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Biomedical subjects

S Kapadia

Publications and source records attributed to S Kapadia.

At least 37 records · Page 2Linked to original sources

On borderline phenomena.

The author describes his struggle to resolve some theoretical and technical problems posed by borderline patients. For this he has made use of an ancient Indian myth of King Trishanku taken from Bhagwat Puran--the Hindu Book of Genesis. He has tried to demonstrate, step by step, how fruitfully this myth has helped him to understand such patients. Special emphasis has been laid on the language used by borderline patients. The contrary and apparently meaningless nature of this language is likened to the formulation of King Trishanku's unique desire, 'to go to heaven without actually dying'. The author then proceeds to show that this language is not quite as meaningless as it appears to be--that it is the result of a complicated system of projective identification devised by these patients to manipulate their objects in order to achieve their own omnipotent ends. Detailed clinical examples are given to describe the handling of the problems of appropriation, manipulation and consequent suspended state of such patients. Taken from three different stages of various analyses these examples show how a very slow and gradual change was brought about in the mental structures of the patients treated by the author.

Adult↗

Cardiac outcomes in coronary patients with submaximum dobutamine stress echocardiography.

This study evaluated the prediction of cardiac events (cardiac death, myocardial infarction, unstable angina, or late myocardial revascularization) in patients with submaximum responses to dobutamine stress, defined by attainment of <85% age-predicted heart rate. Of 1,772 patients undergoing dobutamine echocardiography over a 2-year period, 425 had a submaximum heart rate response. After exclusion of patients treated with beta-adrenoceptor blocking agents, 255 patients formed the study group. In these patients, the test was terminated after administration of the maximum dose of 40 microg/kg/min of dobutamine with atropine (end of protocol, n = 186), severe angina, ischemic ST-segment changes, or intolerable side effects (n = 69). Dobutamine-induced changes (ischemia, viability, or both) were detected in 46 patients, involving ischemia in 133 segments, viability in 23, and ischemia and viability in 16 segments. Patients were followed for an interval of 28 +/- 17 months; 5 (1.2%) were lost to follow-up. Of the medically treated patients, cardiac events occurred in 73 of 228 (31%), including cardiac death in 25 (11%), nonfatal myocardial infarction in 11 (4.8%), severe unstable angina in 35 (15%), and late revascularization in 2 (0.9%). Cardiac events occurred in 11 of 30 (36%) with inducible abnormalities, and 62 of 198 without inducible abnormalities (31%, p = NS). Thus, cardiac event rates are high in patients with inadequate chronotropic responses to dobutamine stress, irrespective of whether stress-induced changes are detected. A negative dobutamine echocardiogram at submaximum heart rate should be considered nondiagnostic.

Aged↗

Are normal hearing thresholds a sufficient condition for click-evoked otoacoustic emissions?

Transiently evolked otoacoustic emissions (TEOAE) have been reported in several studies as absent in a small minority of normal ears. Other studies have reported TEOAEs in all normal ears. Differences between studies may arise directly from criteria for TEOAE identification, criteria for selection of normals, or statistically due to limited sample sizes. In order to understand and model cochlear processes involved in TEOAE generation, it needs to be known whether the presence of normal hearing leads automatically to generation of TEOAEs. The present study set out to establish in a large sample if any ears could be found that lacked TEOAEs despite normal hearing threshold levels (HTL). A total of 397 ears from highly cooperative adult subjects were examined under laboratory conditions. Using cross correlation between replicate nonlinear waveforms as the criterion, TEOAEs were present in 99.2% of the sample (lower CI 98.1%). However, careful visual assessment of the recorded waveforms for the remaining ears did not unequivocally show absence of TEOAE characteristics in any ear with normal HTLs. While TEOAE strength varies widely among ears, no clear evidence was found to show that TEOAEs can be absent when HTLs are normal.

Acoustic Stimulation↗

Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces negative inotropic effects in the heart. Recently, elevated levels of TNF-alpha have been reported in patients with advanced congestive heart failure. Although TNF-alpha is thought to exert its deleterious effects by binding to two cell surface receptors, TNFR1 and TNFR2, the level of expression and regulation of TNF receptors in the heart in cardiac disease states is not known. METHODS AND RESULTS: We examined mRNA and protein levels for TNFR1, TNFR2, and TNF-alpha in explanted hearts from organ donors as well as in patients with end-stage dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). Northern blot analysis revealed that mRNA for TNFR1 and TNFR2 was present in nonfailing, DCM, and IHD hearts. TNFR1 and TNFR2 receptor protein levels, as measured by ELISA, were decreased 60% in DCM and IHD patients compared with nonfailing hearts (P < .005). To determine a potential mechanism for the decrease in TNF receptor expression, we measured levels of circulating soluble TNF receptors (sTNFRs) in DCM and IHD patients. This analysis showed that there was a significant one-and-a-half to threefold increase in sTNFRs in DCM (P < .03) and IHD patients (P < .001). Another important finding was that TNF-alpha mRNA and TNF-alpha protein were present in the explanted hearts from DCM and IHD patients but not in nonfailing hearts. CONCLUSIONS: In summary, the results of this study constitute the initial demonstration that TNF receptor proteins are dynamically regulated in patients with advanced congestive heart failure. Moreover, the observation that failing hearts express elevated levels of TNF-alpha suggests that overexpression of this cytokine may be one of several different maladaptive mechanisms responsible for the progressive cardiac decompensation that occurs in advanced heart failure.

Adult↗

Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD).

OBJECTIVES: This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization. BACKGROUND: Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is. METHODS: Tumor necrosis factor-alpha and interleukin-6 levels were analyzed by enzymes-linked immunoassay using randomly selected plasma samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy subjects served as the control group. RESULTS: Plasma levels of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([mean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was a trend toward significance between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha levels, there was no significance correlation between neurohormonal and proinflammatory cytokine levels. CONCLUSIONS: Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neurohumoral axis is unlikely to completely explain the elaboration of proinflammatory cytokines in heart failure.

Aged↗

Optic nerve elongation: does it exist?

The length of the optic nerves is a reflection of normal postnatal cranio-orbital development. Unilateral elongation of an optic nerve has been observed in two patients with orbital and skull base neoplasms. In the first case as compared to the patient's opposite, normal optic nerve, an elongated length of the involved optic nerve of 45 mm was present. The involved optic nerve in the second patient was 10 mm longer than the normal opposite optic nerve. The visual and extraocular function was preserved in the second patient. The first patient had only light perception in the affected eye. In this paper, the embryology, anatomy, and physiology of the optic nerve and its mechanisms of stretch and repair are discussed.

Journal Article↗

Expression and functional significance of tumor necrosis factor receptors in human myocardium.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine with potent negative inotropic properties, is elaborated in septic shock, acute myocarditis, reperfusion injury, and congestive heart failure. TNF-alpha acts by binding to two specific receptors: TNFR1 and TNFR2. However, neither the presence nor the significance of TNF receptors has been studied in the adult mammalian heart. METHODS AND RESULTS: In the present study, we showed that the adult heart expresses mRNA and receptor proteins for TNFR1 and TNFR2. Moreover, immunohistochemical staining studies localized TNFR1 and TNFR2 to the cardiac myocyte, providing a potential signaling pathway for the deleterious effects of TNF-alpha. The functional significance of the expression of TNFR1 and TNFR2 was explored with the use of a simple cell motion assay in which we assessed the effect(s) of TNF-alpha mutants known to bind selectively to human TNFR1 and TNFR2. We showed that the negative inotropic effect of wild-type TNF-alpha in isolated feline cardiac myocytes was mimicked by the TNF mutant that binds to TNFR1, whereas the TNF mutant that binds to TNFR2 had no significant effect on cell motion. CONCLUSIONS: Results of the present study show that the adult human heart expresses both mRNA and receptor proteins for TNFR1 and TNFR2; moreover, the negative inotropic effects of TNF-alpha in adult cardiac myocytes appear to be initiated by activation of TNFR1.

Adolescent↗

Tumor necrosis factor-alpha and the failing human heart.

Tumor necrosis factor-alpha (TNF alpha) is a proinflammatory cytokine with negative inotropic effects. Recently, elevated levels of TNF alpha have been identified in patients with advanced heart failure. Although the clinical significance of this finding is unclear at present, there is increasing evidence that this cytokine may play a primary pathophysiologic role in the development and pathogenesis of heart failure in humans. Indeed, many of the clinical hallmarks of heart failure, including left ventricular dysfunction, cardiomyopathy, and pulmonary edema can be explained by the known biological effects of TNF alpha in humans. The present review will summarize recent evidence with regard to the biological role for TNF alpha in the adult mammalian heart, as well as summarize the increasing body of clinical information that implicates this cytokine in the pathophysiology of heart failure.

Adult↗

Soluble TNF binding proteins modulate the negative inotropic properties of TNF-alpha in vitro.

Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-alpha in isolated contracting cardiac myocytes. Three TNF-BPs were evaluated: two natural monomeric human TNF monomeric binding proteins, TNF-BP1 and TNF-BP2, and sTNFR:Fc, a dimer of two molecules of human TNF-BP2 linked by the Fc portion of the human immunoglobulin G1 molecule. When TNF-alpha (25 pM) was allowed to form TNF-BP-TNF-alpha complexes, the negative inotropic effects of TNF-alpha were completely prevented by "neutralizing concentrations" of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-alpha. The dimeric binding protein sTNFR:Fc was more effective on a molar basis than either of the monomeric binding proteins (TNF-BP1 or TNF-BP2) with respect to blocking the negative inotropic effects of TNF-alpha. When cardiac myocytes that had been treated with TNF-alpha (25 pM) were exposed to neutralizing concentrations of TNF-BP1, TNF-BP2, and sTNFR:Fc, the negative inotropic effects were completely reversed within 30 min. Thus these studies show for the first time that TNF-BPs are sufficient to prevent, as well as reverse, the negative inotropic properties of TNF-alpha in vitro.

Animals↗

Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration.

TNF alpha mRNA and protein biosynthesis were examined in the adult feline heart after stimulation with endotoxin. When freshly isolated hearts were stimulated with endotoxin in vitro, de novo TNF alpha mRNA expression occurred within 30 min, and TNF alpha protein production was detected within 60-75 min; however, TNF alpha mRNA and protein production were not detected in diluent-treated hearts. Immunohistochemical studies localized TNF alpha to endothelial cells, smooth muscle cells, and cardiac myocytes in the endotoxin-treated hearts, whereas TNF alpha immunostaining was absent in the diluent-treated hearts. To determine whether the cardiac myocyte was a source for TNF alpha production, two studies were performed. First, in situ hybridization studies, using highly specific biotinylated probes, demonstrated TNF alpha mRNA in cardiac myocytes from endotoxin-stimulated hearts; in contrast, TNF alpha mRNA was not expressed in myocytes from diluent-treated hearts. Second, TNF alpha protein production was observed when cultured cardiac myocytes were stimulated with endotoxin, whereas TNF alpha protein production was not detected in the diluent-treated cells. The functional significance of the intramyocardial production of TNF alpha was determined by examining cell motion in isolated cardiac myocytes treated with superfusates from endotoxin- and diluent-stimulated hearts. These studies showed that cell motion was depressed in myocytes treated with superfusates from the endotoxin-treated hearts, but was normal with the superfusates from the diluent-treated hearts; moreover, the negative inotropic effects of the superfusates from the endotoxin-treated hearts could be abrogated completely by pretreatment with an anti-TNF alpha antibody. Finally, endotoxin stimulation was also shown to result in the intramyocardial production of TNF alpha mRNA and protein in vivo. Thus, this study shows for the first time that the adult mammalian myocardium synthesizes biologically active TNF alpha.

Animals↗

Artificial nutrition support in hospitals in the United Kingdom - 1991: Second national survey.

Objective - to determine current clinical practice of nutrition support in hospitals in the UK and to determine whether there have been any apparent changes in practices since 1988. Design - An 81 question survey about enteral and parenteral nutriton was sent to all District Dietitians registered with the British Dietetic Association. Information was collected additionally from pharmacists and clinicians. Results - 61.2% of questionnaires distributed were completed and returned. 32.5% of respondents had access to nutrition support teams, compared with 27% in 1988. The documentation of usage of nutrition support was poor, only 33% being able to accurately quantify administation of enteral nutrition, and 53% parenteral nutrition. Since 1988 the number of respondents using peripheral parenteral nutrition had doubled to 15%. Those using percutaneous gastrostomies had increased from 6% to 74%. Those using respiratory enteral diet formulations had quadrupled to 33%. There have been no other apparent major changes in nutrition support practice in the UK, in the last 3 years. Conclusions - Despite increasing awareness about the role of artificial nutrition support, and the value of Nutrition Support Teams there has been little or no progress in the provision or monitoring of support in the last 3 years. This has important implications when considering audit of such practices.

Journal Article↗

Topical nonsteroidal anti-inflammatory gel for the prevention of peripheral vein thrombophlebitis. A double-blind, randomised, placebo-controlled trial in normal subjects.

A double-blind, randomised, placebo-controlled study was undertaken to determine whether topical application of a nonsteroidal anti-inflammatory gel to skin overlying peripheral vein cannula sites has a role in reducing the incidence or delaying the onset of peripheral vein thrombophlebitis. Fifty normal subjects had intravenous cannulae placed in right and left arms. Subjects were randomised to receive twice daily application of either active nonsteroidal anti-inflammatory gel or placebo gel to each cannula site. Cannula sites were observed and signs and symptoms of inflammation recorded up to 108 h. If any site had signs extending beyond 2 cm then the cannula was removed. Cannula sites that had 'active' gel applied had half the incidence of marked signs at 108 h (44% vs 22%, p less than 0.05). These results suggest that local application of topical nonsteroidal anti-inflammatory gel to cannula sites may have a significant role to play in the prevention of peripheral vein thrombophlebitis.

Administration, Topical↗

Early experience with the Bower percutaneous endoscopic gastrostomy tube.

Percutaneous endoscopic insertion of gastrostomy tubes is a technique becoming more widely used in the UK. It allows insertion of a gastrostomy tube without laparotomy, under local anaesthesia and sedation, and so operative insertion may eventually become a rarity. We report on our successful early experience with a new gastrostomy tube (Bower PEG) which does not require endoscopy if eventual removal is required, and describe the methods of insertion and removal.

Adolescent↗

Leukemic myelomatosis (plasma cell leukemia).

Six cases of leukemic myelomatosis (plasma cell leukemia), are reported. A spectrum of leukemic plasmacellular proliferation was observed in this group: in two cases the plasmacytic leukemia was a terminal event of multiple myeloma, in one of a chronic lymphocytic leukemia, and in the remaining three cases the peripheral blood plasmacytosis was a presenting manifestation of an acute immunocytic dyscrasia. The clinical features, frequencies of extraosseous plasmacytic infiltrations, hypercalcemia and Bence Jones proteinuria, and cytomorphologic difficulties in differentiating plasmacytic from chronic lymphocytic leukemia are discussed.

Adult↗

The effects of alterations in villus shape on the intestinal mucosal surface of the albino rat; the relationship between mucosal surface area and the crypts.

The villi and crypts of the small intestine of the albino rat (Rattus norvigicus) have been enumerated and measured at different ages from 2 weeks to 8 months. The number of villi increased up to the third month of age and the number of crypts up to the eighth month. In the proximal intestine, the mean length of the villus base increased up to the fifth month as ridge-shaped villi were formed. Villus height was greater proximally than distally and this, and the crypt depth, remained constant from the end of the first month of age. The total villus circumference per unit area of intestine, and the villus circumference per crypt was the same proximally and distally, and was relatively constant after the first month of age. The total circumference of the crypt mouths per square millimeter of intestine was the same proximally and distally and, at all ages, was greater than the total villus circumference. The villus surface area per square millimeter of intestine, or per crypt, remained relatively constant after the first month and was greater proximally than distally, due only to the taller villi proximally. The change from finger-shaped to ridge-shaped villi did not affect the villus mucosal surface area. The changes in villus shape are probably not determined by differences in the rate of crypt cell production.

Aging↗