Wayne W. Ferguson

Blunt abdominal trauma: Exploratory laparotomy or peritoneal lavage?

In contrast to other series purporting advantages of routine lavage [20], our data support the position that, in patients with blunt abdominal trauma, certain criteria eliminate the need for peritoneal lavage and make this procedure an unwise investment of valuable time on a routine basis. Criteria such as evidence of hollow organ rupture on radiologic studies, gross abdominal wall defects (excluding simple lacerations), rapidly increasing abdominal distention, uncorrectable hypotension and isolated rigidity on abdominal examination in an otherwise intact and cooperative patient, should be considered indications for laparotomy. In a stable patient with associated injuries or altered central nervous system status, abdominal examination should be viewed as suspect and peritoneal lavage considered mandatory. However, in over one fourth of cases, positive lavage may fail to correlate with intraabdominal injury of a degree that necessitates operative repair. In patients admitted for observation of abdominal injuries with concurrent alterations in central nervous system status or associated injuries that hinder accurate abdominal examination when no urgency exists, we support the opinion that selective use of peritoneal lavage will save unnecessary delay in diagnosis and operative treatment. The highly lethal nature of multiple injuries and central nervous system damage is confirmed by our data, veryfying reports by Davis et al [6] of a 70 percent or greater mortality rate among comatose patients hospitalized with multiple trauma.

Transcatheter embolic control of iatrogenic hematobilia

For the patient with hematobilia, a serious complication of liver injury, angiography is the definitive diagnostic procedure. In addition to localizing precisely the source of the hemorrhage, angiography also provides an effective alternative to surgery for the control of hemorrhage. In two cases of iatrogenic hematobilia discussed, the bleeding sites were identified by angiography, and the bleeding was controlled by transcatheter embolization.

Correlation of lysosomal enzymes and cachexia in the tumor-bearing rat

Abstract This study describes an implantable mammary adenocarcinoma in the female Fischer 344 rat which appeared to be quite stable, growing locally and subcutaneously with no metastasis and with readily definable effects on the host. The effects of tumor cachexia were easily studied in this model and were compared to the effects of starvation. Animals bearing tumors gained slightly in weight over controls at first, but then the carcass of the tumor-bearing animal began to lose weight while the tumor continued to accelerate in growth. By Day 20, food and water consumption in the tumor group started declining more than in the control group. Liver weight was significantly elevated in the tumor group and decreased in the starvation group compared to controls. The dry weight to wet weight ratio was decreased in both groups compared to controls. The calculated total dry weight increased in the tumor group and decreased markedly in the starvation group. White blood cell counts were markedly elevated in the tumor group with a high percentage of polymorphonuclear leukocytes. Plasma lysosomal enzyme activity was relatively low for all three groups. There were significant elevations of lysosomal enzymes in the tumor group in liver and muscle compared to controls. Most of this increased activity appeared to be in the free or nonlysosomally bound fraction of the homogenized tissue. It is suggested that these tissue lysosomal enzyme changes may be contributing to tissue alterations seen in the tumor cachectic host.

Mechanism of the lack of a beneficial response to inotropic drugs in hemorrhagic shock.

Lanatoside C, glucagon, and isoproterenol, three inotropic agents were found to be ineffective in prolonging survival or in improving the over‐all circulatory status of dogs in hemorrhagic shock, despite their temporary effectiveness as inotropic agents. Lanatoside C constricted the splanchnic circulation leading to lysosomal disruption, release of cathepsin D, and production of a myocardial depressant factor (MDF). Glucagon dilated the splanchnic circulation only transiently but directly disrupted splanchnic lysosomes and thus MDF was produced. Isoproterenol dilated the peripheral vasculature to such an extent that circulatory collapse ensued. Other inotropic agents may be of value in the treatment of postoligemic shock, but potentially deleterious side effects must be considered when they are administered in circulatory shock.

Functional characteristics and lysosomal integrity of the isolated perfused cat pancreas

Abstract The isolated cat pancreas perfused with a physiological salt solution plus low molecular-weight dextran functions satisfactorally for at least 2 1 2 hours. Evidence for stability and functional integrity of the preparation included measurements of vascular resistance, arterial and venous pH, PO2, and PCO2, pancreatic juice volumes and trypsin concentrations, and studies of acinar cell ultrastructure. Total specific β-glucuronidase activity of the unstimulated perfused pancreas was comparable to that seen in the intact cat pancreas. However, pancreozymin and secretin decreased the total β-glucuronidase activity of the perfused pancreas. Pancreozymin also increased the release of β-glucuronidase from lysosomal suspensions of liver and pancreas. β-Glucuronidase activity rose in the pancreatic juice, duodenal secretion, perfusate, and the bathing medium of the hormonally stimulated perfused pancreas concomitant with a decreased number of zymogen granules and lysosomes in the acinar cells. The data are consistent with the hypothesis that pancreozymin increases the fragility of pancreatic lysosomes liberating β-glucuronidase into the pancreatic duct, extracellular space, and intravascular compartment. Lysosomal enzymes released into the duct may have an auxiliary digestive function in the duodenum, and the increased extracellular lysosomal enzyme activity may play a role in the pathophysiology of pancreatitis or other pancreatic disease states in which the pancreatic lysosomes become compromised.

Lysosomal enzyme levels and tumor growth in steroid-treated rat model☆

Abstract Elevations in lysosomal enzyme levels have been shown to correlate with tumor progression or metastasis. Furthermore, evidence suggests that liberation of lysosomal enzymes may affect tumor growth patterns, immunologic responses, and development of cachexia in the host. As glucocorticoids are known to stabilize lysosomal membranes, as well as to produce significant effects in overall cellular metabolism and growth, effects of methylprednisolone acetate (MPA) on lysosomal enzymes and tumor growth were studied using a nonmetastasizing mammary carcinoma model. Fischer 344 rats ( N = 41) were randomly divided into six groups: control (C), tumor (T), rats steroid-treated for 2 weeks prior to sacrifice (MP 2 ), or those given a single steroid dose 2 days before sacrifice (MP), and animals with tumor given steroids in a single dose (TMP), or for 2 weeks (TMP 2 ). At the time of sacrifice, carcass, liver, and tumor weights were calculated: samples of plasma, muscle, liver, and tumor were assayed for cathepsin D, a proteolytic lysosomal enzyme. With prolonged MPA treatment (TMP 2 ), as compared to groups T and TMP, significant reduction in tumor size was noted. Lysosomal enzymes in liver and muscle were increased with either MPA therapy or tumor, except in group TMP 2 , where liver and muscle cathepsin D was markedly decreased. While elevation in cathepsin levels resulted from steroid treatment in nontumor rats, reduction in tumor size and concomitant decline in cathepsin D levels in rats with tumor implicate lysosomes as indicators of tumor regression, and suggest a role of lysosomal enzymes in host-tumor interaction.

Effect of propylthiouracil on rat thyroid lysosomal enzymes

Abstract Dietary propylthiouracil (PTU) is goitrogenic in young rats and also decreases their growth rate. Twenty-seven rats were administered PTU for 60 days with 10 rats serving as controls. Rat thyroid weight progressively increased from a normal level of 0.037 ± 0.003 to 0.13 ± 0.1g. Comparable amounts of thyroid tissue from control rats and those with PTU-induced goiter were assayed at varying time intervals for the lysosomal enzymes, cathepsin D and β-glucuronidase. The nonsedimentable or free fraction, total, and the percentage free/total lysosomal activity were significantly reduced in the goitrous tissue. When additional thyroid tissue from 28 more rats fed dietary PTU was incubated at 37°C with exogenous thyrotropin added, the tissue secreted substantial amounts of cathepsin D, but not β-glucuronidase. Our finding that PTU-induced goitrous tissue can specifically secrete cathepsin D in vitro is a unique observation which may have clinical implications.