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Biomedical subjects

D Banks

Publications and source records attributed to D Banks.

At least 19 recordsLinked to original sources

Protective effects of antioxidants against benomyl-induced lipid peroxidation and glutathione depletion in rats.

The present in vivo study was designed to examine the effects of the antioxidants, N,N-diphenyl-p-phenylenediamine (DPPD) and a 21-aminosteroid (U74389G), on methyl 1-(butylcarbamoyl)-2-benzimidazole-carbamate (benomyl)-induced lipid peroxidation and glutathione depletion in rats. Male Sprague Dawley rats weighing 200 250 g were used in this study and were fasted for 8 12 h before treatment. Benomyl (200 mg/kg/day in olive oil) was administered orally for 7 days to groups of untreated rats and to rats pretreated with two doses (15 mg/kg) of either DPPD or U74389G. Benomyl treatment resulted in a significant increase in serum hydroperoxides and a significant decline in hepatic reduced glutathione (GSH) levels. These results indicate that benomyl induces lipid peroxidation and glutathione depletion in rats. Benomyl-induced lipid peroxidation was blocked by DPPD pretreatment but was not significantly altered by U74389G. However, both antioxidants, DPPD and U74389G, were able to inhibit glutathione depletion induced by benomyl. The present findings indicate that the in vivo toxicity of benomyl may be associated with oxidative stress to cellular membranes and that some degree of protection against this toxicity could be afforded by antioxidants.

Animals

Intraoperative hetastarch infusion impairs hemostasis after cardiac operations.

BACKGROUND: An outbreak of excessive bleeding after cardiac operations occurred at our institution when 5% albumin was in short supply and hetastarch became the preferred intraoperative colloid. As hetastarch may impair coagulation, we investigated the effects of its intraoperative administration on post-cardiac surgical hemostasis. METHODS: Indices of postoperative hemostasis were analyzed in 189 consecutive patients undergoing coronary artery bypass grafting. Three groups were compared: one group (n = 68) received a mean of 796 mL of hetastarch only in the operating room (a few minutes after cessation of cardiopulmonary bypass), another group (n = 59) received a mean of 856 mL postoperatively only, and a third group (n = 62) received no hetastarch. RESULTS: Compared with the other two groups, those patients administered hetastarch intraoperatively exhibited significant reductions in hematocrit and platelet count, a significant prolongation in the prothrombin time, and significant increases in both blood loss and hemostatic drug requirement. Also identified were obvious trends toward a greater transfusion requirement and reexploration rate for bleeding in the latter group. CONCLUSIONS: Hetastarch infusion just after weaning from cardiopulmonary bypass produces a clinically important impairment in post-cardiac surgical hemostasis. Intraoperative use of this agent during heart operations should be avoided until the safe timing of its administration is clarified.

Blood Loss, Surgical

Intravenous phenylephrine preconditioning of cardiac grafts from non-heart-beating donors.

BACKGROUND: Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heartbeating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning. METHODS: Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 microg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia. RESULTS: Phenylephrine 25 microg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 +/- 0.5 versus 7.7 +/- 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 +/- 5.3 versus 41.0 +/- 3.4 mm Hg; p = 0.04). Phenylephrine 25 microg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09). CONCLUSIONS: Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.

Analysis of Variance

Is vertical vein ligation necessary in repair of total anomalous pulmonary venous connection?

BACKGROUND: In the repair of total anomalous venous connection, vertical vein ligation is recommended to eliminate left-to-right shunting. However, the small left heart chambers may not always tolerate the immediate increase in blood flow after combined repair and vein ligation. METHODS: A retrospective review of 23 infants and children undergoing correction of total anomalous pulmonary venous connection was undertaken to determine whether vertical vein ligation is a necessary component of successful surgical repair. In 14 patients this vein was ligated, whereas in 9 it was left patent. Six patients who underwent ligation and 5 who did not had pulmonary venous obstruction before operation. RESULTS: The operative mortality rate was 36% (5 of 14 patients) for the ligated group compared with 0% (0 of 9 patients) for the nonligated group (p = 0.06). All deaths occurred in patients with preoperative obstruction and a low mean left atrial pressure, and four of the deaths were directly attributable to left heart failure. Follow-up echocardiography in patients in whom the vertical vein was not ligated revealed adequate cardiac function and no residual left-to-right flow through the previously patent venous conduit. CONCLUSION: Vertical vein ligation during the repair of total anomalous pulmonary venous connection is not routinely necessary and actually may be undesirable in patients with preoperative obstruction, in whom the left heart chambers are particularly small.

Cardiac Surgical Procedures

Controlled reperfusion of cardiac grafts from non-heart-beating donors.

BACKGROUND: Hearts harvested from non-heart-beating donors sustain severe injury during procurement and implantation, mandating interventions to preserve their function. We tested the hypothesis that limiting oxygen delivery during initial reperfusion of such hearts would reduce free-radical injury. METHODS: Rabbits sustained hypoxic arrest after ventilatory withdrawal, followed by 20 minutes of in vivo ischemia. Hearts were excised and reperfused with blood under conditions of high arterial oxygen tension (PaO2) (approximately 400 mm Hg), low PaO2 (approximately 60 to 70 mm Hg), high pressure (80 mm Hg), and low pressure (40 mm Hg), with or without free-radical scavenger infusion. Non-heart-beating donor groups were defined by the initial reperfusion conditions: high PaO2/ high pressure (n = 8), low PaO2/high pressure (n = 7), high PaO2/low pressure (n = 8), low PaO2/low pressure (n = 7), and high PaO2/high pressure/free-radical scavenger infusion (n = 7). RESULTS: After 45 minutes of reperfusion, low PaO2/ high pressure and high PaO2/low pressure had a significantly higher left ventricular developed pressure (63.6 +/- 5.6 and 63.1 +/- 5.6 mm Hg, respectively) than high PaO2/high pressure (40.9 +/- 4.5 mm Hg; p < 0.0000001 versus both). However, high PaO2/high pressure/free-radical scavenger infusion displayed only a trend toward improved ventricular recovery compared with high PaO2/ high pressure. CONCLUSIONS: Initially reperfusing nonbeating cardiac grafts at low PaO2 or low pressure improves recovery, but may involve mechanisms other than decreased free-radical injury.

Animals

Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion.

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers, show very high precursor frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific T cells were demonstrated to be directed predominantly against one HTLV-1 epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An analysis of the T-cell receptor (TCR) repertoire of these cells revealed an absence of restricted variable (V) region usage. Different combinations of TCR V alpha and V beta genes were utilized between, but also within, the individual patients for the recognition of Tax11-19. Sequence analysis of the TCR showed evidence for an oligoclonal expansion of few founder T cells in each patient. Apparent structural motifs were identified for the CDR3 regions of the TCR beta chains. One T-cell clone could be detected within the same patient over a period of 3 years. We suggest that these in vivo clonally expanded T cells might play a role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific TCR which may elucidate the nature of the T cells that infiltrate the central nervous system in HAM/TSP patients.

Amino Acid Sequence

Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy.

UNLABELLED: Copper-67 (67Cu) is an attractive radionuclide for radioimmuno-therapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. METHODS: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. RESULTS: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25% of the total activity, less than 10% of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu. Although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (CGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25% of the total activity, there was less than a 10% decrease in the therapeutic index. CONCLUSION: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 64Cu. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.

Bone Marrow

Long-term safety of statin-fibrate combination treatment in the management of hypercholesterolaemia in patients with coronary artery disease.

OBJECTIVE: To evaluate the long-term safety profile of treatment with a statin-fibrate combination in a cohort of patients with documented coronary artery disease. DESIGN: Retrospective cohort analytical study. SETTING: District general hospital. PATIENTS: 102 (81 male and 21 female) hypercholesterolaemic (total cholesterol concentration > 6.5 mmol/l) patients with documented coronary artery disease and who had been treated with a statin-fibrate combination for over 1 year. Coronary artery disease was confirmed by angiography in 93 patients and by a positive (Bruce protocol) exercise test in the remainder. Fifty eight patients had a history of previous coronary bypass graft surgery. INTERVENTIONS: Twice daily lipid lowering treatment was given, with the fibrate administered in the morning (either bezafibrate 400 mg (n = 101) or fenofibrate 200 mg (n = 1)) and the statin in the evening (either simvastatin 10 mg (n = 23), 20 mg (n = 72), or 40 mg (n = 2) or pravastatin 10 mg (n = 1) or 20 mg (n = 4)). Treatment continued for 1 (n = 9), 2 (n = 58), or 3 (n = 35) years. MAIN OUTCOME MEASURES: Selected laboratory variables (total cholesterol concentration and liver (aspartate transaminase (AST)) and muscle enzyme (creatine kinase (CK)) activities) and documented symptomatology. RESULTS: A mean (SD) total cholesterol concentration of 5.2 (0.8) mmol/l was achieved after combined treatment for 1 year which was maintained at annual follow up. Over a maximum 3 year follow up no patient reported myalgic symptoms and none had a measured CK activity > 10 times above nomal. Four men on a simvastatin-bezafibrate combination had a CK activity rise to less than three times normal. Fourteen patients with a negative history of alcohol excess (consumption < 21 units/week) had borderline raised AST values. CONCLUSIONS: Statin-fibrate combination treatment for up to 3 years in a cohort of patients with coronary artery disease was not associated with serious disturbances in biochemical markers of muscle or liver function.

Adult

An experimental evaluation of an incentive program to reduce serum cholesterol levels among health fair participants.

OBJECTIVE: To evaluate the impact of a health fair and incentive program on the reduction of serum cholesterol levels among participants. DESIGN: Pretest-posttest control group design, with a 6-month delay between pretest and posttest screenings. SETTING: Health fair program for employees of a large midwestern school district. PARTICIPANTS: Volunteer sample among persons with serum cholesterol levels above 5.17 mmol/L (200 mg/dL). Participants were randomly assigned to experimental (N = 29) and comparison groups (N = 34). INTERVENTION: The intervention consisted of four components: a health fair, health risk information, announcement of follow-up screening, and an incentive program. The incentive program consisted of five $100 cash prizes for reducing serum cholesterol levels by 20% or below 5.17 mmol/L (200 mg/dL). The comparison group received only the first three components. MAIN OUTCOME MEASURE: Serum cholesterol levels were measured by a venipuncture, nonfasting, chemical analysis process. RESULTS: The experimental group showed a 13.2% reduction in serum cholesterol levels, and the comparison group exhibited an 11.3% reduction (P < .05). CONCLUSIONS: A health fair, consisting of information on the level of risk and how to reduce risk, and announcement of follow-up screening and incentives can reduce the risk for cardiovascular disease.

Adult

Treatment of high-dose intrathecal morphine overdose. Case report.

The case is reported of a 45-year-old woman who was being treated for chronic back and right leg pain with intrathecal morphine administered via a subcutaneous continuous-infusion device. She received an accidental 450-mg bolus injection of morphine intrathecally and developed hypertension, status epilepticus, intracerebral hemorrhage, and respiratory failure. Treatment with continuous intravenous naloxone infusion, lumbar catheter drainage of cerebrospinal fluid, and control of hypertension and status epilepticus resulted in an excellent outcome with return to neurological baseline. Care providers who refill pump reservoirs with morphine must be knowledgeable about these devices and the life-threatening consequences associated with errors in refilling them. This case describes the complications and successful treatment of high-dose intrathecal morphine overdose.

Drug Overdose

A technique for recording the activity of brain-stem neurones in awake, unrestrained cats using microwires and an implantable micromanipulator.

A new technique is described which is suitable for long-term recording of the activity of neurones in the brain of an awake, unrestrained cat. By using telescopic electrodes, neurones up to 39 mm from the cranial surface can be reached with a miniature micromanipulator which is small enough to be left in place between recording sessions. The most stable recordings have been obtained with electrodes made from microwire, with which units have been held for up to 8 h.

Animals

Exposure of rats to hyperoxia: alteration of lavagate parameters and macrophage function.

Exposure of rats to hyperoxia (100% oxygen for 64 h) resulted in striking alterations in the properties of samples obtained by bronchoalveolar lavage. The yield of neutrophils, lymphocytes, and red blood cells was increased, while the number of harvested alveolar macrophages decreased. The acellular lavage fluid level of protein was elevated, indicating lung damage. However, acellular phospholipid levels were unchanged. The ability of alveolar macrophages to produce reactive forms of oxygen in response to zymosan was significantly decreased by oxygen exposure. This impaired function was not fully explained by a decrease in viability of these phagocytes. In contrast, stimulant-induced chemiluminescence was elevated after hyperoxia. This rise was not due to a change in cellular antioxidant levels or to a discernible increase in arachidonic acid metabolites. However, it was associated with increased cellular lipid peroxidation.

Animals

Vertebral artery dissection from neck flexion during paroxysmal coughing.

Vertebral artery dissection has a characteristic presentation that should be considered when symptoms are preceded by any trauma that causes neck movement. We present the case of a man with vertebral artery dissection following severe coughing that presented as a postero-inferior cerebellar artery territory stroke. The patient was anti-coagulated, and his neurologic deficits were partially resolved. The mechanism and presentation of vertebral artery dissection are discussed with an emphasis on early detection.

Adult

High-dose magnesium sulfate attenuates pulmonary oxygen toxicity.

BACKGROUND AND METHODS: Rats rapidly develop respiratory distress when exposed to 100% oxygen and die within a few days. Autopsy of the lung shows severe histologic damage characteristic of the adult respiratory distress syndrome. The purpose of this study was to evaluate the effects of magnesium sulfate loading in a rat model of acute oxygen toxicity. Thirty-four rats were divided into three groups. Group 1 (n = 18) served as a control (no magnesium therapy), while group 2 (n = 8) and group 3 (n = 8) received varying amounts of magnesium sulfate. All animals were exposed to 100% oxygen for 96 hrs or until death. Lung damage was quantitated by measuring the lung injury score on histologic examination. RESULTS: Administering magnesium sulfate in moderate doses at infrequent intervals to rats (group 2) resulted in less severe oxygen-induced lung damage than that which occurred in rats not receiving magnesium (control group). However, the difference was not statistically significant. Rats (group 3) given doses of magnesium sulfate in amount and frequency adequate to maintain a serum magnesium concentration recognized as therapeutic in eclampsia significantly reduced oxygen-induced lung damage. CONCLUSION: High-dose magnesium sulfate therapy can reduce lung injury caused by acute oxygen toxicity in rats.

Animals

Modulation by peripheral conditioning stimuli of the responses of trigeminal brain stem neurones and of the jaw opening reflex to tooth pulp stimulation in chronically prepared, anaesthetized cats.

The effects of peripheral conditioning stimuli on the thresholds of the jaw opening reflex (JOR) and of trigeminal brain stem neurones to tooth pulp stimulation were examined in chronically prepared, anaesthetized cats. High intensity electrical conditioning stimuli applied to the ipsilateral forepaw produced an increase in the thresholds of both responses, with the JOR thresholds being elevated significantly more, and remaining elevated for significantly longer, than those of the neurones. These findings suggest that the elevation of the JOR cannot be explained just by inhibitory effects on the brain stem neurones.

Animals

Methods for recording the jaw-opening reflex to tooth-pulp stimulation in awake cats.

Techniques are described for use in awake, unrestrained cats which enable recordings to be made from the digastric muscle, electrical stimuli to be applied to the teeth, and intravenous injections to be made via an indwelling cannula. A headpiece was fixed to the skull of the animal and leads were passed subcutaneously from it to electrodes in the muscle and the teeth. A silicone rubber cannula was inserted into the external jugular vein and connected to an injection port in the headpiece. The headpiece incorporated a miniature 9-way connector which was connected to the electrode leads.

Animals

A technique for recording from brain-stem neurones in awake, unrestrained cats.

A method is described which enables single unit recordings to be made from neurones over a wide area of the brain-stem of awake, unrestrained cats. A small headpiece, made from titanium and acrylic, was fixed to the skull over a craniotomy at pre-set stereotaxic co-ordinates. Between recording sessions the craniotomy was sealed. During recording, a miniature micro-manipulator and adjustable titanium support was screwed into the headpiece and recordings were made with tungsten electrodes.

Animals