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Biomedical subjects

D C Smith

Publications and source records attributed to D C Smith.

At least 109 records · Page 6Linked to original sources

Evaluation of two warming systems after cardiopulmonary bypass.

We have compared the Thermomat electric undermattress (JMW Systems, Edinburgh, UK) and the Bair Hugger (Augustine Medical, Courtelary, Switzerland) forced-air warming blanket in 30 adult patients after cardiac surgery. All patients were warmed to an oesophageal temperature of 38 degrees C before termination of cardiopulmonary bypass (CPB); those with oesophageal temperatures < 35.5 degrees C at skin closure were allocated randomly to be rewarmed in the intensive care unit either on the Thermomat (n = 15) or under the Bair Hugger blanket (n = 15), at their highest settings. Oesophageal and lateral thigh skin temperatures were recorded every 15 min for 4 h. There was a significantly faster increase in core temperature (0.5 vs 0.75 degrees C h-1; P < 0.0002) and skin temperature (0.86 vs 1.3 degrees C h-1; P < 0.001) in the Bair Hugger group. However, there was no difference in the number of patients who reached a core temperature of 36 degrees C (15 Bair Hugger, 14 Thermomat) or 37 degrees C (11 Bair Hugger, seven Thermomat), or in the number of patients who reached a skin temperature of 37 degrees C in 4 h (four Bair Hugger, one Thermomat). Twelve patients in the Bair Hugger group reached a skin temperature of 36 degrees C compared with two in the Thermomat group (P < 0.001). The Bair Hugger warmed faster than the Thermomat both centrally and peripherally, and warmed more patients to a core temperature of 37 degrees C in 4 h, but did not reduce the time to tracheal extubation or alter important clinical aspects of postoperative course.

Adult↗

The influence of staining procedure on differential round cell analysis in stained smears of human semen.

Giemsa and Bryan-Leishman smear staining techniques have been quantitatively evaluated for their ability to determine round cells in human semen. Samples of fertile and vasectomy ejaculates were compared against counts obtained from semithin Araldite sections stained with toluidine blue. TEM studies and immunogold staining of the Pradite section permitted identification and quantitation of nucleated cell profiles. Differential counts from each of the three stains on the same set of semen samples were compared using regression analysis. Counts of seminiferous tubule elements from stain to stain correlated well (r > 0.9). Numerical analyses indicated, however, that leucocytes were commonly misidentified. The r values for neutrophils were less than 0.8 and as low as 0.55 for lymphocytes. These low correlations presumably were due to failures to distinguish between these cells and seminiferous tubule elements.

Humans↗

RNA and protein synthesis in the nonspermatozoal cells of normal human semen.

A series of semen samples from recently fertile men was obtained by masturbation. They were washed and placed in short term culture in BWW medium, and labelled either with tritiated uridine or tritiated tyrosine. Control samples were labelled in the presence of actinomycin D and puromycin respectively, and examined by light and electron microscopy. Ejaculated spermatocytes, spermatids of various stages and certain anucleate bodies proved to be labelled with tritiated tyrosine and hence to be protein synthetic. Ejaculated spermatocytes were also active in RNA synthesis. Macrophages and neutrophil leucocytes both heavily incorporated tritiated uridine and tritiated tyrosine. The significance of these results is discussed in relation to the possible role of exfoliated sperm precursors in ejaculates.

Autoradiography↗

Carmustine and streptozocin in refractory melanoma: an attempt at modulation of O-alkylguanine-DNA-alkyltransferase.

The activity of the enzyme O6-alkylguanine-DNA-alkytransferase (AGAT) protects cells from the cytotoxic effects of alkylating agents. This Phase II trial was designed to assess the efficacy of a strategy designed to modulate the resistance to carmustine (BCNU) mediated by AGAT using streptozocin (STZ) in patients with advanced refractory melanoma. Seventeen patients who had failed prior chemotherapy were treated with STZ at 500 mg/m2 daily for 4 days with BCNU at 150 mg/m2 on day 3. Peripheral blood lymphocytes for assay of AGAT activity levels were collected prior to therapy and following the third dose of STZ. There were two partial responses in the 15 patients evaluable for response (13%). Most patients received only a single cycle of therapy due to rapidly progressive disease. Two patients developed fatal pulmonary toxicity, and one developed myelodysplasia. Other toxicities included transient rises in liver function tests. AGAT levels decreased by a mean of 53% in 9 patients but actually increased over baseline in 3 patients while on therapy. Based on these data, BCNU and STZ are not an effective combination for the therapy of advanced refractory melanoma, and pulmonary toxicity due to this combination appears to be increased compared with BCNU alone. STZ is not an effective modulator of AGAT activity when given on this schedule. New strategies designed to deplete AGAT activity using O6-benzylguanine or temozolomide should be explored with careful attention to the possibility that this approach may potentiate both the toxicity and efficacy of BCNU.

Adult↗

Post-training unilateral vagal stimulation enhances retention performance in the rat.

Many peripherally administered substances which modulate memory do not freely enter the brain. Such compounds may act through peripheral receptors that send messages centrally through vagal afferents. To explore this hypothesis, rats were chronically implanted with cuff electrodes on the left cervical vagus nerve. Each animal was trained 48 h after surgery on a one-trial inhibitory-avoidance task with a 0.75-mA, 1.0-s footshock. Immediately following training, each animal received either no stimulation or vagal stimulation (0.5-ms biphasic pulses; 20 Hz, 30 s) at one of three intensities (0.2, 0.4, 0.8 mA; eight animals per group). Retention was tested 24 h later. Neither the 0.2-in or 0.8-mA groups (22.1-s; 53.7-s median latency) showed altered retention performances, whereas the 0.4-mA group showed significantly improved retention (881.0 s) compared to unstimulated controls (21.1 s; U = 6, p < .01). This inverted-U shaped function indicates that vagal activation during memory consolidation modulates retention for memory tasks.

Animals↗

A phase I trial of high-dose oral tamoxifen and CHOPE.

Drug resistance is a common phenomenon in clinical oncology. In vitro, tamoxifen has been shown to be an effective inhibitor of P-glycoprotein and a modulator of the multidrug resistance phenotype. We have previously shown that vinblastine can be given safely in combination with tamoxifen at doses that may modulate P-glycoprotein activity. In this phase I trial, tamoxifen (150 mg/m2 twice a day) was given with CHOPE (cyclophosphamide/doxorubicin/vincristine/prednisone/etoposide) in order to assess the toxicities of the combination. Resistance to three of these cytotoxic agents (doxorubicin, vincristine, and etoposide) may be mediated by P-glycoprotein. A total of 13 patients were evaluable on this trial, which showed that the maximum tolerated doses of cyclophosphamide and etoposide were 750 and 80 mg/m2, respectively. The dose-limiting toxicity was myelosuppression with 50% of the patients (3/6) treated at this dose level developing febrile neutropenia and 85% (6/7) developing grade 4 neutropenia. Tamoxifen at a dose of 150 mg/m2 twice a day can be given safely with the lymphoma regimen CHOPE at standard doses, but this combination may result in increased myelosuppression.

Administration, Oral↗

Open operative balloon angioplasty of the internal carotid artery: a technique in evolution.

Open operative balloon angioplasty is a treatment alternative for certain nonatherosclerotic lesions of the internal carotid artery (ICA) including fibromuscular dysplasia (FMD). Standard operative exposure of the carotid bifurcation is performed with atraumatic passage of a guidewire and balloon through a carotid bulb arteriotomy. Under direct fluoroscopic guidance, precise dilatation of the involved area is possible with minimal risk of intimal tear/flap or distal embolization as compared with graduated intraluminal dilatation or percutaneous balloon angioplasty. Vascular control of the common and external carotid arteries lessens the risk of embolization resulting from the constant backflow of blood through the ICA before, during, and after balloon angioplasty, adding to the overall safety and efficacy of the procedure. We report a case of asymptomatic critical carotid artery stenosis associated with FMD successfully treated with open operative balloon angioplasty and review the current literature regarding treatment options for FMD of the ICA.

Aged↗

Population pharmacokinetics of hydroxyurea in cancer patients.

The pharmacokinetics of hydroxyurea (HU) were investigated in cancer patients after intravenous infusion or oral administration. On the basis of the minimal value of the objective function (MVOF) and prior knowledge of the disposition of HU in animals and man, the data were best described by a one-compartment pharmacokinetic model with parallel Michaelis-Menten metabolism and first-order renal excretion. The computer program NONMEM (nonlinear mixed effects model) was used to perform the nonlinear regression and provide estimates of the population parameters. For the combined intravenous and oral data set, these parameters were estimated to be: maximal elimination rate (Vmax), 0.097 mmol h-1 l-1; Michaelis constant for HU elimination (KM), 0.323 mmol/l; renal clearance (ClR), 90.8 ml/min; volume of distribution (Vd), 0.186 x (body weight) + 25.4 l; absorption rate constant (Ka), 2.92 h-1; and availability to the systemic circulation (F), 0.792. The principal findings of the investigation are that HU undergoes nonlinear elimination in cancer patients and that HU is reasonably well absorbed following oral administration.

Administration, Oral↗

Experimental assessment of a new, low-cost antivenom for treatment of carpet viper (Echis ocellatus) envenoming.

Morbidity and mortality due to envenoming by the carpet viper (Echis ocellatus) in northern Nigeria remains unacceptably high and constitutes a severe economic and public health problem to the local farming community in particular. The only effective treatment of systemic envenoming is antivenom, but supplies are very limited as the little that is available is either too expensive, ineffective or both. Here, we describe a new ovine antivenom, designed both to be effective and to be available at low cost. The antivenom, a polyclonal ovine Fab preparation, provides superior protection, both in vivo and in vitro, to the best alternatives, the monospecific South African Institute of Medical Research antivenom and the polyspecific Pasteur Isper Africa antivenom. Fab fragments, which have the advantages of large volumes of distribution and, theoretically, low immuno-reactivity, are produced by a reusable solid-phase papain matrix which eliminates enzyme contamination of the product and reduces cost. The antivenom is lyophilised for increased stability and extended shelf-life in tropical climates where it is often impossible to keep such products cool.

Animals↗

Frequency and explanation of false negative diagnosis of aortic dissection by aortography and transesophageal echocardiography.

OBJECTIVES: This study was designed to define the frequency and explanation of false negative diagnosis of aortic dissection by aortography and transesophageal echocardiography. BACKGROUND: Aortography and transesophageal echocardiography have been widely utilized to diagnose aortic dissection. Previous reports have not fully addressed the reasons why these studies yield false negative results in a large number of patients with aortic dissection. METHODS: Sixty-five consecutive patients with aortic dissection underwent aortography and transesophageal echocardiography. Diagnosis of aortic dissection was confirmed at operation or by computed tomography in all patients. RESULTS: Biplane transesophageal echocardiograms yielded false negative results in two patients (sensitivity 97% [63 of 65]). Both patients had well localized DeBakey type II aortic dissection. The diagnosis was probably missed because of image interference from the air-filled trachea and mainstem bronchi. In both patients, the dissection was readily identified by aortography. Aortograms yielded false negative results in 15 patients (sensitivity 77% [50 of 65]); the aortic dissection was type I in 7 patients, type II in 1 and type III in 7. The dissection in all 15 patients was readily identified by transesophageal echocardiography. The missed diagnosis was probably due to a completely thrombosed false lumen or intramural hematoma with noncommunicating dissection in 13 patients and to a large ascending aortic aneurysm with nearly equal flow on both sides of the intimal flap in 2. In no patient was the diagnosis missed by both aortography and transesophageal echocardiography. CONCLUSION: Transesophageal echocardiography is an excellent screening tool for aortic dissection. However, it may miss small type II aortic dissections localized to the upper portion of the ascending aorta because of image interference from the air-filled trachea. An intramural hematoma cannot be easily visualized by aortography, and this lesion is the principal reason for false negative aortographic findings.

Adult↗

Auditory evoked responses and near infrared spectroscopy during cardiac arrest.

We describe a patient who had a cardiac arrest during anaesthesia, in whom regional cerebral oxygen saturation was being measured by near infrared spectroscopy and the auditory evoked responses (AER) were being recorded. Both of these monitors provided useful information on cerebral oxygenation during cardiac arrest. Changes in the AER as the result of either reduced circulation or hypothermia are similar, and should these two situations occur simultaneously there could be difficulty in the interpretation of the AER.

Anesthesia, General↗

Effect of temperature and cardiopulmonary bypass on the auditory evoked response.

We have recorded auditory evoked potentials before and during cardiopulmonary bypass in 10 adult patients undergoing cardiac surgery under moderate hypothermia to 27-28 degrees C. The immediate effect of bypass was a small decrease in latency and increase in amplitude of the early cortical response. We also studied two adults and two children during profound hypothermia with circulatory arrest during cardiopulmonary bypass. Reduction in core temperature to 25 degrees C resulted in an increase in latency and amplitude of the brain stem responses; below this temperature the amplitude decreased but latency continued to increase until the auditory evoked response trace became completely flat between 21 and 19 degrees C. These changes were reversible on rewarming.

Aged↗

The auditory evoked potential and paediatric anaesthesia.

We have examined the raw EEG activity and auditory evoked responses (AER) in 35 children, aged 3 days to 13 yr (median 1.5 yr), undergoing general anaesthesia for routine surgery. Binaural stimuli were presented at a frequency of 6.12 Hz and the EEG was recorded and stored using the Northwick Park auditory evoked response software. AER were generated by averaging 512 sweeps each of 125-ms duration. In children less than 2 yr of age, the AER was often irregular, whereas children older than 2 yr had AER patterns similar to those in adults. In children less than 2 yr, regular artefact activity was superimposed on the background EEG which was at the same frequency as the instantaneous heart rate and which was often identifiable as the ECG. We conclude that the AER may be unreliable in children less than 2 yr of age, and modification of current methodology may be required if this technique is to become useful in paediatric anaesthetic practice.

Adolescent↗

Sonoclot analysis.

Assessment of perioperative bleeding disorders, especially those related to platelet dysfunction, remains a clinical challenge. The management of the bleeding patient in the operating theatre or on the postoperative ward is often empirical with little scientific basis. Much of the reason for this is that conventional clotting studies are not immediately available and there is a perceived urgency, particularly among trainee doctors, to treat bleeding disorders without first establishing the exact nature of the coagulopathy. SCT provides useful information on platelet function, particularly in patients after cardiopulmonary bypass, and has enabled practitioners to rationalize the management of bleeding disorders and not expose their patients to the risks of unnecessary transfusion of blood products. Undoubtedly further studies are required before this instrument can be used reliably in the clinical setting but it may prove to be a useful addition to the available techniques for monitoring perioperative bleeding disorders.

Blood Coagulation Tests↗