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Biomedical subjects

D Segal

Publications and source records attributed to D Segal.

At least 55 records · Page 3Linked to original sources

Vasoconstrictive activity of meconium stained amniotic fluid in the human placental vasculature.

OBJECTIVE: The purpose of this study was to study was to determine the effect of meconium stained amniotic fluid on the vasculature of isolated perfused human placental cotyledon. STUDY DESIGN: Isolated placental cotyledons were dually perfused. Fetal perfusion pressure was used as an index of vascular resistance. Meconium stained amniotic fluid (MSAF) was collected from patients after artificial rupture of membranes in term gestation. A dilution of meconium (1:2; 1:4; 1:8; 1:16) was performed. Optical density (OD) of MSAF varied between 0 and 35.0 units/g as determined by spectrophotometry. Bolus injections of 1.0 ml of MSAF at different concentrations were injected into the fetal circulation. Heated and dialyzed MSAF after adequate dilution and evaluation of optical density were injected into fetal circulation in separate experiments. RESULTS: Analysis of variance (ANOVA) and paired t-test were used for statistical analysis. Bolus injections of MSAF into the fetal circulation resulted in a concentration-dependent increase in perfusion pressure. MSAF with the highest OD resulted in a greater change in perfusion pressure as compared to more dilute MSAF (P=0.0001). After high OD amniotic fluid injections the provoked contractions lasted longer compared to dilute MSAF (P=0.006). MSAF after dialyzation did not exhibit any vasoconstrictive effect. CONCLUSION: Meconium is a vasoconstrictive agent in the fetal-placental vasculature and has a concentration dependent effect.

Amniotic Fluid↗

A mouse monoclonal antibody to a thyrotropin receptor ectodomain variant provides insight into the exquisite antigenic conformational requirement, epitopes and in vivo concentration of human autoantibodies.

We used the secreted TSH receptor (TSHR) ectodomain variant TSHR-289 (truncated at amino acid residue 289 with a 6-histidine tail) to investigate properties of TSHR autoantibodies in Graves' disease. Sequential concanavalin A and Ni-chelate chromatography extracted milligram quantities of TSHR-289 (approximately 20-40% purity) from the culture medium. Nanogram quantities of this material neutralized the TSH binding inhibitory activity in all 15 Graves' sera studied. We generated a mouse monoclonal antibody (mAb), 3BD10, to partially purified TSHR-289. Screening of a TSHR complementary DNA fragment expression library localized the 3BD10 epitope to 27 amino acids at the N-terminus of the TSHR, a cysteine-rich segment predicted to be highly conformational. 3BD10 preferentially recognized native, as opposed to reduced and denatured, TSHR-289, but did not interact with the TSH holoreceptor on the cell surface. Moreover, mAb 3BD10 could extract from culture medium TSHR-289 nonreactive with autoantibodies, but not the lesser amount (approximately 25%) of TSHR-289 molecules capable of neutralizing autoantibodies. Although the active form of TSHR-289 in culture medium was stable at ambient temperature, stability was reduced at 37 C, explaining the mixture of active and inactive molecules in medium harvested from cell cultures. In conclusion, studies involving a TSHR ectodomain variant indicate the exquisite conformational requirements of TSHR autoantibodies. Even under "native" conditions, only a minority of molecules in highly potent TSHR-289 preparations neutralize patients' autoantibodies. Therefore, Graves' disease is likely to be caused by even lower concentrations of autoantibodies than previously thought. Finally, reciprocally exclusive binding to TSHR-289 by human autoantibodies and a mouse mAb with a defined epitope suggests that the extreme N-terminus of the TSHR is important for autoantibody recognition.

Animals↗

Characteristics of parturients who choose to deliver without analgesia.

The purpose of the study was to characterize parturients who prefer to deliver without the use of analgesia. The study population consisted of 446 consecutive low risk laboring women in early active stage of labor. Data were collected prospectively by an obstetrician, using a structured questionnaire. The degree of pain was assessed by using a visual analog scale (VAS). An obstetrician and a midwife together estimated the degree of pain as was exhibited by the parturients, using the same scale. Univariate analysis found women who undertake labor without analgesia to be significantly older, with higher birth order, of Bedouin ethnicity and to be of lower educational level than those taking analgesics during labor. Women who refused analgesia had experienced and apparently expressed lower degrees of pain (mean VAS score = 7.4 and 6.7, respectively) than those who consented to analgesia (mean VAS score = 8.6 and 8.0, respectively; p < 0.001). A multiple logistic regression model found only the severity of pain (odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.51-0.88; p = 0.004), as well as high maternal age (OR = 1.12, 95% CI 1.16-2.04; p = 0.038) to be independent factors affecting the decision not to accept analgesia during labor. In conclusion, parturients refusing analgesia were older and had experienced less pain during labor than women using analgesia.

Adult↗

The "crushed open pelvis" in children.

A retrospective analysis was performed in order to review the outcome of open pelvic fractures in children. Medical records, radiographs and CT scans of 15 children with open pelvic fractures admitted to our trauma centre between 1983 and 1995 were reviewed. The minimal follow-up on the survivors was two years. Out of 15 open pelvic fractures ten were vertically unstable. The mechanism of injury was auto-pedestrian collision in 93% (n = 14) of the cases. 86% (n = 13) of the fractures were a result of a "run-over" mechanism, 40% (n = 6) were caused by heavy duty vehicles. All children had injuries in the proximity of the pelvis. Despite the severity of trauma, we found mortality to be 20% (n = 3). Sepsis and deep infection originating from anorectal and genitourinary excretions were found to be the most frequent complications. The improvement in surgical techniques of the pelvis influenced the orthopaedic treatment in these 15 children. External fixation of the pelvis is not always sufficient and to achieve better stabilization of the pelvis, open reduction and internal fixation should be considered. In order to minimize complications, aggressive intervention is needed including irrigation, debridement, intravenous antibiotics, diverging colostomies and cystostomies and fracture fixation. The coordination between trauma teams of different disciplines throughout all stages of the treatment is crucial to achieving better results.

Accidents, Traffic↗

Surgical treatment of intercondylar fractures of the humerus in adults.

The rarity, complexity, and intra-articular involvement of intercondylar fractures, along with the osteopenic nature of the elbow joint, make surgical repair of these fractures a difficult and challenging task. When the procedure is properly executed, open reduction and internal fixation can promote proper reduction of the articular fragments and allow early range-of-motion exercises, which are so important for good functional results. We report the results of 30 such fractures treated surgically with good or excellent results. The pros and cons of the transolecranon approach are discussed, along with the options of fracture fixation and importance of early postoperative mobilization.

Adolescent↗

The "rubber band technique": a simple method for closing large skin defects.

Traditional methods of obtaining definitive soft-tissue cover in open wounds after high-energy trauma necessitate repeated surgical procedures and sophisticated soft-tissue reconstructions. A simple one-stage technique to treat skin loss in severe open fractures is described. The "rubber band technique" enables postoperative exposure and drainage of the fracture site. The wound closes gradually by facilitated mobilization of skin in response to continuous tension from the rubber band. This technique may prevent the need for additional procedures. Continuous drainage is achieved. When deep infection is suspected, removal of the elastic rubber band permits sufficient exposure of the deep tissues. The "rubber band technique" has proved to be a safe, simple, and efficient method for treating extensive soft-tissue loss in open fractures and after incisions for open reduction or fasciotomy.

Dermatologic Surgical Procedures↗

Acetabular fractures. Clinical outcome of surgical treatment.

Sixty patients with acetabular fractures were treated surgically. All fractures were a result of high energy trauma, most with significant associated injuries. Fifty-three of the patients were followed up for at least 2 years. Clinical outcome was analyzed clinically using the Harris hip score and radiographically. In 41 (77.4%) of the patients, the surgical procedure was judged successful (Harris hip score greater than 80 points). Three factors were found to be statistically significant predictors of such an outcome: patient age younger than 40 years; simple fractures based on the classification of Letournel and Judet; and absence of damage to the femoral head. Possible influential factors that were not found to be statistically significant in this population included additional injuries, immediate complications, quality of reduction, heterotopic ossification, ipsilateral femoral fracture, and sciatic nerve damage. Open reduction and internal fixation of the displaced acetabular fracture, although a demanding procedure, can result in a satisfactory clinical outcome given a consistent approach with a dedicated team.

Acetabulum↗

Hypoxia and chest pain due to acute constipation: an underdiagnosed condition?

An obese, previously healthy, 10-year-old boy presented with acute respiratory distress, chest, and abdominal pain. He was hypoxic and dyspneic in the emergency room. The abdomen was distended and tender, and the rectum was full of hard stool. Following catharsis, he made a complete recovery with resolution of all clinical signs. A review of the literature reveals that acute constipation as a cause of hypoxia and respiratory distress has been recognized, but has rarely been reported. We believe that this is a common phenomenon but probably infrequently recognized.

Acute Disease↗

Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial.

AIMS: To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period. As a secondary objective, outcomes were determined concurrently for patients treated with two other dose levels. DESIGN: Patients were randomized to four dosage groups and treated double-blind. SETTING: Twelve outpatient opiate maintenance treatment centers throughout the United States. PARTICIPANTS: Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment. INTERVENTION: Patients received either 1, 4, 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context, including a 1-hour weekly clinical counseling session. MEASUREMENT: Retention in treatment, illicit opioid use as determined by urine toxicology, opioid craving and global ratings by patient and staff. Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events. FINDINGS: Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains. No deaths occurred in either group. The 8 mg group did not show an increase in the frequency of adverse events. Most reported adverse effects were those commonly seen in patients treated with opioids. CONCLUSIONS: The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy.

Buprenorphine↗

Overexpression Beadex mutations and loss-of-function heldup-a mutations in Drosophila affect the 3' regulatory and coding components, respectively, of the Dlmo gene.

LIM domains function as bridging modules between different members of multiprotein complexes. We report the cloning of a LIM-containing gene from Drosophila, termed Dlmo, which is highly homologous to the vertebrate LIM-only (LMO) genes. The 3' untranslated (UTR) of Dlmo contains multiple motifs implicated in negative post-transcriptional regulation, including AT-rich elements and Brd-like boxes. Dlmo resides in polytene band 17C1-2, where Beadex (Bx) and heldup-a (hdp-a) mutations map. We demonstrate that Bx mutations disrupt the 3'UTR of Dlmo, and thereby abrogate the putative negative control elements. This results in overexpression of Dlmo, which causes the wing scalloping that is typical of Bx mutants. We show that the erect wing phenotype of hdp-a results from disruption of the coding region of Dlmo. This provides molecular grounds for the suppression of the Bx phenotype by hdp-a mutations. Finally, we demonstrate phenotypic interaction between the LMO gene Dlmo, the LIM homeodomain gene apterous, and the Chip gene, which encodes a homolog of the vertebrate LIM-interacting protein NLI/Ldb1. We propose that in analogy to their vertebrate counterparts, these proteins form a DNA-binding complex that regulates wing development.

Animals↗

Effect of moderate bone hyperthermia on cell viability and mechanical function.

Extracorporeal hyperthermia treatment of bone followed by its reimplantation may be an optional treatment of bone tumors. In this study, the authors examined the minimal hyperthermic condition in which complete eradication of all viable cells in rat bone can be achieved and the mechanical effect of this treatment on the tested bone. When the results were evaluated histologically by special lactate dehydrogenase activity staining, it was found that complete bone cell death occurred after 30 minutes of heating at 60 degrees C. Cartilage cells, including those of the epiphysis, were more resistant to thermal damage. When the ability of the specimens to proliferate in cell cultures was tested, no growth was observed after heating at temperatures of 50 degrees C or greater. The mechanical stiffness tested in the Instron machine showed decreased bone stiffness at 70 degrees C but no change in the breaking load of the bones. Controlled hyperthermia's ability to eradicate viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.

Animals↗

Traumatic myositis ossificans of the quadriceps in infants.

Acute traumatic myositis ossifications is uncommon and usually occurs in adolescents and young adults after a significant direct blow to the affected muscle. It is extremely rare in infants, and we have been able to find only two other cases in the English literature. We present two cases of traumatic myositis ossificans in infants who, except for the use of diagnostic ultrasonography, would have been misdiagnosed as having osteomyelitis (Patient 1) and a possible malignancy (Patient 2).

Acute Disease↗

Metal ions suppress the abnormal taste behavior of the Drosophila mutant malvolio.

A mutation in the malvolio (mvl) gene affects taste behavior in Drosophila melanogaster. The malvolio gene encodes a protein (MVL) that exhibits homology to the mammalian natural resistance-associated macrophage proteins. It is also homologous to the Smf1 protein from Saccharomyces cerevisiae, which we have recently demonstrated to function as a Mn2+/Zn2+ transporter. We proposed that the Drosophila and mammalian proteins, like the yeast SMF1 gene product, are metal-ion transporters. To test this hypothesis, malvolio mutant flies were allowed to develop, from egg to adulthood, on a medium containing elevated concentrations of metal ions. Mutant flies that were reared in the presence of 10 mmol l-1 MnCl2 or FeCl2 developed into adults with recovered taste behavior. CaCl2 or MgCl2 had no effect on the mutant's taste perception. ZnCl2 inhibited the effect of MnCl2 when both ions were supplied together. Similar suppression of the abnormal taste behavior was observed when mvl mutants were fed MnCl2 or FeCl2 only at the adult stage. Furthermore, exposure of adult mutant flies to these ions in the testing plate for only 2 h was sufficient to restore normal taste behavior. The suppression of the defective taste behavior suggests that MVL functions as a Mn2+/Fe2+ transporter and that Mn2+ and/or Fe2+ are involved in the signal transduction of taste perception in Drosophila adults.

Animals↗

Midshaft femoral fracture, concomitant ipsilateral hip joint injury, and disruption of the knee extensor mechanism: a unique triad of dashboard injury.

Our experience with 10 patients who suffered midshaft fractures of the femur and injuries to their ipsilateral hips has resulted in a treatment protocol that we believe can avoid unnecessary complications. The surgical protocol is a three-stage procedure based on (1) intramedullary nailing of the femur with interlocking for preserving the anatomic length and rotation of the femur; (2) treatment of the hip joint injury by means of open reduction and internal fixation of the acetabular fracture and/or reduction and fixation of the fractured femoral neck; and (3) repair of the extensor mechanism. Eight patients received this treatment and had fast recoveries. Union of the femoral fracture and full range of motion of the knee joint were observed within 3 months. In contrast, two patients who had received different surgical treatment had incomplete functional recoveries. This study offers a treatment protocol for ipsilateral disruption of the extensor mechanism, hip joint injury, and midshaft fracture of the femur in the multiply injured patient that can achieve full recovery with no complications. This relatively rare combination of injuries is definitely worthy of special attention.

Accidents, Traffic↗

[Immediate orthopedic surgery in multiple trauma].

The increase in mortality and morbidity from multiple trauma due to road accidents, industrial trauma and combat injuries obligates treatment based on emergency systems and trauma centers. Follow-up of the frequency of different types of injury calls attention to increasing involvement of the orthopedic surgeon in primary treatment. This situation calls for appropriate deployment of immediate surgical treatment which will rapidly enable mobility. We present several methods for immediate orthopedic treatment of multiple-trauma patients.

Bone and Bones↗

Alkynyl phosphates are potent inhibitors of serine enzyme.

Propynyl, hexynyl and t-butylethynyl diethyl phosphates were found to be very powerful covalent inhibitors of serine enzymes. Esterases were inhibited with second-order rate constants of 10(7)-10(8) m(-1) min(-1). Most proteases were inhibited with a rate constant of 10(4)-10(5) M(-1) min(-1). By inhibiting chymotrypsin with (3-14C)-1-propynyl diethyl phosphate, it was established that inhibition was caused by binding of the phosphate group to the enzyme active site.

Aldehyde Dehydrogenase↗