Biomedical subjects
Publications and source records attributed to E Benjamin.
Toxic shock syndrome is an uncommon disease associated with staphylococcal infections. Although most frequently reported in menstruating women and associated with tampon use, toxic shock syndrome has been described following many types of surgical procedures. In this report we describe a case of toxic shock syndrome occurring in a previously healthy young man after elective surgery for a pilonidal cyst.
BACKGROUND AND METHODS: It is hypothesized that pentoxifylline may be beneficial during shock states by improving tissue oxygenation. To test this hypothesis, we examined the effect of pentoxifylline on hemodynamics, oxygen delivery (DO2), and tissue metabolism during severe hemorrhagic shock. We conducted a placebo-controlled, randomized trial using anesthetized, mechanically ventilated dogs in hemorrhagic shock maintained at a mean arterial pressure of 45 to 50 mm Hg. Six animals were treated with a 10-mg/kg bolus of iv pentoxifylline followed by a continuous infusion at 5 mg/kg.hr. The controls consisted of six animals treated with saline. RESULTS: There were no significant differences between the groups before treatment. During 150 mins of posttreatment, repeated measurements of the control and pentoxifylline groups showed no significant differences in heart rate (HR), cardiac output, systemic and pulmonary vascular resistances, DO2, or blood lactate concentration (repeated-measures analysis of variance). CONCLUSIONS: In this acute, nonresuscitated, canine hemorrhagic shock model, pentoxifylline did not act as a vasodilator, or have any significant effect on HR, cardiac output, oxygen transport, or lactic acidosis.
We previously demonstrated that the area encompassing residues 147-162 of the envelope protein of simian retrovirus serotype-1 (SRV-1) is the target for rhesus anti-SRV-1 neutralizing antibodies. A peptide representing amino acids 142-167 of envelope protein (gp70) is capable of inducing virus-neutralizing antibodies in mice. The virus receptor was immunoprecipitated from Raji cells using gp70 as the ligand. Antibodies to peptide 142-167 inhibit the immunoprecipitation, indicating that the receptor recognizes residues 142-167 of the viral envelope protein.
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The determination of intra-abdominal pressures (IAP) may be useful in many clinical situations. The authors recently demonstrated in the canine model a close correlation between actual IAP and the bladder pressure measurements obtained from a transurethral catheter. The purpose of this study was to clinically validate this technique. The authors studied 16 patients, and compared IAP in three positions (supine, with compressions, and semi-erect) utilizing both direct intraperitoneal pressure monitoring and the pressure obtained with a transurethral bladder catheter. Their results demonstrated a linear relationship between the two methods described, with a mean r value of 0.95 in the supine and semi-erect positions, and 0.99 with abdominal compressions (P less than 0.0001). The authors conclude that transurethral monitoring of bladder pressure offers a safe, simple, and highly accurate method for evaluating IAP at the bedside. Studies evaluating the indication for its use in the operating room and intensive care settings appear warranted.
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The hemodynamic effects of intravenous ranitidine were studied in a prospective double-blind fashion in postoperative intensive care unit patients to determine if this H2 blocker produced the same transient fall in mean arterial pressure and systemic vascular resistance known to occur with cimetidine infusion. We found no statistically significant hemodynamic changes from baseline associated with infusion of 50 mg ranitidine over a 5-minute period. The different chemical ring structure of ranitidine and its effect on H2 vascular and cardiac receptors may account for these observations.
We evaluated the use of percutaneous endoscopic gastrostomy in 30 ICU patients. There was a 14% incidence of minor complications, no major complications, and no mortality. We conclude that percutaneous endoscopic gastrostomy is a useful alternative to operative gastrostomy in the ICU patient.
We studied the use of sodium bicarbonate administration in a canine model of hemorrhagic shock to determine its effect on hemodynamics, arterial and venous blood gases, respiratory gases, and blood lactate levels. Thirteen dogs were anesthetized, paralyzed, mechanically ventilated, and hemodynamically monitored. Hypotension was induced and maintained at a mean arterial pressure of 40 to 45 mm Hg using controlled hemorrhage and reinfusion. After 2.5 h of shock, the dogs were randomized into two groups: one group (n = 6) received NaCl infusion; the other (n = 7) received sodium bicarbonate (1 mEq/kg followed by a continuous infusion of 2.5 mEq/kg.h for 2.5 h). CO2 production was increased in the alkali group, but there was no statistically significant difference between groups in any measured hemodynamic, blood gas, or respiratory gas variable. These included heart rate, BP, cardiac output, arterial and venous pH, CO2 production, and bicarbonate levels. Blood lactate levels, however, in the bicarbonate treated animals were significantly (p less than .01) higher than in the group treated with NaCl alone (10.1 +/- 3.2 vs. 5.1 +/- 1.2 mEq/L). These results are similar to the effects of bicarbonate found in other models of lactic acidosis, and suggest that bicarbonate therapy may have limited usefulness in the treatment of lactic acidosis.
We studied the use of the head-down tilt position (Trendelenburg) in elderly postoperative patients in the intensive care unit to determine its effect upon cardiac and pulmonary function. Twenty-two patients (mean age 68.4 years) were placed in a 12 degrees head-down tilt position for 15 minutes. No deterioration was shown in any measured cardiac parameter; mean arterial pressure, cardiac index, and right and left ventricular stroke work increased significantly (P less than .05). Further, there were no observed changes in arterial or venous oxygenation, or in venous admixture. Because of the uncertain effect of the head-down tilt position upon cerebral blood flow, the routine use of this position is not recommended for the treatment of hypotension or during cardiopulmonary resuscitation. The results of this study, however, show that the cardiopulmonary effects are well tolerated if the position is required, as during central venous access procedures.
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O6-Alkylguanine, a DNA adduct formed by nitrosoureas, becomes the site of a point mutation during DNA synthesis by preferentially base mispairing with thymine rather than correctly base pairing with cytosine. To repair this adduct, cells contain a limited amount of O6-alkylguanine-DNA alkyltransferase (alkyltransferase), a protein which removes the alkyl group in a stoichiometric reaction. To prevent mutations, repair must occur before DNA replication takes place. Consequently, formation of point mutations is related inversely to the number of alkyltransferase molecules and directly to the rate of DNA synthesis. Bone marrow hematopoietic precursors, the target for nitrosourea-induced leukemia, are deficient in alkyltransferase activity. We questioned whether regenerating bone marrow is more susceptible to nitrosoureas than other organs due to persistently low levels of alkyltransferase activity during periods of increased cell proliferation and DNA synthesis. Following syngeneic bone marrow transplantation, murine hematopoietic cells underwent rapid cell proliferation but alkyltransferase activity remained well below the activity in liver. After N-nitrosomethylurea exposure, [3H]thymidine incorporation in rat bone marrow increased 3-fold and stem cell proliferation over 10-fold within 2 days of exposure, but alkyltransferase activity remained low. The relative susceptibility of bone marrow to mutagenic damage from O6-alkylguanine adducts was determined by comparing the ratio of alkyltransferase activity to [3H]thymidine incorporation in marrow, kidney, and liver. In untreated animals, the ratio was lowest in bone marrow and decreased further 48 h after N-nitrosomethylurea exposure to only 21% that of kidney and 1% that of liver. Thus, proliferating hematopoietic precursors appear more likely to form point mutations following nitrosourea exposure than other rodent tissues because they undergo rapid proliferation soon after DNA damage and before O6-alkylguanine adducts can be repaired. The combination of rapid cell proliferation and low DNA repair capacity may be the mechanism of nitrosourea induced leukemic transformation of the bone marrow.
The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord-stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli-Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli-Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non-neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co-expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli-Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.
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The venous-arterial PCO2 gradient may increase in certain low-flow states, such as CPR and canine endotoxemia. To determine whether venous hypercarbia also occurs in hemorrhagic shock, we studied 12 anesthetized, mechanically ventilated dogs. We performed laparotomies on the animals, inserting catheters into their renal, superior mesenteric, and external iliac veins. Flow in the corresponding arteries were determined using electromagnetic flow probes. The dogs were randomized into a control group (n = 6), and a hemorrhagic shock group (n = 6) which was bled to a mean arterial pressure of 45 to 50 mm Hg and maintained at this pressure for the 6-h study. The results demonstrated a significant (p less than .05) increase in lactate and venous-arterial PCO2 gradient systemically and in all three regional beds. A significant decrease of venous blood pH accompanied these changes which are consistent with our previous findings in low-flow, canine endotoxemia. We conclude that venous hypercarbia is a nonspecific phenomenon, common to low-flow states. The increased CO2 represents both an increased CO2 production and a decreased removal, secondary to low-flow.
The determination of intra-abdominal pressure (IAP) may be useful in a variety of clinical situations. Despite this, invasive IAP monitoring is seldom performed due to the risks involved. Using a standard canine model of increased IAP, we evaluated the accuracy of transurethral bladder catheter pressure in reflecting IAP. Throughout the range of IAP studied (10 +/- 5 to 70 +/- 10 mm Hg), bladder pressure did not differ significantly from the direct measurement of IAP. We conclude that the measurement of bladder pressure using a standard transurethral bladder catheter provides an accurate determination of IAP.
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