Search PubMed⌕ Search

Biomedical subjects

R Winter

Publications and source records attributed to R Winter.

At least 181 records · Page 10Linked to original sources

Nonsyndromic cleft lip with or without cleft palate: evidence of linkage to BCL3 in 17 multigenerational families.

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using an anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds only. Homogeneity testing on the two-point data gave evidence of heterogeneity at APOC2 under the affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities > = 50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families.

B-Cell Lymphoma 3 Protein↗

Solitary metastasis in the tarsus preceding the diagnosis of primary endometrial cancer. A case report.

A solitary metastasis in the left tarsus led to the diagnosis of primary endometrial cancer in a 61 year-old patient with no history of postmenopausal bleeding. Lower leg amputation, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy were performed. Histopathology showed a well-differentiated endometrioid adenocarcinoma of the uterus with a low mitotic rate, but infiltration of the outer third of the myometrium and lymph vessel invasion (FIGO Stage IVb). Immunostaining was positive for progesterone receptors, but negative for estrogen receptors and p53. The lymph nodes were free of metastases. Ascites was positive for malignant cells. Postoperatively the patient received carboplatin, cyclophosphamide and medroxyprogesterone acetate and is alive with no evidence of disease 10 months after diagnosis.

Adenocarcinoma↗

Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial.

Ninety patients with cervical intraepithelial neoplasia (CIN) were randomly assigned to loop excision (n = 38) or cold-knife conization (n = 52). All specimens were well evaluable at histology. The average width of the lesions at histology was 10.2 and 9.7 mm, respectively (ns). The average weight of the specimens was 2.6 and 5.6 g (P < 0.01) and the average depth was 9.2 and 15.8 mm (P < 0.01), respectively. The distance between the cervical resection margin and CIN was 14 mm after loop excision and 24 mm after cold-knife conization (P < 0.06). The margins of the specimen were not clear of disease in 8 patients after loop excision and in 12 patients after conization (ns). Two patients after loop excision and in three patients after cold-knife conization had postoperative bleeding. The results suggest that, compared with cold-knife conization, loop excision removes less healthy tissue without reducing the chances for cure.

Adult↗

Lymphadenectomy in stage I ovarian cancer.

OBJECTIVE: Our experience with systematic lymphadenectomy in stage I ovarian cancer (defined as intraabdominal disease confined to the ovaries) was reviewed. We analyzed whether it would be possible to predict lymph node metastases on the basis of clinical-morphologic factors at the time of surgery. STUDY DESIGN: Forty of 100 evaluable patients operated on between 1980 and 1990 underwent comprehensive surgical staging, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and systemic pelvic +/- paraaortic lymphadenectomy. RESULTS: Nine of the 40 (23%) patients who underwent lymphadenectomy were found to have lymph node metastases; five of these were < or = 2 mm in maximum diameter. Four of the nine patients with positive nodes had ovarian tumors with a maximum diameter of only 5 cm, eight had grade 2 or 3 tumors, and eight tumors were classified as serous cystadenocarcinomas. Other clinical-morphologic factors such as ascites, adherence, or extracystic excrescences did not predict lymph node metastasis. Four of the nine patients with positive nodes survived > or = 5 years with no evidence of disease. CONCLUSIONS: Lymph node metastases, some < r = 2 mm in diameter, occur in an appreciable percentage of patients with intraabdominal disease confined to the ovaries. Clinical-morphologic factors at surgery cannot be relied on to predict the status of the lymph nodes. Thus we cannot recommend limiting lymphadenectomy to any specific subgroup of patients with intraabdominal disease confined to the ovaries.

Adult↗

Amelioration of lactic acidosis with dichloroacetate during liver transplantation in humans.

BACKGROUND: Marked lactic acidosis occurs during orthotopic liver transplantation (OLT), especially during the anhepatic phase. Current standard therapy is NaHCO3, although it may exacerbate intracellular acidosis, increase plasma lactate, and contribute to hypernatremia. Alternatively, dichloroacetate (DCA) stimulates pyruvate oxidation in vivo, reduces plasma lactate, and moderates intracellular acidosis. The aims of this study were to test the efficacy of DCA to control lactic acidosis, reduce the NaHCO3 requirement and incidence of hypernatremia, and stabilize perioperative acid-base homeostasis. Others aims were to examine the DCA pharmacokinetic profile during OLT and the role of lactate metabolism in OLT-associated hyperglycemia. METHODS: Patients (n = 66) for OLT were divided into two equal groups to receive or not receive DCA during OLT. DCA 40 mg.kg-1 was infused over 60 min after induction of anesthesia and 4 h later. Plasma DCA concentration was measured by gas chromatography-mass spectroscopy, and pharmacokinetics were assessed by a one-compartment model. Serial arterial blood gases, lactate, Na+, glucose, and hemodynamic measurements were compared, as were intraoperative utilization of blood products, CaCl2, and NaHCO3. RESULTS: Plasma DCA concentration was maintained between 0.28 and 1.18 mM during OLT, with peak concentrations of 0.73 +/- 0.06 (mean +/- SE) and 1.18 +/- 0.09 mM, respectively after the first and second doses. In control patients, plasma lactate was 1.07 +/- 0.04 at baseline and 1.20 +/- 0.06 before incision and reached a peak of 7.30 +/- 0.41 mM after graft reperfusion. In DCA-treated patients, the respective values were 1.07 +/- 0.06 (difference not significant), 0.63 +/- 0.05 (P < 0.001), and 3.39 +/- 0.20 (P < 0.001) mM. Intraoperative changes in arterial blood pH, HCO3(-1), and base excess were comparable though less marked in DCA-treated patients, whose NaHCO3 requirement was reduced (0.59 +/- 0.36 vs. 2.83 +/- 0.53 mEq.kg-1 in control patients, P < 0.001). There was no difference between groups in requirements for CaCl2 or blood products, in intraoperative hemodynamics, in duration of the surgical stages, or in graft ischemia times. Twelve control and 4 DCA-treated patients exhibited a plasma Na+ concentration > 145 mEq/1 at completion of surgery (P < 0.05). Hyperglycemia was not attenuated by DCA despite decreased plasma lactate concentration. Sixteen and 28 h after graft reperfusion, when plasma DCA had been eliminated, plasma lactate and degree of metabolic alkalosis did not differ between groups. CONCLUSIONS: DCA safely and effectively attenuated lactic acid accumulation and moderated acidosis during OLT. DCA decreased the requirement for NaHCO3 therapy and the incidence of hypernatremia. OLT-associated hyperglycemia did not result from lactate-induced stimulation of hepatic gluconeogenesis. Postoperative metabolic alkalosis was not substantially influenced by lactate metabolism.

Acidosis, Lactic↗

Deep venous thrombosis and pulmonary embolism after major reconstructive operations on the spine. A prospective analysis of three hundred and seventeen patients.

We performed a prospective study of 317 patients in order to determine the prevalence of deep venous thrombosis after reconstructive operations on the spine; 126 of the patients were examined with duplex ultrasound assessments of the lower extremities to ensure that no asymptomatic thrombi were being missed. Thigh-high stockings and sequential pneumatic compression of the lower extremities were used, in all patients, for prophylaxis against venous thrombosis. No antiplatelet agents or anticoagulant medications were administered. There was no evidence of thrombosis on any of the duplex ultrasound studies. Subsequently, venous thrombosis developed and was treated successfully in one of the 126 tested patients and in one of the 191 untested patients, and a fatal pulmonary embolus developed in one of the untested patients. The over-all clinical prevalence of thrombotic complications was 0.9 per cent (three complications in 317 patients). All three of the patients who had clinical evidence of thrombosis had had an anterior lumbar procedure because of a degenerative disorder or trauma; however, we could not prove that this approach or these diagnoses were significant risk factors for thrombosis (p < 0.05). While it is possible that some thrombi may have escaped both clinical and ultrasonic detection, such thrombi apparently were not enough of a danger to warrant the use of intensive prophylactic procedures that are associated with more risk. On the basis of this prospective study, therefore, we think that routine screening for the detection of asymptomatic thrombosis in patients who have had a procedure on the spine is unwarranted.

Adolescent↗

Increase in immunoreactivity to endothelin-1 in the mucosal vasculature and epithelium of the large intestine during chronic hypoxia.

Endothelin-1 is thought to play a role in the regulation of gastrointestinal function including its secretory role. This study investigated the localisation of endothelin-1 in the mucosa of the large intestine of normoxic and chronically hypoxic rats. Chronic hypoxia was produced by maintaining the animals in a hypoxic chamber. After animal perfusion/fixation, colonic segments from normoxic and hypoxic rats were investigated by the postembedding immunogold labelling procedure. In the microvasculature from normoxic (control) animals immunolabelling visualised as single particles was low and confined to the cytoplasm of endothelial cells. In the epithelium, immunolabelling was found mainly at the basal and apical regions of the cells. Chronic hypoxia for 10 d greatly enhanced the level of immunolabelling both in endothelial and epithelial cells of the mucosa. In endothelial cells clusters of gold particles were found in the cytoplasmic matrix and the subendothelium. Epithelial cells showed intense labelling, located mainly in the luminal/apical region within vacuole-like spaces and in the brush-border. In conclusion, hypoxia induces increase in immunoreactivity to endothelin-1 in gut endothelial and especially epithelial cells in the colonic mucosa.

Animals↗

[Problems in perforating keratoplasty with large diameter].

The follow-up of 52 perforating corneal grafts with a diameter of more than 9 mm is presented. The indications for surgery in this series were different from those in a control group. In the 3-year follow-up time most transplants were clear and had a good final visual outcome. Secondary glaucomas were not significant, but a high endothelial cell density decrease could be demonstrated.

Adolescent↗

[Reversible translimbal suture fixation of the ciliary body in treatment of ocular persistent hypotonia after surgical cyclodialysis].

UNLABELLED: After surgical or traumatical cyclodialysis dangerous hypotony can occur. In cases with peripheral anterior synechia the fixation of the ciliary body by reversible suture can bring about the desired pressure rise. PATIENTS: In nine eyes with persistent ocular hypotony after cyclodialysis 13 ciliary body fixations were performed. RESULTS: In four eyes the operation was successful. In two eyes a second operation was necessary. In two cases there was a high postoperative pressure rise. Cutting of the sutures led to a sudden decrease in pressure. In these eyes a second operation with slightly different fixation position was successful. One eye remained hypotonic. CONCLUSIONS: This operative technique entail only slight risk while having good results in patients with aphakia and extensive peripheral anterior synechia. During the early postoperative periods there is the opportunity to reverse the operative effect.

Adolescent↗

Pelvic lymphadenectomy in the surgical treatment of endometrial cancer.

Between 1982 and 1991, 76 of 322 (24%) patients with primary endometrial adenocarcinoma and morphologic risk factors underwent surgery including systematic pelvic lymphadenectomy (LA). A mean number of 37 lymph nodes per patient was removed. The number of removed nodes did not differ with respect to mode of LA, FIGO stage, depth of myometrial invasion, and histologic subtype or grade. Twenty-seven of 76 (36%) patients had lymph node metastases; 37% of lymph node metastases were < or = 2 mm in diameter. The incidence of lymph node metastases correlated significantly with the depth of myometrial invasion but not with histologic subtype and grade. Twenty-four patients with positive nodes who had stage I disease according to the clinical classification (FIGO 1971) were upstaged to stage IIIc according to the surgical staging system (FIGO 1988). This study underlines the need for complete, systematic LA and the need for thorough histologic processing with step-serial sections for correct staging of patients with endometrial cancer.

Adult↗

Pelvic and parametrial lymph nodes in the quality control of the surgical treatment of cervical cancer.

Between 1971 and 1989 a total of 420 patients underwent radical abdominal hysterectomy with pelvic lymphadenectomy at our hospital for stage Ib, IIa, or IIb cervical cancer. The entire lymph node material was processed in serial sections and stained with hematoxylin and eosin. Lymph nodes were counted and the sizes of metastases measured. The entire surgical specimen was fixed as a whole with the parametria spread out. The size of the tumor was measured by morphometry. Cases treated between 1971 and 1979 were compared with those treated between 1980 and 1989. The median number of pelvic lymph nodes removed per patient was 24 between 1971 and 1979 and 35 between 1980 and 1989 (P = 0.0001). Significantly more nodes were removed at each node group (P = 0.01). Between 1971 and 1979 no common iliac nodes were obtained in 56 patients and no left common iliac nodes in 74 patients, compared to only 1 and 6 patients, respectively, between 1980 and 1989. The rate of patients with positive lymph nodes was 33% (63/195) between 1971 and 1979 and 55% (101/225) between 1981 and 1989 (P = 0.008). In the first study period the median number of parametrial lymph nodes was 2 compared to 3 in the second period. The rate of patients with positive parametrial lymph nodes increased from 15 to 24% (P = 0.027). The results of this review indicate that exacting morphologic processing of the entire lymphatic tissue obtained at surgery permits accurate postoperative staging and assessment of risk factors for decisions on adjuvant treatment. Histologic evaluation objectifies the radicality of the procedure and is useful in the quality control of the surgical treatment of cervical cancer.

Female↗

Influence of the local anesthetic tetracaine on the phase behavior and the thermodynamic properties of phospholipid bilayers.

We investigated the influence of the local anesthetic tetracaine on the thermodynamic properties and the temperature- and pressure-dependent phase behavior of the model biomembrane 1,2-dimyristoyl-sn-glycero-3-phosphocholine by using volumetric measurements at temperatures ranging from 0 degrees to 40 degrees C and at pressures from ambient up to 1000 bar. The pVT measurements were complemented by temperature-dependent differential scanning calorimetric measurements. Information about the influence of different concentrations of the local anesthetic on the thermodynamic changes accompanying the lipid phase transitions, and on the thermal expansion coefficient, the isothermal compressibility, and the volume fluctuations of the lipids in their different phases, could be obtained from these experiments. The incorporation of tetracaine leads to an overall disordering of the membrane, as can be inferred from the depression of the main transition temperature and the reduction of the volume change at the main lipid phase transition. The expansion coefficient alpha p and the isothermal compressibility chi T of the lipid bilayer are enhanced by the addition of tetracaine and strongly enhanced values of alpha p and chi T, and the lipid volume fluctuations are found in the direct neighborhood of the main phase transition region. As tetracaine can be viewed as a model system for amphiphilic molecules, these results also provide insight into the general understanding of the physicochemical action of amphiphilic molecules on membranes. The experimental results are compared with recent theoretical predictions for the phase behavior of anesthetic-lipid systems, and the biological relevance of this study is discussed.

Biophysical Phenomena↗