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Biomedical subjects

N Rich

Publications and source records attributed to N Rich.

At least 19 recordsLinked to original sources

Expression of the gene for the alpha-subunit of inhibin in human adrenocortical tumours.

BACKGROUND: To determine whether the pathogenesis of human adrenocortical tumours is associated with variations of inhibin expression, we assayed the mRNA of the alpha-subunit of inhibin in 5 normal adrenals and 48 adrenocortical tumours, including 10 paediatric tumours. RESULTS: mRNA of alpha-subunit of inhibin was detected in all adrenocortical tissues. It was similarly abundant in the three pathological groups of adult tumours (benign, suspect and malignant) and in normal adrenal tissues, irrespective of the hormonal pattern. However, in paediatric tumours, the levels of the mRNA for the alpha-subunit of inhibin were significantly higher than those in adult tumours (p < 0.01). CONCLUSION: Inhibin is more abundant in the foetal than in the adult adrenal cortex and therefore these data suggest that the paediatric tumours may have a foetal pattern.

Adrenal Cortex Neoplasms↗

Effects of fibronectin bonding on healing of high porosity expanded polytetrafluoroethylene grafts in pigs.

BACKGROUND: We developed a new fibronectin bonding to expanded polytetrafluoroethylene (ePTFE) and previously reported that, in a dog carotid implant model, fibronectin bonding improves graft healing in high porosity ePTFE grafts. The purpose of this study was to further investigate the effect of the fibronectin bonding on graft healing in a pig carotid implant model. METHODS: Fifteen pigs received a high porosity ePTFE graft treated with the fibronectin bonding (fibronectin-bonded graft) on one side and an untreated graft (non-bonded graft) on the contralateral side. The grafts were explanted at intervals of 3 and 6 weeks and subjected to histological studies. RESULTS: At 3 weeks, the neointima of fibronectin-bonded grafts was better organized than that of non-bonded grafts. At 6 weeks, the morphologic features of the neointima were the same in fibronectin-bonded and non-bonded grafts. The neointima was completely organized. CONCLUSIONS: Together with the previous results with the dog model, fibronectin bonding could be expected to improve healing of the high porosity ePTFE grafts in humans.

Animals↗

Pulmonary surfactant protein A interacts with gel-like regions in monolayers of pulmonary surfactant lipid extract.

Epifluorescence microscopy was used to investigate the interaction of pulmonary surfactant protein A (SP-A) with spread monolayers of porcine surfactant lipid extract (PSLE) containing 1 mol % fluorescent probe (NBD-PC) spread on a saline subphase (145 mM NaCl, 5 mM Tris-HCl, pH 6.9) containing 0, 0.13, or 0.16 microg/ml SP-A and 0, 1.64, or 5 mM CaCl(2). In the absence of SP-A, no differences were noted in PSLE monolayers in the absence or presence of Ca(2+). Circular probe-excluded (dark) domains were observed against a fluorescent background at low surface pressures (pi approximately 5 mN/m) and the domains grew in size with increasing pi. Above 25 mN/m, the domain size decreased with increasing pi. The amount of observable dark phase was maximal at 18% of the total film area at pi approximately 25 mN/m, then decreased to approximately 3% at pi approximately 40 mN/m. The addition of 0.16 microg/ml SP-A with 0 or 1.64 mM Ca(2+) in the subphase caused an aggregation of dark domains into a loose network, and the total amount of dark phase was increased to approximately 25% between pi of 10-28 mN/m. Monolayer features in the presence of 5 mM Ca(2+) and SP-A were not substantially different from those spread in the absence of SP-A, likely due to a self-association and aggregation of SP-A in the presence of higher concentrations of Ca(2+). PSLE films were spread on a subphase containing 0.16 microg/ml SP-A with covalently bound Texas Red (TR-SP-A). In the absence of Ca(2+), TR-SP-A associated with the reorganized dark phase (as seen with the lipid probe). The presence of 5 mM Ca(2+) resulted in an appearance of TR-SP-A in the fluid phase and of aggregates at the fluid/gel phase boundaries of the monolayers. This study suggests that SP-A associates with PSLE monolayers, particularly with condensed or solid phase lipid, and results in some reorganization of rigid phase lipid in surfactant monolayers.

4-Chloro-7-nitrobenzofurazan↗

Survival after emergency department thoracotomy: review of published data from the past 25 years.

BACKGROUND: Emergency department thoracotomy (EDT) has become standard therapy for patients who acutely arrest after injury. Patient selection is vitally important to achieve optimal outcomes without wasting valuable resources. The aim of this study was to determine the main factors that most influence survival after EDT. STUDY DESIGN: Twenty-four studies that included 4,620 cases from institutions that reported EDT for both blunt and penetrating trauma during the past 25 years were reviewed. The primary outcomes analyzed were in-hospital survival rates. RESULTS: EDT had an overall survival rate of 7.4%. Normal neurologic outcomes were noted in 92.4% of surviving patients. Factors reported as influencing outcomes were the mechanism of injury (MOI), location of major injury (LOMI), and signs of life (SOL). Survival rates for MOI were 8.8% for penetrating injuries and 1.4% for blunt injuries. When penetrating injuries were further separated, the survival rates were 16.8% for stab wounds and 4.3% for gunshot wounds. For the LOMI, survival rates were 10.7% for thoracic injuries, 4.5% for abdominal injuries, and 0.7% for multiple injuries. If the LOMI was the heart, the survival rate was the highest at 19.4%. The third factor influencing outcomes was SOL. If SOL were present on arrival at the hospital, survival rate was 11.5% in contrast to 2.6% if none were present. SOL present during transport resulted in a survival rate of 8.9%. Absence of SOL in the field yielded a survival rate of 1.2%. There was no clear single independent preoperative factor that could uniformly predict death. CONCLUSIONS: The best survival results are seen in patients who undergo EDT for thoracic stab injuries and who arrive with SOL in the emergency department. All three factors-MOI, LOMI, and SOL-should be taken into account when deciding whether to perform EDT. Uniform reporting guidelines are needed to further elucidate the role of EDT taking into account the combination of MOI, LOMI, and SOL.

Emergencies↗

Malignant carotid body tumor: a case report.

Carotid body tumors (CBTs) have an unpredictable history with no correlation between histology and clinical behavior. Of reported cases since 1891, local and distant metastases appear in approximately 10% of cases and remain the hallmark of malignancy. Currently, there are not enough data to support a single treatment regimen for malignant CBTs. The reported case demonstrates some unanswered issues with regard to malignant CBTs to include lymph node dissection, the need for carotid resection, and the role of radiation therapy. A 46-year-old pathologist underwent a resection of a Shamblin I CBT, to include jugular lymph node sampling, without complication. There was lymph node involvement, and tumor cells were found on the margins of the pathologic specimen. Subsequent carotid resection with reversed interposition saphenous vein graft and modified neck dissection were performed again without complication. Follow-up at 4 years has been uneventful. Diagnosis of CBTs with the use of magnetic resonance angiography, magnetic resonance imaging, color flow duplex scanning, and the role of arteriography are reviewed. The current treatment options are discussed with reference to primary lymph node sampling, carotid resection, and neck dissection in malignant cases. This case demonstrates that the unpredictable nature of CBTs and their malignant potential warrant aggressive initial local treatment to include jugular lymph node sampling and complete tumor resection.

Carotid Body Tumor↗

Lactated ringer's solution and hetastarch but not plasma resuscitation after rat hemorrhagic shock is associated with immediate lung apoptosis by the up-regulation of the Bax protein.

BACKGROUND: We previously demonstrated that the type of resuscitation fluid used in hemorrhagic shock affects apoptosis. Unlike crystalloid, whole blood seems to attenuate programmed cell death. The purpose of this study was to determine whether the acellular components of whole blood (plasma, albumin) attenuated apoptosis and to determine whether this process involved the Bax protein pathway. METHODS: Rats were hemorrhaged 27.5 mL/kg, kept in hypovolemic shock for 75 minutes, then resuscitated over 1 hour (n = 44). Control animals underwent anesthesia only (sham, n = 7). Treatment animals were bled then randomly assigned to the following resuscitation groups: no resuscitation (n = 6), whole blood (n = 6), plasma (n = 6), 5% human albumin (n = 6), 6% hetastarch (n = 7), and lactated Ringer's solution (LR, n = 6). Hetastarch was used to control for any colloid effect. LR was used as positive control. Immediately after resuscitation, the lung was collected and evaluated for apoptosis by using two methods. TUNEL stain was used to determine general DNA damage, and Bax protein was used to specifically determine intrinsic pathway involvement. RESULTS: LR and hetastarch treatment resulted in significantly increased apoptosis in the lung as determined by both TUNEL and Bax expression (p < 0.05). Plasma infusion resulted in significantly less apoptosis than LR and hetastarch resuscitation. Multiple cell types (epithelium, endothelium, smooth muscle, monocytes) underwent apoptosis in the lung as demonstrated by the TUNEL stain, whereas Bax expression was limited to cells residing in the perivascular and peribronchial spaces. CONCLUSION: Apoptosis after volume resuscitation of hemorrhagic shock can be affected by the type of resuscitation fluid used. Manufactured fluids such as lactated Ringer's solution and 6% hetastarch resuscitation resulted in the highest degree of lung apoptosis. The plasma component of whole blood resulted in the least apoptosis. The process of apoptosis after hemorrhagic shock resuscitation involves the Bax protein.

Animals↗

Sutureless vascular reconstruction with titanium clips.

Attempts to find alternatives to sutured vascular reconstruction techniques has continued for decades and include various forms of rings, tubes, endoluminal stents as well as gluing or welding techniques of large vessel anastomoses. One recently introduced technique uses nonpenetrating titanium clips for everted vessel approximation and closure. Experimental work on their use in various types of large vessel repairs and reconstructions has shown that the clips are easily applied with a short learning curve, create good conditions for vessel wall healing without causing excessive inflammation or fibrosis, and are considerably faster to apply when compared to standard suture techniques. Although there are some clinical reports of defective clipped closures causing postoperative bleeding complications, they are rare and most probably related to technical errors in applying the clips. The main disadvantages of the clips include the limited experience of their applicability in atherosclerotic vessels, lack of long term follow-up and cost. Potentially, the clips could be useful in the repair of multiple vascular injuries, in vessel repair or ligation performed in confined spaces, and in vascular procedures requiring the shortest possible cross-clamping time. Future applications could include endoscopic procedures as well as the use of a one-shot device which simultaneously applies up to a dozen clips to symmetrically everted and approximated vessel edges.

Animals↗

Resuscitation with lactated Ringer's solution in rats with hemorrhagic shock induces immediate apoptosis.

BACKGROUND: We hypothesize that different resuscitative fluids may immediately affect the degree of apoptosis after hemorrhagic shock. METHODS: Rats (n = 35) were hemorrhaged 27 mL/kg over 5 minutes followed by 1 hour of shock, then resuscitation over 1 hour. The six treatment groups were sham hemorrhage, sham resuscitation, whole blood resuscitation, lactated Ringer's solution (LR) resuscitation with three times the volume bled, sham hemorrhage with LR infusion, and 7.5% hypertonic saline resuscitation (9.7 mL/kg). Liver and small intestine were harvested immediately after resuscitation. Apoptosis was evaluated by using in situ cell death detection method. RESULTS: Resuscitation with LR resulted in a significant increase in small intestinal and liver apoptosis. Animals that received LR infusion without hemorrhage had an increased level of apoptosis in the intestine. Apoptosis in the intestine was observed in both the mucosa and muscularis externa. There was no increase in apoptosis in either organ in the animals resuscitated with sham resuscitation, whole blood, and hypertonic saline compared with the sham hemorrhage group. CONCLUSION: Resuscitation with LR solution after hemorrhagic shock increased immediate cell death by apoptosis in both the small intestine and liver. There was no significant increase in apoptosis in the animals resuscitated with hypertonic saline, whole blood, or in unresuscitated animals. Thus, the type of resuscitation fluid used may affect the apoptotic cellular response to shock.

Animals↗

The effects of idazoxan on reaction times, eye movements and the mood of healthy volunteers and patients with upper respiratory tract illnesses.

An experiment was carried out to determine whether idazoxan, a drug which increases the turnover of central noradrenaline, removes the malaise (reduced alertness, slower psychomotor performance) associated with upper respiratory tract illness (URTI). Eighty-one volunteers were tested when healthy and 17 returned to the laboratory when they developed URTIs. Those who remained healthy were then recalled as a control group. Volunteers were tested before and after receiving either idazoxan (40mg) or a lactose placebo. Idazoxan removed the URTI-induced slowing in a simple reaction time task and this group performed at a comparable level to the healthy group. No significant stimulant effect of idazoxan was found in the healthy subjects. The results suggest that at least part of the malaise induced by URTIs may reflect reductions in central noradrenaline and that this can be reversed by compounds such as idazoxan.

Adrenergic alpha-Antagonists↗

GnRH signalling pathways and GnRH-induced homologous desensitization in a gonadotrope cell line (alphaT3-1).

Exposure of the gonadotrope cells to gonadotropin-releasing hormone (GnRH) reduces their responsiveness to a new GnRH stimulation (homologous desensitization). The time frame as well as the mechanisms underlying this phenomenon are yet unclear. We studied in a gonadotrope cell line (alphaT3-1) the effects of short as well as long term GnRH pretreatments on the GnRH-induced phospholipases-C (PLC), -A2 (PLA2) and -D (PLD) activities, by measuring the production of IP3, total inositol phosphates (IPs), arachidonic acid (AA) and phosphatidylethanol (PEt) respectively. We demonstrated that although rapid desensitization of GnRH-induced IP3 formation did not occur in these cells, persistent stimulation of cells with GnRH or its analogue resulted in a time-dependent attenuation of GnRH-elicited IPs formation. GnRH-induced IPs desensitization was potentiated after direct activation of PKC by the phorbol ester TPA, suggesting the involvement of distinct mechanisms in the uncoupling exerted by either GnRH or TPA on GnRH-stimulated PI hydrolysis. The levels of individual phosphoinositides remained unchanged under any desensitization condition applied. Interestingly, while the GnRH-induced PLA2 activity was rapidly desensitized (2.5 min) after GnRH pretreatments, the neuropeptide-evoked PLD activation was affected at later times, indicating an important time-dependent contribution of these enzymatic activities in the sequential events underlying the GnRH-induced homologous desensitization processes in the gonadotropes. Under GnRH desensitization conditions, TPA was still able to induce PLD activation and to further potentiate the GnRH-evoked PLD activity. AlphaT3-1 cells possess several PKC isoforms which, except PKCzeta, were differentially down-regulated by TPA (PKCalpha, betaII, delta, epsilon, eta) or GnRH (PKCbetaII, delta, epsilon, eta). In spite of the presence of PKC inhibitors or down-regulation of PKC isoforms by TPA, the desensitizing effect of the neuropeptide on GnRH-induced IPs, AA and PEt formation remained unchanged. In conclusion, in alphaT3-1 cells the GnRH-induced homologous desensitization affects the GnRH coupling with PLC, PLA2 and PLD by mechanism(s) which do not implicate TPA-sensitive PKC isoforms, but likely reflect time-dependent modification(s) on the activation processes of the enzymes.

Arachidonic Acid↗

Rapid arterial anastomosis with titanium clips.

BACKGROUND: The obvious advantages of rapid arterial anastomoses have prompted the continuing search for more rapid anastomotic techniques to complement the standard sutured anastomosis. Nonpenetrating, arcuate-legged titanium vascular closure staple (VCS) clips were initially developed for microvascular anastomoses. The purpose of this study was to compare VCS clips with sutured arterial end-to-end anastomosis in larger vessels. METHODS: In 6 pigs, transacted iliac arteries were reanastomosed with VCS clips on one side and continuous 6-0 polypropylene suture on the other. RESULTS: The reconstruction time was 8.4+/-5.2 minutes for clip closure and 12.0+/-6.6 minutes for suture closure (P = 0.033). All vessels were patent half an hour after completing the anastomoses with no signs of early thrombosis. CONCLUSIONS: Arterial end-to-end anastomosis can be performed more rapidly with VCS clips than continuous sutures, and are potentially useful in situations where the clamp time of the vessel is critical.

Anastomosis, Surgical↗

A polymorphism in the 5' untranslated region of the human ob gene is associated with low leptin levels.

OBJECTIVE: To search the human ob gene for mutations and evaluate their role in massive obesity. DESIGN: Direct mutation screening of the gene and case-control association study. Multivariate analyses for evaluation of differences in clinical parameters. SUBJECTS: Primary mutation screening: 24 morbidly obese subjects (body mass index (BMI) > 40 kg/m2). Association study: 395 unrelated morbidly obese subjects (BMI > 40 kg/m2), 121 lean, non-diabetic control individuals, 72 women of a random sample with an average BMI 32.5 kg/m2. RESULTS: We report the finding of a DNA variant in exon 1 of the human ob gene (A --> G substitution, base + 19). This variant showed a prevalence of 62% in our study population. Association analyses under different genetic models (dominant, co-dominant, recessive) showed no significant evidence for an association of this variant with BMI. However, obese individuals homozygous for the G-allele showed significantly lower leptin concentrations compared to obese patients either heterozygous or homozygous for the A-allele after correction for BMI. CONCLUSION: Recent linkage studies have shown evidence for linkage of the hsob locus with obesity. Our study provides further evidence that a defect in the ob gene in linkage disequilibrium with the G-allele of exon 1 might be involved in obesity by affecting leptin concentrations.

Adult↗

Effects of consumption of snacks on simulated driving.

The present study investigated the effects of snacks on simulated driving for 24 volunteers who carried out a driving task three times. On each occasion a presnack baseline of 1 hr. of driving was taken. The snack conditions were (a) no snack (b) a 65 g-filled chocolate bar, and (c) an equicaloric snack of cheese and biscuits. Following the snack the volunteers then carried out another hour of driving. Analysis showed that following consumption of the chocolate the volunteers drove more carefully and hit the side of the track less often.

Automobile Driving↗

Insulin and body fat distribution have no direct effect on plasma leptin levels in obese Caucasian women with and without type 2 diabetes mellitus.

Leptin, a hormone produced by adipose tissue, is potentially involved in the regulation of adiposity. The effects of insulin and body fat distribution on human plasma leptin have not yet been clearly defined. The present study investigated the relationships between plasma leptin and total and regional body fat parameters measured by anthropometry and bienergetic absorptiometry associated or not with computed tomography, taking glucose metabolism into account. A cohort of 51 obese Caucasian women (23 with normal glucose tolerance, 11 with impaired glucose tolerance, and 17 with Type 2 diabetes) was analysed. All non-diabetic subjects had an oral glucose tolerance test together with plasma glucose and insulin measurements. Moreover, a subgroup of 7 diabetic subjects with failure to oral antidiabetic treatment was submitted to about 12 days of intensive subcutaneous insulin therapy. Plasma leptin was essentially dependent on total body fat mass (r = 0.83, p < 0.0001, for the whole population), but not related to adipose tissue distribution. An independent correlation between leptin adjusted on body fat mass and fasting insulinaemia (R = 0.72, p < 0.02) or C-peptide (R = 0.62, p < 0.03) was found significant only in the diabetic group. Insulin treatment was associated with a moderate and transient increase of plasma leptin. The relative variations of plasma leptin levels were strongly negatively correlated with those of free fatty acids. The present data confirm that plasma leptin is not dependent on body fat distribution and suggest an indirect effect of insulin on leptin secretion in clinical conditions.

Adipose Tissue↗

Common bile duct repair with titanium staples. Comparison with suture closure.

BACKGROUND: Vascular Closure Staple (VCS) clips made of titanium were initially developed for microvascular anastomoses with little experience of their use in larger tubular structures. This study compares VCS clips and sutures in the closure of supraduodenal choledochotomy. METHODS: In nine pigs, two longitudinal incisions of the common bile duct (CBD) were randomly assigned to closure with 4-0 interrupted polyglactin sutures or VCS clips. RESULTS: Clip closure was significantly faster (116 +/- 28 vs 581 +/- 88 s). All nine CBDs were patent and without signs of calculus formation after 3 months. Clip closure resulted in slightly less narrowing of the duct lumen and thinner scar at the repair site. At histological examination, all 18 incisions had healed without signs of fistula formation or marked fibrosis. CONCLUSIONS: Choledochotomy closure with VCS clips results in as good or better wound healing than suture closure, with a comparable degree of narrowing. The time required for clip closure is only about one-fifth that of suture closure.

Animals↗

Arterial and venous repair with vascular clips: comparison with suture closure.

PURPOSE: Nonpenetrating, arcuate-legged titanium vascular closure staple (VCS) clips were initially developed for microvascular anastomoses with little experience of their use in larger vessels. The purpose of this study was to compare the VCS clips with standard suture closure of arteriotomies and venotomies in common iliac vessels of pigs. METHODS: In nine pigs, longitudinal 1 cm iliac arterial and venous incisions were repaired with VCS clips on one side and continuous 6-0 polypropylene suture on the other, and the macroscopic and microscopic results were assessed after 3 months. RESULTS: The time required for vessel repair was significantly shorter with clips than with sutures both in arteries (51 +/- 9 vs 414 +/- 36 seconds) and in veins (100 +/- 32 vs 439 +/- 45 seconds). There was no significant difference in the inner diameter, intimal thickness, or intima-to-media height ratios of the arteries or veins after either method of closure. CONCLUSIONS: Repair of 1 cm incisions in small-diameter arteries and veins with VCS clips results in wound healing as good as that achieved with standard suture closure, when assessed for patency, leakage, degree of narrowing, and intimal reaction. The time required for clip closure is considerably shorter than for suture closure.

Animals↗

Low-energy impedance-compensating biphasic waveforms terminate ventricular fibrillation at high rates in victims of out-of-hospital cardiac arrest. LIFE Investigators.

INTRODUCTION: New automatic external defibrillators (AEDs), which are smaller, lighter, easier to use, and less costly make the goal of widespread AED deployment and early defibrillation for out-of-hospital cardiac arrest feasible. The objective of this study was to observe the performance of a low-energy impedance-compensating biphasic waveform in the out-of-hospital setting on 100 consecutive victims of sudden cardiac arrest. METHODS AND RESULTS: AEDs incorporating a 150-J impedance-compensating biphasic waveform were used by 12 EMS systems. Data were obtained from the AED PC card reporting system. Defibrillation was defined as conversion to an organized rhythm or to asystole. Endpoints included: defibrillation efficacy for ventricular fibrillation (VF); restoration of an organized rhythm at the time of patient transfer to an advanced life support (ALS) team or to the emergency department (ED); and time from AED power-on to first defibrillation. The AED correctly identified 44 of 100 patients presenting in VF as requiring a shock (100% sensitivity) and 56 of 100 patients not in VF as not requiring a shock (100% specificity). The time from 911 call to first shock delivery averaged 8.1 +/- 3.0 minutes. A single 150-J biphasic shock defibrillated the initial VF episode in 39 of 44 (89%) patients. The average time from power-on to first defibrillation was 25 +/- 17 seconds. At patient transfer to ALS or ED care, an organized rhythm was present in 34 of 44 (77%) patients presenting with VF. Asystole was present in 7 (16%) and VF in 3 (7%). CONCLUSIONS: Low-energy impedance-compensating biphasic waveforms terminate long-duration VF at high rates in out-of-hospital cardiac arrest. Use of this waveform allows AED device characteristics consistent with widespread AED deployment and early defibrillation.

Adult↗