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Biomedical subjects

D C Smith

Publications and source records attributed to D C Smith.

At least 127 records · Page 7Linked to original sources
PubMed1995

Comparison of a new ovine antigen binding fragment (Fab) antivenin for United States Crotalidae with the commercial antivenin for protection against venom-induced lethality in mice.

Snake venom poisoning is a medical emergency requiring immediate attention and the exercise of considerable judgment. Of the estimated 8,000 bites inflicted by venomous snakes in the United States each year, approximately 6,000 are treated with commercial antivenin. The only commercially available antivenin for North American Crotalidae envenomation is Antivenin (Crotalidae) Polyvalent (equine origin) (ACP; Wyeth Laboratories, Philadelphia, PA). A common complication is the high incidence of hypersensitivity reactions, occurring in more than 75% of patients treated with ACP. To minimize these side effects, a novel, affinity-purified, antigen binding fragment (Fab) antivenom (FabAV) for Crotalidae venom poisoning has been produced from the sera of sheep. The new product is Antivenin Polyvalent Crotalid (Ovine) Fab (Crotab; Therapeutic Antibodies, Inc., Nashville, TN). The current report compares the potencies in mice of FabAV and ACP against venom-induced lethality. The results indicate that FabAV is 3.1-9.6 times more potent than ACP for the prevention of lethality of the nine United States venoms tested. For one of the venoms, Crotalus viridis helleri, FabAV was efficacious while ACP was not.

Animals↗
PubMed1995

An SEM examination of etched dentin and the structure of the hybrid layer.

The clinical requirements of dentin bonds are that they should be non-permeable to oral fluids, seal dentinal tubules, protect the pulp, and be long lasting and durable. Dentin bonding systems that use acidic agents to remove the smear layer are currently being used. Acid conditioning not only removes the smear layer, but also demineralizes the surface of the intertubular dentin and produces intratubular demineralization and funnelling. A dentin bond is produced when hydrophillic resin monomers infiltrate the dentinal tubules and collagen of the demineralized intertubular zone, producing a hybrid layer. The use of a critical point drying technique and SEM allows a clear visualization of the structure of the hybrid layer. This study showed that currently used hydrophillic resin monomers are unable to completely infiltrate the demineralized zone, and it is speculated that this failure could contribute to microleakage and influence the long-term durability of the bond. It is also apparent that these bonds depend on the mechanical investment of collagen by the infiltrating monomer. Since none of the unfilled resins tested seem capable of completely infiltrating the demineralized collagenous zone, the degree of demineralization produced by the commercial acid concentrations in current use is questioned. More dilute acids than those available commercially are shown to reduce both the degree and depth of demineralization, and we suggest that the resultant thinner layer may lend itself to more complete resin infiltration of the collagen.

Acid Etching, Dental↗
PubMed1995

Dimenhydrinate pretreatment in patients receiving intra-arterial ioxaglate: effect on nausea and vomiting.

OBJECTIVE: To determine the effectiveness of the antihistamine dimenhydrinate (Dramamine) as a prophylactic agent against the nausea and vomiting that occasionally accompany the use of ioxaglate. PATIENTS AND METHODS: Three hundred patients (165 men and 135 women, ranging in age from 18 to 89 [mean 62] years) undergoing noncoronary arteriography received dimenhydrinate or placebo before the injection of the low-osmolality contrast material ioxaglate (Hexabrix). The patients were observed and questioned about nausea and vomiting, as well as many other possible reactions to the contrast material. RESULTS: There were no statistical differences in the occurrence of adverse reactions between the groups receiving dimenhydrinate and placebo (chi 2 or Fisher's exact test, p > 0.05). CONCLUSION: Dimenhydrinate, as administered in this study, was ineffective as a prophylactic agent against adverse reactions accompanying administration of ioxaglate.

Adolescent↗
PubMed1994

Pharmacokinetic and biotransformation studies of ormaplatin in conjunction with a phase I clinical trial.

Ormaplatin is a second-generation platinum (Pt) analogue with in vitro activity against some cisplatin-resistant malignant cell lines. We have evaluated the pharmacokinetics and biotransformations of ormaplatin during a phase I trial in which ormaplatin was administered by daily 30-min infusions on 5 consecutive days every 28 days. Sixteen patients received 25 courses at doses ranging from 5.0 to 11.6 mg/m2 per day. Pharmacokinetic parameters determined for ultrafilterable Pt measured by atomic absorption spectrophotometry revealed a short half-life (t1/2 16 min), moderate volume of distribution (Vd 12 l/m2), and relatively fast systemic clearance (Cls 544 ml/min per m2). Cls and percentage of drug unbound decreased during the 5-day administration period. Average systemic exposure increased with dose; however, inter-individual variability in Cls produced overlap in systemic exposure between the dose levels. The major active biotransformation product [PtCl2(dach)] was evaluated at the highest dose level by HPLC. This product decayed monoexponentially with a mean t1/2 of 13 min and a higher degree of pharmacokinetic variability than that of ultrafilterable Pt at this dose. No unreacted ormaplatin was detected; however, several inactive biotransformation products persisted for at least 120 min. Approximately 32% of the dose was excreted in the urine during the first day, one-third of this during the initial 1.5 h. The human pharmacokinetic characteristics of ormaplatin resemble those of cisplatin; however, additional study will be required to discern which analyte of ormaplatin correlates best with clinical effects.

Adult↗
PubMed1994

A new antivenom to treat eastern coral snake (Micrurus fulvius fulvius) envenoming.

An Fab based ovine antivenom has been prepared and compared both in vitro and in vivo with two commercial preparations. The product was found to be at least four times more effective on a weight basis. The increased potency, combined with the low incidence of side-effects associated with ovine Fab, should result in a safer, more effective antivenom.

Animals↗
PubMed1994

A comparison of ovine and equine antivenoms.

Commercial antivenoms produced in horses were compared with monospecific antivenoms raised in sheep against Crotalus durissus terrificus, Crotalus atrox, Crotalus adamanteus, Micrurus fulvius fulvius, Naja naja, Naja kaouthia, Echis ocellatus, Vipera lebetina deserti, Vipera berus berus and Vipera ammodytes ammodytes venom. Antibodies raised by immunizing sheep with C. d. terrificus venom were more effective than their equine counterparts in preventing lethal toxicity in mice (ED50), in inhibiting the venom's pharmacological effects (haemolysis, platelet aggregation and coagulation), and in neutralizing phospholipase A2 activity. Comparison of one ovine and three equine F(ab)2 products raised against V. a. ammodytes venom showed that all were at least 95% pure; that all protected mice; and that all contained antibody populations directed against most components of V. a. ammodytes and V. b. berus venoms. The ovine antivenoms generally contained a higher concentration of specific antibodies than the equine products. Finally, the ovine antivenoms raised against E. ocellatus, V. lebetina deserti, V. b. berus, M. f. fulvius and N. naja venoms provided better in vivo protection to mice than the equine antivenoms, but the equine antivenoms to N. kaouthia and C. atrox were more protective than the ovine product.

Animals↗
PubMed1994

Experimental evaluation of ovine antisera to Thai cobra (Naja kaouthia) venom and its alpha-neurotoxin.

Conventional treatment of Naja kaouthia (Thai cobra) envenoming requires large volumes (up to 600 ml) of equine antivenom, which results in a high incidence of serum reactions. The inefficiency of the antivenom is assumed to be related to the high percentage (approx. 20%) of alpha-neurotoxin, a relatively weak and highly toxic immunogen, present in the native venom. First, antibodies to N. kaouthia venom were raised in sheep, which protected mice against challenge with whole venom. Second, ovine antibodies to the purified neurotoxin and to three different neurotoxin conjugates were developed and their neutralising abilities against either whole venom or neurotoxin were compared using murine ED50 tests. High titre antibodies, assessed by enzyme immunoassay and Western blot, were obtained from all four neurotoxin immunisation regimens. Neurotoxin conjugated to rabbit anti-sheep IgG produced the highest titres against both neurotoxin and whole venom. This antiserum provided protection against neurotoxin challenge but failed to protect against whole venom. Furthermore, the addition of neurotoxin antibodies to whole venom antiserum did not enhance the neutralisation efficacy of the latter. These findings raise the possibility that in mice other toxins apart from the neurotoxin may significantly contribute to the lethal effect of N. kaouthia venom.

Animals↗
PubMed1994

Recurrent urinary conduit bleeding in a patient with portal hypertension: management with a transjugular intrahepatic portosystemic shunt.

OBJECTIVE: To determine if a transjugular intrahepatic portosystemic shunt can control recurrent urinary conduit bleeding in a patient with portal hypertension. METHODS: Following transjugular catheterization of the right hepatic vein, a long curve Colapinto needle was advanced through the liver parenchyma into the portal vein near its bifurcation. After a guide wire exchange, a catheter was advanced into the portal system and venogram was obtained. Following another guide wire exchange, a balloon angioplasty catheter was used to create the shunt by dilating the parenchymal tract between the hepatic and portal veins. A self-expandable stent was used to ensure patency of the shunt. RESULTS: After shunt placement, bleeding from the ileal conduit and stroma decreased significantly. A duplex ultrasound at five-month follow-up demonstrated the shunt to be completely patent. CONCLUSIONS: Based on this limited experience, it appears that the transjugular, intrahepatic, portosystemic shunt is an acceptable method to control massive, recurrent urinary conduit bleeding in patients with portal hypertension.

Aged↗
PubMed1994

Respiratory function after cardiopulmonary bypass: a comparison of bubble and membrane oxygenators.

A consecutive sample of 500 adults undergoing cardiac surgery was randomly allocated to extracorporeal circulation with either a Bard bubble oxygenator H1700 or a Bard membrane oxygenator HF5700 (Bard Ltd, Crawley, UK). Alveolar-arterial oxygen tension gradient (AaDO2) was calculated prebypass, then 20, 90, 180, and 420 minutes postbypass. Preoperative, initial postoperative, and first-day postoperative chest x-rays were assigned an extravascular lung water (EVLW) score and an atelectasis score. There was a comparable increase in AaDO2 after bypass in each group. The increase in EVLW score was significantly greater in the bubble group (mean 2.91, 95% CI 2.28-3.54) than the membrane group (mean 2.06, 95% CI 1.43-2.69) for the initial postoperative x-rays (P < 0.01) and also for the x-rays on the first postoperative day (P < 0.01). The increase in atelectasis score was significantly greater in the bubble group (mean 1.06, 95% CI 0.94-1.18) than the membrane group (mean 0.86, 95% CI 0.74-0.98) for the initial postoperative x-rays (P < 0.01) but not for the x-rays on the first postoperative day. There was no difference in duration of ventilation, intensive care, hospital stay, or hospital mortality between bubble and membrane groups. Although there was a statistically significant difference in x-ray scores between oxygenator groups, neither intrapulmonary shunting nor clinical outcome was influenced by the type of oxygenator used during bypass.

Adult↗
PubMed1994

Influence of muscle temperature and forearm position on evoked electromyography in the hand.

We have examined the correlation between the evoked electromyographic response in the first dorsal interosseous muscle of the hand, temperature and forearm position in 40 female patients after enflurane anaesthesia with spontaneous breathing. In 20 patients the supinated forearm with the wrist extended was immobilized on an armboard with adhesive tape (group A). In the other 20 patients (group B), the hand was strapped into a fist with adhesive tape and laid supine on an armboard. During the 30 min after induction of anaesthesia, the mean response to the first stimulus in the train-of-four was the same in both groups and decreased from a baseline value of 99.7% (95% confidence interval (CI) 99.1-100.4%) to 86.2% (95% CI 83.3-89.0%). The final response was less than 90% of baseline in 28 patients. There was an inverse linear correlation between the electromyographic response and both skin and muscle temperature in both groups (r > 0.98), although there was no correlation between change in the electromyogram and change in temperature (r < -0.26). After 30 min, pronation of the forearm resulted in a further decrease in the electromyographic response in 13 of 18 patients in group B (two patients in this group were excluded from analysis). Pressure was then applied to the scaphoid tubercles of all patients to produce maximal supination of the forearm. This had no effect on the electromyogram in 10 patients. In 28 patients the electromyographic response increased after scaphoid pressure, although it remained 90% of baseline in five patients. The measured temperatures did not alter during these manoeuvres.

Anesthesia, General↗
PubMed1994

Influence of serum concentrations of catecholamines and i.v. or volatile anaesthesia on evoked electromyography in the hand.

We have examined the correlation between serum concentrations of catecholamines and the evoked electromyographic (EEMG) response from the first dorsal interosseous muscle of the hand in 20 patients during minor surgery under propofol or enflurane anaesthesia without neuromuscular blocking drugs. The supinated forearm, with the wrist fully extended, was strapped firmly to an armboard and immobilized with adhesive tape. In the propofol group, the mean EEMG response to the first stimulus in the train-of-four (T1) decreased to 83.0% (95% confidence intervals (CI) 78.7-87.3%) of baseline, while in the enflurane group the mean EEMG T1 response decreased to 84.0% (95% CI 81.6-86.4%) of baseline. The decrease in the EEMG response occurred over 20 min and did not correlate with plasma concentrations of adrenaline or noradrenaline (correlation coefficients all < 0.26). We conclude that the decrease in EEMG response during the first 30 min of anaesthesia occurred during both i.v. and inhalation anaesthesia, and that changes in plasma concentrations of catecholamines did not cause the decrease in the EEMG response.

Anesthesia, General↗
PubMed1994

Modulation of autonomic responses in normal and denervated isolated canine atria by substance P.

The experiments were performed to determine whether the neuromodulatory effect of substance P (SP) could be demonstrated in the isolated atrium. Strips from the right (RA) and left atria (LA) of normal (control) and denervated canine hearts were placed in an isolated muscle bath, and isometric muscle tension was measured. Inotropic responses to direct muscarinic stimulation were obtained with 1 x 10(-9) to 1 x 10(-8) M acetylcholine (ACh), and responses to stimulation of the intramyocardial intrinsic cardiac nerves (ICN) were produced with nicotine (Nic), 1.0-10 x 10(-6) M. The same drugs were tested in the presence of 1 x 10(-6) M SP, which had no significant inotropic effects of its own. Responses to ACh were unaffected by SP. The primary negative inotropic response to Nic was greatly attenuated by SP in both control and denervated atria, whereas the secondary positive response in control atria was unaffected. This inhibition was very pronounced in LA but less so in the RA. We conclude that SP appears to modulate the responses of the ICN to nicotinic stimulation in a manner similar to that previously observed in intact animals. This mechanism may provide a means of direct modification of efferent cardiac responses by afferent nerves within the heart itself.

Acetylcholine↗
PubMed1994

Cyclic sequential endocrine therapy for advanced breast cancer using a combination of tamoxifen and megestrol acetate.

A cyclical, sequential combination of tamoxifen and megestrol acetate (group B) was compared with conventional therapy (tamoxifen alone, group A) in 261 breast cancer patients. There was no statistically significant difference between groups for overall response rate (complete+partial response: group A, 35.8%, group B, 40.8%; p = 0.505) or for median response duration in responders (group A, 128 weeks, group B, 136 weeks; p = 0.488). Median survival from randomization was longer in those patients receiving sequential therapy (group A, 90 weeks, group B, 134 weeks) with a significantly lower relative death rate (group B/group A = 0.67; p = 0.011). This survival benefit appears to be due to a delay in progression among nonresponders in the sequential therapy group.

Adult↗
PubMed1994

A survey of priming solutions used for cardiopulmonary bypass.

We conducted a postal survey of all National Health Service centres where cardiac surgery is performed. We requested information about the priming solutions and additives used in the cardiopulmonary bypass circuit, and specifically asked whether changes were made in priming solutions for diabetic patients. Hartmann's solution was used by 63% of respondents, either alone or mixed with colloid. Heparin was added to the prime by 89% of respondents. Only two centres and one anaesthetist at a third centre altered the prime for diabetic patients.

Adult↗