Biomedical subjects

R G Hoffman

Publications and source records attributed to R G Hoffman.

At least 37 records · Page 2Linked to original sources

PubMed1992

Effects of indomethacin on myogenic contractile activation and responses to changes in O2 and CO2 in isolated feline cerebral arteries.

We used an isolated, pressurized, and perfused feline middle cerebral artery preparation to measure how changes in intraluminal pressure and alterations in O2 and CO2 affect vessel diameter and myogenic contractile activation before and after treatment with indomethacin (IND). Vessel diameters were measured over the pressure range 60-140 mm Hg. The arteries were then exposed to low O2 (50 torr) and/or high CO2 (65 torr) and diameters remeasured over the same range. Under control conditions, the arteries exhibited myogenic contractile activation. Exposure to low O2, high CO2, or a mixture of low O2/high CO2, increased vessel diameter but did not change the vessels' myogenic contractile responsiveness to changes in pressure. Arteries exposed to IND decreased in diameter but retained myogenic contractile activity. In the presence of IND, vessels dilated to both low O2 and a mixture of low O2/high CO2, but did not dilate to high CO2 alone. Under all conditions, vessels retained myogenic contractile activity. Results obtained under control conditions and low O2 confirm those of others using similar systems. Myogenic contractile activity in the presence of high CO2 or a mixture of low O2/high CO2 has not been previously reported. The dilation to low O2 but not to high CO2 in the presence of IND suggests that this drug's effects in cerebral arteries are not limited solely to inhibition of prostaglandin synthesis.

Animals↗

PubMed1992

Factors affecting response of cows to biweekly injections of sometribove.

Seventy-eight lactating Holstein cows (18 primiparous and 60 multiparous) were used to study certain factors affecting response in milk yields to biweekly injections of bST. Cows were intramuscularly injected with placebo or with 500 mg of bST every 14 d for 36 wk beginning 60 d postpartum. Primiparous cows responded less to bST than did multiparous cows. Cows were separated into three yield groups within each treatment based on pretreatment yield: low (27.0 kg/d), medium (32.0 kg/d), and high (39.0 kg/d). Response of low yielding cows to bST was numerically greater than that of medium or high yielding cows, but there was no significant interaction between treatment and pretreatment milk yield. Individual cow index for milk yield was used as a measure of genetic potential of cows, which were divided into two index groups: high cow index (greater than -23 kg) and low cow index (less than -23 kg). Cows in the high index group showed significantly higher milk yields than the low index group during treatment, but treatment by cow index interaction was not significant, suggesting that cows of widely ranging genetic potential respond similarly to bST. Response of cows to bST in mid to late lactation was slightly greater than in early lactation (15.9 and 10.6% vs. 17.8%, respectively), but no significant interaction of treatment by days postpartum was noted. Finally, even though cows treated with bST exhibited slightly higher rectal temperatures during the hot summer months, no significant difference in milk yield response to bST was noted during periods of moderate versus high ambient temperatures.

Animal Feed↗

PubMed1991

Neurohumoral and metabolic effects of short-term dietary NaCl restriction in men. Relationship to salt-sensitivity status.

Published observations suggest that not everyone benefits from severe dietary NaCl restriction, since blood pressure responses appear heterogeneous and adverse metabolic effects may occur. We studied the cardiovascular, neurohumoral, and metabolic effects of 7 day periods of 20 v 200 mEq/day NaCl diets in 27 men. Twelve subjects were salt sensitive (SS), defined as mean intraarterial pressure (MAP, mm Hg) during high NaCl greater than or equal to 5% above MAP on low NaCl. Eleven subjects were salt resistant (SR), defined as MAP during the low NaCl phase greater than or equal to MAP during the high NaCl phase. The SR subset had a tendency to greater neurohumoral activity, assessed by changes in mean values for plasma norepinephrine (NE, P = .12) and plasma renin activity (PRA, P less than .001) on the low v high NaCl diet. In SR subjects the low v high NaCl diet also raised mean values for creatinine (P = .03), uric acid (P = .001), and low density cholesterol (LDL-C, P = .03), but not fasting insulin (P = .15). In SS subjects, the low v high NaCl diet did not raise NE (P = .35), although the PRA was greater (P = .002). Among SS subjects, mean values for uric acid (P = .005) and insulin (P = .02) were greater during the low v high NaCl phase, while creatinine (P = .15) and LDL-C (P = .67) were not different. The data suggest that severe, short-term NaCl restriction can be undesirable, especially in SR subjects, since potentially adverse neurohumoral and metabolic changes are not counterbalanced by the benefits of a lower MAP.

Adult↗

PubMed1991

Isobolographic analysis of analgesic interactions between intrathecally and intracerebroventricularly administered fentanyl, morphine and D-Ala2-D-Leu5-enkephalin in morphine-tolerant and nontolerant mice.

Concurrent administration of morphine sulfate i.c.v. and i.t. produces a multiplicative interaction for analgesia in the tail flick response in mice. This interaction decreases to an additive interaction in mice which are tolerant to s.c. morphine. To test the responses of opioids selective for mu or delta receptors, the present study examined the interactions between fentanyl citrate (mu agonist) and D-Ala2-D-Leu5 enkephalin (DADLE, a relatively selective delta agonist) administered i.c.v. and i.t. using the tail flick test in control and morphine pellet-implanted mice. A method was developed for assigning statistical significance to the resulting ED50 values when analyzed isobolographically. When fentanyl or DADLE was administered i.c.v. plus i.t., an additive interaction between sites occurred in control animals, which changed to an antagonistic interaction for fentanyl and a multiplicative interaction for DADLE after morphine pellet treatment. When morphine was given i.c.v. along with i.t. fentanyl or DADLE in control animals, multiplicative interactions occurred when equipotent doses were given. Thus, opioids which were more receptor-selective than morphine did not produce multiplicative interactions, but were multiplicative when given with morphine. These results suggest that activation of combinations of receptors (by morphine) was required for the multiplicative interaction. The supraspinal site involved mu receptors (which are not self-sufficient and require an additional component) and the spinal site involved mu or delta receptors. The use of isobolographic analysis required that the drugs, when administered concurrently at two sites, be given in a constant dose ratio.

Animals↗

PubMed1991

Comparison of efficacy of automatic implantable cardioverter defibrillator in patients older and younger than 65 years of age.

PURPOSE: The efficacy of the automatic implantable cardioverter defibrillator (AICD) was compared in elderly patients and younger patients with life-threatening ventricular tachyarrhythmias. Clinical characteristics, surgical complications, and long-term survival rates were compared between the two age groups. PATIENTS AND METHODS: A retrospective study was conducted of 54 elderly patients (greater than 65 years) and 79 younger patients (less than 65 years) who had had AICDs implanted for recurrent symptomatic ventricular tachycardia and/or ventricular fibrillation. RESULTS: In 85% of elderly patients and 78% of younger patients, coronary artery disease was the underlying disease (NS). The mean left ventricular ejection fraction was 31.4 +/- 14.3% in the elderly patients and 35.7 +/- 17.6% in the younger patients (NS). Concomitant myocardial revascularization was performed in 37% of elderly patients and 29% of younger patients (NS); however, only 4% of elderly patients had concomitant left ventricular resection or cryoablation, compared with 15% of younger patients (p less than 0.001). Two patients in each age group died perioperatively (4% versus 3%, NS), and no significant difference in surgical morbidity or length of hospital stay following AICD implantation was noted between the age groups. In conjunction with AICD, elderly patients more commonly received antiarrhythmic drugs, with 54% of elderly patients taking amiodarone at the time of hospital discharge compared with 29% of the younger patients (p less than 0.008). In contrast, beta-blockers were more commonly used in younger patients (16% versus 2%, p less than 0.03). At a mean follow-up of 25 months, 11 (20%) elderly patients and 16 (20%) younger patients had died. Six deaths in elderly patients and five deaths in younger patients were classified as arrhythmic deaths (NS); however, only one younger patient and three elderly patients died suddenly (NS). Calculated survival curves demonstrated similar survival rates in the two age groups with approximately 90%, 87%, and 80% of the patients alive at 1, 2, and 3 years, respectively. Theoretic survival curves calculated from appropriate AICD shocks demonstrated significantly lower survival compared with actual survival. CONCLUSION: It is concluded that AICD is a very effective treatment for life-threatening ventricular tachyarrhythmias, and this benefit applies to elderly patients as well as younger patients.

Adolescent↗

PubMed1991

Effects of acute hypoxemia on responses to dopamine and dobutamine in neonatal swine.

The effects of acute hypoxemia on cardiovascular responses to dopamine (DA) and dobutamine (DB) were studied in 2-4 day (n = 21) and 13-17 day (n = 27) old swine under sodium pentobarbital anesthesia. Sequential 10-min infusions of 2, 5 and 15 mu/kg/min of DA or DB or normal saline were administered under conditions of normoxemia and repeated during hypoxemia. Data are presented as mean percent of baseline value +/- SE. During normoxemia, DA increased aortic pressure, cardiac output, heart rate, LV dP/dt max and renal resistance and decreased mesenteric resistance in both ages, while DB increased heart rate, LV dP/dt max and cardiac output in both age groups and decreased total arterial resistance and renal resistance in the youngest. Increases in LV dP/dt max were larger with DA as compared to DB (p less than 0.05) with the highest dose in younger (152 +/- 5% vs. 124 +/- 4%) and older (201 +/- 29% vs. 157 +/- 9%) animals. Hypoxemia reduced heart rate responses to DA and DB in older piglets, contractility responses to DB in older animals, aortic pressure responses to DA in all animals and renal resistance responses to DA in older animals. Hypoxemia had little or no effect on cardiac output and total arterial, mesenteric and carotid resistance responses to DA and DB. Thus, in the newborn: 1) DA is a stronger inotropic agent during normoxemia and hypoxemia while the chronotropic effects of the two drugs did not differ. 2) Changes in cardiac output with both drugs did not differ significantly during normoxemia and were not affected by hypoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1990

Treatment of meningeal relapse in childhood acute lymphoblastic leukemia: II. A prospective study of intellectual loss specific to CNS relapse and therapy.

Changes in intellectual function during the course of treatment for acute lymphocytic leukemia were studied. Twenty-four children had baseline psychological evaluations and annual reevaluations for 3-6 years postdiagnosis. Treatment in all patients included combination chemotherapy, 2,400 cGy prophylactic cranial irradiation, and intrathecal methotrexate. Central Nervous System (CNS) relapse occurred in eight of these children. It was then treated with 3,000 cGy cranial plus 1,800 cGy spinal irradiation. Patients who remained in continuous complete remission showed no decline in global intelligence quotient (IQ). Patients who experienced CNS relapse had a mean decline of 16 IQ points by 3 years postdiagnosis and the long-term survivors displayed a mean loss of 25 IQ points 5-6 years postdiagnosis. Three of the five long-term survivors of CNS relapse function within the retarded range of mental ability and require special education. The other two have learning problems and display poor academic performance relative to same-age peers. There was no association noted between age at diagnosis and ultimate loss of IQ points. This prospective study suggests that children who receive a second course of cranial irradiation for treatment of CNS relapse are at high risk for significant and progressive intellectual loss.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Dietary intake of Americans reporting adherence to a low cholesterol diet (NHANES II).

We studied the dietary intake of persons age 18 and over participating in the 1976-80 National Health and Nutrition Examination Survey (NHANES II). We compared the diets of those on a "low cholesterol" diet (dieters, n = 296) with the diets of individuals not following a special diet (non-dieters, n = 10,052). Dietary intakes were assessed by 24-hour recall and food frequency reports and were adjusted for differences in age, sex, race, education, smoking, and socioeconomic status by multivariate statistical techniques. Dieters consumed 16 percent (99% confidence interval(-) -24, -9 fewer calories than non-dieters, and had decreased intake of saturated fat by 25 percent (-34, -15) and cholesterol by 21 percent (-32, -10). However, their intake of vitamin A, thiamine, riboflavin, niacin, calcium, and iron were not significantly different from non-dieters and their ascorbic acid intake was 18 percent (1, 36) higher. The nutrient density (nutrient/1000 kcal) among dieters was increased over non-dieters by 35 percent (-3, 72) for vitamin A, 35 percent (1, 70) for thiamine, 30 percent (-4, 65) for riboflavin, 27 percent (9, 44) for niacin, 60 percent (40, 80) for vitamin C, 14 percent for calcium (-5, 32), and 15 percent for iron (6,25). Compared with non-dieters, dieters consumed 27 percent (9, 45) more poultry and 39 percent (12, 66) more fish, but consumed 30 percent (-44, -16) less eggs and 15 percent (-24, -6) less meat.

Adult↗

PubMed1989

Changes in cortical functioning with acute hypoglycemia and hyperglycemia in type I diabetes.

In this study, 18 type I (insulin-dependent) diabetic subjects aged 22-35 yr (mean age 29.3) and within 10 yr of diagnosis (mean 7.7) performed a battery of cognitive and psychomotor tasks under conditions of hypoglycemia (50 mg/dl), normoglycemia (100 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels during testing were precisely maintained at the preselected level via a Biostator insulin/glucose-infusion system. The order of glycemic level was counterbalanced across subjects in a single-blinded design. Performance on tasks requiring visual tracking, visuomotor speed, concentration, and planning ability (pursuit rotor and trails B) were significantly impaired under conditions of hypoglycemia compared with normoglycemic levels. Visual reaction time was not significantly impaired under conditions of hypoglycemia or hyperglycemia.

Adolescent↗

PubMed1989

Experimental hypothermia and cold perception.

Twelve subjects clothed in flotation suits were immersed in 10 degrees C cold water and their surface temperatures at the back and groin, as well as core temperatures, were continuously monitored. Subjects were unable to reliably assess how cold they were, with the highest correlation observed between perceived temperature and actual temperature reaching only 0.51. This was felt to be partially due to the uneven distribution of surface temperatures seen in this experiment and in most cold water immersions. Rapid cooling in cold water also produced the perceptual phenomenon of "overshooting" previously observed in cold air studies, characterized by sudden temperature drops being perceived as cold sensations of greater magnitude. The results suggest that subjects who are rapidly cooled in water may have considerable difficulty separating feelings of cold from feelings of pain and discomfort, which can have serious implications in survival situations and highlights the subjective and highly variable nature of cold perception. Perceived cold sensation may be a very poor, and possibly dangerous, predictor in cold water immersion situations.

Adult↗

PubMed1988

Cross-validation of six short forms of the WAIS-R in a healthy geriatric sample.

A number of methods have been developed in recent years to estimate full-scale IQ scores from abbreviated versions of the revised Wechsler Adult Intelligence Scale (WAIS-R), including Silverstein's (1982) two- and four-subtest short forms, Reynolds, Willson, and Clark's (1983) four-subtest short form, and Brooker and Cyr's (1986) two-, three- and four-subtest short forms. Short forms are of particular interest to the clinician and researcher who need a brief screening scale of cognitive abilities for the elderly, but their effectiveness with a normal aging sample has not been established. The present study examines the accuracy of six methods of estimating full-scale IQs from abbreviated versions of the WAIS-R in a middle-aged to elderly nonpsychiatric sample of 28 healthy males. Although all six methods were found to yield scores that were correlated highly with full scale scores, the method of Reynolds et al. (1983) resulted in short-form IQ estimates that were significantly different statistically from full-scale IQ scores. Although most of the six short-form methods appear to be useful screening measures for cognitive functioning and longitudinal changes in intellectual functions in the elderly, their use for classification purposes is not supported in the present study.

Achievement↗

PubMed1988

Effects of cholecystokinin and hydrocortisone on DNA and protein synthesis in immature rat pancreas.

To define the developmental pattern of the trophic effects of cholecystokinin octapeptide (CCK-8) and hydrocortisone on immature rat pancreas, we injected newborn rats, rats aged 4, 7, 11, 18, and 25 days and 3 months, and adult rats with CCK (5 and 10 micrograms/kg) in gelatin and hydrocortisone (10 mg/kg) for 3 days. Animals were killed, the pancreata were removed, and the concentrations of DNA and protein were measured and DNA and protein synthesis rates determined by incorporation of [3H]thymidine and [14C]leucine, respectively. These values were compared with those of saline-injected controls. DNA concentration was significantly increased over control at ages 2 days to adult by hydrocortisone and by CCK (10 micrograms/kg) in the adult. Protein concentration was increased on days 3-14 by hydrocortisone. DNA synthesis was increased by CCK and decreased by hydrocortisone at 3 months and adult. Protein synthesis was decreased by hydrocortisone at ages 3-14 days. Thus, each agent has its own developmental pattern with age on the rat pancreas.

Age Factors↗

PubMed1987

Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia.

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Ontogeny of secretory function and cholecystokinin binding capacity in immature rat pancreas.

Isolated acini were prepared from the pancreas of immature rats (age less than 1 hr. - 48 hrs) in order to study the development of the secretory process. The ultrastructural integrity of the acinar cells was maintained after digestion and stimulation with secretagogues. Acini prepared from rats aged 24 - 48 hours responded to both CCK-8 and carbachol with significant increases in amylase release. Although typical biphasic dose response curves were obtained, the curves were shifted to the right by 1 - 2 log units, compared to the responses of adult acini. At ages younger than 24 hours, acini were insensitive to secretagogues but were sensitive to the calcium ionophore A23187. CCK receptors were virtually absent from membranes prepared from newborn pancreases, but binding of CCK, although small, was measurable at 12 hours and slowly increased up to 48 hours. A greater amount of binding was seen at 72 hours, which appeared constant up to 14 days. At 21 days, adult levels of binding were found. These results confirm previous studies that the rat pancreas is insensitive to secretagogues in the first 24 hours of life. After age 24 hours the secretory process is intact but less sensitive to secretory agents than the more mature pancreas. In the case of CCK, this may be due to lesser numbers of CCK receptors and/or affinity of CCK for its receptor.

Age Factors↗

PubMed1987

Influences on the distribution of blood flow during cardiac tamponade in the conscious dog.

Cardiac tamponade is a spectrum ranging from pericardial effusions with minimal hemodynamic impairment to effusions causing circulatory collapse. In this study, we examined the roles played by the sympathetic nervous system and the renin-angiotensin system in controlling the distribution of blood flow in chronically instrumented conscious dogs during progressive cardiac tamponade. Fifty-one episodes of acute cardiac tamponade were induced to decompensation (decline in mean aortic blood pressure to 70% of the level present when the pericardium was free of fluid) in 6 dogs by intrapericardial infusion of warmed saline solution. Cardiac output (electromagnetic flow probe), intrapericardial pressure, aortic and right atrial blood pressures, and renal, coronary, and mesenteric artery blood flows (Doppler flow probes) were recorded during tamponade in the absence of blockade (control), during alpha-adrenergic blockade (phenoxybenzamine), beta-adrenergic blockade (propranolol), or angiotensin-converting enzyme blockade (captopril). Aortic and mesenteric artery blood flow decreased progressively during cardiac tamponade regardless of the presence or absence of blockade. Coronary artery blood flow did not significantly change during alpha-adrenergic blockade, suggesting that the continuous decline observed during cardiac tamponade in the absence of blockade was at least in part mediated by alpha-adrenergic mechanisms. Renal artery blood flow, in contrast, was well maintained in all situations, confirming the importance of autoregulation in this vascular bed during cardiac tamponade.

Adrenergic alpha-Antagonists↗

PubMed1986

The pathophysiologic and roentgenologic effects of chest irradiation in breast carcinoma.

We studied the effects of radiation therapy on lung function in 21 patients who underwent modified radical mastectomy and radiotherapy for breast carcinoma. The patients had pulmonary function studies and chest X rays prior to radiation therapy and at six weeks, and three, six, and twelve months following radiation therapy. All pulmonary function studies showed a small but statistically significant decline within the first three months following radiation therapy. Changes in the moderate and large airways continued to occur after three months. None of the changes in pulmonary function were reversible. Radiographic changes occurred in 12 patients. These changes occurred later than the lung function changes (median time for the changes was twelve months) and were unrelated to changes in lung function.

Adult↗

PubMed1985

Effects of intravascular volume state on the value of pulsus paradoxus and right ventricular diastolic collapse in predicting cardiac tamponade.

Both pulsus paradoxus and right ventricular diastolic collapse detected by two-dimensional echocardiography are noninvasive markers of impaired cardiac function in cardiac tamponade, yet the reliability of each may vary with the patient's state of hydration. To examine the relative value of these noninvasive markers at various states of hydration, we studied five chronically prepared, conscious mongrel dogs during 37 episodes of cardiac tamponade at three different intravascular volumes. We continuously measured cardiac output (electromagnetic flowmeter), aortic blood pressure, right atrial blood pressure, intrapericardial pressure, and respirations. Intravascular volume was varied by adjusting the mean right atrial blood pressure to hypovolemic (-2 to -6 mm Hg), euvolemic (0 to 4 mm Hg), or hypervolemic (6 to 10 mm Hg) levels. The sensitivity and specificity of right ventricular diastolic collapse in predicting increases in intrapericardial pressure remained high at all levels of hydration. Pulsus paradoxus showed good sensitivity and specificity at low intravascular volumes, but both sensitivity and specificity declined at higher intravascular volumes. Thus right ventricular diastolic collapse was more sensitive and more specific than pulsus paradoxus in detecting increases in intrapericardial pressure during euvolemia and hypervolemia whereas the two tests were equally valuable in hypovolemic states.

Animals↗

PubMed1985

Randomized study of adjuvant chemotherapy for head and neck cancer.

The ability of surgery and radiotherapy to control advanced squamous cell carcinoma of the head and neck has reached its maximal potential. We initiated a randomized, prospective, stratified study of adjuvant chemotherapy. Patients with stage II disease of the pyriform sinus and stage II and IV disease of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses were eligible. Patients were randomized to receive either standard therapy alone or two courses of 5-fluorouracil (B-CMF) chemotherapy prior to and two courses after the completion of standard therapy. Standard therapy consisted of preoperative irradiation followed by radical surgery. Of 133 patients with advanced disease, 83 were included in the study--43 in the chemotherapy group and 40 in the control group. Rates of residual and recurrent disease, as well as distant metastases, were similar for the two groups. The survival rates of patients without persistent disease at the end of treatment showed no significant difference for the two groups. The study has been discontinued because statistical analysis indicated that the addition of more patients would not materially increase the statistical significance of the study.

Antineoplastic Combined Chemotherapy Protocols↗