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Biomedical subjects

S Rosen

Publications and source records attributed to S Rosen.

At least 163 records · Page 9Linked to original sources
PubMed1991

Ventricular fibrillation threshold is influenced by left ventricular stretch and mass in the absence of ischaemia.

STUDY OBJECTIVE: Ischaemic heart disease is known to contribute to the development of ventricular arrhythmias. However, the role of non-ischaemic variables has been less well defined. We therefore studied the effect of myocardial stretch and ventricular mass on the vulnerability of the rat heart to ventricular fibrillation. DESIGN AND EXPERIMENTAL MATERIAL: Two groups of rat hearts were studied in an isolated buffer perfused apparatus: group I, mature female animals with an average dry left ventricular weight of 73 mg and group II, a group of retired breeders with an average left ventricular weight of 122 mg. Hearts performed isovolumetric work at either low (0 mm Hg) or high (20 mm Hg) left ventricular end diastolic pressures. MEASUREMENTS AND MAIN RESULTS: Ventricular fibrillation was provoked by trains of ventricular extrastimuli delivered at increasing current until development of the arrhythmia. The current required to provoke ventricular fibrillation decreased in both groups at the high left ventricular end diastolic pressure and the larger hearts in group II were more vulnerable to ventricular fibrillation than those in group I. The decrease in ventricular fibrillation threshold occurred in the absence of an increase in myocardial lactate production or a decrease in endocardial to epicardial flow ratios. CONCLUSIONS: This study thus identified two variables, myocardial stretch and ventricular mass, which influence the development of ventricular fibrillation and which are independent of myocardial ischaemia in this animal model. These observations may be relevant to an understanding of the increased incidence of lethal arrhythmias which occur in patients with dilated cardiomyopathies.

Animals↗
PubMed1991

Right ventricular function in severe non-ischaemic mitral insufficiency.

Mitral insufficiency (regurgitation) is a disease of both ventricles. To determine the pathophysiological implications and clinical value of assessment of right ventricular function in this disease, right ventricular ejection fraction was determined by radionuclide cineangiography (r = 0.73, P less than 0.01, vs contrast angiography, n = 30) in patients with severe, non-ischaemic mitral regurgitation. Among 31 patients with isolated mitral regurgitation treated medically, five died, all within 2 years of follow-up; all five were among the eight patients with left ventricular ejection fraction less than or equal to 45% (lower limit of normal), and among the six patients with right ventricular ejection fraction less than or equal to 30% (almost invariably associated with at least mild pulmonary hypertension). During the same period, valve replacement was performed in 22 patients with isolated mitral regurgitation; among the six patients with right ventricular ejection fraction less than or equal to 30% before operation, only one died (P less than 0.05), indicating the risk-mitigating effect of valve replacement. Among eight pre-operative patients with combined mitral and aortic regurgitation, four died within 7 years after double valve replacement; all patients with right ventricular ejection fraction during exercise less than 20% died. After mitral valve replacement for isolated mitral regurgitation, right ventricular ejection fraction improved rapidly (average 8% in less than 1 year (P less than 0.05); 3% more at 3 years after operation (P less than 0.05)). Post-operative symptom persistence was predictable from ventricular ejection fraction before operation less than 30% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Factors differentiating hospital transfers from long-term care facilities with high and low transfer rates.

This paper examines the factors that account for differences among nursing homes in terms of the rates at which they transfer patients to hospitals. Data from nursing staff and charts were collected on the 286 most recent transfers from 10 nursing homes. Discriminant function analyses indicated that from relatively equivalent patient populations, high-rate facilities tended to transfer the more chronically ill, physically frail patients; patients with infection (a potentially treatable condition within the long-term care facility); and to make transfers because of lack of resources such as a lab and X-ray equipment. Lack of IV therapy, while a frequently cited primary nonmedical reason for transfer, did not discriminate between high- and low-transfer-rate facilities.

Female↗
PubMed1991

Experimental nephrotoxicity of the radiocontrast agents iohexol, ioxaglate, and iothalamate. An in vitro and in vivo study.

The authors compared the renal toxicity of the low osmolality radiocontrast agents, iohexol and ioxaglate, and the ionic agent, iothalamate, at equivalent iodine dose, using experimental models in vitro and in vivo. In isolated perfused rat kidneys, all agents induced comparable biphasic hemodynamic changes, associated with similar declines in glomerular filtration rate (GFR) and tubular necrosis. In two different in vivo models (using multiple insults combined with the administration of radiocontrast), iothalamate appeared to induce more severe morphologic injury. Despite similar nephrotoxic potential in vitro, the newer radiocontrast agents, iohexol and ioxaglate, cause in vivo less renal injury than iothalamate in the experimental models.

Angiotensin II↗
PubMed1991

Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys.

We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of O2 supply to the renal medulla, a region normally operating on the verge of hypoxia. Sensitive Clark-type O2 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibitor of NO formation, L-NG-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary pO2 from 23 +/- 3 mmHg to 12 +/- 3 (P less than 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses the LNMMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90% of the tubules (P less than 0.02). These changes were prevented by L-arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model of radiocontrast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3 +/- 2 mg% to 3.4 +/- 3, P less than 0.005) and the proportion of damaged thick limbs (from 24 +/- 6% to 53 +/- 9, P less than 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the prevention of medullary hypoxic injury.

Acute Kidney Injury↗
PubMed1991

Individual variability in the perception of cues to place contrasts in initial stops.

Synthetic continua of two minimal pairs, BAIT-DATE and DATE-GATE, closely modeled on natural utterances by a female speaker, were presented to a group of 16 listeners for identification in full-cue and reduced-cue conditions. Grouped results showed that categorization curves for full- and reduced-cue conditions differed significantly in both contrasts. However, an averaging of results obscures marked variability in labeling behavior. Some listeners showed large changes in categorization between the full- and reduced-cue conditions, whereas others showed relatively small or no changes. In a follow-up study, perception of the BAIT-DATE contrast was compared with the perception of a highly stylized BA-DA continuum. A smaller degree of intersubject and between-condition variability was found for these less complex synthetic stimuli. The amount of variability found in the labeling of speech contrasts may be dependent on cue salience, which will be determined by the speech pattern complexity of the stimuli and by the vowel environment.

Adult↗
PubMed1991

Cocaine in decomposed human remains.

From March 1988 through March 1990, at the Philadelphia Medical Examiner's Office toxicology laboratory, samples from 77 decomposed human bodies were tested for the presence of cocaine, employing gas chromatography/mass spectrometry (GC-MS). The material analyzed included decomposed soft tissue, bloody decomposition fluid, mummified tissue, maggots, and beetle feces. Twenty-two cases (28.6%) were positive for cocaine, many of these cases in states of advanced decomposition. These findings indicate the usefulness of testing decomposed tissue for cocaine in all cases where its presence is suspected. This is contrary to what might be expected, since cocaine is generally labile and rapidly broken down by both enzymatic and nonenzymatic mechanisms.

Animals↗
PubMed1991

Passive inhalation of free-base cocaine ('crack') smoke by infants.

Cocaine is one of the most widely abused substances in the United States, in part due to the availability of its inexpensive alkaloidal free-base form, "crack". A variety of medical complications, including sudden death, are known to occur in the adult-user population, regardless of the route of cocaine administration. We report 16 cases of infant death registered by the Philadelphia (Pa) Medical Examiner's Office over a 2-year period (1987 through 1989), where toxicologic analyses revealed the presence of cocaine and/or its metabolite, benzoylecgonine. Scene investigation documented that these infants, shortly before death, had been exposed to environments that contained the smoke from crack. We conclude that the route of cocaine administration in this infant population was the passive inhalation of crack smoke. It is possible that the cocaine may have contributed to the death of these infants. Thus, in addition to the adult users, infants and children exposed to environments where crack is smoked may inhale cocaine and potentially suffer from its adverse effects.

Cocaine↗
PubMed1990

The effect of stannous and sodium fluoride on coronal caries, root caries and bone loss in rice rats.

Sixty rice rats (Oryzomys palustris) were divided by littermate into 3 groups of 20 each. The 3 groups received either SnF2 (1000 parts/10(6) F), NaF (1000 parts/10(6] or double-distilled water (control). Test solutions were topically applied to molar teeth, twice daily, for 7 days. All rats were also provided with double-distilled drinking water and diet 2000 ad libitum. Experiments ended after 9 weeks. Alveolar bone loss, root and coronal caries were recorded and scored. SnF2 significantly reduced bone loss (p less than 0.05), but NaF did not. Root caries was significantly different in all 3 groups (p less than 0.05). SnF2 and NaF both reduced coronal caries significantly (p less than 0.05) in comparison to the control. However, the fluoride groups were not significantly different from each other. SnF2 may influence root caries via remineralization and an antimicrobial effect of the stannous ion.

Animals↗
PubMed1990

Transdermal versus subcutaneous leuprolide: a comparison of acute pharmacodynamic effect.

Transdermal administration of peptides has been limited by the barrier properties of the skin. We compared the acute luteinizing hormone (LH) response to subcutaneous and transdermal administration of an LH-releasing hormone agonist (leuprolide). Eighteen volunteers received 5 mg leuprolide added to electrically powered patches delivering a current of 0.22 microA (transdermally). One week later, they received a 5 mg subcutaneous dose. LH response was measured. The area under the curve for LH response, maximum LH response, and time to maximum LH response were similar. Time to first response was shorter (147 +/- 108 minutes [transdermally] and 73 +/- 74 minutes [subcutaneously]; p less than 0.05), and the area under the curve for the first 150 minutes was greater (3655 +/- 2246 mIU.min/ml [transdermally] and 8666 +/- 4067 mIU.min/ml [subcutaneously]; p less than 0.05) for subcutaneous delivery. No major adverse effects were seen. This electrically powered transdermal technique merits further study.

Administration, Cutaneous↗
PubMed1990

Hypercalcemic nephropathy: chronic disease with predominant medullary inner stripe injury.

Because of the recently observed augmentation of medullary hypoxic injury by calcium in isolated perfused rat kidneys (Kidney Int 34:186-194, 1988), renal morphology of chronic, prolonged hypercalcemia was investigated in vivo. Rats were treated with repeated injections of vitamin D2 (400,000 units/week) for two to eight weeks. Chronic elevation of plasma calcium from 2.1 to 2.8 mmol/liter (P less than 0.001) was associated by a fall in maximal urine osmolality with no change in glomerular filtration rate. The most significant morphological alterations occurred in the inner stripe of the outer medulla; these changes were characterized by a sequence of active injury with subsequent destruction and atrophy of the medullary thick ascending limbs, fibroblastic and lymphocytic infiltration, and secondary dilatation of collecting ducts. Similar changes occurred in the medullary rays. These alterations were accompanied by increased renal prostanoid production and a predisposition to acute kidney failure from indomethacin. Because of its selective occurrence in zones of poorest oxygen supply, this inner stripe injury may derive from vulnerability to hypoxia and may play a role in some chronic nephropathies.

Animals↗
PubMed1990

Chronic cyclosporine-induced nephropathy in the rat. A medullary ray and inner stripe injury.

Cyclosporine CsA nephrotoxicity was examined in male Sprague-Dawley rats with or without prior uninephrectomy, injected daily with 12.5 mg/kg CsA, and fed a salt-depleted or normal diet for 3-10 weeks. Control rats received the CsA vehicle. CsA induced a fall in creatinine clearance in salt-depleted rats, from 1.3 +/- 0.1 to 0.8 +/- 0.1 ml/min (P less than 0.001), and in normally fed rats from 1.8 +/- 0.2 to 1.0 +/- 0.2 ml/min (P less than 0.02). Vehicle treatment had no effect. The most striking morphologic changes were those of thick ascending limb cell atrophy with concomitant fibroblastic proliferation and collagen formation; these alterations were present in the inner stripe of the outer medulla and the medullary ray. The medullary-ray findings included S2-S3 degenerative changes as well and apparently correspond to the striped fibrosis described in human CsA nephropathy. The alterations were specific to the CsA group, progressive, and most severe in the salt-depleted, CsA-injected rats (on a scale of 0-4: 1.7 +/- 0.2 for medullary rays, and 2.0 +/- 0.2 for inner stripe, P less than 0.001). Morphologic changes predicted renal failure (r = 0.3, P less than 0.01 for cortical alterations, and r = 0.5, P less than 0.001 for medullary alterations). Prior uninephrectomy did not enhance these changes. Thus, chronic CsA administration impaired kidney function and induced morphologic alterations found in regions characterized by, and in nephron segments particularly vulnerable to, limited O2 availability. Salt depletion appears to accelerate the development of chronic CsA renal injury in the rat.

Animals↗
PubMed1990

Angiotensin II augments medullary hypoxia and predisposes to acute renal failure.

The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigated in vitro and in vivo. Synthetic AII added to perfusate of isolated rat kidneys reduced perfusion flow from 48 +/- 2 ml min-1 (+/- SE) to 19 +/- 1 (P less than 0.001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P less than 0.001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 +/- 4% of tubules to 79 +/- 3 (P less than 0.05) in correlation with filtration fraction (r = 0.8, P less than 0.001). Addition of indomethacin (10(-4) mol l-1) further extended medullary hypoxic damage to 89 +/- 2% of mTAL (P less than 0.001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0.1-0.8 microgram min-1) and indomethacin (10 mg kg-1 day-1) for 24 h. Creatinine clearance declined from 1.3 +/- 0.1 ml min-1 to 0.6 +/- 0.06 (P less than 0.001). Morphological examination revealed either selective necrosis of mTAL (in 12 +/- 4% of tubules) or luminal collapse (in 63 +/- 8%). Both necrosis and collapse correlated inversely with creatinine clearance and with each other (r = -0.5, P less than 0.001), the latter correlation suggesting protection from hypoxic injury by cessation of solute delivery. By increasing filtration fraction and decreasing blood flow, AII decreases renal oxygen supply while maintaining oxygen consumption for solute reabsorption. AII may predispose to acute renal failure by augmenting medullary hypoxia.

Acute Kidney Injury↗
PubMed1990

Influence of endogenous prostaglandins on mTAL injury.

We altered renal prostaglandin production by isolated rat kidneys in several ways to see if this would influence the susceptibility of cells lining the medullary thick ascending limb to injury. Rats were fed a diet containing either safflower oil (high in linoleic acid) or fish oil (low in arachidonate precursors) as a source of fat. After 90 min of perfusion, the kidneys of rats fed safflower oil showed only 32.7 +/- 6.7% of medullary thick ascending limb cells near the inner medulla with severe damage, whereas the same zone in perfused kidneys of rats fed fish oil showed 96.6 +/- 1.3% severely damaged cells (P less than 0.01). The protection afforded by safflower oil was accompanied by a doubling of urinary excretion of PGE2 and 6-keto-PGF1 alpha, and was eliminated by indomethacin, which suppressed prostaglandin synthesis. Perfusion with bradykinin also greatly increased prostaglandin excretion and reduced severe medullary thick ascending limb damage in the deepest zone of the outer medulla from 51.3 +/- 6.6% in controls to 28.5 +/- 5.9% (P less than 0.02). The protection provided by bradykinin was also completely reversed by indomethacin. The results suggest that endogenous prostaglandins serve a protective function against hypoxic injury for cells of the medullary thick ascending limb.

Animals↗