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Biomedical subjects

R D Bell

Publications and source records attributed to R D Bell.

At least 19 recordsLinked to original sources

The effect of acute and chronic hematocrit changes on cardiovascular hemodynamics in spontaneously hypertensive rats.

Heparin given over a long term by a subcutaneous route consistently lowers blood pressure in the hypertensive rat models. The decrease in blood pressure is accompanied by a parallel decrease in hematocrit suggesting a causal relationship between hematocrit and blood pressure. The aim of this study was to define the relationships between acute and chronic hematocrit changes and blood pressure in the normotensive and hypertensive states. Normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats were used. Hematocrit was decreased acutely by blood-letting, and chronically by treatment with either heparin (H) or phenylhydrazine (P) for 4 weeks. Acute and chronic hematocrit increase was accomplished by packed cells transfusion. Systolic blood pressure was measured weekly; and at the end of the experimental period, plasma volume, cardiac output, and mean arterial pressure were obtained. Acute hematocrit decrease or increase (hematocrit ranging from 25 to 65%) did not affect blood pressure in either strain of rats; whereas chronic hematocrit changes (hematocrit ranging from 35 to 61%) significantly affected blood pressure only in SHR. Thus, chronic hematocrit decrease induced by H or P resulted in a significant fall in blood pressure compared to control (201 +/- 3 v 175 +/- 4, 167 +/- 4 mm Hg, respectively; P < .05). Conversely, a chronic hematocrit increase resulted in a significant rise in blood pressure (201 +/- 3 v 219 +/- 4 mm Hg; P < .05). Similar hematocrit changes produced in NWR, as in SHR, did not affect blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A novel treatment for ischemic intracranial hypertension in cats.

There is no accepted efficacious treatment for ischemic cerebral edema. We show in a cat model of focal cerebral ischemia that infarct volume can be reduced (p less than 0.05) by ventriculocisternal perfusion with an oxygenated fluorochemical emulsion (bis-perfluorobutylethylene). An accompanying effect of such ventriculocisternal perfusion is a reduction in intracranial pressure. At 18 hours following the start of the perfusion, there was a significant (p less than 0.05) difference in intracranial pressure between nonperfused controls (mean 11.4 [range 2.3-23.0] torr, n = 6) and cats perfused with an oxygenated nutrient solution not containing fluorochemical (mean 11.3 [range 3.0-29.0] torr, n = 8) or animals perfused with the oxygenated fluorochemical emulsion (mean 2.21 [range 0-3.5] torr, n = 7). Perfusion with this oxygenated fluorochemical emulsion warrants further study as a treatment for elevated intracranial pressure.

Animals

An electron microscopy study of urinary sediment: relationship between myeloid body excretion and gentamicin nephrotoxicity in the rat.

We studied renal function, urinary enzymes, urinary sediment, and renal histopathology in Fischer 344 rats that were treated with one dose of mercuric chloride (HgCl2) alone, HgCl2 followed by gentamicin, gentamicin alone, or gentamicin, followed by HgCl2. HgCl2 was administered intraperitoneally at 1 mg/kg body weight. Gentamicin was injected subcutaneously at 40 mg/kg body weight. Renal function was assessed by creatinine clearance. Urinary sediment was examined using transmission electron microscopy; particular attention was given to the numbers by myeloid bodies in the urinary sediment. Renal tissue was assessed using light microscopy for acute tubular necrosis (ATN). In either HgCl2- or saline-treated rats urinary sediment showed no myeloid bodies, and renal morphology was essentially normal. The rats given HgCl2 48 h prior to initiation of gentamicin therapy showed significant decrease of myeloid bodies excretion. This was accompanied by significantly less impairment of renal function, mild renal lesion, and no necrotic tubule cells in urinary sediment. The rats treated with either gentamicin alone or gentamicin followed by HgCl2 developed significant impairment of renal function in association with marked elevation of the urinary enzymes, and variable extent of ATN. In both of these groups, urinary sediment showed a profusion of free myeloid bodies and many necrotic renal tubule cells. The urinary sediment findings, however, did not aid in distinguishing between these two treatment groups. From these data we conclude that (1) a tentative relationship exists between the concentration of the urinary myeloid bodies and severity of gentamicin nephrotoxicity; (2) prior treatment with compound(s) analogous to HgCl2 which could minimize urinary excretion of the myeloid bodies might be useful in the mitigation of gentamicin nephrotoxicity.

Animals

Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog.

Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO-induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period.

Animals

Protective mouthguards and sports injuries.

In summary the advantages of providing custom-fitted mouthguards for athletes, especially those involved in contact sports, has been discussed along with the methodology of construction. Because of the apparent lack of negative effects on physical performance and the superior protective characteristics of custom-fitted mouthguards, it seems logical to recommend their use in the competitive sports arena.

Athletic Injuries

Local cerebral glucose metabolism after global ischemia: treatment by ventriculocisternal perfusion with a fluorocarbon emulsion.

The local cerebral metabolic rate for glucose (LCMRg) was measured in cats subjected to global cerebral ischemia (GCI). Control (nonperfused) cats showed decreased LCMRg (P less than 0.01) in the frontal, temporal, parietal, and occipital cortex 9.5 hours after a 10-minute exposure to GCI. Cats perfused ventriculocisternally with oxygenated nutrient solution (ONS) for 8 hours showed significant increases in the LCMRg (p less than 0.05) at 9.5 hours postischemia in the parietal and occipital areas over the levels found in untreated ischemic cats. Supplementing the ONS perfusion medium with fluorocarbon (OFNS) increased the LCMRg (P less than 0.05) in the frontal, as well as the parietal and occipital areas, over that seen in untreated ischemic brains. The increase of LCMRg in three (rather than only two) cortical areas may be a result of the ability of the fluorocarbon in OFNS to deliver greater quantities of oxygen to the brain than ONS without fluorocarbon. Perfusion with OFNS without glucose, or with low (50 mg%) glucose, was more effective than OFNS with high (200 mg%) glucose in restoring LCMRg to normal in all four cortical areas affected by GCI. In five brain areas not affected by GCI, perfusion with OFNS having no glucose significantly increased LCMRg as compared to normal animals. This study demonstrates that OFNS perfused by the ventriculocisternal route can restore toward normal the LCMRg following GCI and that different concentrations of glucose in the perfusing fluid will have variable effects on LCMRg in certain brain areas.

Animals

Effect of phenytoin on bone and vitamin D metabolism.

Calcium and vitamin D metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Significant decreases occurred in serum concentrations of calcium, albumin, and 25-hydroxy-cholecalciferol. The decreases in serum calcium paralleled those in serum albumin. Significant increases occurred in serum alkaline phosphatase and 1 alpha, 25-dihydroxycholecalciferol, in urinary hydroxyproline, and in the fractional gastrointestinal absorption of calcium. Urinary cyclic adenosine monophosphate and serum parathyroid hormone did not change. The results suggest that the bone disease resulting from phenytoin therapy may be associated with a deficiency of 25-hydroxycholecalciferol and not of 1 alpha, 25-dihydroxycholecalciferol, and that reduced gastrointestinal absorption of calcium or changes in parathyroid function may not be necessary for the development of bone disease.

Adult

Lorazepam in status epilepticus.

Lorazepam, a dichloro-3-hydroxy-1,4-benzodiazepine, has been shown to be a potent anticonvulsant in animal models of epilsepsy and has minimal depressant effects on respiration and circulation in humans. The effects of this compound were studied in status epilepticus. Twenty-five patients were given intravenous lorazepam during status epilepticus of varying cause. Four or 8 mg of the drug controlled status in 22 of the 25 patients. Although single seizures recurred in 5 of the 22 patients, none experienced recurrence of status during a prolonged follow-up period. Transient respiratory arrest occurred in 1 patient, but no other significant complications were observed. Studies of plasma drug levels suggest that most patients attain good seizure control at concentrations between 30 and 100 ng per milliliter. Clinical observations indicate that repetitive injections are not required for continuing control of seizures in patients whose seizures are initially controlled. Lorazepam appears to be an effective and safe drug for treatment of status epilepticus, with a duration of control longer than that achieved with diazepam.

Adolescent

Unusual parapharyngeal lesions.

Six cases of unusual parapharyngeal lesions are presented in detail along with discussions of the anatomy, pathology, clinical aspects, and treatment methods of lesions in the parapharyngeal space. Newer techniques of CT scanning and selective embolization are discussed as they apply to management of such lesions. A plasmalymphocytic tumor with amyloidosis is described. The authors believe that such a lesion has not been reported previously in the parapharyngeal space.

Adenoma, Pleomorphic

Creatine kinase BB isoenzyme levels by radioimmunoassay in patients with neurological disease.

Creatine kinase BB (CK-BB) isoenzyme was measured by radioimmunoassay in serum and in cerebrospinal fluid from 61 patients with various neurological disorders. Statistically significant elevations of CK-BB isoenzyme in the serum were observed in patients with acute cerebrovascular accidents and in those with seizures and a prolonged alteration in level of consciousness. Statistically significant elevations of CK-BB isoenzyme in the cerebrospinal fluid were also found in patients who had suffered acute cerebrovascular accidents. Some patients with central nervous system infections, acute demyelinating disease, certain drug overdoses, head trauma, and complex migraine also had elevations of serum and CSF CK-BB isoenzyme. In 2 patients with elevations of CK-BB isoenzyme, the elevations in serum occurred later than those detected in the cerebrospinal fluid. If CK-BB elevations determined by radioimmunoassay can be demonstrated to be quantitatively related to the extent of brain damage, then these determinations in conjunction with experimental animal models and newer radiological techniques should allow evaluation, in an objective and precise manner, of measures designed to decrease that damage.

Brain Damage, Chronic

Effect of dopamine agonist (Lergotrile mesylate) therapy on twenty-four hour secretion of prolactin in treated Parkinson's disease.

Plasma PRL was measured at 20-min intervals in six patients with Parkinson's disease under various treatment protocols. In addition, 24-h mean GH levels were measured. The results of these studies showed that two untreated patients with Parkinson's disease had normal 24-h mean PRL levels with the normal increase during sleep. During chronic treatment with L-dopa-carbidopa (Sinemet), the 24-h PRL level was 12.8 +/- 4.9 ng/ml (mean +/- SD) and there was persistence of augmented PRL secretion during sleep. The 24-h mean GH level ranged from 1.5-4.4 ng/ml, with a mean of 2.5 ng/ml. The addition of a dopamine agonist (Lergotrile mesylate) resulted in a significant (P less than 0.01) suppression of the 24-h mean PRL levels and abolition of the normal sleep augmentation after 2 weeks of therapy. This suppression was maintained in one patient who was restudied 4 months after the addition of dopamine agonist therapy to L-dopa-carbidopa. The 24-h mean GH levels did not change significantly after the addition of the dopamine agonist when compared to L-dopa-carbidopa alone. These results suggest a dichotomy between the PRL and GH responses to combined L-dopa-carbidopa and dopamine agonist therapy. In addition, the preservation of normal PRL regulation in the two untreated patients with Parkinson's disease suggests that dopaminergic neurons are not universally affected in this disorder.

Adult

Oncocytic lesions of the larynx.

Eight cases of laryngeal oncocytic lesions treated at Toronto Western Hospital between 1957 and 1977 are reviewed. The typical clinical course was of a benign lesion with prolonged dysphonia. A smaller number with bulkier lesions developed symptoms of airway obstruction. The lesions were supraglottic and cystic. They were excised either endoscopically or via a laryngofissure. The pathologic features support the concept that the lesion represents a metaplasiahyperplasia, and therefore the term 'oncocytic cyst' is preferred to terms which imply a neoplastic process. Three patients with oncocytic cysts had associated squamous dysplasia of the vocal cord. Pathologically this supports the theory of tissue response to chronic irritation, since all three were heavy smokers. Clincially the finding necessitates longterm follow-up with a view to possible squamous cell carcinoma that may arise on the true cords. Follow-up in this series showed no recurrence of symptoms in six of eight cases, two being lost to follow-up.

Adult

Effects of acute and chronic splenectomy on experimental acute renal tubular lesions.

The first half of this study describes the effects of acute splenectomy on epinephrine-induced ATL in the dog. Renal morphology and hematocrit were compared in 12 dogs without splenectomy (group I), six dogs with antecedent splenectomy (group II), and seven dogs with antecedent splenectomy after splenic contraction was induced by topical application of epinephrine (group III). Splenectomy was performed in groups II and III 20 to 30 min prior to epinephrine infusion; all three groups received equal infusions (4 microgram/kg/min) for 6 hr before the kidneys were harvested. ATL and renal congestion were consistently severe in group I but infrequent and less severe in groups II and III. The second half of this study describes the apparent protective effect of chronic (2-week) splenectomy on epinephrine-induced ATL. Renal morphology and hematocrits were compared in 13 intact dogs (group IV) and 10 dogs splenectomized 2 weeks before the epinephrine infusion (group V). The severity of the ATL and the degree of renal congestion were significantly less in the chronically splenectomized dogs. This chronic protection afforded by acute and chronic splenectomy observed after epinephrine infusion remains unclear.

Animals