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Biomedical subjects

J R Cook

Publications and source records attributed to J R Cook.

At least 19 recordsLinked to original sources

Structural analysis of the human interferon gamma receptor: a small segment of the intracellular domain is specifically required for class I major histocompatibility complex antigen induction and antiviral activity.

Mutations of the human interferon gamma (IFN-gamma) receptor intracellular domain have permitted us to define a restricted region of that domain as necessary for both induction of class I major histocompatibility complex antigen by IFN-gamma and protection against encephalomyocarditis virus. This region consists of five amino acids (YDKPH), all of which are conserved in the human and murine receptors. Tyr-457 and His-461 are essential for activity. Approximately 80% of the amino acids of the intracellular domain of the receptor is not required for major histocompatibility complex class I antigen induction or for antiviral protection against encephalomyocarditis virus. The observation that there was no protection by IFN-gamma against vesiculostomatitis virus indicates that other factors, in addition to chromosome 21 accessory factor(s), are required to generate the full complement of transduction signals from the human IFN-gamma receptor.

Amino Acid Sequence

Comparison of decremental and burst overdrive pacing as treatment for ventricular tachycardia associated with coronary artery disease.

Several forms of antitachycardia pacing have been used successfully for terminating cardiac arrhythmias, and implantable devices now incorporate a tier of overdrive pacing for treating of ventricular tachycardia (VT). No consensus exists regarding the optimal mode of pacing therapy. Accordingly, a prospective, randomized, crossover study of antitachycardia pacing was performed to analyze the effects of 2 decremental forms (10 and 5 ms) and a synchronized burst overdrive pacing mode on episodes of VT. Overdrive antitachycardia pacing was an effective therapy (78%) for terminating VT. Burst overdrive pacing and an autodecremental pacing protocol, incorporating a 10 ms decrement, were found to be effective and comparable forms of therapy. Both of these pacing methods were superior in terminating VT when compared with a pacing scheme using a 5 ms coupling decrement (p less than 0.01). Tachycardia acceleration occurred in 6.4% of the episodes of VT. None of the pacing methods displayed a specific propensity for tachycardia acceleration, and no measure of tachycardia segments identified a predilection for pace terminability. Antitachycardia pacing is an effective therapy for VT and different pacing formulas have variable effects. Further, these effects appear to be independent of tachycardia cycle length and variability.

Adult

Substance abuse.

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Humans

Decompressive procedures. Indications and techniques.

Hemilaminectomy and dorsal laminectomy are the surgical techniques most suited for decompression of the thoracic, thoracolumbar, lumbar, and lumbosacral spine. Hemilaminectomy is preferred for decompressing the spinal cord before applying fixation devices for fractures/luxations. Dorsal laminectomy is the method of choice for exploration of the spinal canal and for decompression of the lumbosacral region. Either method is applicable to removal of herniated intervertebral disc material and fenestration of other disc spaces.

Animals

Proarrhythmic effects of procainamide and tocainide in a canine infarction model.

A canine model of myocardial infarction (MI) was used to study the type and frequency of ventricular antiarrhythmic and proarrhythmic effects due to procainamide and tocainide and the risk factors associated with development of proarrhythmia. An anterior MI was created by a 2-h occlusion of the left anterior descending artery (LAD) with complete reperfusion. Programmed ventricular stimulation was performed on two occasions after MI, on days 4-6 and on days 8-10, before drug and during antiarrhythmic drug infusion at three dose levels. The antiarrhythmic drugs were given in a randomized cross-over design. Only procainamide caused a dose-dependent increase in QRS, JTc, and right ventricular effective refractory period (ERP). Neither procainamide nor tocainide made sustained ventricular tachycardia (VT) noninducible, but procainamide slowed the tachycardia rate. Both drugs successfully made ventricular fibrillation (VF) noninducible: procainamide in 78% of trials and tocainide in 50% of trials. Proarrhythmia (development of inducible VT during drug when not present before drug or inability to terminate VT during drug administration) developed in 29% of dogs that received procainamide and 25% of dogs that received tocainide. There was no apparent correlation of QRS, JTc, and right ventricular ERP after drugs and proarrhythmia due to procainamide or tocainide. There was no significant difference in the size of MI between dogs with one or more proarrhythmic response to either drug and dogs that had no proarrhythmia. In this model, procainamide and tocainide had no antiarrhythmic efficacy for VT, but had moderate proarrhythmia potential that was unpredictable.

Animals

Cerebrospinal fluid changes after iopamidol and metrizamide myelography in clinically normal dogs.

Cerebrospinal fluid samples from 2 groups of clinically normal dogs were compared after iopamidol (n = 9) and metrizamide (n = 8) myelography. Iopamidol (200 mg of I/ml) and metrizamide (170 mg of I/ml) were administered by cerebellomedullary injection at dosage of 0.45 ml/kg of body weight. In dogs of both groups, postmyelographic CSF changes included high specific gravity, Pandy score, protein concentration, and WBC count. The high specific gravity and Pandy score were false-positive effects attributed to nonionic contrast media. Although postmyelographic protein concentration and total WBC count were greater in CSF samples from dogs given metrizamide than in those given iopamidol, differences were not statistically significant. The differential WBC counts were consistent with mild, acute leptomeningitis; these findings were supported by results of histologic examination. Iopamidol and metrizamide should be considered low-grade leptomeningeal irritants in dogs.

Animals

The use of rectal temperature to monitor heat stroke.

The diagnosis and treatment of heat stroke has relied on rectal temperature monitoring. A twenty-year retrospective review of heat stroke and heat exhaustion victims reveals a 24% mortality and a 33% incidence of overcooling. An experimental protocol using hot and cool baths demonstrates marked rectal temperature lag during periods of rapid body heating and cooling. Auditory canal temperature measurements provide an attractive alternative to rectal temperature measurement during rapid temperature change. Rectal temperature monitoring of heat stroke victims is not recommended. This work suggests that shivering during treatment of heat stroke might be the result of vascular and brain overcooling with elevated rectal temperatures.

Aged

Stability over time of variables measuring heart rate variability in normal subjects.

Both time and frequency domain measures of heart rate (HR) variability have been used to assess autonomic tone in a variety of clinical conditions. Few studies in normal subjects have been performed to determine the stability of HR variability over time, or the correlation between and within time and frequency domain measures of HR variability. Fourteen normal subjects aged 20 to 55 years were studied with baseline and placebo 24-hour ambulatory electrocardiograms performed 3 to 65 days apart to assess the reproducibility of the following time domain measures of cycle length variability: the standard deviation of all normal cycle intervals; mean normal cycle interval; mean day normal cycle interval; night/day difference in mean normal cycle interval; root-mean-square successive cycle interval difference; percentage of differences between adjacent normal cycle length intervals that are greater than 50 ms computed over the entire 24-hour electrocardiographic recording (proportion of adjacent intervals greater than 50 ms); and the frequency domain measures of high (0.15 to 40 Hz), low (0.003 to 0.15) and total (0.003 to 0.40) power. The mean and standard deviations of these measures were virtually identical between placebo and baseline measurements and within the studied time range. Variables strongly dependent on vagal tone (high-frequency, low-frequency and total power, root-mean-square successive difference, and percentage of differences between adjacent normal cycle intervals greater than 50 ms computed over the entire 24-hour electrocardiographic recording) were highly correlated (r greater than 0.8). It is concluded that measures of HR variability are stable over short periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Vincristine-induced peripheral neuropathy in a dog.

A 12-year-old spayed Golden Retriever with mycosis fungoides was treated by use of a chemotherapy protocol that included vincristine. After 16 weekly vincristine injections, the dog began to have signs of peripheral neuropathy. Results of electromyographic examination were consistent with muscle denervation, and motor nerve conduction velocity was depressed. Histologic examination of a common peroneal nerve biopsy specimen revealed severe nerve fiber degeneration. Clinical response and pathologic evidence of improvement were observed after the drug had been discontinued for 2.5 months.

Animals

Congenital peripheral vestibular disease attributed to lymphocytic labyrinthitis in two related litters of Doberman pinscher pups.

Five Doberman Pinscher pups from a litter of 10 (litter A) and 3 of 9 pups from a subsequent mating of the same bitch (litter B) had clinical signs consistent with unilateral or bilateral peripheral vestibular disease. Results of CBC, serum biochemical analysis, urinalysis, ophthalmologic examination, deep otoscopic examination, and CSF analysis were normal in all affected pups. Bacteriologic culture results from CSF were negative and affected pups did not have canine distemper antibody titers in CSF. The most severely affected littermates were euthanatized and necropsied at the owner's request. Gross lesions were not found at necropsy, but marked lymphocytic labyrinthitis was discovered microscopically in decalcified sections of the labyrinthine system. The case history and histologic findings were suggestive of an infectious, most likely viral, cause, but organisms were not isolated from specimens of CNS tissue. The involvement of the same bitch in the 2 litters suggests heritable factors. One mildly affected pup apparently recovered or compensated for its vestibular dysfunction.

Animals

Plasma and cerebrospinal fluid pharmacokinetics of cytosine arabinoside in dogs.

Cytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1 +/- 4.5 min and the mean elimination half-life was 69 +/- 28 min. The mean plasma clearance was 227 +/- 125 ml min-1 m-2. The peak concentration of ara-C in the CSF was 29 +/- 11 microM, which occurred at 57 +/- 13 min after the ara-C bolus. The CSF elimination half-life was 113 +/- 26 min. During a 12-h infusion of ara-C (50 mg m-2 h-1), the plasma steady-state concentration was 14.1 +/- 4.2 microM, the CSF steady-state concentration was 8.3 +/- 1.1 microM, and the CSF: plasma ratio was 0.62 +/- 0.14. The plasma elimination half-life was 64 +/- 19 min and the plasma clearance was 214 +/- 69 ml min-1 m-2. The CSF elimination half-life was 165 +/- 28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS.

Animals

Effect of atenolol and diltiazem on heart period variability in normal persons.

Several time and frequency domain measures of heart period variability are reduced 1 to 2 weeks after myocardial infarction, and a reduced standard deviation of normal RR intervals over a 24 h period (SDNN) is associated with increased mortality. The predictive accuracy of heart period variability may be reduced by drugs used to treat patients after myocardial infarction. Accordingly, a randomized, three period, placebo-controlled, crossover (Latin square) design was used to determine the effect of atenolol and diltiazem on time and frequency measures of heart period variability calculated from 24 h continuous electrocardiographic recordings during treatment with atenolol, diltiazem and placebo in 18 normal volunteers. During atenolol treatment, the 24 h average normal RR (NN) interval increased 24% (p less than 0.001). The three measures of tonic vagal activity were significantly increased (p less than 0.001) during atenolol treatment: percent of successive normal RR intervals greater than 50 ms = 69%, root mean square successive difference of normal RR intervals = 61% and high frequency power in the heart period power spectrum = 84%. Low frequency power also increased 45% (p less than 0.01), indicating that this variable also is an indicator of tonic vagal activity over 24 h. Diltiazem had no significant effect on the 24 h average NN interval or on any measure of heart period variability. The decreased mortality rate after myocardial infarction associated with beta-adrenergic blocker but not calcium channel blocker therapy may be attributed in part to an increase in vagal tone caused by beta-blockers.

Adult

Variability of electrocardiographic precordial lead placement: a method to improve accuracy and reliability.

Variability in precordial lead placement is a recognized source of electrocardiographic inaccuracy and lack of reproducibility. In an attempt to reduce error, we evaluated a new device to facilitate and guide precordial lead placement. This study involved three phases: (1) comparison of device-guided electrocardiogram with ECGs obtained by deliberate misplacement of precordial leads on the same patient; (2) electrocardiograms obtained by using the precordial lead device versus those obtained by standard technician methods; (3) reproducibility of precordial electrocardiographic leads between two technicians using the device to guide lead placement. Deliberate misplacement of precordial leads by 2 cm resulted in significant electrocardiographic interpretation changes in all patients. Comparing electrocardiograms obtained after device-guided precordial placement with those obtained after technician placement resulted in variations in 60% of patients including changes in R-wave amplitude, ST segments, Q waves, and transition zone. Significant Q-wave appearance/disappearance and/or significant ST-segment elevation/depression occurred in 19% of patients in Phase II. Sixteen percent of electrocardiograms showed significant changes when analyzed by an experienced electrocardiographer and 10% when interpreted by computer. Variable lead placements and resulting electrocardiographic alterations were not seen by either of two technicians when the device was used. This study confirms the widespread variability in precordial electrocardiograms secondary to lead misplacement. The use of a device to assist in the placement of precordial leads ensures accuracy and reproducibility of electrocardiography. Improved precision and quality control in this laboratory test have important implications in health care and its costs.

Electrocardiography

Pudendal reflexes and effects of conditioning stimuli in cats.

Evaluation of pudendal reflexes and effects of pudendal branch conditioning on those reflexes was carried out in 2 studies. In the first study of pudendal reflexes, 20 adult male and female mixed-breed cats underwent surgical isolation of the anal branch, urethral branch, and distal trunk (consisting primarily of the dorsal nerve of the penis/clitoris) of the pudendal nerve. Reflexes were tested in all possible ipsilateral and contralateral test-response combinations. Latency values and effects of increasing stimulus rate on response amplitude were recorded. Reflexes were detected in all combinations, with response latencies between 6.3 and 13.0 ms. Response amplitudes were diminished at stimulus rates of 3 to 5 Hz, and responses were apparently abolished at 4 to 16 Hz, suggesting that pudendal reflexes are polysynaptic. In the second study of conditioning effects, 9 adult male and female mixed-breed cats underwent preparation similar to that for study 1. A train of conditioning stimuli was applied to branches of the pudendal nerve prior to attempting to induce reflex responses, as performed in study 1. Conditioning completely abolished reflex responses for a period of 70 to 130 ms. Reflex responses were diminished in amplitude, compared with those observed during preconditioning trials, for 180 to 300 ms after conditioning.

Anal Canal

Comparison of genitoanal and bulbospongiosus reflexes and measurement of penile nerve conduction velocity in cats.

The bulbospongiosus reflex, genitoanal reflex, and nerve conduction velocity of the dorsal nerve of the penis were evaluated in cats. Seven adult sexually intact or castrated male mixed-breed cats underwent surgical isolation of the bulbospongiosus (analagous to bulbocavernosus) branch, anal branch, and distal trunk of the pudendal nerve. The bulbospongiosus and genitoanal reflexes were recorded from the bulbospongiosus and anal branches, respectively, by electrical stimulation, in turn, of the distal pudendal trunk and the penis itself. Nerve conduction velocity of the dorsal nerve of the penis was calculated by measuring response latency differences in the anal branch after stimulation of 2 sites on the extruded penis. The bulbospongiosus reflex had response latencies of 8.1 to 10.3 ms (distal trunk stimulation) and 11.0 to 13.0 ms (penile stimulation). The genitoanal reflex had latencies of 8.1 to 10.5 ms (distal trunk stimulation) and 11.2 to 13.2 ms (penile stimulation). Response amplitudes diminished at stimulus rates of 5 to 10 Hz; responses were abolished at rates of 12 to 15 Hz, suggesting that the reflexes are polysynaptic. There was no significant difference between latency values for the bulbospongiosus and genitoanal reflexes. Mean +/- SD nerve conduction velocity in the dorsal nerve of the penis was calculated to be 3.8 +/- 0.34 m/s, which was considerably slower than that found in human beings. This may represent technical difficulties in performing the test in cats, but could also indicate a difference between cats and human beings in the predominant population of cutaneous sensory fiber types of the penis.

Anal Canal

Measurement of anal and genitoanal reflexes in cats.

Noninvasive determination of anal and genitoanal reflexes was evaluated in clinically normal cats. Thirty adult mixed-breed cats (15 sexually intact or castrated males, 15 sexually intact or spayed females) were sedated by IV administration of ketamine, acetylpromazine, and atropine. Anal reflexes were recorded from the anal sphincter muscle after ipsilateral and contralateral electrical stimulation of the perineal skin. Genitoanal reflexes were recorded from the anal sphincter muscle after electrical stimulation of the penis or clitoris. An anal sphincter response to tibial nerve stimulation was attempted. Anal reflexes from ipsilateral and contralateral stimulations and a genitoanal reflex were detected in all cats. Anal sphincter responses to tibial nerve stimulation were inconsistent (4/30) and were not included in any analyses. Anal reflexes had response latencies of 7.5 to 12.0 ms (ipsilateral stimulation) and 6.5 to 13 ms (contralateral stimulation). Genitoanal reflexes had latencies of 9.0 to 13.0 ms (males) and 6.5 to 9.0 ms (females). Anal reflex latencies were significantly (P less than 0.05) longer for contralateral, opposed to ipsilateral, stimulation and were significantly (P less than 0.05) longer in males than in females. Genitoanal reflex latencies were also significantly (P less than 0.05) longer in males than in females, reflecting the more peripheral stimulation site in males. Anal reflex responses could be recorded in 2 feline clinic patients with such severe perineal trauma that pudendal nerve function could not be manually evaluated A potentially favorable prognosis was given in each instance on the basis of detection of the response. One cat eventually recovered.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal Canal