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Biomedical subjects

R B Smith

Publications and source records attributed to R B Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses in obese and normal-weight men.

This study was designed to determine whether differences in alpha-1 acid glycoprotein and free drug concentrations result in an altered response to triazolam. Twelve normal-weight and 12 obese adult male subjects received intravenous doses of triazolam, 0.5 mg, on two occasions separated by 1 week. There was a small difference in the alpha-1 acid glycoprotein concentrations between groups but no difference in free fraction of triazolam. There was a longer terminal half-life (t1/2 beta) in the obese subjects (3.16 +/- 0.87 vs. 3.83 +/- 1.24, p = 0.0098). Overall, week 1 data revealed no difference in effect between normal and obese subjects. However, response data reveal a pattern of increased sensitivity with the second exposure to triazolam. For example, area under the effect curve (AUEC) on all tests was significantly greater in week 2 for both groups of subjects. For a memory test and sedation from 0 to 12 hours, AUEC/free AUC ratios were significantly greater in week 2 for all subjects. The obese had a higher ratio on week 2 than on week 1 for all psychomotor tests and sedation (0 to 4.5 hours; p < 0.05). The results of modeling psychomotor impairment-concentration data pooled by group for each week continue the pattern: week 1 data are similar between the obese and normal-weight subjects. Although EC50 values are up to 15% lower in week 2 for the normal-weight subjects, EC50 values are as much as 66% lower in week 2 for the obese, where a lower EC50 indicates greater sensitivity. Logistic regression of the recognition data is consistent with these results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Triazolam pharmacokinetics after intravenous, oral, and sublingual administration.

This study was designed to evaluate the relative and absolute bioavailability of triazolam, 0.25 mg, after the administration of the marketed oral tablet and a sublingual prototype wafer; an intravenous dose was used as a reference. Twelve men were evaluated in a three-way crossover study; study days were separated by 1 week. A single dose was administered to each subject at approximately 8 a.m.; serial blood samples were obtained for the determination of triazolam concentration. The fraction absorbed relative to intravenous was 20% higher in the sublingual than in the oral treatment (p = 0.0128); the difference between treatments was greatest in the first 2 hours as indicated by the area under the curve from 0 to 2 hours (p < 0.05). The extraction ratio ranged from 0.05 to 0.25, and the predicted availability after oral administration was 86% with a range of 75 to 95%. In contrast, the observed mean absolute availability was 44% (oral) and 53% (sublingual). A potential explanation for this discrepancy between predicted and observed bioavailability is that after oral administration, a fraction of triazolam may be metabolized by cytochrome P450IIIA4 in the gut wall, with a separate fraction subject to first-pass metabolism in the liver. Although this study was not designed to identify sites of triazolam metabolism, the proposed explanation is consistent with the occurrence of P450IIIA4 in the stomach, small intestine, and liver. Doses administered sublingually avoid first-pass metabolism, producing earlier and higher peak concentrations than do doses administered orally.

Administration, Oral↗
PubMed1995

Surgery from a US perspective.

Prostate screening has made it possible to detect organ confined prostate carcinoma in men with a life expectancy of 20 years and longer. These clinically significant malignancies may be successfully eradicated by means of anatomical dissection of the prostate, which minimizes both morbidity and mortality. In a retrospective series of patients with clinically localized prostate cancer who were treated with a radical retropubic prostatectomy and lymph node dissection, 5 and 10 year crude survival rates were 96% and 86%. Survival was compromised by penetration of tumour through the prostatic capsule, and even more significantly by involvement of the seminal vesicles. The use of prostate specific antigen (PSA) concentrations to monitor disease progression before any clinical manifestation revealed that disease free survival was less than previously reported. Patients diagnosed and treated more recently had longer disease free survival than the overall group mainly because of earlier detection with PSA, with consequent lower tumour volumes and stage. In addition, 92 +/- 3(SD)% patients with pathologically organ confined tumours, without capsular or seminal vesicle invasion, are clinically disease free with non-detectable PSA at 5 years. Our data therefore show that radical prostatectomy can cure patients with organ confined prostate cancer, with acceptable morbidity. Although the need for cure may be questioned in many patients, young patients with prostate cancer almost certainly benefit from eradication of the malignancy.

Adult↗
PubMed1994

Subclavian artery revascularization: a decade of experience with extrathoracic bypass procedures.

Extrathoracic revascularization has become the most popular form of surgical correction of symptomatic subclavian artery lesions. During a 10-year period ending in December 1991, 41 extrathoracic bypass procedures were performed on 37 patients for proximal subclavian artery stenosis or occlusion. This included 25 females and 12 males, with a mean age of 56 years. Surgery was performed for manifestations of upper extremity ischemia in 19 patients (51%), vertebrobasilar insufficiency in four patients (11%), and both upper extremity ischemia and vertebrobasilar insufficiency in 11 patients (30%). Three patients (8%) had angina pectoris caused by "coronary-subclavian steal" following internal mammary-coronary artery bypass. Severe proximal stenosis or complete occlusion of the subclavian artery was demonstrated angiographically in all cases. Procedures performed included: carotid-subclavian bypass (n = 28), subclavian-carotid transposition (n = 6), axilloaxillary bypass (n = 4), and subclavian-subclavian bypass (n = 3). Saphenous vein was used as the bypass conduit in 6 of the carotid-subclavian bypass procedures, and prosthetic grafts were used for the remainder. There were no perioperative strokes or deaths in this series, and the mean postoperative hospital stay was 4 days. Follow-up ranged from 2 to 96 months (mean, 35.6 months). The overall patency rate was 95% at 1 year, 86% at 3 years, and 73% at 5 years. Patency at 5 years was significantly higher for procedures utilizing the common carotid artery as the donor vessel as compared with those using the contralateral subclavian or axillary arteries (83% versus 46%, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Carotid endarterectomy in the octogenarian.

During a 10-year period from January 1983 to December 1992, 79 carotid endarterectomies were performed in patients aged 80 years or older. This represented 7.4% of the total patient population undergoing carotid endarterectomy at Emory University Hospital. The indications for surgery in this elderly population were transient ischemic attacks in 24 (30.3%), cerebrovascular accident in 12 (15.2%), amaurosis fugax in seven (8.9%), vascular tinnitus in one (1.3%), and asymptomatic stenosis in 35 (44.3%). The average degree of ipsilateral stenosis was 76.8%. Concomitant risk factors included coronary artery disease in 43%, systemic arterial hypertension in 51.9%, diabetes mellitus in 10.1%, and significant smoking history in 53.2%. Seventy-six percent of the procedures were performed under local anesthesia, and in all but two intraluminal shunts were used. Combined 30-day mortality and postoperative stroke morbidity in this population was 1.3% (one patient). Long-term follow-up ranging from 1 to 10 years (average 35 months) revealed no ipsilateral strokes. This experience suggests that carotid endarterectomy can be performed in an elderly population with morbidity and mortality rates similar to those in a younger cohort.

Aged↗
PubMed1994

The prognostic significance of urinary albumin in Polynesians with non-insulin-dependent diabetes.

Polynesian (59 Maori and 30 Pacific Island) patients were identified from two diabetes clinic registers and followed for a mean of 4.8 years, in order to determine the prognostic significance of urinary albumin excretion. Events were defined as death or entry onto a renal replacement programme. Fourteen events occurred during the period of follow-up. Urinary albumin/creatinine ratio was treated as a continuous variable in a proportional hazards analysis. A 10-fold increase in albumin/creatinine ratio was associated with a 5-fold increase in the risk of an event (95% C.I. = 2.05-12.09). In conclusion, elevated urinary albumin/creatinine predicted mortality and renal morbidity in Maori and Pacific Island patients with non-insulin-dependent diabetes.

Albuminuria↗
PubMed1994

Paradoxical embolism and acute arterial occlusion: rare or unsuspected?

PURPOSE: The high prevalence of clinically silent venous thrombosis and the presence of a patent foramen ovale (PFO) in up to 35% of the general population suggests that paradoxical emboli may be the cause of an ischemic stroke or a peripheral thromboembolic occlusion more often than is presently considered. This study was undertaken to review our experience with presumed paradoxical embolism. METHODS: Hospital records were reviewed for all patients diagnosed with both a documented PFO and a thromboembolic event between January 1970 and June 1993. Patients with a ventricular or an atrial septal defect or a probable pulmonary arteriovenous fistula were excluded. RESULTS: The presumptive diagnosis of paradoxical embolism was made in seven patients. There were five men and two women, with a median age of 43 years. Four patients were admitted with an acute cerebral ischemic event, and in three others hospitalization was prompted by the development of an acutely ischemic limb (two upper extremity; one lower extremity). In none was there evidence of angiographically significant peripheral or extracranial atherosclerotic occlusive disease. Symptoms suggestive of pulmonary emboli were noted in two patients, and in only one patient was there evidence on physical examination of a deep venous thrombosis. Before 1988 the diagnosis of paradoxical embolism had been made in only one patient after postmortem examination. All six patients who were discharged were available for follow-up (mean 20 months; range 6 to 60 months). There was one late death from lung cancer. Recurrent paradoxical emboli have not been documented during the follow-up period. CONCLUSIONS: The incidence of presumed paradoxical embolism has increased dramatically in the recent past as a consequence of our improved ability to unequivocally detect PFO with associated physiologic shunting. The suspicion of this heretofore "rare" event should be raised, particularly in the young or middle-aged adult diagnosed with an acute thromboembolic event. Until the risk of recurrent ischemic events in the presence of a PFO is better defined, we currently recommend closure of the foramen ovale after a significant or recurrent paradoxical embolus. Otherwise, the selective use of intracaval filters, antiplatelet therapy, and oral anticoagulation remain undefined.

Acute Disease↗
PubMed1994

The incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy.

A total of 601 patients who underwent radical retropubic prostatectomy for localized prostate cancer at our institution was followed with serial prostatic specific antigen (PSA) determinations. Three separate groups were delineated by pathological stage: 293 patients with organ confined disease, 215 with involvement of the capsule or positive margins and 93 with extension to the seminal vesicles. Followup ranged from 12 to 237 months (median 34). Five and 10-year disease-free survival rates for the 601 patients were 86 +/- 2% and 78 +/- 3%, respectively. The rate of detectable PSA (greater than 0.4 ng./ml.), used as an indicator of cancer progression, revealed 5 and 10-year disease-free rates of 69 +/- 2% and 47 +/- 3%, respectively. When comparing the patients from an earlier series to those who underwent surgery after 1986, an improvement in the 5-year clinical disease-free rate was noted (78 +/- 2% versus 93 +/- 2%, respectively). Similarly, an improvement in the 5-year disease-free survival rate with nondetectable PSA level was demonstrated in our contemporary series (80 +/- 3%) compared to our historical series. Of the 601 patients 123 had a detectable post-prostatectomy PSA level with or without clinical evidence of metastasis. A PSA doubling time before onset of adjuvant therapy was determined in 94 patients. Post-prostatectomy PSA doubling times were significantly different when comparing the patients who ultimately had progression to distant metastases (median 4.3 months) to those with either clinical local recurrence or a PSA elevation as the sole indicator of recurrence (median 11.7 months). Radical retropubic prostatectomy, whether assessed by clinical or biochemical means, has demonstrated excellent disease-free survival rates, especially since the advent of PSA and anatomical radical prostatectomy.

Adult↗
PubMed1994

Ischemic nephropathy and concomitant aortic disease: a ten-year experience.

PURPOSE: The durability of renal preservation after surgical intervention has not been well defined, particularly in patients with associated aortic disease. A review of all patients at the Emory University Hospital with renal insufficiency (creatinine level > or = 1.8) and concomitant atherosclerotic aortic and renovascular disease was undertaken. METHODS: Fifty patients underwent both renal revascularization (71 kidneys) and the repair of aneurysmal or symptomatic aortic occlusive disease between 1982 and 1992. Hypertension was present in 96% of patients and diabetes was present in 10%. The preoperative estimated glomerular filtration rate (EGFR) was 25.18 +/- 8.29 ml/min (creatinine level 3.1 +/- 1.5 mg/dl). Operative management included bilateral renal artery repair (n = 21), unilateral repair alone (n = 17), and unilateral repair with contralateral nephrectomy (n = 12). The relative percent change in the postoperative EGFR (> or = 7 days after operation) increased by at least 20% in 42% of the patients, had decreased by 20% or more in only 4%, and was otherwise categorized as unchanged in the remaining 54% of the study group. RESULTS: The 30-day operative mortality rate was 2.0% (1 of 50). Forty-five of the surviving 49 patients (91.8%) were available for follow-up (median 49 months). During this period nine patients (18.4%) eventually required dialysis, four within 6 months of operation, and 19 patients died. Neither subgroup experienced a retrieval of renal function after operation. Five-year survival rate was 61%, and a trend was noted between the risk of death and the relative change in EGFR after operation (p = 0.13). The likelihood of eventually requiring long-term dialysis was highest among those patients with low preoperative functional renal reserve as measured by preoperative creatinine level of 3 mg/dl or greater (p < 0.0001), or preoperative EGFR less than 20 ml/min (p = 0.0001). Blood pressure was cured or improved in 50% at late follow-up. CONCLUSIONS: Early improvement of renal function may be observed in nearly one half of patients subjected to combined aortic and renal revascularization. Nonetheless, renal preservation may not be sustainable in patients with compromised preoperative function. Intervention before marked functional decline remains the best option for minimizing the risk of eventual dialysis.

Aged↗