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Biomedical subjects

R N Garrison

Publications and source records attributed to R N Garrison.

143 records · Page 8Linked to original sources

Hepatocellular function and nutrient blood flow in experimental peritonitis.

The pathophysiologic basis of organ failure and reduced oxygen consumption in peritoneal infection remains undefined. Plausible explanations include alteration of tissue nutrient blood flow and a primary cellular injury that impairs oxygen metabolism. To define this controversy, we created peritonitis in rats by cecal ligation and puncture. Controls had sham operation. Rats were sacrificed at 6 or 18 hours, liver mitochondria were isolated, and oxidative phosphorylation was studied polarographically. In additional animals indocyanine green (ICG) clearance was studied at low (5 mg/kg) or high (15 mg/kg) doses. The low-dose ICG clearance reflects total hepatic blood flow; a Lineweaver-Burk plot of clearance versus the dose permits extrapolation of clearance to an infinite dose as an indicator of cellular function. Mitochondria studied at 6 hours (n = 10) and 18 hours (n = 10) indicated no differences when compared to paired controls. ICG clearance was unchanged between peritonitis and control rats at 6 hours. However, at 18 hours peritonitis rats had a prolonged half-life of 2.49 +/- 0.31 minutes for the low-dose and 5.29 +/- 0.41 minutes for the high-dose compared to 1.65 +/- 0.07 and 4.34 +/- 0.10 minutes, respectively, for the controls. The Lineweaver-Burk plot of clearance versus dose resulted in peritonitis and control clearance rates intercepting each other at an extrapolated infinite dose. These data indicate that hepatocellular function measured by mitochondrial function and ICG clearance was unaltered. Low-dose ICG clearance indicated reduced total hepatic blood flow. The reduced oxygen consumption in peritonitis appears to have its genesis in altered nutrient blood flow.

Animals↗

The effects of peritonitis on murine renal mitochondria.

To examine the coupled respiratory functions of murine kidney mitochondria, peritonitis was created in 29 male Sprague-Dawley rats; 29 rats were paired-controls. Peritonitis was created by cecal ligation and perforation. Experimental and control animals were sacrificed at two hours (N = 12), four hours (N = 8), and 6 hours (N = 9), mitochondria were isolated, and state 3, state 4, and Respiratory Control Indices (RCI) were determined. The state 3, state 4, and RCI were unchanged from control values by analysis of variance. From these data, we conclude that the defective oxygen consumptions and organ failure in sepsis is not due to a primary cellular insult to the kidney mitochondria.

Animals↗

Surgery in elderly patients.

Operations on patients over 65 years old are increasing steadily in number and complexity. Demographic trends indicate that future increases will be even greater. We reviewed patients having operations of diverse type and magnitude to determine results, with emphasis on the influence of age. Increased risk in older persons was most evident in emergency situations where the frequently associated systemic diseases and the inevitable diminution in organ functional reserves could not be adequately treated or compensated. Appropriate management of elderly patients through surgical procedures requires knowledge of the peculiarities in their responses to disease, medications, and other stimuli.

Aged↗

Atypical clostridial bacteremia.

Forty-seven patients identified with clostridial bacteremia not characterized by histotoxicity were studied to define better the clinical presentation and results of treatment. Patients were categorized into three groups--one, elderly debilitated patients with multiple associated illnesses and no identifiable focus of infection; two, patients with alcoholism and systemic complications of alcohol abuse and no primary focus of infection, and three, patients with a mechanically treatable primary focus of infection. The over-all mortality was an unacceptable 57 per cent. Antibiotic therapy apparently did not affect the survival rate. Portal bacteremia and ineffective hepatic reticuloendothelial function may be significant factors in those patients without a primary focus of infection.

Aged↗

Patterns of morbidity and mortality in splenic trauma.

The cases of 337 consecutive patients undergoing splenectomy for trauma have been reviewed. The combination of physical examination and peritoneal lavage is effective and safe in establishing the need for operation. Associated injuries are the major determinants of mortality. Exsanguination, infection, and neurologic injuries are the major causes of death.

Female↗

Determinants of death in patients with intraabdominal abscess.

To better define determinants of death in patients with intraabdominal abscess, 143 patients from a 5-year hospital experience were reviewed. Abscesses were most commonly results of trauma, spontaneous gastrointestinal perforations, and technical errors. Clinical presentation of abscess was quite variable as were criteria to justify reoperation for drainage. Abscesses occurred most commonly in the subphrenic space, pelvis, or subhepatic space. Complete abdominal exploration was employed most frequently for drainage. Those factors that were associated with a fatal outcome were: organ failure (P < 0.001), lesser sac abscess (P < 0.001), positive blood culture (P < 0.01), recurrent and/or persistent abscess (P < 0.01), multiple abscesses (P pE 0.01), age > 50 years (P < 0.03), and subhepatic abscess (P < 0.03). These data suggest that deaths from abdominal abscess are consequences of ineffective surgical drainage and failure of host defense mechanisms.

Abdomen↗

The nonoperative approach to esophageal perforation due to celestin tube placement.

Perforation of the esophagus during placement of esophageal tubes for palliation of obstructing inoperable cancer is a well-known complication that may preclude satisfactory amelioration of symptoms. Experience with two such patients suggests that the complication can best be treated by proper placement of the tube so that it seals the leak and bypasses the obstruction. Judicious use of antibiotics is beneficial. Drainage of the mediastinum may also be necessary. Resectional or extensive operative therapy is probably not wise in these ill and debilitated patients, particularly if the cancer is incurable.

Aged↗

Effects of concurrent sepsis with clinically significant pulmonary embolic disease.

Forty-one patients with significant pulmonary emboli were reviewed. The presence of heart disease and obesity was found with relatively constant frequency throughout the groups presented. Postoperative infections (wounds or abscess) were frequently associated with fatal or significant pulmonary embolism, particularly after abdominal and pelvic operations. The infection rate (65 per cent) in patients in whom significant pulmonary embolism developed after abdominal and pelvic operations is particularly striking when compared to the overall infection rate of 7 per cent for major operations in our hospital. Recent studies of prophylactic minidose heparinization reveal an increased number of complications due to the heparin [24], and thus the proper selection of cases for prophylactic minidose heparin is mandatory. The data suggest that patients at high risk for the development of postoperative complications of infection are also at high risk for the development of significant pulmonary emboli and should be considered candidates for prophylactic minidose heparinization.

Adult↗

Colorectal carcinoma: overview of management techniques.

The fact that the national death rate from carcinoma of the colon and rectum has remained static over the past two decades is strong incentive for future investigation of measures to allow detection in its early and more favorable stage. Although no significant improvements in surgical techniques have afforded improvement in longevity, certain technical factors are known to inhibit tumor implantation during surgery. Data suggest that the extent of en bloc resection is the most crucial factor in avoiding recurrence. Extensive use of radiotherapy as the sole method of treatment or as preoperative or postoperative adjunctive therapy remains investigational, but it seems likely that this form of treatment will play an increasing role in the future. Preoperative radiotherapy seems to be useful in reducing the stage of the neoplasm and the incidence of extraserosal involvement; postoperative radiotherapy is beneficial for palliation. Chemotherapy, particularly with the fluorinated pyrimidines (5-FU and 5-FUDR), is being evaluated for its usefulness in lengthening survival time; response to 5-FU is occasionally dramatic. It remains for major investigational centers to clarify the role of combination chemotherapy in metastatic disease. Immunotherapy at present must be considered an unproven mode of treatment and of inconclusive benefit in any stage of colorectal carcinoma. Carcinoembryonic antigen assay is a useful prognostic and diagnostic tool in localizing primary tumor and in subsequent evaluation of response to treatment.

BCG Vaccine↗

Evaluation of management of the emergency right hemicolectomy.

To evaluate the morbidity and mortality attending emergency resection of the right colon, we studied retrospectively 119 consecutive patients from two major centers, particularly examining the role of delayed anastomosis (initial ileostomy with subsequent ileocolic anastomosis). Emergency right colectomy was defined as an operative procedure in which partial resection of the terminal ileum and total or partial resection of the cecum and/or ascending colon were necessary before the colon could be evacuated and prepared as might be the case in elective resection. Ninety patients underwent primary anastomosis; hospital mortality and morbidity were 26 and 11%, respectively. Among 29 patients who underwent ileostomy, hospital mortality was 38%; hospital morbidity was 10%. In general, the patients selected for ileostomy were somewhat more ill or had more severe injury. only 17% of all deaths and 8% of all serious complications could be attributed to the anastomosis, leaving little statistical opportunity for improvement by deleting it. The data indicate that a very high mortality (29%) attends emergency right hemicolectomy. Our study indicates that ileostomy in lieu of anastomosis does not reduce this high mortality.

Adolescent↗

Clinical implications in bacteroides bacteremia.

The clinical presentation and results of treatment of 98 patients with documented bacteroides bacteremia have been reviewed. Surgically treatable causes were documented in three-quarters of the patients. No one antibiotic or combination thereof significantly influenced survival. Patterns of death from sepsis were through multiple organ failure. Early recognition, or surgical drainage or debridement, or both, and specific aerobe directed antibiotic therapy remain the first line of therapeutic endeavor.

Adolescent↗

A community-wide experience with jejunoileal bypass for obesity.

The records of seventy-nine patients who had jejunoileal bypass operations for morbid obesity were reviewed. The data represent the entire experience of surgeons in the Louisville, Kentucky metropolitan area for the period studied. Retrospective evaluations of criteria for selecting patients for bypass operation, type of shunt done, and clinical results were recorded. Sixty-eight patients (86 per cent) weighed more than 100 pounds over ideal weight. Operative mortality was 5 per cent. Only 31 patients (47 per cent) were judged as having satisfactory results. Two patients died of hepatic failure and five required restoration of intestinal continuity. Comparison of this community experience with published data supports the concept that these operations are best confined to those institutions where there is special interest in the full range of medical and surgical care of obese patients.

Adolescent↗

Calcium channel blockade in rats with cyclosporine-induced vasoconstriction.

Calcium channel blockade has been found to attenuate nephrotoxicity of cyclosporine. However, it is not known whether intrarenal vasoconstriction caused by cyclosporine is totally mediated by vascular smooth muscle calcium influx. To study the protective effects of two calcium blockers on cyclosporine-induced intrarenal vasoconstriction and renal microvascular blood flow, hydronephrotic rat kidneys were suspended in an environmentally controlled tissue bath. Renal microvessel diameters and microvascular blood flow were determined by in vivo videomicroscopy and Doppler velocimetry. Calcium channel blockade was achieved by adding verapamil hydrochloride (5.6 x 10(-5) M) or diltiazem hydrochloride (2.8 x 10(-5) M) to the tissue bath, which respectively resulted in a 15 +/- 2% and 16 +/- 3% interlobular arteriolar dilation, a 13 +/- 3% and 12 +/- 2% afferent arteriolar dilation, and a 60 +/- 8% and 46 +/- 14% increase in interlobular blood flow. When cyclosporine (1.7 x 10(-3) M) was added to the tissue bath, there was a constriction of the interlobular arterioles to 4 +/- 3% below baseline in rats receiving verapamil and 9 +/- 3% below baseline in rats receiving diltiazem. Microvascular blood flow was reduced by the addition of cyclosporine to 3 +/- 4% above original baseline values in the verapamil group and 22 +/- 6% below baseline in the diltiazem group. Afferent arterioles were similarly constricted by cyclosporine. The results indicate that calcium blockade causes preglomerular vasodilation and protects the microvascular blood flow induced by cyclosporine. Since verapamil or diltiazem did not prevent arteriolar constriction as observed when cyclosporine was added, it was concluded that the mechanism of acute cyclosporine-induced vasoconstriction is not solely mediated by vascular smooth muscle calcium influx through potential dependent channels.

Animals↗

Microcirculatory responses to complement activation are blunted by hypertension.

Vasodilation of small arterioles in skeletal muscle during sepsis is an endothelium-dependent response. Renovascular hypertension significantly attenuates this response. Complement activation by zymosan infusion causes small arteriole dilation in skeletal muscle similar to that seen during sepsis. This study was conducted to show whether renovascular hypertension alters the skeletal muscle microcirculatory responses in normotensive rats to systemic activation of the alternative complement system. We found that hypertension abolished the constriction of large A1 arterioles (+3 +/- 2% change at 45 min) and dilation of small A4 arterioles (-2 +/- 2% change at 45 min) in skeletal muscle. Hypertension attenuated but did not abolish (A4: +70 +/- 13% change in hypertensive vs +111 +/- 18% in normotensive rats) the ability of small arterioles to dilate to nitroprusside, an endothelium-independent vasodilator. This suggest that hypertension modifies some type of receptor-level mechanism to reduce small arteriolar dilation during complement activation. We next used hydroquinone to topically block endothelium-derived relaxing factor (EDRF) in hypertensive animals whose complement systems were activated. Hydroquinone did not change the response of large A1 arterioles (+5 +/- 4% hydroquinone change vs +3 +/- 2% non-hydroquinone at 45 min) to complement activation. However, hydroquinone allowed construction of small A4 arterioles (-12 +/- 5% hydroquinone change vs -2 +/- 2%, non-hydroquinone at 45 min) during complement activation in hypertensive rats. We conclude that during hypertension the release of EDRF in small arterioles after complement activation is counterbalanced by a constrictor-producing mechanism.

Animals↗

Vena cava replacement with a peritoneum-lined vascular graft.

The use of the peritoneum as a venous conduit was analyzed because of the inherent fibrinolytic properties of the mesothelium. A canine model in which the infrarenal inferior vena cava was replaced with interposition grafts (2 cm) of either a peritoneal tube, polytetrafluoroethylene (PTFE), or PTFE lined with peritoneum (lined graft) was studied. Venograms were performed 1 and 6 weeks after graft implantation for the percent area reduction of the lumen. Grafts were explanted at 6 weeks for light and scanning electron microscopy. The percent area reduction at 1 week for all grafts was found to be predictive of graft clotting by 6 weeks. At 6 weeks, one of three peritoneal tube grafts (33%), six of seven PTFE grafts (86%), and four of seven lined grafts (57%) were patent. Histologic studies demonstrated that stenosis of PTFE grafts was due to intraluminal thrombus formation, whereas lined grafts stenosed due to granulation tissue growth between the mesothelium and PTFE. A cellular circumferential intraluminal lining was found in four of four lined grafts, but in none of six PTFE grafts (p < 0.01). Furthermore, none of four lined grafts had intraluminal thrombus, but all of six PTFE grafts did (p < 0.01). Peritoneum-lined PTFE grafts maintain a continuous circumferential cellular lining, but have no improvement in short-term patency compared to PTFE alone.

Analysis of Variance↗