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Biomedical subjects

C Marks

Publications and source records attributed to C Marks.

At least 19 recordsLinked to original sources

Beta-carbolines in chronic alcoholics undergoing elective tumor resection.

The prevalence of chronic alcoholism in patients with carcinomas of the upper digestive tract exceeds 60%. The patient's history and laboratory markers, preoperatively, are often not sensitive or specific enough to detect alcohol-dependent patients, preoperatively, who are at risk of developing alcohol withdrawal syndrome (AWS) during their postoperative intensive care unit (ICU) stay. Previously, it was found that plasma norharman was elevated in chronic alcoholics, suggesting marker characteristics for chronic ethanol misuse and possibly alcohol dependence. We investigated whether beta-carbolines (i.e., harman and norharman) were different between chronic alcoholics and nonalcoholics with carcinoma, and how the levels change in alcohol-dependent patients during their hospital stay. Ninety-seven patients with oral, pharyngeal, laryngeal, or esophageal carcinomas were evaluated regarding their drinking habits. Sixty patients were transferred to the ICU following tumor resection. Chronic alcoholics met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in chronic alcoholics was > or = 60 g. Blood samples were collected on admission to the hospital, preoperatively, on admission to the ICU and on days 2, 4, and 7 in the ICU. Harman and norharman were determined by HPLC. Elevated norharman was found in chronic alcoholics on admission to the hospital, whereas harman did not differ between groups. On admission, the area under the receiver operating characteristics curve was significantly larger for carbohydrate-deficient transferrin and preoperatively for norharman. The preoperative norharman levels were significantly correlated with the period of mechanical ventilation and the length of ICU stay. Postoperatively, norharman decreased in all patients, except a group of 11 alcohol-dependent patients who developed AWS during their ICU stay. The finding that elevated norharman levels were found in chronic alcoholics on admission to the hospital and preoperatively supports the view of a specific marker for alcoholism. Preoperative norharman was superior to carbohydrate-deficient transferrin and was associated with a prolonged ICU stay and a prolonged period of mechanical ventilation. Further studies are required to determine whether norharman aids in the preoperative diagnosis of chronic alcohol misuse with respect to the prevention of postoperative complications.

Adult

Physiologic responses to recumbent versus upright cycle ergometry, and implications for exercise prescription in patients with coronary artery disease.

To clarify the influence of body position on exercise prescription, 14 men (mean age +/- standard deviation 60.0 +/- 6.1 years) with coronary artery disease who underwent randomized recumbent and upright cycle ergometer tests to volitional fatigue were studied. At 100 watts, heart rate (HR), systolic blood pressure, oxygen consumption (VO2), rate pressure product and rating of perceived exertion were greater (p less than 0.05) in the upright than in the recumbent position. At peak exercise, however, these variables were not significantly different. Regressions of relative HR versus VO2 for recumbent and upright cycle ergometry were comparable: y = 1.24x - 32.7 and y = 1.26x - 31.5, respectively, where y = % maximal VO2, and x = % maximal HR. These findings indicate that recumbent exercise prescriptions may be based on the peak HR and VO2 values obtained during upright cycle ergometry, and vice versa. However, differences in the cardiorespiratory responses at submaximal exercise preclude the interchangeability of upright and recumbent training work rates.

Aged

A three-year experience with serum anodal trypsinogen as a biochemical marker for rejection in pancreatic allografts. False positives, tissue biopsy, comparison with other markers, and diagnostic strategies.

Serum values of immunoreactive anodal trypsinogen (sAT) have been claimed to correlate well with rejection occurring in pancreatic allografts. We have studied the behavior of sAT in serial serum samples obtained from 39 type I diabetics undergoing whole-organ pancreas transplantation during the past 3 years. Patients had either received a pancreatic allograft simultaneously with a transplanted kidney (SPK, n = 33) or after a previous kidney transplant (pancreas after kidney [PAK] n = 6). The behavior of sAT was studied in relation to the clinical diagnosis of rejection. Graft amylase output for all 39 patients and serum creatinine for the 33 SPK recipients were also studied. Tissue biopsies were obtained from 11 patients with elevated sAT values and a presumptive diagnosis of rejection. Nine of these patients had SPK grafts and simultaneously elevated creatinine values. Tissue was obtained from the simultaneously transplanted kidney; all specimens revealed rejection. Two of the 11 patients had PAK allografts. Biopsies performed on the graft duodenum were consistent with acute rejection. Three additional patients with unchanged sAT values had biopsies for other reasons; these biopsies failed to demonstrate signs of acute rejection. Thus graft biopsy correlated exactly with sAT behavior in every case in which rejection was suspected. Five patients had elevations of sAT not associated with rejection: one resulted from direct trauma, two had outlet obstruction, and two had clinical diagnoses of graft pancreatitis. The sAT was more sensitive and specific than GAO and as sensitive as creatinine for SPK recipients. These studies confirm that sAT is a reliable, graft-specific biochemical marker for the early diagnosis of pancreatic rejection. The use of sAT should allow for the proper timing of graft biopsies and the judicious use of immunosuppressive agents, which will result in increased allograft survival for PAK and pancreas-alone allografts.

Algorithms

The immunochemical distribution of cyclophilin in normal mammalian tissues.

Cyclophilin, a 17 Kd proline cis-trans isomerase, high-affinity (Kd 10(-8) M) target for the immunosuppressive drug cyclosporine has ubiquitous phylogenic distribution, but its tissue localization in mammals has not been detailed. To explore a potential relationship between the multiple systemic effects of CsA and the cellular and tissue distribution of CYP, thirty-three different normal porcine tissues were examined using an immunohistochemical technique. Tissue was obtained from farmbred pigs, immediately fixed in buffered formalin, and prepared as embedded 5-mu sections. Immune-specific staining was accomplished using an ABC immunoperoxidase method and an affinity-purified, monospecific, rabbit anti-CYP IgG. Cut sections served as their own blanks and controls, and all tissues were stained in batch to minimize the effects of variation in technique. Consistent with earlier reports, CYP was present in all tissues studied, however, there was remarkable heterogeneity in CYP distribution. Renal parenchymal cells, cardiac and striated muscle, pulmonary and skin demonstrated cytoplasmic immunospecific CYP--however, the cellular localization varied. Cytoplasmic staining of endothelial, neural, and glandular elements was consistently observed. Contrasting with previous reports, CYP localized to the nucleus as well as the cytoplasm of some lymphoid cells, hepatocytes, and cells of the large intestine. Generally, greater CYP-specific staining was noted in organs amenable to CsA immunosuppression (heart, liver, kidney), compared with organs deemed more immunologically vulnerable when allografted under CsA (pancreas, lung, small bowel). Similarly, CYP-immunospecific staining was abundant in tissues susceptible to CsA toxicities (neural tissue, smooth muscle, kidney, liver). This detailed immunohistological examination affords a correlation between CYP content and sensitivity to CsA. It also raises some new questions about tissues with little extractable CYP but significant histological staining.

Amino Acid Isomerases

Gender dimorphism in size, shape and body composition of child-onset obese and nonobese adolescents.

Gender dimorphism (percent GD) for stature (S), body size, body mass (BM) distribution and body composition for obese and nonobese male and female adolescents (mean age 12.7 years, range 10.5-14.5) was compared for 22 girths, 13 bony widths, five skin + fat folds (SF), fat mass (FM), fat free mass (FFM), body density (Db), and calculated variables (BMI, BSA, unit-size mass, waist:hip ratio (WHR), and FFM/S). BM distribution was computed with the ponderal mass equivalent somatogram. There was significant (P less than or equal to 0.05) percent GD for FM, FFM, Db, for the nonobese, but not obese. Only the neck, forearm and wrist girths revealed small but significant (P less than or equal to 0.05) percent GD for the obese. There was no girth percent GD for the nonobese. The elbow, wrist and ankle diameters revealed significant (P less than or equal to 0.05) percent GD for the obese; there was no significant percent GD for the nonobese for the same bony widths. Only the subscapula and iliac SF revealed significant (P less than or equal to 0.05) percent GD for the obese. For nonobese, percent GD was significant (P less than or equal to 0.05) for the triceps, subscapula and thigh SF, Comparisons between obese and nonobese indicated significant (P less than or equal to 0.05) differences between obese and nonobese males and females for FM, FFM, all girths and SF, but not S. Surprisingly, the obese and nonobese had nearly identical trunk diameters; the sum of biacromion, chest, biilac, and bitrochanter diameters were different by only 4.6 percent (n.s.) for the obese and nonobese males, and 1.3 percent (n.s.) for the obese and nonobese females. Thus, a large central frame-size cannot be used to justify the acquisition or maintenance of a larger than average BM for the obese. The ponderal equivalent analyses revealed that the obese's abdomen was the size of a person projected to have a BM in excess of 100 kg. The use of surface anthropometry in the study of adolescent obesity was supported.

Adipose Tissue

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties.

Human protein S (HPS), a regulator of hemostasis, is a vitamin K-dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl-elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium-nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.

1-Carboxyglutamic Acid

The effects of ketanserin on ventricular ectopic activity in humans.

Ketanserin is a serotonin S2-receptor antagonist that lowers blood pressure and inhibits platelet aggregation. Ketanserin treatment is also associated with prolongation of the corrected QT interval. The recently reported Prevention of Atherosclerotic Complications with Ketanserin (PACK) trial confirmed this prolongation of QT and also revealed a significant excess of deaths in patients receiving ketanserin together with potassium-losing diuretics. The investigators suggested that this excess of deaths may have been attributable to exacerbation of hypokalemia-induced ventricular arrhythmias by the repolarization-prolonging effect of ketanserin. However, drugs that prolong the QT interval may affect ventricular ectopic activity beneficially, and our study was designed to evaluate the effects of ketanserin on ventricular ectopic activity. Twenty patients (18 male, 2 female) aged 42-73 years were studied, each having at least 15 ventricular ectopic beats/hour. The study design was a double-blind, crossover comparison of ketanserin, 40 mg twice daily, and placebo, both given for 1 week. Ventricular ectopic activity was assessed by 48-hour Holter electrocardiogram (ECG) tapes at the end of each treatment period. Ketanserin treatment was associated with prolongation of repolarization, as reflected by the significant mean increases in both QT interval (+30 ms; p less than 0.001) and corrected QT interval (+20 ms; p less than 0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p less than 0.05). This was associated with a concordant improvement in the individual indices of ectopic activity. Our results show that ketanserin significantly suppressed ventricular ectopic activity in our normokalemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Serum immunoreactive anodal trypsinogen and urinary amylase as biochemical markers for rejection of clinical whole-organ pancreas allografts having exocrine drainage into the urinary bladder.

Rejection of pancreas allografts is best measured today by co-monitoring the creatinine of a simultaneously transplanted kidney allograft from the same donor. This methodology discourages pancreas transplantation for patients who have previously received a kidney allograft and preuremic patients. Thus, an early, graft-specific marker of rejection is desirable. In this study we compared 2 putative biochemical markers for rejection of pancreas allografts, serum immunoreactive anodal trypsinogen and urinary amylase, with serum creatinine in 15 simultaneously transplanted type I diabetics. Serial values during hospitalizations were determined. Follow-up ranged from 18 to 134 postoperative days. Rejection was diagnosed clinically and considered real if the patient received a course of anti-rejection medication. Ten of these 15 patients experienced a total of 21 rejection episodes. For all episodes of rejection, serum trypsinogen rose from a baseline of 398.1 +/- 25 ng/ml to 1686.2 +/- 317.9 ng/ml (P less than 0.001) on the day of rejection. Urinary amylase fell from 88,310 +/- 7877 U/24 hr to 37,508 +/- 7142 U/24 hr (P less than 0.001). For 10 patients in whom rejection was diagnosed on the initial hospitalization so that serial prediagnosis sera and urines were available, anodal trypsinogen rose from a baseline of 756 +/- 263 ng/ml to 1936 +/- 582 ng/ml (P less than 0.001). Urinary amylase values for these same 10 patients did not change significantly (baseline = 55,788 +/- 18,404 U/24 hr, rejection = 47,133 +/- 14,737 U/24 hr, (P = 0.7). We conclude that serum anodal trypsinogen behaves as a graft-specific biochemical marker for rejection of vascularized pancreas allografts.

Amylases

Essentials of open heart surgery.

As Parirenyatwa continues its successful OPEN-HEART SURGERY PROGRAMME, it becomes important to emphasize that the essential determinants for cardiac surgical success include a comprehensive preoperative assessment of the patient; accurate definition of the fundamental lesion; ameliorative treatment of secondary effects such as cardiac failure, electrolyte imbalance and arrhythmia. In addition to the application of technical expertise in the performance of the operation, an optimal outcome depends on good intraoperative anesthetic management, the collaboration of pump technicians, and dedicated intensive care management in the postoperative period.

Cardiac Surgical Procedures

Dose-ranging study of isosorbide-5-mononitrate in chronic congestive heart failure treated with diuretics and angiotensin-converting enzyme inhibitor.

The hemodynamic response of isosorbide-5-mononitrate (IS-5-MN) to the addition of the widely used therapy of diuretic drugs and the maximally tolerated dose of enalapril for heart failure was assessed in 8 patients with congestive heart failure (CHF) (New York Heart Association class II and III). The diuretic therapy was furosemide, 40 to 80 mg/day, with or without amiloride, 5 to 10 mg/day. The dose of enalapril was 5 to 20 mg/day. Four hours after the administration of the morning dose of enalapril, a Swan-Ganz catheter was positioned in the pulmonary artery. Patients received increasing doses of IS-5-MN to produce a satisfactory decrease in pulmonary capillary wedge pressure. Two of the first 3 patients studied had a large reduction in blood pressure when given 10 mg of IS-5-MN. Subsequent patients were therefore given an initial dose of 5 mg, the total dose being 5 to 20 mg over 2 hours. Results at baseline and 1 hour after the final dose of IS-5-MN are expressed as mean +/- standard deviation. Both pulmonary artery systolic and diastolic pressures decreased significantly (p less than 0.05) by 12.2 +/- 8.9/4.2 +/- 5.2 mm Hg, from 47.2 +/- 16.0/21.6 +/- 6.0 mm Hg to 35.0 +/- 15.2/17.4 +/- 9.3 mm Hg. Pulmonary capillary wedge pressure decreased by 8.6 +/- 4.4 mm Hg, from 22.1 +/- 5.4 to 13.6 +/- 7.5 mm Hg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Circulating concentrations of porcine ileal peptide but not hexosaminidase are elevated following 1 hr of mesenteric ischemia.

Porcine Ileal Peptide (PIP) is located in the mucosa of the small bowel. We hypothesized that PIP may be useful as a marker for early intestinal ischemia or other acute processes of the mucosa. To test this hypothesis we developed a model of acute reversible intestinal ischemia in the pig. Following isolation of a 100-cm segment of ileum on a vascular pedicle baseline, serum and tissue samples were obtained. The vessels were then occluded for 60 min and the segment was reperfused. Serial serum samples were taken and analyzed for PIP and hexosaminidase (HEX). HEX enzyme activity in serum is known to be elevated in animals having intestinal necrosis. The Student t test for paired data was used. In preliminary studies we found that circulating HEX activity became elevated following 3 to 4 hr of vessel occlusion followed by reperfusion. In the current experiments, following 1 hr of ischemia, PIP rose significantly in the peripheral circulation, being 153.8 +/- 76.8, 909.0 +/- 150.4, and 898.3 +/- 128.1 ng/ml (P less than 0.001) at 0, 60, and 360 min after reperfusion of the segment. HEX on the other hand did not change significantly throughout the experiment, having been 766.0 +/- 28.1, 752.0 +/- 71.3, and 780.1 +/- 53.7 nM/liter (ns) at 0, 60, and 360 min following reperfusion of the segment. Histology demonstrated some clubbing, shortening and fracturing of villi with thinning of the tips of the villi in many cases. Immunospecific staining for PIP was present along the intact borders of the villi.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Oxygen uptake and energy output during walking of obese male and female adolescents.

Oxygen uptake and steady-rate energy output of 7 obese male and 13 obese female adolescents (greater than 178% ideal body weight) walking at four different speeds (1.167, 1.5667, 1.7833, and 2.125 m/s) were studied. Body composition was measured by hydrostatic weighing, and steady-rate energy output by open circuit spirometry. Energy output was expressed as kJ/min (kcal/min) and indexed to body mass and fat-free mass. A 2-by-4 ANOVA (sex by speed) revealed significant differences in the energy output between the speed conditions. There was no significant difference between the sexes. A nonlinear increase in calorie output with increasing speed indicated a decreasing efficiency with increasing speed of walking. Possible reasons include biomechanical factors such as increased upper-body forward lean needed to maintain balance at faster speeds of movement, increased energy output due to increased inertia, extra energy output needed to accelerate the limbs and torso, and increased body fat.

Adolescent

Basal metabolism of obese adolescents: inconsistent diet and exercise effects.

Effects of 20 wk of diet-plus-behavior (DB) therapy or exercise-plus-diet-plus-behavior (EDB) therapy on changes in basal energy expenditure (BEE) were studied in 36 obese male and female adolescents. BEE was assessed by open-circuit spirometry and body composition by hydrostatic weighing. Dietary restriction was based on the dietary-exchange program. Behavioral treatment included record-keeping, stimulus-control, and reinforcement techniques. EDB therapy included 50 min/d, 3 d/wk of aerobics. A time-by-group (2 X 3) repeated-measures ANOVA was used to analyze pre-to-postintervention differences between groups (DB, EDB, and control). Results revealed small but statistically significant (p less than 0.05) differences in body composition between the two experimental groups and control subjects. There were no differences in body composition between the DB and EDB groups, although all control subjects gained body mass (p less than 0.05). There was no group-by-time interaction for BEE. Moderate correlations of r = less than or equal to 0.61 were obtained between change in BEE and change in body composition for the subjects in the experimental groups.

Adolescent

Chylothorax causing reversible T-cell depletion.

Study of a patient with traumatic chylothorax after blunt chest trauma defines the changes in cellular immunocompetence during nonoperative management and emphasizes the importance of defining these parameters in addition to documenting the effects of metabolic deterioration.

Adult

Thymoma and aregenerative anemia.

Among 32 patients with thymoma treated at the Louisiana State University Medical Center, there was one patient with aregenerative anemia attributable to thymoma (an incidence of 3.3%). Despite successful surgical removal of the thymoma, there was only slight improvement of the hematologic status three years after thymectomy. The result in this patient approximates the general experience, with hematologic remission being likely in less than 20% of cases. Experience casts doubt on whether treatment with adrenocortical steroids, mediastinal irradiation, or splenectomy provides significant beneficial effects.

Anemia, Aplastic