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Biomedical subjects

W Merrill

Publications and source records attributed to W Merrill.

17 recordsLinked to original sources
PubMed1996

Thalidomide inhibits tumor necrosis factor alpha, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats.

A hyperdynamic circulatory state frequently is observed in portal hypertension with liver failure or extensive portal-systemic shunting. Tumor necrosis factor alpha (TNF) causes marked hypotension in mammals by inducing nitric oxide synthesis and has been shown to play a role in the development of the hemodynamic changes observed in portal hypertension. Thalidomide selectively inhibits TNF production by enhancing messenger RNA degradation. We investigated the systemic and portal hemodynamic effects of thalidomide in a prehepatic model of portal hypertension and evaluated whether suppressing TNF synthesis decreases NO production. Portal hypertension was induced by partial ligation of the portal vein (PVL). Animals received thalidomide (T) (50 mg/kg/d) + water or water alone (W), orally, daily for 2 days before and 13 days after PVL operation, at which time hemodynamic studies were performed and TNF plasma levels were obtained. Sham-operated animals were studied identically. In an additional group of PVL animals, 24-hour urinary excretion of NO2- and NO3- was measured during treatment. PVL animals receiving T presented with a significantly higher mean arterial pressure and systemic vascular resistance and significantly lower portal pressure, TNF plasma levels, and 24-hour urinary excretion of NO2- and NO3-, in comparison with rats receiving W. A significant correlation (r = -0.61) was observed between TNF plasma levels and mean arterial pressure among PVL animals. Thalidomide did not have any significant effects on sham rats. Thalidomide inhibits TNF synthesis and reduces NO production, blunts the development of the hyperdynamic circulation, and decreases portal pressure in PVL-operated rats.

Animals↗
PubMed1994

Effects of gamma-irradiation on the M-CSF-promoter linked to a chloramphenicol aminoacyl transferase reporter gene expressed in a clonal murine bone marrow stromal cell line.

The effects of cytokines produced by bone marrow stromal cells on closely associated hematopoietic cells constitute a major component of the physiology of the hematopoietic microenvironment. A major cytokine produced by marrow stromal cells is macrophage colony-stimulating factor (M-CSF). To determine the effect of gamma-irradiation on the M-CSF promoter in bone marrow stromal cells, we selected a clonal cell line from the C3H/HeJ mouse marrow stromal cell line D2XRII and stably transfected a reporter construct containing the murine M-CSF-promoter linked to a chloramphenicol aminoacyl transferase (CAT) gene. CAT activity was measured at serial time points after gamma-irradiation in vitro to doses between 500 and 10,000 cGy at a dose rate of 116 cGy/min. D2XRII marrow stromal cells treated with phorbol myristate acetate (40 micrograms/ml, four h), demonstrated a significant two-fold increase in CAT activity. In contrast, CAT activity measured immediately, 24 h, 72 h or 1 week after gamma-irradiation, showed no significant increase or decrease in CAT activity. An increase in CAT activity was detected 48 h after irradiation with cells that received 5,000 cGy. Thus, single fraction gamma-irradiation of plateau phase bone marrow stromal cells did not decrease M-CSF-promoter activity. These results are consistent with prior experimental data demonstrating stable levels of release of M-CSF protein following gamma-irradiation of bone marrow stromal cells and imply that the stability of transcription of the gene for this important cytokine is protected from irradiation.

Animals↗
PubMed1991

Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer.

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.

Adenocarcinoma↗
PubMed1990

Prophylactic administration of histamine1 and histamine2 receptor blockers in the prevention of protamine-related haemodynamic effects.

We studied the effects of the prophylactic administration of histamine1 and histamine2 receptor blockers on haemodynamic changes, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MBP), central venous pressure (CVP), and heart rate (HR, beats.min-1) before and after the administration of protamine in two groups of patients having coronary artery bypass graft surgery. Group I patients received no histamine blockers, whereas patients in Group II were treated prophylactically with both H1 (diphenhydramine) and H2 (cimetidine) receptor blockers. The mean SBP, DBP, MBP, CVP, and HR before (and after) administration of protamine in group I patients were 114 +/- 16 (90 +/- 16) mmHg, 64 +/- 11 (51 +/- 8) mmHg, 81 +/- 11 (65 +/- 10) mmHg, 10 +/- 3 (11 +/- 7) mmHg, and 92 +/- 10 (87 +/- 13) before (and after) protamine administration. Group II patients had mean SBP, DBP, MBP, CVP, and HR of 113 +/- 19 (113 +/- 17) mmHg, 61 +/- 12 (62 +/- 11) mmHg, 79 +/- 15 (80 +/- 13) mmHg, 9 +/- 3 (9 +/- 2) mmHg, and 88 +/- 6 (86 +/- 4) before (and after) protamine administration. Our data show that only in Group I patients who did not receive histamine receptor blockers, were there significant haemodynamic changes following protamine administration (P less than 0.05). We conclude that the prophylactic administration of histamine receptor blockers prevents some of the adverse haemodynamic effects associated with protamine administration.

Aged↗
PubMed1990

Substance P, acetylcholinesterase, and beta-endorphin levels in the plasma and pericardial fluid of patients with and without angina pectoris.

We measured substance P-like immunoreactivity (SPLI), beta-endorphin-like immunoreactivity (BELI), acetylcholinesterase activity, and total protein content in pericardial fluid and plasma of patients with angina pectoris and patients with no angina pectoris. SPLI and BELI levels, acetylcholinesterase activity, and total protein content were determined by radioimmunoassay, a colorimetric method, and by the method of Lowry et al. (J Biol Chem 1951; 193:265-75), respectively. In the pericardial fluid, patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 1.69 +/- 0.23 fmol/mg protein, 0.16 +/- 0.13 fmol/mg protein, 0.06 +/- 0.02 units, and 25.7 +/- 3.2 mg/ml, respectively. Patients with no angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.93 +/- 0.17 fmol/mg protein, 0.19 +/- 0.10 fmol/mg protein, 0.16 +/- 0.02 units, and 44.6 +/- 5.3 mg/ml, respectively. SPLI levels were significantly higher (p less than 0.03), and acetylcholinesterase (less than 0.002) and total protein content (less than 0.004) were significantly lower in the pericardial fluid of patients with angina when compared with those of patients with no angina. BELI levels were not significantly different between the two groups. In the plasma, no significant differences were found in SPLI, BELI, acetylcholinesterase, and total protein values between the two groups of patients. Patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.47 +/- 0.26 fmol/mg protein, 0.06 +/- 0.06 fmol/mg protein, 0.29 +/- 0.15 units, and 68.2 +/- 8.7 mg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1988

Bronchoalveolar lavage: clinical role and quantitative assessment.

The field of research bronchoalveolar lavage has grown exponentially in the past decade. Despite this growth, the clinical role of lavage is uncertain. The authors review the clinical areas in which lavage has made its greatest impact as a diagnostic test (e.g. eosinophilic pneumonia, eosinophilic granuloma, alveolar proteinosis, infection, and neoplasia). The importance of the test early in the evaluation of undiagnosed diffuse alveolar diseases is considered. Finally we discuss the possibility that urea marks the recovered lining fluid volume and thus serves as a standard denominator. Results from our laboratory indicate that it does not. We feel that lavage is clinically useful and should be employed in the evaluation of undiagnosed diseases. Although it has provided data about the pathogenesis of chronic inflammatory diseases, its role in the longitudinal evaluation of these illnesses remains to be proven.

Bronchoalveolar Lavage Fluid↗
PubMed1987

Evaluation of long-term results of homograft and heterograft valves in extracardiac conduits.

Between 1971 and 1982, 249 patients received right heart extracardiac conduits. The 173 patients who survived 30 days were reviewed retrospectively; 72 had antibiotic-sterilized aortic homografts, 97 had xenografts of various types, and four had valveless tubes. Reoperation for conduit obstruction was required as early as 13 months after the original operation, but actuarial analysis showed no differences in overall performance of homograft and heterograft conduit groups with respect to late death or survival free of conduit obstruction. More important risk factors for late death or the need for reoperation were the severity of the underlying cardiac lesions and the influence of early postoperative complications. When analyzed statistically, the performance of conduits bearing homografts was disappointing, influenced sometimes by complications in the Dacron extension tubes. Repairs dispensing with conduits entirely should be evaluated.

Actuarial Analysis↗
PubMed1986

Implications of hypercalcemia with respect to diagnosis and treatment of lung cancer.

This study had two objectives. The first was to determine if hypercalcemia presents as an isolated finding in patients with lung cancer prior to the development of abnormalities on chest radiography. The second was to correlate the presence of hypercalcemia with survival after surgical therapy. A review of clinical material over a seven-year period yielded 67 patients with diagnoses of hypercalcemia and lung cancer. No patient presented with surgically curable lung cancer associated with hypercalcemia. A review of the literature disclosed only four cases in which a putative cure occurred in the presence of hypercalcemia. Review of the clinical material and the literature revealed no instance in which hypercalcemia per se led to the diagnosis of clinically occult lung cancer. Hypercalcemia was almost always associated with large tumor masses. Median survival after the discovery of hypercalcemia complicating carcinoma of the lung was one month.

Adenocarcinoma↗
PubMed1983

Common bile duct complications of pancreatitis evaluation and treatment.

Five cases that illustrate the spectrum of biliary complications of pancreatitis and pancreatic pseudocyst are discussed. Obstructive jaundice, hemobilia, and bilious ascites were the major problems in these five patients. Sonography, transhepatic cholangiogram, endoscopic retrograde cholangiopancreatography, operative cholangiography, and arteriography are important in establishing the diagnosis and planning the treatment. Three patients had biliary obstruction caused by chronic pancreatitis, a pancreatic pseudocyst, or both. Two patients had a fistula between the common duct and the pseudocyst. Simple decompression of the pseudocyst was curative for only one patient. Three patients required decompression of the biliary tract, which emphasizes the need for intraoperative cholangiography. One patient required a Whipple operation to control hemorrhage but died in the immediate postoperative period. The operative findings determine the specific procedures for biliary tract decompression and pseudocyst drainage.

Alcoholism↗
PubMed1982

Kinetic analysis of respiratory tract proteins recovered during a sequential lavage protocol.

Although bronchoalveolar lavage (BAL) has been used as a research tool for over a decade, the technique of lavage has varied markedly between laboratories. For example, lavage instillate volumes from 50 to 300 ml have been used, and yet the influence of the variable of total lavage volume on subsequent protein recovery is uncertain. We performed sequential BAL (50 ml/aliquot; total volume, 300 ml) of the right middle lobe of 14 normal volunteers and separately processed and analyzed recovered aliquots for the absolute and relative concentrations of several protein substances. These proteins include free secretory component and secretory IgA, which emanate from airway secretions, and IgG, which is thought to transude from more distal alveolar sites. Analysis of these data showed a marked decrease in the absolute concentration of all proteins measured in serial aliquots. Analysis of protein ratios in sequential aliquots, however, revealed no significant change from the first to the fifth recovered aliquot. Finally, we analyzed the influence of the size of the first recovered aliquot on absolute and relative concentrations of proteins. Here there seemed to be a trend indicating preferential recovery of airway proteins in smaller aliquots. This was significant for the ratio of free secretory component to albumin (p less than 0.05). We conclude that lung proteins are efficiently and homogeneously sampled with 100 ml of lavage instillate. Larger volumes will add more protein but not alter protein ratios. Lavage with smaller volumes may preferentially sample airway proteins.

Adolescent↗
PubMed1980

Unstable angina pectoris. Factors influencing operative risk.

Experience was reviewed with 471 consecutive patients who had coronary artery bypass (CAB) operation alone. The hospital mortality rate was 2% in 341 patients operated on for treatment of stable angina pectoris. There were ten deaths (7.7%) in the 130 patients who underwent CAB for treatment of unstable angina. In this series, age greater than 70 years, poor left ventricular function, distal coronary arteries unfavorable for grafting and the presence of main left coronary artery disease were factors associated with increased operative mortality. In 78 patients with unstable angina who had none of these increased risk factors, the mortality rate was 1.3%. Hospital mortality was 33% in patients older than 70 years and 29% in patients with poor left ventricular function and/or distal vessels unfavorable for grafting. In 23 of the 130 patients, the only increased risk factor present was severe stenosis of the main left coronary artery and one of them (4.3%) died. Thus, when elderly patients and patients with poor left ventricular function or poor distal vessels were excluded, the hospital mortality rate associated with CAB in patients with unstable angina was low (2.0%, 2/101 patients) and equal to that for operation in patients with stable angina pectoris.

Adult↗
PubMed1976

Late cardiac tamponade: a potentially lethal complication of open-heart surgery.

Cardiac tamponade occurring late after open-heart surgery is a frequently fatal complication. Of the 13 cases previously reported in the literature, there were seven deaths. In this report, three additional patients with late cardiac tamponade successfully treated are presented. Postoperative anticoagulation with Coumadin appeared to contribute to this complication. Increased awareness of late cardiac tamponade allowing prompt recognition and immediate decompression of the pericardial sac should lower the high mortality rate previously associated with the condition.

Adult↗
PubMedDate not supplied

Relationship of cardiac allograft size and pulmonary vascular resistance to long-term cardiopulmonary function.

The purpose of this study was to evaluate the long-term cardiopulmonary function of heart transplant patients who received disproportionately sized allografts for varying levels of pulmonary vascular resistance. Resting hemodynamics and oxygen uptake during exercise were recorded at 1 year after transplantation in 52 patients. No differences in resting heart rate, cardiac output, stroke volume, peak oxygen uptake during exercise, and exercise duration were found in recipients of undersized hearts (donor:recipient weight ratio [D:R] < 0.75), sized-matched hearts (D:R = 0.75 to 1.25), and oversized (D:R > 1.25) hearts. In a further analysis according to preoperative pulmonary vascular resistance, resting cardiac output (5.8 +/- 1.3 L/min) was normal, and peak exercise oxygen uptake (22.7 +/- 8.0 ml/kg/min) was mildly decreased in recipients of size-matched allografts with a pulmonary vascular resistance of less than 3 Wood units (size-matched hearts, with mild or no pulmonary vascular resistance). Of patients with moderate pulmonary hypertension (pulmonary vascular resistance > or = 3 Wood units), resting cardiac output was normal (5.1 +/- 0.6 L/min) in recipients of oversized hearts and was reduced (4.7 +/- 1.0 L/min) in recipients of sized-matched hearts (p < 0.05 versus recipients of size-matched hearts with pulmonary vascular resistance less than 3 Wood units).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗