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Biomedical subjects

K M Keller

Publications and source records attributed to K M Keller.

At least 37 records · Page 2Linked to original sources
PubMed1997

Benign recurrent intrahepatic cholestasis (BRIC): evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease characterized by multiple episodes of cholestasis without progression to chronic liver disease. The gene was previously assigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. In the present study we report the linkage analysis of an expanded sample of 14 BRIC families, using 15 microsatellite markers from the 18q21 region. Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-point linkage analysis. Moreover, we identified one family in which the BRIC gene seems to be unlinked to the 18q21 region, or that represents incomplete penetrance of the BRIC genotype.

Cholestasis, Intrahepatic↗
PubMed1997

Validation of cutaneous pressure threshold measurements for the evaluation of hand function.

The relationship of measures of pressure perception to hand function was evaluated by correlating the results of the Mayo Dexterity Test and a timed object recognition test with the one- and two-point static and moving touch thresholds for the index finger pulp of 44 hands. The Mayo Dexterity Test permits the use of vision, while the object recognition test does not. Quantitative sensory testing was done with the Pressure-specifying Sensory Device. Cutaneous pressure threshold measurements with this device had a statistically significant correlation with the small-object subset of the Mayo Dexterity Test (p < 0.006) and with the object recognition test (p < 0.001), demonstrating that the Pressure-specifying Sensory Device is a valid tool for evaluating the sensory aspect of hand function.

Adolescent↗
PubMed1997

Computer-assisted quantitative sensorimotor testing in patients with carpal and cubital tunnel syndromes.

This study reports the use of computer-assisted sensorimotor testing in 75 patients with chronic peripheral nerve compression. Pinch and grip strength, and the cutaneous pressure threshold were measured. The reliability of this equipment for repeated measurements was excellent (r = 0.95). The pressure threshold at which a one-point static stimulus could be distinguished from a two-point static stimulus was found to be the first variable to become abnormal with computer-assisted sensorimotor testing. Criteria are suggested for screening with this equipment to detect carpal and/or cubital tunnel syndrome.

Adult↗
PubMed1997

Fecal alpha 1-antitrypsin in newborn infants.

BACKGROUND: Fecal alpha 1-antitrypsin is used as a marker for intestinal protein loss reflecting increased intestinal permeability. Exact data of fecal alpha 1-antitrypsin in newborn infants are not available. METHODS: 30 healthy mature neonates and three infants with impaired gastrointestinal passage due to stenoses and atresia respectively, were investigated during the first days of life. The amniotic fluid of 13 and the serum of 17 infants was available. alpha 1-antitrypsin was determined using the radial immunodiffusion method. RESULTS: Normal newborns showed mean fecal alpha 1-antitrypsin levels (+/-SD) of 2061 +/- 817 mg/dl (day 1), 1186 +/- 720 mg/dl (day 2), 308 +/- 380 (day 3), 35 +/- 27 (day 5), and 27 +/- 21 mg/dl (day 6). Two infants with esophageal atresia presented a much lower pattern, and one with annular pancreas had a fecal alpha 1-antitrypsin pattern comparable with that of normal babies. Serum alpha 1-antitrypsin was normal (275 +/- 52 mg/dl), and amniotic fluid contained 20 +/- 12 mg/dl alpha 1-antitrypsin. CONCLUSIONS: The pattern of neonatal fecal alpha 1-antitrypsin content appears to reflect the meconium clearance of the gut rather than intestinal permeability and "gut closure." We hypothesize that the origin of increased fecal alpha 1-antitrypsin is the result of accumulated secretions from bile, the pancreas, and the duodenum, but alpha 1-antitrypsin originating from swallowed amniotic fluid during pregnancy may play an additional role.

Amniotic Fluid↗
PubMed1997

Comparison of total alkaline phosphatase and three assays for bone-specific alkaline phosphatase in childhood and adolescence.

We compared serum levels of total alkaline phosphatase (TAP) and bone-specific alkaline phosphatase (BAP) as determined by three different assays (lectin affinity electrophoresis, immunoradiometric assay, enzyme-linked immunosorbent assay) in subjects aged 5-20 years suffering from X-linked hypophosphatemic rickets (n = 14), chronic renal failure (n = 10) and chronic cholestatic liver disease (n = 16). Results were compared to controls of the same age and were expressed as standard deviation scores (SDS). TAP correlated significantly with BAP (r > 0.9 for each assay; p < 0.001) in controls. In children with cholestatic diseases, TAP (median SDS + 2.0) was elevated, but BAP, as measured by the electrophoretic assay, was within the reference range for most patients (median SDS: -0.4; p = 0.003 for the difference between the median SDS of TAP and BAP). In contrast, results for BAP as determined by the two immunoassays were not significantly different from TAP in any of the three patient groups (p > 0.05 in each group for both assays). In this study, the two immunoassays did not have a detectable advantage over lectin affinity electrophoresis in the determination of BAP.

Adolescent↗
PubMed1997

Novel and characteristic CFTR mutations in Saudi Arab children with severe cystic fibrosis.

More than 600 different CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations have been identified so far that are considered to cause the fatal genetic disorder cystic fibrosis (CF). We have investigated 15 Arab children from 12 families, who were diagnosed as having CF, for mutations in the coding region and in the flanking intron sequences of the CFTR gene. Six different CFTR mutations were identified including two novel mutations, 1548delG in exon 10 and 406-2A-->G in intron 3. Prominent mutations were the splice mutation 3120 + 1G-->A (intron 16) followed by N1303K (exon 21) and 1548delG (exon 10). Most CF children were homozygotes who presented with a severe form of the disease including failure to thrive, recurrent chest infections, particularly with Pseudomonas aeruginosa, and frequent hospital admissions. Identification of the CFTR mutations facilitates molecular investigation of the disease and better understanding of its pathophysiology in Arab children, among whom CF is probably an underdiagnosed disease.

Child↗
PubMed1996

The diagnostic significance of IgG cow's milk protein antibodies re-evaluated.

UNLABELLED: The effect of different feeding regimens, notably the use of hydrolysed cow's milk formulas, on the development of allergic reactions and the development of cow's milk protein-IgG antibodies is still disputed. We prospectively compared the development of allergic manifestations and cow's milk protein-IgG antibodies in a total of 702 infants who were divided into six groups: 1. exclusively breast milk for at least 4 weeks (n = 206). 2. Breast milk plus initial partially hydrolysed formula (n = 104). 3. Breast milk plus extensively hydrolysed formula (n = 50). 4. Breast milk plus initial conventional cow's milk formula (n = 73). 5. Conventional cow's milk with or without breast milk throughout (n = 187). 6. Extensively hydrolysed cow's milk formula for 2 months, followed by conventional cow's milk (n = 82). Cow's milk protein antibodies were determined by an indirect immunofluorescent test. Antibody titres rose slowly in groups 1, 3 and 6. Children in group 5 showed two high peaks. There were no significant differences in the frequency and type of allergic manifestations between the groups. Introduction of cow's milk formula during the first trimenon resulted in elevated antibody titres in all breast fed infants compared with introduction at a later date. CONCLUSION: In contrast to a previous study from the same laboratory, there is no diagnostic significance of cow's milk protein-IgG antibodies for allergic manifestations. The occurrence of these antibodies is a physiological phenomenon: the shorter the breast feeding period and the earlier cow's milk formula is introduced, the higher the antibody levels.

Age Factors↗
PubMed1995

Rational design and synthesis of small molecule, non-oligosaccharide selectin inhibitors: (alpha-D-mannopyranosyloxy)biphenyl-substituted carboxylic acids.

The calcium dependent E-selectin/sialyl Lewisx (sLex) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLex binding, along with previously reported structure-activity relationships of sLex-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLex expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLex tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.

Animals↗
PubMed1993

[Clostridium difficile in early childhood ulcerative pancolitis].

Ulcerative colitis is a rare disease in young infants. Less than one per cent of cases occur during the first two years of life. We describe a male child who developed frequent bloody diarrhea at the age of 20 months. More common causes like infections or gastrointestinal food allergy were excluded. Endoscopy and histopathological evaluations revealed ulcerative colitis of the entire colon. Treatment with sulfasalazine and prednisone resulted in a clinical remission after seven weeks. The follow-up of 15 months was complicated by Rotavirus infection. Two relapses were caused by Clostridium difficile infections. The latter were successfully treated with oral vancomycine, but in the last relapse an increased dosage of prednisone was required, too. In relapses of inflammatory bowel disease gastrointestinal infections, especially caused by Clostridium difficile should be considered and treated adequately.

Biopsy↗
PubMed1992

Use of the polymerase chain reaction to demonstrate hepatitis B virus DNA in serum of children with chronic hepatitis B.

The polymerase chain reaction was used to investigate the presence of hepatitis B virus DNA in sera of 61 children with chronic hepatitis B and negative results on dot blot hybridization tests. Our results demonstrate that most chronic carriers of hepatitis B surface antigen in childhood have hepatitis B virus DNA detectable by polymerase chain reaction in their serum and must be considered infectious.

Adolescent↗
PubMed1992

Detection of hepatitis B virus DNA in the liver of children with chronic hepatitis B by in situ hybridization and its relation to other viral markers.

The aim of the study was to detect hepatitis B virus (HBV) DNA by in situ hybridization (ISH) with a 35S-labeled radioactive probe in frozen liver biopsy tissue sections of 63 hepatitis B virus surface antigen (HBsAg)-positive children. The results were compared to other markers of viral replication. HBV DNA was detected in 48 children. Of the 15 negative cases, four had hepatitis B envelope antigen (HBeAg), 10 anti-HBe, and one neither HBeAg nor anti-HBe. Free HBV DNA in serum and liver was positive in one patient. Forty of the positive children were HBeAg- and six anti-HBe-positive; two were negative for both. Of 45 36 had HBV DNA in serum. In 38 of 47 HBV DNA and in 31 of 42 HBcAg could be detected in the liver. The HBV DNA signals were located mainly over the cytoplasm of hepatocytes. The distribution of HBV DNA in the tissue was classified as homogeneous, inhomogeneous with focal patches, and focal. It is concluded that in situ hybridization is a reliable method for detection of HBV DNA in liver tissue of children with chronic hepatitis B. The technique, which can be applied to small amounts of liver tissue, provides informations about the distribution of replicative viral sequences, complementing laboratory data, liver histochemistry, and histology.

Adolescent↗
PubMed1992

Hepatitis B virus DNA in liver tissue of chronic HBsAg carriers in childhood and its relationship to other viral markers.

The aim of the study was to examine the state of hepatitis B virus (HBV) DNA in liver tissue of 103 children with chronic hepatitis B aged 0.5-18 years to detect free and integrated viral sequences by Southern blot hybridization. HBV DNA was found in 74 patients. Seventy-two were seropositive for hepatitis B e antigen (HBeAg) and two had anti-HBe antibodies. Integrated sequences could be demonstrated in two children. One of them had only integrated HBV DNA and was anti-HBe seropositive. The other one presented both free and integrated viral sequences and developed seroconversion from HBeAg to anti-HBe 5 months after biopsy. In 29 hepatitis B surface antigen (HBsAg) carriers, no HBV DNA could be detected in the liver. Ten were HBeAg and 19 anti-HBe seropositive. HBV DNA in serum was found in 65 of the 74 Southern blot-positive and only in two cases of the Southern blot-negative patients. In conclusion, most of the HBeAg-positive children had free HBV DNA in their liver tissue and all patients with anti-HBe except one were negative. According to our results, HBV DNA integration into the liver cell genome can occur at an early stage of chronic disease but is not a frequent event.

Adolescent↗
PubMed1992

[Hepatitis C virus (HCV). Low infection rate in premature and full-term neonates following multiple transfusions].

BACKGROUND: Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by hepatitis C virus (HCV). Data for HCV infection in childhood are limited. METHODS: 262 Children who received poly-transfusion between 1979 and 1983 were re-examined at a mean age of 3.5 years for HCV infection using an first-generation enzyme immunoassay to detect anti-HCV antibodies. RESULTS: 14 of 262 children had positive anti-HCV titers (5.3%), 7 of them showed border line results. In further two patients HCV infection was suspected by clinical means, but initial serology was not available. 6.5 years later, 15 of these 16 children were re-examined at a mean age of 9.8 years. All had normal liver enzymes and positive anti-HCV serology was shown in 3 patients (1%). CONCLUSIONS: This study demonstrates a low incidence of HCV infection after poly-transfusion during neonatal age. The rate of HCV infection may be even higher, if other more specific tests for HCV serology or PCR will be routinely available in the near future.

Child, Preschool↗
PubMed1992

[Chronic hepatitis B. Treatment in childhood with alpha-interferon].

BACKGROUND: In adults several trials of successful therapy for chronic hepatitis B using alpha-interferon with rates of seroconversion from HBeAg to anti-HBe of 30-40% have been reported. Despite the experiences in children are limited, alpha-interferon seems to be a promising drug in this age group as well. We report on our results in the treatment of chronic hepatitis B virus carrier using the recombination interferon alpha-2b. METHODS: 24 children aged 0.6-16 years with chronic active or chronic persistent hepatitis B were included in the study. 12 children received 9 million units of alpha-interferon/m2 body surface area three times a week during four months. 12 control patients were not treated. The follow-up period was 9-12 months after the beginning of therapy. HBsAg, anti-HBs, anti-HBe and Hepatitis-B-Virus-DNA were assessed during this time on a regular basis. RESULTS: Only seroconversion of HBe-Ag to anti-HBe was considered as response to interferon treatment. During the follow-up period anti-HBe could be detected in 5 (41.6%) of the treated and in one (8.3%) of the untreated children. In one case additional seroconversion of HBsAg to anti-HBs due to virus elimination was observed. In all children a marked reduction of viral replication could be shown. 9 patients cleared Hepatitis-B-Virus-DNA at least for one time during therapy. Alpha-interferon was well tolerated and no severe side effects were observed. CONCLUSION: Our results demonstrate that alpha-interferon can be successfully applied to a considerable number of children with chronic hepatitis B. In patients responding to alpha-interferon usually serum transaminases become normal and infectivity of the disease is markedly reduced. alpha-Interferon treatment should be primarily recommended for children with chronic active inflammation.

Adolescent↗