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Biomedical subjects

L Schmidt

Publications and source records attributed to L Schmidt.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Determination of menarche and primary amenorrhea].

It was the aim to determine recalled ages at menarche and prevalence of primary amenorrhea in a random sample of 3743 women, aged 15-44 years, in a Danish county. It was a further object to examine agreement between results obtained by the recall and the status quo method. Response rate was 78%. The prevalence of primary amenorrhea (menarche after the 18th birthday) was 0.48%. In the calculations the reported menarcheal ages were treated as age-at-nearest-birthday, i.e. the usual 0.5 year mid-point correction was omitted. The resulting mean ages showed close agreement with Danish menarcheal ages, obtained by the status quo method, covering the same period of time. On the other hand, previously published recall data for this period, including the 0.5 year correction, were almost consistently 0.5 year higher. It is argued that the 0.5 year midpoint correction should be omitted in recalled whole-year data.

Adolescent↗
PubMed1998

Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene.

Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia.

3T3 Cells↗
PubMed1998

Assessment of office-based care of sexually transmitted diseases and vaginitis and antibiotic decision-making by obstetrician-gynecologists.

OBJECTIVE: Survey office-based obstetric-gynecologic practitioners regarding their knowledge of infectious disease care and antibiotic use. METHODS: A survey questionnaire of multiple-choice questions was mailed to Fellows of the American College of Obstetricians and Gynecologists about clinical entities for which recommendations have undergone recent changes or about which there was a lack of consensus in a prior similar survey (Gibbs RS, McGregor JA, Mead PB, et al.: Obstet Gynecol 83:631-636, 1994). RESULTS: Respondents indicated that oral metronidazole was their most frequent choice to treat bacterial vaginosis. Ampicillin (57%) was used more often than penicillin (39%) for intrapartum group B streptococcus prophylaxis. Azithromycin was preferred (61%) over erythromycin-base (38%) for chlamydia treatment during pregnancy. There were several modes of practice that deviated from accepted care: 27% and 29% did not screen for chlamydia and gonorrhea, respectively, in pregnancy; 17% used cultures for Gardnerella vaginalis to diagnose bacterial vaginosis; 25% considered quinolones to be safe in pregnancy; 93% felt metronidazole should never be used in pregnancy; and the majority (66%) would send a patient treated successfully for pelvic cellulitis home with an oral antibiotic. CONCLUSION: Respondents' infectious disease knowledge and practices in obstetrics and gynecology is appropriate in treating sexually transmitted diseases, bacterial vaginosis, and group B streptococcus. Numerous deficiencies still exist in screening for sexually transmitted diseases in pregnancy and diagnosing bacterial vaginosis, as well as in the choice of antibiotics to use or avoid for certain infections.

Adult↗
PubMed1998

Acute acid exposure increases rabbit esophageal cell proliferation.

In the present study we examined whether an acute infusion of HCl into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCl or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division. Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H+ infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H+ infusion (31%+/-6%) as compared with that in control animals infused with NSS (15%+/-4%). This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H+ infusion. Rete pegs were infrequent in control tissues (4+/-4 rete pegs per 100 microm of esophageal length) or in animals examined 24 hours after acid exposure (4+/-2 rete pegs per 100 microm). However, rete pegs were very prominent 48 hours after acid infusion (22+/-6 rete pegs per 100 microm). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.

Animals↗
PubMed1998

Management of diabetes by obstetrician-gynecologists.

OBJECTIVE: To examine the rates of diagnosis and treatment of diabetes mellitus by ACOG Fellows in pregnant and nonpregnant patients. METHODS: We sent a questionnaire to 1250 ACOG Fellows. Thirty-nine percent responded. Responses were examined for potential differences between recently and less recently trained obstetrician-gynecologists. RESULTS: Ninety-six percent of obstetricians routinely screen for gestational diabetes mellitus (GDM). Fifty-five percent of obstetrician-gynecologists screen for diabetes in nonpregnant patients if there is a history of diabetes in the patient's family. Moreover, 33% care for women with type-1 diabetes mellitus, and 39% for women with type-2 diabetes mellitus who are not pregnant. Sixty-two percent believed that their patients with GDM are at increased risk for developing nongestational diabetes later in life, and 71% will recommend an evaluation of glucose tolerance in the future for these women. Finally, 99% are willing to prescribe oral contraceptives to women diagnosed previously with GDM. CONCLUSION: Obstetrician-gynecologists are aware of the need to screen for GDM and the importance of postpartum follow-up in GDM patients to detect type-2 diabetes mellitus. This practice is important because half of the 14 million people with type-2 diabetes mellitus are unaware they have this disorder, and many learn about it only after a serious complication has occurred.

Diabetes Mellitus↗
PubMed1998

Molecular evidence of bone marrow involvement in advanced case ot Tgammadelta lymphoma with secondary myelofibrosis.

We describe the case of a middle-aged man with long indolent course of generalized Tgammadelta lymphoma. The onset of secondary myelofibrosis made cytological monitoring of the bone marrow infiltrates impossible. As during progression of the disease splenectomy revealed typical histological features of a high-grade hepatosplenic Tgammadelta lymphoma, the low-grade bone infiltrate was considered a secondary lymphoma. The use of the polymerase chain reaction helped to detect a constant and identical monoclonal rearrangement pattern of the T-cell receptor gamma-chain gene in both bone marrow and splenic T-cell infiltrates. The notion of a secondary spread of malignant T-cells to the bone marrow was thereby confirmed despite striking cytological differences between bone marrow and splenic infiltrates. This is the first report of a diagnostic DNA-based molecular approach using fixed decalcified bone marrow. This method may provide a major tool when dealing with myelofibrosis, which normally hampers sampling of cytological specimens.

Adult↗
PubMed1998

Infertile couples' assessment of infertility treatment.

BACKGROUND: The purpose of this study was to describe infertile patients' experiences and assessment of infertility treatment. METHODS: Sixteen couples undergoing infertility treatment at the Fertility Clinic, Herlev Hospital in Copenhagen County. Denmark, were interviewed using a semi-structured qualitative interview. The participants were selected by purposeful sampling with maximum variation. The interviews were audiotaped and transcribed in full. Data were analyzed by the Grounded theory method. RESULTS: Infertility patients preferred treatment that was organized in a separate clinic where there were only a few staff-members, proceeded without waiting time, and followed a plan known to both the doctor and the couple. Satisfaction or dissatisfaction with treatment was not related to length of infertility, sex, or social class. Surprisingly, assessment of treatment was not related to either outcome or type of treatment. The participants experienced infertility treatment as a psychological strain and they felt that their emotional needs were not met in the health care system. The desire for services from the health care system was related to how the participants managed their infertility problem in relation to other people. The more open-minded the participant was, the more was expected from the professionals. These participants wanted detailed information about technical aspects of infertility and treatment as well as psychosocial and sexual advice and support. CONCLUSION: The public health care system does not meet the needs of infertile couples for information, psychological and sexual counselling, and discussions of alternative ways of becoming parents. High-quality treatment has to consider the patients' different needs and ensure successful pregnancies as well.

Adult↗
PubMed1998

Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas.

The gene defect for hereditary papillary renal carcinoma (HPRC) has recently been mapped to chromosome 7q, and germline mutations of MET (also known as c-met) at 7q31 have been detected in patients with HPRC (ref. 2). Tumours from these patients commonly show trisomy of chromosome 7 when analysed by cytogenetic studies and comparative genomic hybridization (CGH). However, the relationship between trisomy 7 and MET germline mutations is not clear. We studied 16 renal tumours from two patients with documented germline mutations in exon 16 of MET. Fluorescent in situ hybridization (FISH) analysis showed trisomy 7 in all tumours. To determine whether the chromosome bearing the mutant or wild-type MET gene was duplicated, we performed duplex PCR and phosphoimage densitometry using polymorphic microsatellite markers D7S1801 and D7S1822, which were linked to the disease gene locus, and D1S1646 as an internal control. We determined the parental origin of chromosome alleles by genotyping parental DNA. In all 16 tumours there was an increased signal intensity (2:1 ratio) of the microsatellite allele from the chromosome bearing the mutant MET compared with the allele from the chromosome bearing the wild-type MET. Our study demonstrates a non-random duplication of the chromosome bearing the mutated MET in HPRC and implicates this event in tumorigenesis.

Adult↗
PubMed1998

Substance abuse and the course of welfare dependency.

OBJECTIVES: New provisions in welfare reform target recipients with addictions, even though there is limited research on how substance abuse affects people's experiences on welfare. This prospective study examined substance abuse as a determinant of subsequent welfare dependency. METHODS: Representative samples of clients on Aid to Families with Dependent Children (AFDC) and general assistance in a California county were interviewed while applying for services in 1989 and were reinterviewed in 1995. RESULTS: Among AFDC recipients, substance abuse was not a significant determinant of long welfare stays, repeat welfare use, or the total time a person remained on welfare during the 6-year period. However, substance abuse was a strong predictor of repeat welfare use among general assistance recipients. CONCLUSIONS: Alcohol and drug problems have played dramatically different roles in welfare dependency within the AFDC and general assistance populations. Under welfare reform, local general assistance programs will be the final safety net for recipients removed from federal entitlement programs. These programs will probably be confronted with clients with more complex disabilities related to addiction, as well as with greater family needs for cash assistance.

Adult↗
PubMed1997

Activating mutations for the met tyrosine kinase receptor in human cancer.

Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary and sporadic forms of papillary renal carcinoma. We have introduced the corresponding mutations into the met cDNA and examined the effect of each mutation in biochemical and biological assays. We find that the Met mutants exhibit increased levels of tyrosine phosphorylation and enhanced kinase activity toward an exogenous substrate when compared with wild-type Met. Moreover, NIH 3T3 cells expressing mutant Met molecules form foci in vitro and are tumorigenic in nude mice. Enzymatic and biological differences were evident among the various mutants examined, and the somatic mutations were generally more active than those of germ-line origin. A strong correlation between the enzymatic and biological activity of the mutants was observed, indicating that tumorigenesis by Met is quantitatively related to its level of activation. These results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and these results raise the possibility that activating Met mutations also may contribute to other human malignancies.

3T3 Cells↗
PubMed1997

Gene structure of the human MET proto-oncogene.

By direct sequencing of cosmids using primers designed from the known cDNA sequence, we identified 19 exons in the human MET proto-oncogene, and sequenced the corresponding 5' and 3' exon-intron junctions. By homology search in the database of the Washington University Genome Sequence Center (GSC), we identified one additional exon. These 20 exons, together with a previously reported exon, bring the total exon number of MET to 21. Oligonucleotide primers were designed to amplify each exon and adjacent intronic sequences to permit examination of each exon for mutations. By restriction mapping, we assembled a 110 kb genomic contig that covered almost the entire MET proto-oncogene. This information is relevant for the screening of recently reported mutations of the MET gene which cause hereditary papillary renal carcinomas and for the search for additional mutations of the same gene which may play a role in the pathogenesis of common human carcinomas including carcinomas of the breast, ovary and pancreas.

Base Sequence↗
PubMed1997

[Breaking bad news--experience and attitude of young physicians].

This survey reports the attitude among second year medical doctors towards giving patients bad news. The questionnaire contained a mixture of open and closed questions. The questionnaire was returned by 88/119 (74%). All doctors felt that a patient who suffers from a serious, incurable disease has the right to be told the diagnosis, 98% of the doctors had broken bad news-most of them had done it several times. More than 90% of the doctors judged that their knowledge concerning breaking bad news, communication and crisis- and grief-reactions was average or above, but less than 10% thought that their knowledge was adequate. All the responders wanted instructions on how to break bad news, but only 45% had received some.

Adult↗
PubMed1997

[Infertility and treatment in a representative population].

The objective was to investigate lifetime prevalence of infertility, the seeking of infertility treatment and outcomes of treatment. A random sample of 3,743 women, 15 to 44 years old, were asked about infertility, their seeking of infertility treatment, diagnosis provided by their doctors and subsequent parenthood in a postal questionnaire. Response rate was 78%. Of the women who had attempted to have a child, 26.2% had experienced infertility; 4.1% af the women aged 25 to 44 years were currently primary infertile and 8.6% had involuntarily never delivered a child; 47.4% of the infertile women had sought infertility treatment. Significant predictors for seeking treatment were over nine years of school education and not having delivered a child. Of the treated infertile women 54.9% subsequently had a child. Only 30% of these reported that the successful delivery was treatment-related. The health care system should ensure that infertile couples from lower social classes are offered information on the possibility of infertility treatment.

Adolescent↗
PubMed1997

Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours. The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome. Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of both copies of the VHL gene by mutation, and/or by hypermethylation. We found that the HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval between D7S496 and D7S1837. We identified missense mutations located in the tyrosine kinase domain of the MET gene in the germline of affected members of HPRC families and in a subset of sporadic papillary renal carcinomas. Three mutations in the MET gene are located in codons that are homologous to those in c-kit and RET, proto-oncogenes that are targets of naturally-occurring mutations. The results suggest that missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein and papillary renal carcinomas.

Adult↗
PubMed1997

Improving wedged field dose distributions.

Dose profiles produced by wedge filters in the non-wedged direction can exhibit a 7% or greater dose reduction at the outer ends of the field compared with open field profiles. However, many planning systems use open field profiles to model wedged dose distributions. In the present work, wedges have been modified to reproduce open field profile shapes. This modification involved removing varying thicknesses of the wedge using a simple milling machine. The wedge thickness was calculated using the assumption that dose is proportional to primary collision kerma. The discrepancies in dose between wedged field and open field profile shapes of up to 7% were reduced to less than 3% with the modifications, even for varying depths and off-axis distances. The necessary measurements are simple to perform, and hence this technique could be applied to improve wedged field dose distributions in other radiotherapy departments.

Biophysical Phenomena↗
PubMed1996

[Menarche in relation to infertility and adult height and weight].

In order to clarify relationships between menarcheal age and fertility and fecundity later in life, a questionnaire was mailed to 3743 women, aged 15-44 years, selected at random in the county of Copenhagen; 78% responded. Associations were observed between early menarche and increased risk of pelvic inflammatory disease and spontaneous abortion. On the other hand, no association was found between age at menarche and irregular bleedings, amenorrhoea, fertility, or fecundity. Early menarche was associated with excess weight, late menarche with underweight. A positive correlation was found between menarcheal age and final body height. It is concluded that menarche was not associated with fertility or fecundity, whereas early menarche was associated with pelvic inflammatory disease and spontaneous abortion. Age at menarche showed associations with height and weight.

Adolescent↗
PubMed1996

Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.

Germline mutation analysis was performed in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected. Most of the germline VHL mutations (124/137) occurred in 1-2 families; a few occured in four or more families. The common germline VHL mutations were: delPhe76, Asn78Ser, Arg161Stop, Arg167Gln, Arg167Trp, and Leu178Pro. In this large series, it was possible to compare the effects of identical germline mutations in different populations. Germline VHL mutations produced similar cancer phenotypes in Caucasian and Japanese VHL families. Germline VHL mutations were identified that produced three distinct cancer phenotypes: (1) renal carcinoma without pheochromocytoma, (2) renal carcinoma with pheochromocytoma, and (3) pheochromocytoma alone. The catalog of VHL germline mutations with phenotype information should be useful for diagnostic and prognostic studies of VHL and for studies of genotype-phenotype correlations in VHL.

Adrenal Gland Neoplasms↗