[Pelvic triple osteotomy as a treatment for hip dysplasia].
Explore the source record for details and available documents.
Child↗
Biomedical subjects
D Levin
Publications and source records attributed to D Levin.
Urinary frequency caused by a misplaced acetabular reinforcement ring--a case report.
Explore the source record for details and available documents.
Adult↗
Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations.
BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer who have inherited mutations in these genes have a different outcome after breast conservation therapy than women with "sporadic" cancer is unresolved. Consequently, we compared the outcomes after breast conservation therapy in Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA). METHODS: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast cancers. We reviewed their clinical records, retrieved their archival tissue samples, and tested those samples for the founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All Pvalues are two-sided. RESULTS: We detected mutations in BRCA genes in 28 of 305 women. Women with BRCA mutations were more likely to be diagnosed with cancer before the age of 50 years (P<.001) and to have lymph node involvement (P =.04). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative risk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03). Women with mutations were more likely to develop contralateral breast cancer (RR = 3.50; 95% CI = 1.78-8.74; P =.001). Distant disease-free survival was shorter in women with mutations (66.2% versus 84.3% at 10 years; P =.05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P =.02). Tumor stage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis. CONCLUSIONS: Women with BRCA founder mutations are at increased risk for breast cancer-related events after breast conservation. However, mutation status is not an independent predictor of survival and should not influence decisions regarding adjuvant therapy. The increased contralateral breast cancer risk in women heterozygous for BRCA mutations mandates careful surveillance.
Analysis of Variance↗
De novo autoimmunity to cardiac myosin after heart transplantation and its contribution to the rejection process.
Allograft rejection is initiated by an immune response to donor MHC proteins. We recently reported that this response can result in breakdown of immune tolerance to a recipient self Ag. However, the contribution of this autoimmune response to graft rejection has yet to be determined. Here, we found that after mouse allogeneic heart transplantation, de novo CD4+ T cell and B cell autoimmune response to cardiac myosin (CM), a major contractile protein of cardiac muscle, is elicited in recipients. Importantly, CM is the autoantigen that causes autoimmune myocarditis, a heart autoimmune disease whose histopathological features resemble those observed in rejected cardiac transplants. Furthermore, T cell responses directed to CM peptide myhcalpha 334-352, a known myocarditogenic determinant, were detected in heart-transplanted mice. No responses to CM were observed in mice that had received an allogeneic skin graft or a syngeneic heart transplant, demonstrating that this response is tissue specific and that allogeneic response is necessary to break tolerance to CM. Next, we showed that sensitization of recipient mice with CM markedly accelerates the rejection of allogeneic heart. Therefore, posttransplant autoimmune response to CM is relevant to the rejection process. We conclude that transplantation-induced autoimmune response to CM represents a new mechanism that may play a significant role in cardiac transplant rejection.
Amino Acid Sequence↗
Demonstration of gravity-dependent lung perfusion with contrast-enhanced magnetic resonance imaging.
Imaging of lung perfusion using contrast-enhanced dynamic magnetic resonance (MR) was performed in both the supine and prone positions in six volunteers. Regions of interest (ROIs) were chosen in the dependent and non-dependent portions of the right lung. The percentage increase in signal intensity (SI) and the mean slope were calculated. In the supine position, the dorsal ROI had a greater increase in SI (236.0% vs. 156.9%, P < 0.05) and a faster rise in the slope of enhancement (55.1%/sec vs. 30.1%/sec, P < 0.05) than the ventral ROI. After changing to the prone position, higher peak enhancement (234.3% vs. 177.4%, P < 0.05) and faster slopes (59.6%/sec vs. 35.3%/sec, P < 0.05) shifted to the anterior ROI. We conclude that dynamic contrast-enhanced MR imaging is sensitive to demonstrate gravitationally dependent differences in lung perfusion.
Adult↗
Treatment of experimental avascular necrosis of the femoral head with hyperbaric oxygen in rats: histological evaluation of the femoral heads during the early phase of the reparative process.
The healing of vascular deprivation-induced necrosis of the femoral head of rats exposed to hyperbaric oxygen was compared with that in untreated rats. The amount of necrotic bone, extent of osteoneogenesis, degree of remodeling, and changes of the articular cartilage were histologically graded on a semiquantitative scale of 0 to 3+. On the 2nd, 7th, and 21st postoperative days, there were no differences between the two groups. Newly formed appositional and intramembranous bone was more abundant and remodeling was more advanced in the femoral heads of the hyperbaric oxygen-treated than untreated rats sacrificed on the 42nd postoperative day; also there was less necrotic debris in the femoral heads of the treated rats. There were no differences in the severity of the degenerative changes of the articular cartilage of the treated and untreated rats. Exposure of rats to hyperbaric oxygen does not preserve tissue viability after all arteries supplying the femoral head are severed. Yet, resulting in an increased oxygen tension of the tissues, it seems to provide the optimal settings for reparative processes. The results suggest that hyperoxygenation-mediated relief of ischemia enhances the fibroblastic, angioblastic, osteoblastic, and osteoclastic activities such that healing of the rats' necrotic femoral heads is expedited.
Animals↗
Osteoarthritis-like disorder in rats with vascular deprivation-induced necrosis of the femoral head.
The reparative processes following vascular deprivation-induced necrosis of the femoral head were studied histologically in rats sacrificed 2, 7, 14, 21, 42 and 92 days postoperatively. The blood supply was severed by incision of the periosteum at the neck of the femoral head and transection of the ligamentum teres. Granulation tissue and a well-vascularized fibrous tissue originating from the joint capsule invaded the necrotic marrow spaces. With progressive resorption of the necrotic tissues and osteoneogenesis, both appositional and intramembranous, within the fibrotic intertrabecular spaces, the remodeling process led to a shift of the normal spongy architecture of the femoral head to a compacta-like one. In a few cases, osseous bridges bisected a necrotic physeal cartilage at the latest time intervals. The remodeling was associated with flattening of the femoral heads as well as with degenerative, regenerative and reparative alterations of the articular cartilage. In one of the two femoral heads obtained three months postoperatively, cystic spaces developed in the fibrous subchondral zone. Our findings are consistent with the view that ineffective attempts at restoring the prenecrotic state of the femoral head by replacing the necrotic with viable tissue triggers the collapse of the femoral head. Thickening and condensation of the subchondral bone, leading to increased stiffness of the subchondral zone, result in the osteoarthritis-like disorder. Mimicking the well-known phases of human osteonecrosis, the model readily allows for preclinical studies of therapeutic regimens.
Animals↗
[A rare cause of urinary frequency].
Explore the source record for details and available documents.
Adult↗
Minimally invasive surgical treatment of female stress urinary incontinence.
The purpose of this study was to evaluate the safety and efficacy of a new minimally invasive surgical procedure for the treatment of female stress urinary incontinence (SUI). Four miniature bone anchors, each attached to a suture, are inserted transvaginally into the retropubic bone using an inserter on each side of the urethra without opening the vaginal mucosa. Tying the suture on each ipsilateral side creates colposuspension, as is the aim of previously described procedures such as the Marshall-Marchetti-Krantz. Sixty-one women (mean age 52+/-SD 9.9 years) with a mean follow-up of more than 12 months (range 12-30 months) were treated for SUI. Fifty patients (82%) are dry, 7 (14%) reported great improvement and 4 are considered surgical failures. The data presented suggest that our new minimally invasive procedure provides an effective treatment for female SUI. Its main advantages over other procedures are the transvaginal approach and short operating time.
Female↗
BRCA-associated breast cancer in young women.
PURPOSE: To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations. PATIENTS AND METHODS: We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT. RESULTS: Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007). CONCLUSION: BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.
Adult↗
Surfactant versus saline as a vehicle for corticosteroid delivery to the lungs of ventilated rabbits.
Local administration of steroids to the lungs in ventilated newborn infants can minimize the harmful side effects that occur with systemic administration. An efficient system of drug delivery that provides uniform distribution within the lungs is essential for the treatment of bronchopulmonary dysplasia. In this study we compare surfactant with 0.9% saline solution as vehicles for the direct instillation of a steroid (budesonide) into the lungs. Twenty-two anesthetized, ventilated rabbits received [3H]budesonide in either 0.9% saline or surfactant, administered through an endotracheal tube. Before drug administration, bronchial lavage was performed on half of the animals to serve as a model for surfactant deficiency. Lung samples were analyzed by both autoradiography (alveolar versus airway distribution) and liquid scintillation counting (central versus peripheral deposition). As expected, the delivered concentration of [3H]budesonide decreased as airway size decreased and branching increased. Significantly less [3H]budesonide was deposited in the alveolar spaces of all study groups compared with that deposited in the small and large airways (p < 0.05). However, both vehicles were equally efficient in delivering [3H]budesonide to the lungs. Although the alveolar and peripheral areas received less (4-11%) of the drug than the central tissue (14-28%), this was consistent among all the groups and was not affected by altered lung compliance. Therefore, either surfactant or saline could be used to efficiently and reliably deliver budesonide to the lungs at a level greater than that reported using nebulizers. Because normal saline is currently used for tracheal toilette, it is likely to be preferred considering the increased costs associated with surfactant.
Adrenal Cortex Hormones↗
Aspects of national health promotion programmes for youth.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli.
The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.
Animals↗
Gaucher disease: functional expression of the normal glucocerebrosidase and Gaucher T1366G and G1604A alleles in Baculovirus-transfected Spodoptera frugiperda cells.
Gaucher disease is an inherited sphingolipidosis resulting from deficient glucocerebrosidase activity. Three clinical forms of Gaucher disease have been described: type 1 as non-neuronopathic, type 2 as acute neuronopathic, and type 3 as subacute neuronopathic. We recently identified a rare mutation (G-->A at glucocerebrosidase cDNA nucleotide position 1604) [Choy et al., 1994a, Am J Med Genet 51:156-160] and a novel mutation (T-->G at glucocerebrosidase cDNA nucleotide position 1366) in two type 1 Gaucher patients by sequence analysis of the entire glucocerebrosidase coding region [Choy et al., 1994a, 1994b, Hum Mol Genet 3:821-823]. To demonstrate that these are deleterious and not neutral mutations, we cloned the full-length glucocerebrosidase cDNA of patients and of a normal control in the plasmid vector pAcUW1, recombined the human gene into the Baculovirus genome downstream of its polyhedron p10 promoter, and expressed the inserted gene in cultured cells of Spodoptera frugiperda transfected by recombinant Baculovirus. The levels of residual glucocerebrosidase activity determined in transfected cells with the Gaucher G1604A and T1366G alleles are 6.9% and 2.9% of that expressed by the normal allele (normal = 352.0 nmol/hr/mg protein or 100%). By comparison, the enzyme-specific activity expressed in transfected cells by 2 known Gaucher alleles, A1226G and T1448C, that are prevalent in type 1 and type 2 Gaucher disease are 23.4% and 3.3% of normal. No endogeneous glucocerebrosidase activity was detected in cultured cells transfected by either the wild-type Baculovirus or Baculovirus with the pAcUW1 plasmid vector without the glucocerebrosidase cDNA insert. These findings show that the Baculovirus expression system in cultured Spodoptera frugiperda cells is a suitable system for the functional expression and characterization of the normal and mutant glucocerebrosidase alleles. Moreover, the use of this expression system demonstrates that the G1604A and T1366G mutations are both deleterious mutations resulting in profoundly deficient glucocerebrosidase activity and subsequent Gaucher disease.
Adult↗
Randomized, placebo-controlled, double blinded trial of dexamethasone in African children with sepsis.
OBJECTIVE: To determine the effect of moderate dose dexamethasone administered before antibiotics on the outcome of African children with sepsis. METHODS: The design was a randomized, double blinded, placebo-controlled trial of dexamethasone (0.2 mg/kg) vs. placebo given intravenously before antibiotic therapy. Patients were recruited from the patient populations at two missionary hospitals. Primary outcome variables were determined before analysis of data. RESULTS: Seventy-two children with sepsis were enrolled in the study. Treatment with dexamethasone was not associated with improved outcome for any of six outcome variables: survival to discharge (83%, dexamethasone group; 89%, placebo group); hemodynamic stability at 48 h (33%, dexamethasone group; 49%, placebo group); median length of hospital stay (11 days, dexamethasone group; 11 days, placebo group); normal at discharge (90%, dexamethasone group; 75%, placebo group); normal at follow-up (90%, dexamethasone group; 72%, placebo group); and afebrile at 48 to 72 h (61%, dexamethasone group; 44%, placebo group). CONCLUSIONS: These data indicate that a moderate dose of dexamethasone given before antibiotic therapy did not improve outcome in the pediatric patients with sepsis whom we studied.
Adolescent↗
Modified thioglycolate medium: a simple and reliable means for detection of Trichomonas vaginalis.
Despite the declining rate of sexually transmitted diseases in developed countries, trichomoniasis is still one of the most common venereal infections. While diagnosis of this condition is commonly based on the microscopic wet-mount method, culture remains the most accurate single procedure for detecting the presence of Trichomonas vaginalis in clinical samples. In the present study, the efficacy of a modified formula of the commonly available thioglycolate medium was compared with that of the standard Diamond's medium for detection of T. vaginalis in samples from 176 women with vaginal symptoms. Thioglycolate medium supplemented with yeast extract, horse serum, and antimicrobial agents was as reliable as Diamond's medium for detection of T. vaginalis in vaginal fluid samples. Modified thioglycolate medium may be used as a readily available, low-cost substitute for the standard medium for culturing T. vaginalis.
Animals↗
Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle.
Nitric oxide (NO) is a pluripotent molecule that can be secreted by skeletal muscle through the activity of the neuronal constitutive isoform of NO synthase. To determine whether skeletal muscle and diaphragm might also express the macrophage-inducible form of NO synthase (iNOS) during provocative states, we examined tissue from mice at serial times after intravenous administration of Escherichia coli endotoxin. In these studies, iNOS mRNA was strongly expressed in the diaphragm and skeletal muscle of mice 4 h after intravenous endotoxin and was significantly diminished by 8 h after challenge. Induction of iNOS mRNA was followed by expression of iNOS immunoreactive protein on Western immunoblots. Increased iNOS activity was demonstrated by conversion of arginine to citrulline. Immunochemical analysis of diaphragmatic explants exposed to endotoxin in vitro revealed specific iNOS staining in myocytes, in addition to macrophages and endothelium. These results may be important in understanding the pathogenesis of respiratory pump failure during septic shock, as well as skeletal muscle injury during inflammation or metabolic stress.
Animals↗
Peptide and protein antigens require distinct antigen-presenting cell subsets for the priming of CD4+ T cells.
Priming of naive CD4+ T cells to Ag requires an antigen-presenting cell (APC) that can take up the Ag and present peptide bound to MHC class II molecules. We have used both in vivo and in vitro approaches to demonstrate that the APC used to prime naive CD4+ T cells depends on the initial form in which an Ag is administered. Although Ag delivered as a peptide was presented most efficiently to CD4+ T cells by DC, these APC were poor at priming to a protein form of the same Ag. In contrast, the presence of B cells was a requisite for priming to protein Ag.
Animals↗