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Biomedical subjects

J J Collins

Publications and source records attributed to J J Collins.

At least 19 recordsLinked to original sources
PubMed1995

Determinants of early mortality and late survival in mitral valve endocarditis.

BACKGROUND: Infective mitral valve endocarditis continues to be a significant surgical challenge. The objective of this study was to examine our experience with mitral valve endocarditis surgery and identify determinants of early mortality and late survival. METHODS AND RESULTS: Over a 24-year period, mitral valve surgery was performed in 96 patients for infective mitral valve endocarditis. Patient age ranged from 20 to 78 years (median age, 52 years). There were 44 women (46%), and 48 of the 96 patients (50%) were in New York Heart Association functional class IV before surgery. Native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE) were present in 72 patients (75%) and 24 patients (25%), respectively. Surgery during the active phase of endocarditis (AE) was required in 60 patients (62%) and during the healed phase (HE) in 36 (38%). The main indications for surgery in the AE group were congestive heart failure (60%), active sepsis (67%), peripheral emboli (47%), and acute renal failure (20%), and for the HE group the main indication was progressive congestive heart failure (69%). The overall operative mortality was 5.2%. Multivariate logistic regression analysis identified PVE (odds ratio [OR] 22.5; +/- 95% confidence interval, CI, 1.9 to 268; P = .014) and an associated procedure (OR 13.3; +/- 95% CI, 1.5 to 120; P = .021) to be independent predictors for early mortality. Follow-up was 97% complete, with a median of 3.5 years. Overall 5- and 10-year survivals were 83 +/- 4% and 63 +/- 8%, respectively. Multivariate analysis for late mortality identified PVE to be a significant predictor of late mortality (hazards ratio = 3.1, +/- 95% CI, 1.4 to 6.8, P = .006). There were no significant differences in long-term morbidity results among the various subsets of mitral valve endocarditis. CONCLUSIONS: Mitral valve surgery for infective endocarditis is a significant high-risk procedure for PVE and when combined with associated procedures. The activity of endocarditis does not appear to have any influence on early mortality or long-term survival.

Adult↗
PubMed1995

Stochastic resonance without tuning.

Stochastic resonance (SR) is a phenomenon wherein the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular, non-zero level of noise. SR has been proposed as a means for improving signal detection in a wide variety of systems, including superconducting quantum interference devices, and may be used in some natural systems such as sensory neurons. But for SR to be effective in a single-unit system (such as a sensory neuron or a single ion channel), the optimal intensity of the noise must be adjusted as the nature of the signal to be detected changes. This has been thought to impose a limitation on the practical and natural uses of SR. Here we show that the ability of a summing network of excitable units to detect a range of weak (sub-threshold) signals (either periodic or aperiodic) can be optimized by a fixed level of noise, irrespective of the nature of the input signal. We also show that this noise does not significantly degrade the ability of the network to detect suprathreshold signals. Thus, large nonlinear networks do not suffer from the limitations of SR in single units, and might be able to use a single noise level, such as that provided by the intrinsic noise of the individual components, to enhance the system's sensitivity to weak inputs. This suggests a functional role for neuronal noise in sensory systems.

Models, Neurological↗
PubMed1995

Caenorhabditis elegans contains genes encoding two new members of the Zn-containing alcohol dehydrogenase family.

We have characterized two cDNA clones from the nematode Caenorhabditis elegans that display similarity to the alcohol dehydrogenase (ADH) gene family. The nucleotide sequences of these cDNAs predict that they encode Zn-containing long-chain ADH enzymes. Phylogenetic analysis suggests that one is most similar to dimeric class III ADHs found in diverse taxa; the other is most similar to the tetrameric forms of ADH previously described only in fungi.

Alcohol Dehydrogenase↗
PubMed1995

Age-related changes in open-loop and closed-loop postural control mechanisms.

In an earlier posturographic investigation (Collins and De Luca 1993) it was proposed that open-loop and closed-loop control mechanisms are involved in the regulation of undisturbed, upright stance. In this study, stabilogram-diffusion analysis was used to examine how the natural aging process affects the operational characteristics of these control mechanisms. Stabilogram-diffusion analysis leads to the extraction of repeatable center-of-pressure (COP) parameters that can be directly related to the steady-state behavior and functional interaction of the neuromuscular mechanisms underlying the maintenance of erect posture. Twenty-five healthy young males (aged 19-30 years) and twenty-five elderly males (aged 71-80 years) who were free of major gait and postural disorders were included in the study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The COP trajectories were analyzed as one-dimensional and two-dimensional random walks, according to stabilogram-diffusion analysis. Using this technique, it was demonstrated cross-sectionally that healthy aging is associated with significant changes in the 'quasi-static' dynamics of the postural control system. (It was also shown that more traditional posturographic analyses, i.e., summary statistics, were not sensitive enough to detect these age-related differences.) It was found that the steady-state behavior of the open-loop postural control mechanisms in the elderly is more positively correlated and therefore perhaps more unstable, i.e., the output of the overall system has a greater tendency to move or drift away from a relative equilibrium point over the short term. In contrast with this result, it was also found that the steady-state behavior of the closed-loop postural control mechanisms in the elderly is more negatively correlated and therefore perhaps more stable, i.e., over the longer term, there is an increased probability that movements away from a relative equilibrium point will be offset by corrective adjustments back towards the equilibrium position. In addition, it was demonstrated that the elderly utilize open-loop control schemes for longer time intervals and correspondingly larger COP displacements during periods of undisturbed stance. This result suggests that in the elderly there is a greater delay, on average, before closed-loop feedback mechanisms are called into play. Finally, it was shown that there is an increased heterogeneity of postural control abilities in healthy older adults.

Adult↗
PubMed1995

The effects of visual input on open-loop and closed-loop postural control mechanisms.

In an earlier posturographic investigation (Collins and De Luca 1993) it was proposed that open-loop and closed-loop control mechanisms are involved in the regulation of undisturbed, upright stance. In this study, stabilogram-diffusion analysis was used to examine how visual input affects the operational characteristics of these control mechanisms. Stabilogram-diffusion analysis leads to the extraction of repeatable center-of-pressure (COP) parameters that can be directly related to the resultant steady-state behavior and functional interaction of the neuromuscular mechanisms underlying the maintenance of erect posture. Twenty-five healthy male subjects (aged 19-30 years) were included in the study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The subjects were tested under eyes-open and eyes-closed conditions. The COP trajectories were analyzed as one-dimensional and two-dimensional random walks, according to stabilogram-diffusion analysis. Using this technique, it was found that visual input affects the performance of the postural control system in one of two different ways--either it significantly modifies the steady-state behavior of the open-loop postural control mechanisms, or it significantly alters the characteristics of the other closed-loop feedback mechanisms that are involved in balance control. This result is interpreted as an indication that the visual system is integrated into the postural control system in one of two different ways. The experimental population was roughly evenly divided between these two schemes. For the first group (13 of 25 subjects), visual input principally caused a decrease in the "effective" stochastic activity of the open-loop control mechanisms in both the mediolateral and anteroposterior directions. For the second group (12 of 25 subjects), visual input caused an increase in the effective stochastic activity and uncorrelated behavior of the closed-loop control mechanisms in the anteroposterior direction only. On the basis of these results, it is hypothesized that visual input, in both schemes, serves to decrease the stiffness of the musculoskeletal system. In the former case, this may be accomplished by decreasing the level of muscular activity across the joints of the lower limb, whereas, in the latter case, reduced stiffness may be achieved by reducing the gain(s) of the other postural feedback mechanisms, i.e., the proprioceptive and/or vestibular systems. Using stabilogram-diffusion analysis, it was also found that the two groups of subjects behaved similarly under eyes-closed conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

The redundant nature of locomotor optimization laws.

A sagittal-plane model of the lower limb, which considered the possibility of antagonistic and synergistic muscle action and took account of the load-bearing roles of the cruciate ligaments, was applied to a dynamic analysis of level walking. It was hypothesized that: (1) the simple, one-sided constraints that intra-articular contact forces must be compressive and muscle and ligament forces tensile substantially reduce the redundancy of the load-transmitting structures of the lower limb, (2) many previously proposed optimization laws for muscle selection yield equivalent results, when they are applied to a finite set of admissible limiting solutions, and (3) the aforementioned optimization laws, when applied to a finite set of admissible limiting solutions, do not adequately predict the co-contraction of antagonistic muscles during gait. The problem of indeterminacy was resolved by considering all possible limiting solutions of the system unknowns on the dynamic equations. Although 498 limiting solutions of nine unknowns could arise at each sampled point on the gait cycle, the aforementioned one-sided constraints ruled out the large majority of them. It was shown that of the 498 possible, the minimum number of simultaneous admissible solutions for any subject was as few as three and the maximum number was only 18. The Principles of minimal total muscle force, squared muscle force, muscle stress, intra-articular contact force and instantaneous muscle power predicted remarkably similar patterns of muscle activity over the gait cycle. Of the six tested performance criteria, the Principle of minimal total ligament force was the least successful in terms of selecting solutions that closely matched the EMG patterns. This result implied that the muscles do not always act to protect the knee ligaments during gait. Finally, each of the above minimum principles failed to predict any antagonistic quadriceps-hamstrings action at the knee and hip around the event of heelstrike, although such activity was indicated by electromyography.

Adult↗
PubMed1995

Intravenous amitriptyline in pediatrics.

Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia. One patient experienced an extrapyramidal reaction temporally related to the administration of IV amitriptyline, which was successfully managed with diphenhydramine. Further prospective, controlled studies are needed to further assess the safety, efficacy and tolerability of this novel use of amitriptyline.

Adolescent↗
PubMed1995

Control of severe pain in children with terminal malignancy.

OBJECTIVE: To identify the characteristics of the subset of children with malignancy in whom massive opioid infusions are needed during the terminal phase. DESIGN: Retrospective review of the records of the 199 patients who died of malignancy after treatment at Children's Hospital, Boston, from March 1989 to July 1993, identifying characteristics of patients who required massive opioid infusions (operationally defined as infusion of > 3 mg/kg per hour of morphine dose equivalent) during the terminal phase. RESULTS: Twelve patients (6%) required massive opioid infusions, and eight of these patients required extraordinary measures (epidural or subarachnoid infusion and/or sedation) to achieve adequate analgesia. The duration of epidural or subarachnoid infusions in three patients ranged from 3 to 9 days, and minimal complications occurred. The duration of sedation ranged from 1 to 15 days. Maximal intravenous opioid dosing ranged from 3.8 to 518 mg/kg per hour of morphine equivalent. The maximal infusion rate (exceeding all previous published reports) occurred in an infant with an isolated metastasis in the periaqueductal gray matter, a brain-stem site linked to mediating analgesia and defense reactions. The need for massive opioid dosing in 11 of 12 patients was associated with tumor spread to the spinal nerve roots, nerve plexus, large peripheral nerve, or spinal cord compression. CONCLUSIONS: Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management. These problems occur more commonly among patients with solid tumors metastatic to spine and major nerves.

Adolescent↗
PubMed1995

Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans.

A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Adult↗
PubMed1994

An analytic solution for energy deposition in model spherical tumours undergoing ultrasound-hyperthermia treatments.

In this paper, we develop a method to predict the energy deposition in tumours undergoing ultrasound-hyperthermia treatments. Energy depositions are calculated using an exact, analytic solution to the problem of ultrasound scattering from a spherical tumour. The biological tissues are modelled as solid, lossy elastic media so that (i) transverse-wave modes, in addition to longitudinal-wave modes, are considered, and (ii) mode coupling is fully accounted for during the scattering. The model tumour is of arbitrary size and no restrictions are placed on its material parameters relative to the surrounding tissue. Simpler analytic results are given for tumours that differ in densities and rigidities only slightly from the surrounding tissue. We briefly discuss how the above analysis could be extended to more complex systems, i.e., irregularly shaped tumours.

Humans↗
PubMed1992

Surgical treatment of adult atrial septal defect: early and long-term results.

OBJECTIVES: The purpose of this study is to determine the early and late results of the surgical repair of atrial septal defect in adults. BACKGROUND: Progressively limiting, untreated atrial septal defect can lead to the early death of middle-aged adults. Recently it has been suggested that the closure of atrial septal defects might be accomplished with interventional cardiac techniques. Although the long-term results of the transcatheter closure are as yet unknown, the outcome of surgical therapy has been shown to be beneficial for almost 40 years. METHODS: Between 1971 and 1991, 166 consecutive patients underwent surgical repair of a secundum or sinus venosus atrial septal defect, or both, at the Brigham and Women's Hospital, Boston. There were 120 women and 46 men in this group; the mean age was 44 years and 58 (35%) of the patients were > or = 50 years old. The average pulmonary to systemic flow ratio was 3.0, and 57 patients had a peak systolic pulmonary artery pressure > 30 mm Hg. RESULTS: There were two operative deaths (early mortality rate 1.2%), and 13% of the patients had a perioperative complication. One hundred fifty-three of the 164 survivors were followed up for a mean of 90 months (range 2 to 247). There were eight late deaths (late mortality rate 4.9%) and a late morbidity rate of 12.4% (in most cases due to arrhythmias). The 5- and 10-year survival rates are 98% and 94%, respectively, and the probability of event-free survival (with no morbidity or mortality) at 5 years is 97% and at 10 years is 92%. CONCLUSIONS: The results indicate that the surgical correction of atrial septal defect in adults is safe and efficacious as confirmed by 20 years of follow-up.

Adult↗
PubMed1992

Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy.

The long-term results of patients undergoing myotomy/myectomy of the ventricular septum for obstructive hypertrophic cardiomyopathy are documented in 31 patients (15 women, 16 men, age range 21 to 80 years [mean 55]) with mean New York Heart Association functional class III to IV congestive heart failure, who underwent radical myotomy/myectomy at the Brigham and Women's Hospital from 1972 to 1991. Preoperative gradients by catheterization or echocardiography ranged from 26 to 240 mm Hg (average 96). There were no operative deaths. Two patients developed early postoperative complete heart block requiring a transvenous pacemaker. Clinical follow-up was 1 to 14 years (mean 6.5). All surviving patients were restudied by echocardiography and clinical examination. The mean postoperative functional class was II. Postoperative gradients ranged from 0 to 30 mm Hg (mean 4.5) (p less than 0.001 compared with preoperative values). There were 5 late deaths (low cardiac output in 2, stroke in 2, and acute respiratory failure in 1); 4 of 5 deaths occurred in patients with concomitant coronary artery disease. Survival at 10 years was 86 +/- 9%. There were no reoperations for subaortic obstruction.

Cardiomyopathy, Hypertrophic↗
PubMed1992

Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease.

OBJECTIVE: To compare the efficacy of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. DESIGN: Randomized, multicenter, investigator-blinded clinical trial with clinical evaluations during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months post-treatment. SETTING: Three university referral centers and one private practice. PATIENTS: A total of 123 patients with physician-documented erythema migrans. INTERVENTION: Patients were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (63 patients), or doxycycline, 100 mg three times daily (60 patients). MEASUREMENTS: Resolution of erythema migrans and of signs and symptoms related to early Lyme disease as well as prevention of late Lyme disease. RESULTS: A satisfactory clinical outcome (success or improvement) was achieved in 51 of 55 (93%) evaluable patients treated with cefuroxime axetil and in 45 of 51 (88%) patients treated with doxycycline (difference, 5%, 95% Cl, -5% to 14%). The only complication at 1 month post-treatment was Lyme arthritis in one patient who received doxycycline. Of the patients with satisfactory outcomes at 1 month post-treatment who were evaluable at 1 year post-treatment, a satisfactory outcome was achieved in 43 of 48 (90%) and in 35 of 38 (92%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -2%; Cl, -12% to 7%). Lyme arthritis did not develop in any patient after 1 month post-treatment, whereas peripheral neuropathy was suspected in one patient treated with cefuroxime axetil. Thirty percent of patients treated with cefuroxime axetil and 32% of those treated with doxycycline had one or more drug-related adverse events. Doxycycline was associated with more photo-sensitivity reactions (15% compared with 0%; P = 0.001) and cefuroxime axetil with more diarrhea (21% compared with 7%; P = 0.035) and Jarisch-Herxheimer reactions (29% compared with 8%; P = 0.005). CONCLUSIONS: Cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treating of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Adolescent↗
PubMed1992

Symmetry-breaking bifurcation: a possible mechanism for 2:1 frequency-locking in animal locomotion.

The generation and control of animal locomotion is believed to involve central pattern generators - networks of neurons which are capable of producing oscillatory behavior. In the present work, the quadrupedal locomotor central pattern generator is modelled as four distinct but symmetrically coupled non-linear oscillators. We show that the typical patterns for two such networks of oscillators include 2:1 frequency-locked oscillations. These patterns, which arise through symmetry-breaking Hopf bifurcation, correspond in part to observed patterns of 2:1 frequency-locking of limb movements during electrically elicited locomotion of decerebrate and spinal quadrupeds. We briefly describe how our theoretical predictions could be tested experimentally.

Animals↗
PubMed1992

Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis.

PURPOSE: This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis. PATIENTS AND METHODS: Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160). Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks). Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit. RESULTS: Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp. (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%). A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.446). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (p = 0.567). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001). Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events. CONCLUSIONS: Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects.

Acute Disease↗
PubMed1992

Combined carotid and coronary revascularization: the preferred approach to the severe vasculopath.

The timing of carotid endarterectomy (CEA) and coronary revascularization (CABG) for concomitant disease is controversial. Results of combined CEA/CABG in 127 patients (age range, 46 to 82 years; mean age, 65 years; 61% male) from 1978 to 1991 were reviewed. Ninety-five patients (75%) were in New York Heart Association functional class III or IV, 48 (38%) had left main coronary artery disease, and 32 (28%) had depressed ejection fraction ( < 0.50). Forty (32%) had asymptomatic bruits, 61 (48%) transient ischemic attacks, and 26 (20%) prior strokes. Seventy-five (59%) had bilateral carotid stenosis, including 20 (16%) with contralateral occlusions. Perioperative mortality was 7 of 127 (5.5%), and all deaths were cardiac related. Myocardial infarctions occurred in 6 of 127 patients (4.7%) and were nonfatal in 3 (2.3%). Permanent strokes occurred in 7 of 127 (5.5%) and were ipsilateral in 5 (3.9%). Perioperative stroke did not occur in the asymptomatic group, but the risk was higher in those with prior stroke (19%) or with contralateral carotid occlusion (15%). The stroke risk for our patients with carotid disease having CABG without CEA is not known, but the literature reports rates as high as 14%. For our patients without known concomitant disease, the risk of permanent stroke was 1.0% (31/3012) for isolated CABG and 1.5% (7/482) for isolated CEA. The late results after CEA/CABG revealed a 5-year survival of 70% +/- 5%, which correlated with ejection fraction ( > or = 0.50, 81% +/- 5%; < 0.50, 45% +/- 11%; p < 0.003). Freedom from late permanent ipsilateral stroke was 97% +/- 2% at 8 years. Freedom from stroke at 5 years was lower among patients with a previous stroke (71% +/- 10%) compared with transiently symptomatic (90% +/- 4%) and asymptomatic (96% +/- 4%) patients (p < 0.03). Combined CEA/CABG is a useful option in this high-risk group of patients with extensive atherosclerosis; avoids a subsequent hospitalization, anesthetic, and delay period; and provides long-term protection from ipsilateral stroke.

Actuarial Analysis↗
PubMed1992

Subchronic toxicity studies of t-butyl alcohol in rats and mice.

The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an important commodity chemical, an additive to unleaded gasoline, and a contaminant of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4% level of both sexes and species. Weight-gain depression was present in all dose levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female mice. Water consumption was increased at lower dose levels in male rats and decreased in the higher dose levels of both sexes of rats and female mice. Clinical signs in rats were ataxia in both sexes and hypoactivity in males. Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats, urine volumes were reduced, in association with crystalluria. Gross lesions at necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of transitional epithelia and inflammation of the urinary bladder. In male rats treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha-2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1% in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female rats and 4362.9 mg/kg/day for the female mice). The results indicate that in rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and males are more sensitive to t-butyl alcohol toxicity than females.

Animals↗