phenotypic modulation of N-nitrosomorpholine-induced hepatocarcinogenesis by dehydroepiandrosterone.

Hepatocarcinogenesis was induced in male and female rats by continuous administration of the adrenal steroid dehydroepiandrosterone (DHEA; 0.6% in the diet) with and without previous treatment with N-nitrosomorpholine (NNM; 120 mg/l drinking water for 7 weeks). DHEA treatment alone resulted in hepatocellular adenomas (HCA) and carcinomas (HCC) after 72-84 weeks, the incidence of both benign and malignant neoplasms being higher in females than in males. After DHEA administration for up to 32 weeks subsequent to NNM, the incidence of HCA and HCC was significantly higher (HCA, 42%; HCC, 42%) than after NNM alone (HCA, 33%; HCC, 28%). While total tumor incidence was similar in male (63%) and female (60%) rats after NNM treatment alone, it was higher in females (87%) than in males (80%) after NNM/DHEA treatment. The difference between the genders was mainly due to the higher incidence of HCC in females. Morphometric analysis of preneoplastic foci of altered hepatocytes (FAH) yielded that DHEA treatment did not increase the average total number of FAH induced by NNM, but caused a modulation of the phenotype of FAH from the glycogenotic/basophilic to the amphophilic cell lineage. The results confirm that DHEA acts as a hepatocarcinogen and show for the first time that it enhances NNM-induced hepatocarcinogenesis in rats.

Adenoma, Liver Cell↗
PubMed1997

Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta-oxidation enzymes and peroxisome proliferation in rats treated with dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific differences.

Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male and female sex hormones in the adrenal cortex of man. In livers of rats and mice DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation enzymes associated with peroxisome proliferation. Prolonged treatment of rats with DHEA induces liver tumors that are more frequent in females arising mainly in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol. 23, 591-605, 1995). Because of paucity of information on hepatic zonation of peroxisomal response to DHEA and controversial reports on gender-specific differences of its effects the present study was undertaken using qualitative immunohistochemical and quantitative immunoelectron microscopical techniques in addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal beta-oxidation enzymes, which by quantitative analysis was equally strong in male and female animals, whilst catalase and urate-oxidase were not increased. Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than in female rats. Immunohistochemistry confirmed the induction of cytochrome P450 IVA showing a marked lobular gradient in female animals with strong induction in pericentral and almost no induction in periportal regions of the liver lobule. In male animals cytochrome P450 IVA was expressed more uniformly across the liver lobule. A similar sex specific zone-dependent response was observed for peroxisomes. DHEA induced in females a significant zonal gradient with marked peroxisome proliferation and a strong induction of peroxisomal hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in periportal regions. Livers of male animals, in contrast, showed a uniform peroxisomal proliferation to DHEA with only slight zonal differences. The striking homologies of the induction patterns of cytochrome P450 IVA and the peroxisome proliferation in both sexes support the notion of a functional relationship. In view of the almost exclusive periportal localization of DHEA-induced tumors in female rats in contrast to the pericentral localization of the peroxisomal proliferation shown by this study, it seems likely that other factors in addition to peroxisome proliferation may contribute to the hepatocarcinogenic effect of DHEA.

Acyl-CoA Oxidase↗
PubMed1996

Antibiotic treatment for uncomplicated neuropathic forefoot ulcers in diabetes: a controlled trial.

To investigate the effect of oral antibiotics in purely neuropathic ulcers (Wagner grade 1-2, no osteomyelitis), a double blind placebo-controlled study was performed. Forty-four patients were enrolled and subjected to standard treatment with absolute pressure relief (half shoes), daily wound cleansing (topical disinfectant), sterile dressings (specialized nurse). Patients were randomized to an antibiotic (amoxicillin plus clavulanic acid), or placebo. The study was stopped when the antibiotic proved unsuitable according to swab result, or on clinical grounds (no improvement within 6 days of recruitment). Main outcome measure was the ulcer closing rate during 20 days, as assessed by standardized photographs. All ulcers except one were infected. Of the placebo group (n = 22), 2 patients had to be withdrawn within 6 days, versus 3 patients of the antibiotic-group (n = 22). In the placebo group, 10 ulcers were healed versus 6 ulcers in the antibiotic group (NS). Mean (95% CI) reduction in ulcer radius was 0.41 (0.21-0.61) mm day-1 in the placebo group versus 0.27 (0.15-0.39) mm day-1 in the antibiotic group (NS). In conclusion, there is no benefit from antibiotic treatment with amoxicillin plus clavulanic acid as a supplement to standard therapy in uncomplicated neuropathic foot ulcers, provided pressure relief is complete, and wound care is performed strictly supervised. However, a Type-II statistical error cannot be excluded in this small study.

Administration, Oral↗
PubMed1994

Human cytomegalovirus UL97 kinase confers ganciclovir susceptibility to recombinant vaccinia virus.

We analyzed whether the phosphotransferase encoded by the UL97 open reading frame of human cytomegalovirus (HCMV) alone is sufficient to confer ganciclovir (GCV) susceptibility to a foreign virus. Two vaccinia virus recombinants (T1 and A5) containing the UL97 open reading frames from a GCV-sensitive HCMV and from a GCV-resistant strain were constructed. T1 exhibited a GCV-sensitive phenotype in plaque reduction assays, whereas A5 did not. Moreover, T1-infected cell cultures showed a strongly increased incorporation of [14C]GCV triphosphate into macromolecular DNA, compared with recombinant A5 or vaccinia virus controls, which could be inhibited by the addition of guanosine. This shows that UL97 kinase is the only additional gene product required to make vaccinia virus susceptible to GCV, and guanosine seems to be one natural substrate for the enzyme. The system described here should be very helpful for fast and detailed functional analyses of UL97 mutations found in GCV-resistant HCMV isolates.

Base Sequence↗
PubMed1989

Supervision and practice of dental hygienists: report of ADHA survey.

In 1986, the American Dental Hygienists' Association (ADHA) funded a study to examine demographic and practice data concerning the dental hygiene profession. The purpose of this survey was to establish a data base for the current practice of licensed dental hygienists in the United States. Information was collected on the type of supervision under which hygienists worked and the type of supervision they would prefer. Using a stratified random sampling technique, questionnaires were sent to licensed member and nonmember dental hygienists residing in the United States. A total of 9,110 hygienists received surveys and after a second mailing to nonrespondents, a total of 4,522 completed surveys were received, for a response rate of 49.6%. This survey indicates that hygienists' attitudes toward supervision are changing. Although the majority of hygienists still work in a private practice where a dentist is present and usually examines the patient, over half of the respondents prefer that the dentist's presence in the facility not be required. In examining practice behaviors, a collaborative relationship appears to exist between the hygienist and dentist when treating both new and recall patients. The collaborative relationship decreases with the dental hygienist demonstrating an increase in responsibility and independent decision making for recall patients. Traditional practice behaviors are also changing to include more comprehensive dental hygiene services, particularly by baccalaureate degree hygienists.

Dental Hygienists↗