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Biomedical subjects

R Winter

Publications and source records attributed to R Winter.

At least 109 records · Page 6Linked to original sources
PubMed1999

Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: A randomized, prospective, multicenter trial.

BACKGROUND: Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence. However, it has not been clearly demonstrated that adjuvant radiation, adjuvant chemotherapy, or both improve the outcome. To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy, the Austrian Gynecologic Oncology Group conducted a prospective, randomized, multicenter clinical trial between 1989 and 1995. MATERIAL AND METHODS: Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and/or vascular invasion randomly received adjuvant chemotherapy (400 mg/m2 carboplatin, and 30 mg bleomycin), standardized external pelvic radiation therapy, or no further treatment. RESULTS: After a median follow-up of 4.1 years (range, 2-7) there were no statistically significant differences (P = 0.9530) in disease-free survival among the three treatment arms. CONCLUSION: The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy. The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy.

Carcinoma, Squamous Cell↗
PubMed1999

The prognostic significance of peritoneal seeding and size of postsurgical residual in patients with stage III epithelial ovarian cancer treated with surgery, chemotherapy, and high-dose radiotherapy.

OBJECTIVE: The aim of this study was to retrospectively analyze the prognostic importance of age, histologic type and grade, ascites, lymph node status, size and type of postoperative residual disease, and radiation dose on disease-specific (DSS) and progression-free survival (PFS) in stage III epithelial ovarian cancer patients who had been treated with radical surgery, postoperative chemotherapy, and high-dose radiotherapy. METHODS: Consolidation radiotherapy including whole abdominal radiation, pelvic, and upper abdominal boosts was employed in 46 patients who showed no evidence of residual or progressive disease after completion of multiagent chemotherapy. The median follow-up for all patients was 36 months and 103 months for patients at risk. The prognostic impact of pretreatment and treatment parameters on DSS and PFS was tested in univariate and multivariate analyses. RESULTS: The 5-year DSS and PFS rates for all patients were 38 and 33%, and for patients with 0-< or =2 cm residual tumor 65 and 61%, respectively. In univariate analysis, initial peritoneal seeding (both: P = 0.02), ascites (P = 0.03; 0.01), size of residual (0-< or =2 cm vs >2 cm), and residual miliary subdiaphragmatic (MDS) and localized peritoneal seeding (LPS) in the upper abdomen (P = 0.0002; 0.0003) were significantly correlated with DSS and PFS. Dose of radiation (< or =30 vs >30 Gy) correlated with DSS only (P = 0.02). In multivariate analysis size of residual disease (0-< or =2 cm vs >2 cm and/or MDS or LPS) remained the only independent prognostic factor for DSS and PFS (both; P = 0. 001). CONCLUSION: Patients with localized peritoneal seeding who were rendered free of disease elsewhere had an outcome equally poor as that of patients with gross residuals (>2 cm) in the upper abdomen. If our findings can be confirmed, attempted resection of all localized seeding in patients who are otherwise cytoreducible to no or minimal residual disease may be considered in combination with Taxol-containing regimens as are now being utilized for patients with gross disease.

Adult↗
PubMed1999

Percussion--a new way to diagnose a pneumothorax.

We describe a new clinical sign in a case series of three patients who developed pneumothoraces during mechanical ventilation in the intensive care unit. All three patients were in the supine position. Two patients had x-rays that were inconclusive before insertion of chest drains and the third had a pneumothorax diagnosed on clinical findings alone. On each occasion we were able to diagnose pneumothorax using sternal percussion and simultaneous auscultation. The method relies on percussion of the sternum while simultaneously ausculating the anterior (superior) chest on the side of the suspected pneumothorax. The stethoscope is then placed on the other side of the chest. The percussion sound on the affected side has an exaggerated, resonant and booming quality. The percussion note is exaggerated partly because a stethoscope is used and partly because, in the supine patient, air localizes upwards to the anterior thorax.

Female↗
PubMed1999

EYA4, a novel vertebrate gene related to Drosophila eyes absent.

We have isolated a family of four vertebrate genes homologous to eyes absent (eya), a key regulator of ocular development in Drosophila. Here we present the detailed characterization of the EYA4 gene in human and mouse. EYA4 encodes a 640 amino acid protein containing a highly conserved C-terminal domain of 271 amino acids which in Drosophila eya is known to mediate developmentally important protein-protein interactions. Human EYA4 maps to 6q23 and mouse Eya4 maps to the predicted homology region near the centromere of chromosome 10. In the developing mouse embryo, Eya4 is expressed primarily in the craniofacial mesenchyme, the dermamyotome and the limb. On the basis of map position and expression pattern, EYA4 is a candidate for oculo-dento-digital (ODD) syndrome, but no EYA4 mutations were found in a panel of ODD patients.

Alternative Splicing↗
PubMed1999

Rapid prenatal diagnosis of aneuploidy by quantitative fluorescent PCR on fetal samples from mothers at high risk for chromosome disorders.

We report the results of a prospective study using quantitative fluorescent polymerase chain reaction (QF-PCR) and small tandem repeat markers (STR) for the rapid prenatal detection of aneuploidies in a group of pregnant women at increased risk of having fetuses with numerical chromosome disorders. Amniotic fluid samples (n = 52) were collected from mothers undergoing prenatal invasive testing for fetal abnormalities on ultrasonographic examination or abnormal maternal serum aneuploidy screening results. All samples were tested by cytogenetic analysis, but rapid diagnoses of aneuploidies were offered and performed using QF-PCR analysis with several STRs specific for chromosomes 21, 18, 13 and X. All cases with numerical chromosome aberrations involving chromosomes 21, 18 and 13 (n = 8) were correctly diagnosed. Three gonosomal aneuplodies (one 47,XXY and two 45,X) were not detected because they were uninformative for the X markers. Another sample with a deletion (46,XX,7q-), that the present assay was not designed to detect, was not identified. One sample was heavily contaminated with maternal blood and the results of the QF-PCR assays were uninformative. The remaining samples from normal fetuses provided QF-PCR patterns disomic for chromosomes 21, 18, 13 and X. Our study demonstrates that QF-PCR is a rapid method for the detection of common numerical chromosome disorders and it may play an important role in prenatal diagnosis for women at high risk for fetal aneuploidy.

Amniocentesis↗
PubMed1999

Power-law fluctuations in phase-separated lipid membranes.

The spatial structure of three binary lipid mixtures, prepared as multilamellar vesicles, was studied by small-angle neutron scattering. In the fluid-gel coexistence region, large-scale concentration fluctuations appear which scatter like surface fractals for small acyl-chain mismatch and like mass fractals for large mismatch over about one decade of length. The transition is highly discontinuous: The fractal dimension of the boundary between the gel and fluid drops from 2.7 to 1.7, the gel fraction in the fluctuations drops from about 0.5 to 0.07, and the gel domains interlamellar correlation drops from strong to weak. We interpret the fluctuations as long-lived descendants of the incipient two-phase equilibrium state and the transition as due to changes in the gel rigidity and phase diagram.

Deuterium↗
PubMed1999

Elevated plasma concentrations of homocysteine in antiepileptic drug treatment.

PURPOSE: Homocysteine is an experimental convulsant and an established risk factor in atherosclerosis. A nutritional deficiency of vitamin B6, vitamin B12, or folate leads to increased homocysteine plasma concentrations. During treatment with carbamazepine (CBZ), phenytoin, or phenobarbital, a deficiency in these vitamins is common. The objective of the study was to test the hypothesis that antiepileptic drug (AED) treatment is associated with increased homocysteine plasma concentrations. METHODS: A total of 51 consecutive outpatients of our epilepsy clinic receiving stable, individually adjusted AED treatment and 51 sex- and age-matched controls were enrolled in the study. Concentrations of total homocysteine and vitamin B6 were measured in plasma; vitamin B12 and folate were measured in the serum of fasted subjects. RESULTS: Patients and controls differed significantly in concentrations of folate ( 13.5+/-1.0 vs. 17.4+/-0.8 nM and vitamin B6 (39.7+/-3.4 vs. 66.2+/-7.5 nM), whereas serum concentrations of vitamin B12 were similar. The homocysteine plasma concentration was significantly increased to 14.7+/-3.0 microM in patients compared with controls (9.5+/-0.5 microM; p < 0.05, Wilcoxon rank-sum test). The number of patients with concentrations of >15 microM was significantly higher in the patient group than among controls. The same result was obtained if only patients with CBZ monotherapy were included. Patients with increased homocysteine plasma concentrations had lower folate concentrations. CONCLUSIONS: These data support the hypothesis that prolonged AED treatment may increase plasma concentrations of homocysteine, although the alternative explanation that increased homocysteine plasma concentrations are associated with the disease and not the treatment cannot be completely excluded at the moment.

Age Factors↗
PubMed1999

[How much preoperative information? - How can it be documented?].

Preoperative information for patients and documentation of this information are becoming increasingly significant. Opinions diverge especially on how to document the information provided, the information protocol being only an ancillary element. The patient must be in a position to make an informed decision without suffering any prejudice. Information protocols relating to treatment, that is to the operation, aim at ensuring the quality of the treatment and at documenting the information provided. A scheme of the operation is an important element of this information. Twenty-one presurgical information protocols have been tested in a pilot phase and are still being evaluated by a patients' association. Information and documentation concepts need to be set up by professional societies before insurance companies and governmental offices start getting involved.

Documentation↗
PubMed1999

CT angiography and Doppler sonography for emergency assessment in acute basilar artery ischemia.

BACKGROUND AND PURPOSE: Both Doppler sonography (DS) and spiral CT angiography (CTA) are noninvasive vascular assessment tools with a high potential for application in acute cerebral ischemia. The usefulness of CTA for vascular diagnosis in acute basilar artery (BA) ischemia has not yet been studied. METHODS: We prospectively studied 19 patients (mean+/-SD age, 58+/-11 years) with clinically suspected acute BA occlusion by DS and CTA. Prior extracranial and transcranial DS was performed in all but 1 patient, with DS 4 hours after CTA. In 6 of 19 patients, we performed digital subtraction angiography. RESULTS: CTA was diagnostic in all but 1 patient. CTA revealed complete BA occlusion in 9 patients and incomplete BA occlusion with some residual flow in 2 patients. A patent BA was shown in 7 patients. Because of severe BA calcification, CTA results were inconclusive in 1 patient. DS was diagnostic in only 7 of 19 patients, indicating certain BA occlusion in 3 patients and BA patency in 4 patients. In an additional 9 patients, the results of DS were inconclusive. DS was false-negative in 2 patients with distal BA occlusion shown by CTA and digital subtraction angiography. In 1 patient with DS performed after CTA, recanalization was demonstrated. In addition to the diagnosis or exclusion of BA occlusion, CTA provided information on the exact site and length of BA occlusion and collateral pathways. In our series, CTA results prompted indication for intra-arterial thrombolysis in 5 patients. CONCLUSIONS: CTA was superior to DS in the assessment of BA patency in patients with the syndrome of acute BA ischemia in terms of feasibility and conclusiveness, particularly in cases with distal BA occlusion. Our study confirmed the usefulness of combined extracranial and transcranial DS in the diagnosis and exclusion of proximal BA occlusion.

Acute Disease↗
PubMed1999

A genetic study of the human T gene and its exclusion as a major candidate gene for sacral agenesis with anorectal atresia.

Sacral agenesis is a heterogeneous group of congenital anomalies in which most cases are sporadic but rare familial forms also occur. Although one gene has been mapped to chromosome 7q36 in families with hemisacrum, associated with anorectal atresia and presacral mass, it is clear that the genetic aetiology of these disorders is complex and other genes remain to be discovered. Some years ago, the idea of T (Brachyury) as a candidate gene for sacral agenesis was raised, because tail abnormalities associated with T and the t complex, on mouse chromosome 17, resemble spinal defects seen in man. The recent cloning and mapping of the human T gene prompted us to re-evaluate this idea. T is a transcription factor essential for the normal development of posterior mesodermal structures. Although the sequence and function of T are highly conserved in evolution, our genetic study shows that the coding region of the human gene is highly polymorphic. Three common variable amino acid sites in known functional domains have been identified: Gly356Ser, Asn369Ser, and Gly177Asp. For the latter variant, functional studies have shown that the presence of Asp at residue 177 reduces the stability of T dimer formation. A search for rare mutation of T in 28 selected patients with sacral agenesis/anorectal atresia identified a novel, rare variant in one patient and her mother. This mutation leads to an amino acid change within a conserved activation domain. While the functional significance of this single mutation requires further investigation, we can conclude from our studies that if T has a role in the aetiology of sacral agenesis, its contribution is small in this particular set of patients. However, we cannot exclude a more major role in other forms of sacral defect.

Anus, Imperforate↗
PubMed1999

Colposcopic diagnosis: clinical aspects and experiences.

Colposcopy can be applied as an integral part of every gynecologic examination in concert with cytology; to identify and localize lesions suspected on the basis of abnormal cytology findings; and to clarify the nature of clinically suspicious lesions. This implies using colposcopy to clarify the nature of cervical changes seen with the naked eye. This practice is superior to colposcopy which is restricted to evaluating abnormal smears because it can pick up some lesions missed by cytology. But it is not as effective as routine colposcopy because it can miss lesions not picked up by gross inspection of the cervix and because there is no opportunity to inspect the lower tract of the cervical canal. Considering that only 15-20% of lesions are purely endocervical, not too much time is wasted by examining these cases. If colposcopy is limited to evaluating grossly suspicious lesions, then its role is merely to avoid unnecessary biopsies.

Biopsy↗
PubMed1999

Unusual clustering of brain tumours in a family with NF1 and variable expression of cutaneous features.

Neurofibromatosis type 1 (NF1) is one of the commonest autosomal dominant disorders in man. It is characterised by café au lait spots, peripheral neurofibromas, Lisch nodules, axillary freckling, skeletal dysplasia, and optic glioma. Symptomatic brain tumours occur in 1.5-2.2% of patients with NF1. We report here a family where seven members developed brain tumours. Of these, three have a clinical history strongly suggestive of NF1, while two do not fulfil diagnostic criteria for the disorder. A splice site mutation in exon 29 of the NF1 gene was found in these two subjects. This lesion is thought to be disease causative since it creates a frameshift and a premature termination of the neurofibromin protein. Different hypotheses to explain the unusual recurrence of brain tumours in this family, such as the nature of the mutation or cosegregation of other predisposing genes, are discussed.

Adolescent↗
PubMed1998

Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia.

In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x 10(9)/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 x 10(9)/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.

Acute Disease↗
PubMed1998

Structural characterization of the pressure-denatured state and unfolding/refolding kinetics of staphylococcal nuclease by synchrotron small-angle X-ray scattering and Fourier-transform infrared spectroscopy.

The pressure-induced unfolding of wild-type staphylococcal nuclease (Snase WT) was studied using synchrotron X-ray small-angle scattering (SAXS) and Fourier-transform infrared (FT-IR) spectroscopy, which monitor changes in the tertiary and secondary structural properties of the protein upon pressurization. The experimental results reveal that application of high-pressure up to 3 kbar leads to an approximate twofold increase of the radius of gyration Rg of the native protein (Rg approximately 17 A) and a large broadening of the pair-distance-distribution function, indicating a transition from a globular to an ellipsoidal or extended chain structure. Analysis of the FT-IR amide I' spectral components reveals that the pressure-induced denaturation process sets in at 1.5 kbar at 25 degrees C and is accompanied by an increase in disordered and turn structures while the content of beta-sheets and alpha-helices drastically decreases. The pressure-induced denatured state above 3 kbar retains nonetheless some degree of beta-like secondary structure and the molecule cannot be described as a fully extended random coil. Temperature-induced denaturation involves a further unfolding of the protein molecule which is indicated by a larger Rg value and significantly lower fractional intensities of IR-bands associated with secondary-structure elements. In addition, we have carried out pressure-jump kinetics studies of the secondary-structural evolution and the degree of compactness in the folding/unfolding reactions of Snase. The effect of pressure on the kinetics arises from a larger positive activation volume for folding than for unfolding, and leads to a significant slowing down of the folding rate with increasing pressure. Moreover, the system becomes two-state under pressure. These properties make it ideal for probing multiple order parameters in order to compare the kinetics of changes in secondary structure by pressure-jump FT-IR and chain collapse by pressure-jump SAXS. After a pressure jump from 1 bar to 2.4 kbar at 20 degrees C, the radius of gyration increases in a first-order manner from 17 A to 22.4 A over a timescale of approximately 30 minutes. The increase in Rg value is caused by the formation of an extended (ellipsoidal) structure as indicated by the corresponding pair-distance-distribution function. Pressure-jump FT-IR studies reveal that the reversible first order changes in beta-sheet, alpha-helical and random structure occur on the same slow timescale as that observed for the scattering curves and for fluorescence. These studies indicate that the changes in secondary structure and chain compactness in the folding/unfolding reactions of Snase are probably dependent upon the same rate-limiting step as changes in tertiary structure.

Kinetics↗
PubMed1998

Thrombocytosis as a prognostic factor in endometrial carcinoma.

We reviewed the prevalence of thrombocytosis (platelet count >/=400, 000/microL) and its association with outcome in 135 consecutive endometrial carcinoma patients and compared the platelet count with other prognostic factors. Nineteen of 135 patients (14%) had thrombocytosis. Thrombocytosis was significantly more frequent in advanced disease (stage II-IV), unfavorable grade (G2 and G3), deep myometrial invasion, and lymph-vascular space invasion. The overall 5-year survival rate was 92%. The 5-year survival rate of the 19 patients with thrombocytosis was significantly worse than that of the patients without thrombocytosis (61 vs 96%, P < 0.0001). The recurrence rate was significantly higher in patients with thrombocytosis than in those with a platelet count <400,000/microL (7 vs 32%, P < 0.005). In a multivariate analysis, thrombocytosis continued to be a predictor of worse prognosis. In conclusion, we found thrombocytosis to be a prognostic factor for survival in patients with endometrial carcinoma.

Adult↗
PubMed1998

Bacteraemia in the adult intensive care unit of a teaching hospital in Nottingham, UK, 1985-1996.

Bacteraemia is an important cause of morbidity and mortality in the intensive care unit. In this study the distribution of organisms causing bacteraemic episodes in patients in the adult intensive care unit of a large teaching hospital was determined. Particular emphasis was placed on the type of organisms isolated from community- and hospital-acquired bacteraemia, the suspected source of infection, the possible risk factors associated with bacteraemia, and outcome. The incidence of bacteraemia and fungaemia increased from 17.7 per 1000 admissions in 1985 to 80.3 in 1996. A total of 315 episodes of bacteraemia and fungaemia were documented over a 12-year period, of which 18% were considered community-acquired and 82% hospital-acquired. Gram-positive and gram-negative bacteria accounted for 46.9% and 31.5% of the episodes, respectively. Polymicrobial infection accounted for 17.8% and fungi for 3.8% of the episodes. Staphylococcus aureus (22.5%), Staphylococcus epidermidis (7.6%), and Streptococcus pneumoniae (7.9%) were the predominant gram-positive bacteria implicated, whereas Escherichia coli (6%), Enterobacter cloacae (7%), Klebsiella aerogenes (3.8%), Pseudomonas aeruginosa (5.1%), and Acinetobacter spp. (3.8%) were the predominant gram-negative bacteria isolated. The two most common sources of infection were the respiratory tract (39.7%) and an intravascular line (24.5%), but in 8.9% of episodes the focus of infection remained unknown. Bacteraemic patients stayed in the unit for a longer period (12 days) than did non-bacteraemic patients (3 days). The overall mortality related to bacteraemia and candidaemia was 44.4%. Surveillance of bacteraemia in the intensive care unit is important in detecting major changes in aetiology, e.g., the increasing incidence of gram-positive bacteraemia, the emergence of methicillin-resistant Staphylococcus aureus in 1995, and the emergence of Enterobacter cloacae. It is of value in determining empirical antimicrobial therapy to treat presumed infection pending a microbiological diagnosis and in directing the development of guidelines for infection prevention, e.g., guidelines for central venous catheter care.

Adolescent↗