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Biomedical subjects

L H Chow

Publications and source records attributed to L H Chow.

50 records · Page 3Linked to original sources

The use of ketanserin for postoperative hypertension after abdominal surgery.

Eighteen adult patients who developed hypertension (systolic blood pressure greater than 160 mmHg, diastolic blood pressure greater than 90 mmHg or both) at the early recovery period after major abdominal surgery were included in the study. Following intravenous injection of 10 mg ketanserin, eleven out of eighteen patients (61%) had their systolic or diastolic blood pressure fell below the target mark (160 mmHg and 90 mmHg), and the decrease was statistically significant (p less than 0.01 up to 120 min). There was no statistically significant change in heart rate. Four patients (22%) responded to 20 mg of ketanserin. Three patients (17%) did not have significant decrease of the blood pressure after 20 mg of ketanserin and they received other antihypertensives instead. No severe hypotensive episode was noted. We concluded that ketanserin is a moderate, rapid-onset and safe antihypertensive agent in treating postoperative hypertension following major abdominal surgery.

Abdomen↗

Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis.

The clinical suspicion of myocarditis relies strongly on endomyocardial biopsy for confirmation, yet the sensitivity of the procedure in this setting has not been clearly defined. Biopsy sensitivity was determined in 14 hearts with histologically proved myocarditis studied ex vivo, including 12 autopsy hearts and 2 native hearts explanted at cardiac transplantation. With use of the Stanford and Cordis bioptomes, endoymocardial biopsy was performed near the apex on the right side of the ventricular septum (four to five samples/bioptome per patient) and repeated in the nonapical portion of the septum from the moderator band to the subpulmonary infundibulum (additional three to five samples/bioptome per patient). In a casewise assessment, 43% to 57% of the endomyocardial samples were diagnostic for myocarditis, as calculated separately for each bioptome in each region of sampling (apical/nonapical). Both apical and nonapical sensitivity improved to 64% when the findings of the two bioptomes were combined (eight to nine samples/patient in each region). By collectively analyzing all available samples for each patient, 11 (79%) of 14 cases could be diagnosed, but this required a mean of 17.2 samples/patient, a number clinically unrealistic. The exclusion of four cases of fungal myocarditis from analysis did not significantly alter the results. In transmural ventricular sections, none of four patients with sudden death had inflammatory disease confined to the conduction system. In conclusion, despite six to eight negative biopsy samples/patient with suspected myocarditis, repeat biopsy may still be warranted.

Adult↗

The loop gain of autonomic reflex function in orthostatic hypotension.

The loop gain (G) of the autonomic reflex function in orthostatic stress was assessed in anesthetized dogs subjected to 45 and 90 degrees head-up tilt. We observed the magnitude of orthostatic hypotension before and after 1) sinus denervation and vagotomy (SDVT), or 2) ganglionic blockade (GB) with hexamethonium. The decreases in arterial pressure during the orthostatic stress before and after interruption of the autonomic reflex from either the afferent or efferent limb were defined as E and D, respectively. The loop G of the compensatory system was calculated using closed-loop analysis: G = (D/E) - 1. In the SDVT experiments, the average values of E, D, and G were 18.6 mmHg, 62.6 mmHg, and 2.36, respectively, for 45 degrees tilt; and 31.2 mmHg, 82.7 mmHg, and 1.63, respectively, for 90 degrees tilt. The data provide a quantitative measure of the autonomic reflex function in orthostatic hypotension. Furthermore, we found that the corresponding G values in the SDVT and GB experiments were not significantly different. In each experiment, the G value in 90 degrees tilt was lower than that in 45 degrees tilt. The findings suggest that reflexes from the arterial baroreceptors and cardiopulmonary receptors account for a large part of the autonomic compensation to the orthostatic stress. The whole control system operates in a nonlinear fashion, because the gain value tends to decrease as the degree of tilt is increased.

Animals↗

Phenotypic analysis of infiltrating cells in human myocarditis. An immunohistochemical study in paraffin-embedded tissue.

To define the cellular subpopulations that infiltrate the heart in human myocarditis, formaldehyde-fixed, paraffin-embedded sections from 18 hearts with histologically proved myocarditis were examined immunohistochemically. Disease was classified on routine stains as follows: mixed mononuclear cell (7 cases), granulomatous (3), giant cell (1), rheumatic (2), and fungal (5) myocarditis, respectively. On immunohistochemical examination, T-lymphocyte and macrophage predominance was found in nearly every case, except in fungal myocarditis, in which polymorphonuclear leukocytes and macrophages prevailed. In contrast, B lymphocytes and natural killer cells were conspicuously absent, regardless of histologic classification. Giant cells in giant cell myocarditis and in the Aschoff lesions of rheumatic carditis expressed macrophage, but not myocyte, antigens, suggesting derivation along macrophage lineage. Immunohistochemical data obtainable in paraffin-embedded tissues supplement the study of myocarditis, providing information potentially relevant to immunopathogenesis, natural history, and therapy.

Cell Line↗

Chronic relapsing experimental allergic encephalomyelitis in the Lewis rat: studies on immune regulation.

To study immunoregulation of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) in Lewis rats, we adoptively transferred concanavalin A-activated lymph node cells (LNC) or splenocytes, from hind footpad-inoculated donors at the onset (day 11), or recovery (day 16), of the first attack. Popliteal LNC, especially from day 16 donors, provided significant and dose-dependent, but incomplete, protection of recipients from encephalitogenic challenge; maximal mean delay in EAE onset was 10 days later than controls, with subsequent paralysis reduced more than 6-fold. In contrast, particularly from day 11 donors, superficial inguinal LNC recipients developed actively induced disease of normal severity up to 4 days earlier than CR-EAE controls. Furthermore day 11 EAE splenocytes, but not day 16 ones, adoptively transferred disease into 50-88% of naive recipients. In separate studies, we demonstrated unresponsiveness to active induction of disease in all rats re-challenged during stable late remission, as well as in a minority of animals pretreated with antigen in incomplete Freund's adjuvant. These results suggest an organ-dependent and time-dependent balance between effector and suppressor populations in the model.

Animals↗

Syngeneic graft-versus-host disease induced by cyclosporine--a reappraisal.

Cyclosporine-induced graft-versus-host disease has been described in lethally irradiated rats and mice following syngeneic bone marrow reconstitution. To further study this apparently CsA-restricted phenomenon, we followed reported protocols by administering CsA orally at 50 or 100 mg/kg/day to irradiated, syngeneically reconstituted C57B1/6 mice. No clinical evidence of GVHD was observed for more than 8 weeks after CsA discontinuation. Ear biopsies and circulating immunoglobulin levels 2-4 weeks after stopping CsA failed to demonstrate histological or serological evidence of GVHD, respectively, compared with mice allogeneically reconstituted with Balb/c marrow. To further follow a previous report, CsA 50 mg/kg/day orally or 10 mg/kg/day intraperitoneally was given to normal C57B1/6 mice prior to using their spleen or bone marrow cells for reconstitution of lethally irradiated syngeneic mice. Clinical monitoring and histological examination of recipients 2-5 weeks after reconstitution again failed to confirm GVHD. Thus our results were uniformly negative in attempting to reproduce syngeneic GVHD in mice. Existing data on rats and humans are reviewed, showing that syngeneic or autologous GVHD is not CsA-restricted and that the syndrome could be equated to the chronic form of GVHD found in rats and patients after allogeneic bone marrow transplantation.

Animals↗

Closed-loop analysis of the reflex function in orthostatic hypotension.

The arterial baroreceptors and cardiopulmonary receptors are important for the control of blood pressure during orthostatic stress. We assessed the baroreflex loop gain of arterial pressure compensation to orthostatic hypotension in pentobarbital-anesthetized and gallamine-paralyzed dogs subjected to 45 degrees and 90 degrees head-up tilt. The orthostatic hypotension before and after sinus denervation and cervical vagotomy was designated as D' and D, respectively. The loop gain (G) was calculated using closed-loop analysis: G = (D/D')-1. In 10 dogs, the D', D and G were 17.2 +/- 2.2 (mean +/- SE) mmHg, 64.2 +/- 4.4 mmHg and 2.73 +/- 0.26, respectively in 45 degrees tilt; and 30.6 +/- 3.2 mmHg, 80.7 +/- 5.2 mmHg and 1.64 +/- 0.24, respectively in 90 degrees tilt. Atropine sulfate (0.5 mg/kg, i.v.) eliminated the reflex tachycardia, but did not affect the SAP change during the head-up tilt. The effects of cervical vagotomy on the orthostatic hypotension were thus attributed to interruption of the aortic nerves and vagal afferents. The data provide a quantitative measure of the baroreflex function during the orthostatic stress. The loop gain is not a constant function because the value is significantly less in 90 degrees than in 45 degrees tilt (P less than 0.05). The nonlinear control system implies that the baroreflex compensation became less efficient in the face of a greater blood pressure perturbation.

Animals↗

Preventive and therapeutic effects of cyclosporin and valine2-dihydro-cyclosporin in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat.

Cyclosporin (CS) and valine2-dihydro-cyclosporin [(Val2)DH-CS] were tested in adult Lewis rats with chronic relapsing experimental allergic encephalomyelitis (CR-EAE), induced by the immunization of guinea-pig spinal cord emulsified in complete Freund's adjuvant. The drugs were given orally for 15 or 35 days, at 12.5, 25 or 50 mg/kg/day, starting either on the day of sensitization (preventive treatment) or at one of three subsequent times (therapeutic treatment): the onset of the first attack (protocol A); the onset of the first spontaneous remission (protocol B); and the onset of the second attack (protocol C). Used therapeutically in protocol A, at doses above 12.5 mg/kg/day, both drugs prolonged remission past the end of therapy in more than two-thirds of the treated animals, compared to less than 10% of controls. Trends were similar under protocols B and C. Disease developing after preventive treatment with either drug was predominated by chronic and hyperacute attacks, in contrast to the relapsing course of controls. This pattern was also the result after CS was given therapeutically, whereas (Val2)DH-CS in such circumstances eliminated all further attacks in the majority of rats (58-86% at 25 mg/kg/day) and only minimal disease occurred in the remainder. We conclude that both drugs, in this model, are beneficial during administration; however, in contrast to CS, (Val2)DH-CS possesses an important, curative action when applied therapeutically.

Animals↗

Low serum 25-hydroxyvitamin D in hereditary hemochromatosis: relation to iron status.

Under normal conditions, vitamin D absorbed from the diet or synthesized in the skin is transported to the liver where it undergoes hydroxylation. The purpose of this study was to determine whether excess hepatic iron affects this process and the subsequent production of 1,25-dihydroxyvitamin D (1,25-[OH]2D) in the kidney. Mean serum 25-hydroxyvitamin D (25-OHD) concentrations in untreated hereditary hemochromatosis were 13 +/- 6 (SD) in 9 patients with cirrhosis, 13 +/- 6 in 5 patients with hepatic fibrosis, and 22 +/- 6 in 10 patients with normal hepatic architecture aside from siderosis and were significantly lower than the levels found in 24 controls matched for age, sex, and season, p less than 0.05. The mean serum 25-OHD levels in the two groups with hemochromatosis and hepatic damage were significantly lower than the value in the group with normal hepatic architecture, p less than 0.05. Serum 25-OHD levels in individual patients were inversely related to the size of body iron stores as measured by exchangeable body iron, r = -0.64, or serum ferritin, r = -0.47, p less than 0.05. In 15 patients removal of excess body iron by venesection therapy produced a significant increase in the mean serum 25-OHD from 20 ng/ml to 30 ng/ml, p less than 0.05. In contrast, mean serum 1,25-[OH]2D levels were similar in iron-loaded and control subjects, indicating that the regulation of this metabolite was intact in patients with hemochromatosis. The results reveal that the low serum 25-OHD concentration in patients with hemochromatosis is directly related to the extent of iron loading and it is improved by venesection therapy.

Aspartate Aminotransferases↗

Enhanced detection of cardiac myocyte damage by polarized light microscopy. Use in a model of coxsackievirus B3-induced myocarditis.

Although accurate detection of cardiac muscle damage is critical in the diagnosis of acute myocarditis or acute cellular rejection in both clinical and experimental settings, the histologic evaluation is frequently uncertain without specialized stains. In a study of adult male A/J mice infected with 2x10(5) plaque-forming units of myocarditic coxsackievirus B3, cardiac muscle injury causing myofibrillar disruption was detected as a loss of muscle birefringence by polarized light microscopy. The technique was corroborated by comparison with Masson's trichrome stain and was helpful for histologic examination especially at the early preinflammatory stages of lesion development or in fringe territories of focal lesions. Polarized light microscopy is thus an available means to enhance the histologic determination of cardiac myocyte damage and has specific advantage in an absence of specialized stains.

Animals↗

A prospective randomized controlled trial of initial immunosuppression with ALG versus OKT3 in recipients of cardiac allografts.

Thirty-nine heart transplant recipients were randomized prospectively to receive OKT3 or antilymphoblast globulin (ALG) for 7 days, having otherwise identical protocols (group 1: OKT3, n = 20 patients; group 2: ALG, n = 19 patients). No preoperative immunosuppression was given. The protocol consisted of methylprednisolone, 500 mg intraoperatively, followed by 1 mg/kg/day, intravenously or orally, tapering to 0.2 mg/kg/day at 1 month; oral cyclosporine starting 3 to 5 days after transplantation; selective use of azathioprine, 1 to 4 mg/kg/day; and either OKT3, 5 mg/day for 7 days, or ALG, 15 mg/kg/day for 7 days. Of the 39 patients in the study, 34 are alive 6 months to 2 years after transplantation. The actuarial survival at 2 years for the OKT3 and ALG groups was 92% (+/- 0.07%) and 83% (+/- 0.09%), respectively (not significant [NS]). The time to first rejection for group 1 was 5.6 weeks and for group 2 was 5.3 weeks (NS). The mean number of rejections for group 1 and group 2 was 2.1 episodes per patient and 1.4 per patient, respectively (NS). Three patients in each group were free of rejection at 6 months. The total number of infections at 6 months was 1.05 per patient in group 1, 0.74 per patient in group 2 (NS), with 35% of patients receiving OKT3 and 52% of patients receiving ALG actuarially free of infection by 6 months after surgery (NS). During the first 24 hours after surgery, no significant differences were noted in mean blood pressure, central venous pressure, or Po2 between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗