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Biomedical subjects

D Levin

Publications and source records attributed to D Levin.

At least 19 recordsLinked to original sources

Assessing the quality of conformal treatment planning: a new tool for quantitative comparison.

We develop a novel radiotherapy plan comparison index, critical organ scoring index (COSI), which is a measure of both target coverage and critical organ overdose. COSI is defined as COSI=1-(V(OAR)>tol/TC), where V(OAR)>tol is the fraction of volume of organ at risk receiving more than tolerance dose, and TC is the target coverage, VT,PI/VT, where VT,PI is the target volume receiving at a least prescription dose and VT is the total target volume. COSI approaches unity when the critical structure is completely spared and the target coverage is unity. We propose a two-dimensional, graphical representation of COSI versus conformity index (CI), where CI is a measure of a normal tissue overdose. We show that this 2D representation is a reliable, visual quantitative tool for evaluating competing plans. We generate COSI-CI plots for three sites: head and neck, cavernous sinus, and pancreas, and evaluate competing non-coplanar 3D and IMRT treatment plans. For all three sites this novel 2D representation assisted the physician in choosing the optimal plan, both in terms of target coverage and in terms of critical organ sparing. We verified each choice by analysing individual DVHs and isodose lines. Comparing our results to the widely used conformation number, we found that in all cases where there were discrepancies in the choice of the best treatment plan, the COSI-CI choice was considered the correct one, in several cases indicating that a non-coplanar 3D plan was superior to the IMRT plans. The choice of plan was quick, simple and accurate using the new graphical representation.

Algorithms↗

Internal jugular vein thrombosis following mild ovarian hyperstimulation syndrome in women with factor V Leiden mutation.

OBJECTIVE: To study two women who presented with internal jugular vein thrombosis that developed shortly after in vitro fertilization (IVF) therapy complicated by mild ovarian hyperstimulation syndrome (OHSS). METHODS: Evaluation of the past medical history, treatment, laboratory studies, and clinical outcome of both patients. RESULTS: The two patients were found to be carriers for factor V Leiden mutation (FVLM). One was homozygote and the other heterozygote for that mutation. The genetic predisposition probably contributed to the development of an early thrombosis in these patients despite the mildness of their OHSS. In the homozygote patient, the dose of low molecular weight heparin was reduced due to vaginal bleeding. Afterwards, fetal loss due to an extensive placental infarction occurred. Infarction was confined to maternal side while the fetal side vessels were spared. CONCLUSION: We suggest that women of European descent, especially those with personal or familial history of thromboembolic events, should be screened for FVLM before IVF treatment. In those found to be carriers of FVLM, preventive anticoagulation should be considered.

Adult↗

Prolactin affects leptin action in the bovine mammary gland via the mammary fat pad.

One of the roles of the endocrine system is to synchronize mammary function. Hormones, such as estrogen, progesterone, and prolactin act directly on the mammary gland. Metabolic hormones, such as GH, glucocorticoids, insulin, and leptin are responsible for coordinating the body's response to metabolic homeostasis. Leptin has been shown to be an important factor in regulating the metabolic adaptation of nutrient partitioning during the energy-consuming processes of lactation. In the present study, we show that leptin is secreted from the mammary fat, and is regulated by prolactin. The expression of alpha-casein in a co-culture of epithelial cells and fat explants was enhanced by prolactin compared with that in epithelial cells cultured alone. Leptin antagonist abolished the effect of leptin on alpha-casein expression in mammary gland explants when exogenous leptin was not present in the medium. This finding supports our hypothesis that the antagonist abolishes the action of endogenous leptin secreted by the mammary adipocytes. These results lead us to the hypothesis that prolactin and leptin act in the bovine mammary gland, via mammary fat pad/adipocytes.

Adiponectin↗

Inter-observer agreement of tests used for prediction of difficult laryngoscopy/tracheal intubation.

BACKGROUND: Guidelines recommend pre-operative airway evaluation for the prediction of airway management difficulties. Combining tests for evaluation increases the accuracy of the assessment. One model including seven parameters transformed into a simplified airway risk index (SARI) has been proven to be valid. We determined the inter-observer agreement of the specific test combinations included in SARI as well as of the total score. METHODS: Four observers assessed 136 patients, 120 without and 16 with a difficult airway history. Two residents and two specialists in anaesthesia performed the airway assessment consisting of the measurement of the mouth opening, the thyromental distance (TMD), the ability to protrude the mandible and an evaluation of the Mallampati class and head and neck mobility. Body weight was also recorded. Inter-observer agreement between specialists and residents, separately, was analysed using kappa statistics and Spearman's correlation analysis and the limits of agreement were evaluated using the 95% confidence interval. The agreement between pairs of assessors was also evaluated. RESULTS: The inter-observer agreement was good to excellent for both specialists and residents when measuring mouth opening (Spearman's correlation coefficient R=0.88-0.97) and the horizontal distance between the upper and lower incisors during jaw protrusion (R=0.56-0.97). The Mallampati classification assessment demonstrated satisfactory to complete inter-observer agreement (kappa=0.41-1). The assessment of TMD and neck mobility showed considerable discrepancies between observers. CONCLUSIONS: We demonstrated good inter-observer agreement using three tests from SARI and recommend the Mallampati classification, mouth opening and ability of jaw protrusion for pre-operative airway evaluation. A simplification of the assessment of TMD and neck mobility is warranted.

Adult↗

Medical aerosol propellant interference with infrared anaesthetic gas monitors.

BACKGROUND: 1,1,1,2 Tetrafluoroethane is a hydrofluoroalkane (HFA) that is replacing chlorofluorocarbons (CFC) as a medical aerosol propellant in an attempt to reduce damage to the ozone layer. This study compared the effects of HFA- and CFC-based inhalers on four anaesthetic gas monitoring systems. METHODS: The HFA- and CFC-based inhalers were activated in close proximity to the sample line of two Datex Ohmeda, an Agilent and a Siemens infrared anaesthetic agent monitoring systems. The effects were recorded on each system for five common anaesthetic agents. RESULTS: The HFA inhaler caused either maximal false positive readings (with the exception of desflurane) or transient measurement failure on all systems. The Datex Ohmeda AS/3 system misidentified the HFA inhaler as carbon dioxide at low concentration (2 +/- 0 mm Hg). The CFC-based inhaler caused a minor false-positive reading (0.4 +/- 0%) for halothane only on the Datex Ohmeda AS/3 system only and was misidentified as carbon dioxide at 33.3 (sd 2.1) mm x Hg and 22.4 (8.9) mm x Hg by the Agilent and Siemens systems. CONCLUSIONS: The HFA inhaler adversely affected all equipment tested. The infrared spectra of HFA and the common anaesthetic gases have considerable overlap at the 8-12 microm range that is not shared by the CFCs. The differences in spectral overlap explain the different effects of the HFA and CFC propellants. Anaesthetic gas concentration data may be erroneous using the HFA-based inhalers.

Aerosol Propellants↗

Experimental Corynebacterium pseudotuberculosis mastitis in dairy cows.

The inoculation of 2000 colony-forming units of Corynebacterium pseudotuberculosis into one teat canal of each of three cows resulted in severe, chronic, pyogranulomatous mastitis. Within three days the cows had a reduced haematocrit, haemoglobin concentration and red cell count. The anaemia was initially normocytic, normochromic and non-regenerative, and was associated with a brief peak of neutrophilia; a regenerative response became evident two to three weeks later. Clinical signs of mastitis appeared seven to 14 days after the inoculation, with a peak of high fever, more severe anaemia, a second peak of neutrophilia and the complete cessation of milk production from all quarters; extensive and severe pyogranulomatous mastitis developed in the inoculated quarters. No other lesions were detected postmortem, and C pseudotuberculosis was cultured from the affected quarters but not from the supramammary lymph nodes and viscera.

Anemia↗

Hyperbaric oxygen therapy as a treatment for stage-I avascular necrosis of the femoral head.

Avascular necrosis (AVN) of the head of the femur is a potentially crippling disease which mainly affects young adults. Although treatment by exposure to hyperbaric oxygen (HBO) is reported as being beneficial, there has been no study of its use in treated compared with untreated patients. We selected 12 patients who suffered from Steinberg stage-I AVN of the head of the femur (four bilateral) whose lesions were 4 mm or more thick and/or 12.5 mm or more long on MRI. Daily HBO therapy was given for 100 days to each patient. All smaller stage-I lesions and more advanced stages of AVN were excluded. These size criteria were chosen in order to compare outcomes with an identical size of lesion in an untreated group described earlier. Overall, 81% of patients who received HBO therapy showed a return to normal on MRI as compared with 17% in the untreated group. We therefore conclude that hyperbaric oxygen is effective in the treatment of stage-I AVN of the head of the femur.

Adult↗

Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication.

AIMS: Activated charcoal is now being recommended for patients who have ingested potentially toxic amounts of a poison, where the ingested substance adsorbs to charcoal. Combination therapy with gastric lavage and activated charcoal is widely used, although clinical studies to date have not provided evidence of additional efficacy compared with the use of activated charcoal alone. There are also doubts regarding the efficacy of activated charcoal, when administered more than 1 h after the overdose. The aim of this study was to examine if there was a difference in the effect of the two interventions 1 h post ingestion, and to determine if activated charcoal was effective in reducing the systemic absorption of a drug, when administered 2 h post ingestion. METHODS: We performed a four-limbed randomized cross-over study in 12 volunteers, who 1 h after a standard meal ingested paracetamol 50 mg kg(-1) in 125 mg tablets to mimic real-life, where several factors, such as food, interfere with gastric emptying and thus treatment. The interventions were activated charcoal after 1 h, combination therapy of gastric lavage followed by activated charcoal after 1 h, or activated charcoal after 2 h. Serum paracetamol concentrations were determined by h.p.l.c. Percentage reductions in the area under the curve (AUC) were used to estimate the efficacy of each intervention (paired observations). RESULTS: There was a significant (P<0.005) reduction in the paracetamol AUC with activated charcoal at 1 h (median reduction 66%, 95% confidence intervals 49, 76) compared with controls, and a significant (P<0.01) reduction for gastric lavage followed by activated charcoal at 1 h (median reduction 48.2%, 95% confidence interval 32.4, 63.7) compared with controls. There was no significant difference between the two interventions (95% confidence interval for the difference -3.8, 34.0). Furthermore, we found a significant (P<0.01) reduction in the paracetamol AUC when activated charcoal was administered 2 h after tablet ingestion when compared with controls (median 22.7%, 95% confidence intervals 13.6--34.4). CONCLUSIONS: These results suggest that combination treatment may be no better than activated charcoal alone in patients presenting early after large overdoses. The effect of activated charcoal given 2 h post ingestion is substantially less than at 1 h, emphasizing the importance of early intervention.

Acetaminophen↗

High rate of vaginal infections caused by non-C. albicans Candida species among asymptomatic women.

A prospective observational study of patients attending a gynecological clinic and those referred to a clinic for genitourinary infections was undertaken with the purpose of evaluating the relative prevalence of non-C. albicans Candida species among Candida isolates from the vagina in different clinical settings in an area with high occurrence of vulvovaginal candidiasis. The rate of non-C. albicans Candida species was 44.5% among asymptomatic women, 19.4% among those with sporadic vaginitis and 21% among patients with chronic vaginal symptoms (p < 0.001 for asymptomatic vs. pooled symptomatic women). No increase in the rate of non-C. albicans Candida was observed during a period of 4 years (1995-1998) despite a 1.57-fold increase in the sales of azole antifungal agents. Unlike some previous reports we could not document an association of non-C. albicans Candida species with chronic vaginal symptoms or increased use of azole antifungal agents. The significantly higher rate of these yeasts in asymptomatic women is in accord with the known tendency of non-C. albicans Candida species to cause mild symptoms.

Antifungal Agents↗

Computer-assisted image analysis of the rat postosteonecrotic remodeled femoral head.

Osteonecrosis of rat femoral heads was induced by stripping the periosteum of the neck and cutting the ligamentum teres. The epiphyseal marrow and bone were necrotic on the 5th postoperative day. Specimens obtained 18 and 36 days postoperatively showed fibrous and hematopoietic-fatty tissue in the intertrabecular spaces, osteoclastic bone resorption, osteogenesis, and degeneration of the joint cartilage. Morphometrically, the means of the height-to-length ratios of the control, 6-day, 18-day, and 36-day femoral heads were 0.26, 0.28, 0.48, and 0.29, respectively. The shape factor of the femoral heads of the control rats was higher than 0.81 in 80% of the cases, while those of rats killed on the 6th, 18th, and 36th postoperative day were higher than 0.81 in 65, 60, and 50% of cases, respectively. Statistically, the means of the height-to-length ratios and the values of the shape factors of the femoral heads of the rats killed 18 days postoperatively differed significantly from those of the other three groups of rats. The quantitatively gauged data of the remodeled epiphyses negate the authors' subjective impression concerning early flattening of the femoral heads after surgically produced osteonecrosis.

Animals↗

Transphyseal osseous bridges in experimental osteonecrosis of the femoral head of the rat. Histologic study of the bony bridges connecting the epiphyseal with the metaphyseal bony trabeculae through gaps in the physeal cartilage.

In view of the lifelong persistence of the physis, the femoral head of rats may serve to model Perthes disease and slipped capital femoral epiphysis. To produce osteonecrosis, the blood supply of one femoral head of 133, 6-month-old animals was severed by circumferentially incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed 7 days to 90 days postoperatively. Associated with resorption of the necrotic bone and marrow, remodeling of the epiphysis was characterized by an ingrowth of vascularized fibrous tissue, formation of new bone and some cartilage, architectural deformation and flattening of the head. In 22 of 83 rats killed 30 days or more postoperatively, gaps in the continuity of the physeal cartilage were occupied by osseous bridges, connecting newly formed epiphyseal bony trabeculae with either the preexisting or newly formed metaphyseal osseous trabeculae. This healing mode may follow ischemic death of physeal chondrocytes or be owing to another mechanism, e.g., release of mediatory substances of inflammation. These findings raise the possibility that fixation of the healing epiphysis of a child's previously necrotic femoral head to the metaphysis occurs by transphyseal osseous growth in cases in which the physis is involved in the necrotic process.

Age Factors↗

Effects of non-weight bearing and hyperbaric oxygen therapy in vascular deprivation-induced osteonecrosis of the rat femoral head.

We examined the role of hyperbaric oxygenation (HBO2) combined with non-weight bearing (NWB) in the treatment of vascular deprivation-induced osteonecrosis of the femoral head in the rat. Group 1 included 16 rats treated by a combination of NWB and HBO2. Twenty animals treated by NWB alone (group 2), and 18 rats which received no treatment (group 3), served as the control groups. Maximal benefit of HBO2 was observed on Day 30 of the study. The femoral heads were less deformed in group 1 animals (P = 0.07). Preservation of the femoral heads was observed in a larger proportion of the HBO2-treated animals (P = 0.06). A smaller proportion of high-grade new bone formation was observed, and more animals demonstrated well-regenerated hematopoietic tissue (P = 0.08). The tendency for less deformation of the femoral head in the HBO2-treated group might be a predictor of better function of the hipjoint.

Animals↗

Monoclonal antibody MS13 identifies a plasmatocyte membrane protein and inhibits encapsulation and spreading reactions of Manduca sexta hemocytes.

Lepidopterans generally can successfully defend themselves against a variety of parasites or parasitoids. One mechanism they use is to encapsulate the invader in many layers of hemocytes. For encapsulation to occur, the hemocytes must attach to the foreign material, spread, and adhere to each other. The molecules that mediate these processes are not known. One method to identify proteins potentially necessary for adhesion, spreading, and, thus, encapsulation is to use monoclonal antibodies that interfere with these functions. In this paper, we report that a monoclonal antibody against Manduca sexta plasmatocytes effectively inhibited encapsulation of synthetic beads in vitro and in vivo. Furthermore, it inhibited plasmatocyte spreading in vitro. Other anti-hemocyte antibodies did not have these effects. The plasmatocyte-specific monoclonal antibody, mAb MS13, recognized a protein of approximately 90,000 daltons as indicated by Western blot analysis of hemocyte lysate proteins. The epitope recognized by mAb MS13 was present on the exterior surface of plasmatocytes. Using indirect immunohistochemistry with hemocyte-specific antibodies, we also determined that during encapsulation plasmatocytes were the first cells bound to latex beads and later layers consisted of both plasmatocytes and granular cells. Arch.

Animals↗

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↗