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Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 109 records · Page 6Linked to original sources
PubMed1987

Verapamil enhances antitumor activity without increasing myeloid toxicity.

The effectiveness of chemotherapy is limited by drugs' resistance and toxicity to normal host cells. Verapamil increases the cytotoxicity of the Vinca alkaloids and doxorubicin hydrochloride (Adriamycin) in tissue culture. In this experiment the effect of verapamil (VER) on the cytotoxicity of vincristine sulfate (VCR) and 5-fluorouracil (5-FU) was studied with the use of an intravenous lung colonization model. After receiving 5 X 10(4) B16 F10 cells intravenously, mice were randomized into six groups and treated with intraperitoneal injections of saline solution, VER, VCR, VCR plus VER, 5-FU, or 5-FU plus VER. In the first experiment, mice were killed on day 22 and lung colonies counted. In subsequent experiments, animals were monitored until death. The addition of VER to VCR significantly decreased pulmonary tumor formation (14 versus 47 colonies; p = 0.05). This was associated with an increase in mean survival from 40.4 to 53.7 days (p = 0.05). Although the addition of VER to 5-FU also decreased pulmonary tumor colony formation (26 versus 73 colonies; p = 0.001), there was no significant prolongation of survival with this treatment. A quantitative clonal culture of granulocyte-macrophage progenitor cells (GM-CFC) was used to assess the effect of VER on bone marrow toxicity. The addition of 5 mumol VER to 5-FU (5 X 10(-3) to 5 X 10(-7) mol/L) or VCR (5 X 10(-5) to 5 X 10(-9) mol/L) did not significantly reduce GM-CFC growth compared with treatment with either drug alone. In vivo marrow toxicity assessed 18 hours after a single drug injection was also not increased by the addition of VER to VCR or 5-FU. In this model, VER enhances the oncolytic effect of both VCR and 5-FU without a concomitant increase in toxicity to normal host marrow progenitor cells.

Animals↗
PubMed1986

Decreasing the incidence of surgical wound infections. Validation of a surveillance-notification program.

In an attempt to validate the observations of a previously published ten-year study of surgical wounds, we studied 8,474 wounds over an 18-month period using a protocol nearly identical to that of the previous study. Our study corroborated the following predictors of clean-wound infection: increasing duration of surgery, age less than 1 or greater than 50 years, increasing duration of preoperative hospitalization, use of drains, and shaving and emergency surgery. We failed to corroborate use of wound irrigation as a protective measure or time of preoperative shaving as a significant variable. Most importantly, we found a 42% reduction in the clean-wound infection rate during the study period (1.9% to 1.1%), adding support to the concept that a wound surveillance program with surgeon notification is both efficacious and cost-effective.

Adolescent↗
PubMed1986

The effect of disulfiram on cyclophosphamide-mediated myeloid toxicity.

We have previously shown that disulfiram (DSF) blocks the urotoxicity of cyclophosphamide (CYT) in mice and increases the oncolytic effect of CYT in the L1210 murine leukemia. However, mice treated with CYT and DSF appeared to have longer-lasting neutropenia than animals treated with CYT alone. To determine whether DSF uroprotection of CYT-treated mice was associated with increased myeloid toxicity, we examined the effects of DSF plus CYT treatment on the bone marrow granulocyte/macrophage progenitor cell (GM-CFC). Marrow cellularity and GM-CFC numbers were analyzed at 1, 2 and 3 days after injection of CYT (62.5 or 125 mg/kg) or CYT plus DSF (200 mg/kg). CYT alone caused a decrease in total marrow cellularity varying from 20% to 50% of control. Animals given CYT plus DSF had a somewhat greater decrease in total marrow cellularity than those treated with CYT alone. However, in mice treated with CYT plus DSF, the GM-CFC were relatively well preserved and the recovery of the GM-CFC was not prolonged by DSF. It appears from these studies that the acute toxic effect of CYT on the granulocyte/macrophage progenitor cells is not enhanced by DSF.

Animals↗
PubMed1986

Inhibition of wound healing by Corynebacterium parvum.

Corynebacterium parvum (C. parvum), an immunostimulant, was examined for its effects on wound healing in mice. Animals injected intraperitoneally with C. parvum, 1400 micrograms 48 hr prior to wounding had significantly decreased wound strength at 5, 7, 11, 14, and 21 days after wounding compared to saline-injected controls (P less than 0.05-P less than 0.001). Mice injected with C. parvum at 48 or 2 hr before wounding, synchronous with wounding and 2 or 48 hr after wounding had significantly decreased wound disruption strength of 11-day-old wounds (P less than 0.01-P less than 0.001). Formalin fixations of wound strips from C. parvum-treated animals were consistently weaker than similarly treated wound strips from controls (P less than 0.05-P less than 0.01). Histologic analysis of wounds from C. parvum-treated animals revealed decreased amounts of wound collagen and increased inflammatory reaction compared to saline-injected animals. While C. parvum can improve survival following injury or septic challenge, the potential for marked alterations in wound healing may limit its clinical application in surgical and trauma patients.

Animals↗
PubMed1986

The effects of burn injury and fluid resuscitation on cardiac function in vitro.

The effects of a 30% full-thickness total body surface area scald burn on in vitro mechanical cardiac function was studied in Sprague-Dawley rats. The findings were a 50% decrease in tension development and velocities of contraction and relaxation, when papillary muscle functions from sham and unresuscitated burned animals were compared. Fluid resuscitation synchronous with burning completely reversed the defects in papillary muscle function. This defect in function was partially transferable to normal muscles incubated in serum from burned rats.

Animals↗
PubMed1986

Colonic varices. Report of an unusual case diagnosed by radionuclide scanning, with review of the literature.

We report a patient who developed recurrent massive lower gastrointestinal bleeding after successful obliteration of esophageal varices by sclerotherapy. A radionuclide study was very helpful in establishing diagnosis of the lesion responsible, a varix in the cecal area. Bleeding subsided after creation of a portacaval anastomosis. The literature pertaining to colonic varices is reviewed.

Cecum↗
PubMed1985

Refeeding differentially affects tumor and host cell proliferation.

Tumor and host tissue DNA synthesis in C3H female mice with MA16/C tumors were examined for the effects of starvation and refeeding. Animals with subcutaneously implanted tumors were randomized to either regular diet or starvation for 48 hr followed by refeeding for 6, 12, 24, 48, or 72 hr. With starvation, both tumor and host tissues demonstrated a decrease in DNA synthetic activity. After refeeding, resumption in DNA tumor synthesis preceded that of host tissues and was greatest within the first 6-12 hr. Host tissue DNA synthetic activity resumed at different times in the various tissues examined with bone marrow being earlier than spleen or liver. The differential time course between induction of tumor and host DNA synthesis could allow a more precise modeling in studies dealing with the interaction of nutritional repletion and antitumor therapy.

Animals↗
PubMed1985

The quantity and function of pulmonary alveolar macrophages after splenectomy and Corynebacterium parvum.

We have previously shown that Corynebacterium parvum (C. parvum), a nonspecific immunomodulator, partially protects splenectomized and nonsplenectomized mice when challenged with aerosolized pneumococci. We report here the effects of both splenectomy and C. parvum on the phagocytic function of the lavageable pulmonary alveolar macrophage (PAM). Groups of young adult male Sprague Dawley rats underwent splenectomy or sham operation 3 weeks before injection of C. parvum 1.5 mg IP (or saline) per animal. One week postinjection PAM's were harvested. The in vitro phagocytic indices (PI) for PAM incubated with tritiated thymidine-labeled S. aureus or Streptococcus pneumoniae, type 14, opsonized with normal rat serum, were determined. Splenectomy had no effect on lung weights, PAM yield, or PAM phagocytic activity. C. parvum administration significantly increased spleen weight in sham-operated animals, but had no effect on lung weights, PAM yield, or phagocytic activity of either control or splenectomized animals. Splenectomy in the adult rat did not induce a phagocytic defect in the PAM and thus the lavageable PAM cannot be considered a significant site of the postsplenectomy defect. Since C. parvum protects animals from respiratory challenge with Streptococcus pneumoniae but does not alter the number or activity of lavageable alveolar macrophages, we hypothesize that C. parvum protection is more likely related to our previous finding of an increased clearance of blood-borne bacteria by the expanded and enhanced reticuloendothelial system.

Animals↗
PubMed1985

Effect of burn injury on granulocyte and macrophage production.

Using a model of uncomplicated burn injury in mice, we assayed the bone marrow and splenic production of granulocytes and macrophages after burn injury. The effects of burn size and burn wound excision and closure were studied. Using an in vitro quantitative clonal culture technique for granulocyte/macrophage progenitor cells (GM-CFC), myeloid precursors were directly assayed. Burns of a 10% body surface area were equal to burns of larger magnitude for effects on marrow and splenic granulocyte/macrophage production. The total peripheral blood leukocyte and lymphocyte counts were depressed at days 1 and 4 postburn but were elevated at days 8 and 12. Granulocytes, however, remained significantly increased at days 8 and 12. The bone marrow response to burning showed an initial depression in marrow cellularity on day 1 with return to normal values by days 8 and 12. The numbers of GM-CFC were significantly elevated on days 4-12 with a near threefold increase in the number of GM-CFC 12 days following burn injury. The splenic response to burn injury was characterized by a decrease in the splenic index on day 1 but then a persistent increase at days 8 and 12. Total splenic cellularity was depressed on day 1 but significantly increased at days 8 and 12. The total number of splenic GM-CFC was increased on days 4-12 with a 100-fold increase on day 8. The immediate or delayed excision of the burn wound did not alter marrow or splenic response to burning. We conclude that following a cutaneous injury there is a marked alteration in the generation of the phagocytic cells of the granulocyte and macrophage series and that this response is secondary to the wounding process.

Animals↗
PubMed1985

Corynebacterium parvum augments antibody production in splenectomized mice and mice with sham operations.

The antibody response to a variety of antigens, including pneumococcal polysaccharides, is diminished in splenectomized (splx) mice. We investigated the capacity for the biological response modifier Corynebacterium parvum to augment antibody production in splx and sham-splx mice inoculated with pneumococcal polysaccharides and tetanus toxoid. As expected, antibody response to tetanus toxoid was similar in both splx mice and sham-splx mice. C. parvum augmented anti-tetanus toxoid antibody in both sham-splx (P less than 0.05) and splx mice (P less than 0.05). Antibody against pneumococcal type 3 polysaccharides was decreased in splx mice compared with sham-splx mice (P less than 0.05). Both groups treated coincidently with C. parvum and pneumococcal type 3 polysaccharides demonstrated a biphasic antibody response which was greater than that observed in saline-treated controls (sham-splx, P less than 0.001; splx, P less than 0.05). Whereas the secondary peak response to pneumococcal type 3 polysaccharides after treatments with C. parvum appears to be due to persistent elevations of immunoglobulin G and immunoglobulin M in sham-splx mice, it is primarily due to antibody of the immunoglobulin G class alone in the splx mice.

Animals↗
PubMed1984

Experimental tumors and aging: local factors that may account for the observed age advantage in the B16 murine melanoma model.

In the B16 murine melanoma model tumor growth has been shown to be slower in animals of advanced age. One feature associated with this slower growth has been prominent fibrosis demonstrated in biopsies of the tumor in older animals. We have performed experiments to examine the fibrotic response in young and old mice. In non-tumor bearing animals the capacity to regain skin strength after surgical laceration and healing by primary intention was greater in old mice. Histologic preparations suggested a more prominent fibrosis at the wound site. The animals who were injected subcutaneously with B16 melanoma and treated with L 3,4-dehydroproline (an inhibitor of collagen synthesis) local tumor growth was significantly enhanced only for the old animals. Although this inhibition of collagen synthesis produced a differential growth enhancement, there remained a significant difference in tumor volume between young and old animals. We conclude that fibrogenesis is an important host defense for containing local tumor growth and that this mechanism is preserved if not enhanced in mice of advanced age. Nevertheless other factors are needed to account completely for the observed age-advantage in the B16 melanoma model.

Aging↗
PubMed1984

Probability of surviving postoperative acute renal failure. Development of a prognostic index.

Sixty-five patients who developed postoperative acute renal failure requiring hemodialysis were retrospectively analyzed to identify variables that could be used to predict outcome. Our aim was to identify patients who would have an unfavorable outcome despite hemodialysis and to identify those factors that might be altered to improve outcome. A linear discriminant function capable of segregating survivors from nonsurvivors in the retrospective analysis was subsequently validated in a prospective fashion using a second patient population. Variables used were age, sex, number of transfusions, interval from onset of acute renal failure to dialysis, type of surgery, preoperative hypotension, and the presence of cardiac failure. Scores were formulated for each patient and then segregated into three groups: patients with no precedence for survival, patients with an intermediate risk of dying, and patients with low risk of dying. Based on the univariant analysis, the interval from onset of acute renal failure to first dialysis and the maximum serum creatinine prior to first dialysis were the only factors that might be altered to change mortality. The prognostic index we have developed enables one to select patients without a chance of survival.

Acute Kidney Injury↗
PubMed1984

Immunoglobulin production in burned patients.

To further characterize immunologic alterations found in thermally injured patients, a series of experiments dealing with lymphocyte immunoglobulin production were performed. Circulating immunoglobulin levels were measured, plasma antitetanus toxoid was quantitated, and lymphocytes were cultured and in vitro immunoglobulin production recorded. Postburn circulating immunoglobulins were initially depressed but returned to normal at a variable rate. We found a normal response to rechallenge with tetanus toxoid. However, culture of lymphocytes in vitro showed that lymphocytes from burned patients had an elevated spontaneous immunoglobulin production and no augmentation with mitogen stimulation. This alteration in immunoglobulin production was not found in a group of postoperative or trauma patients and appears to be unique to burned patients.

Adolescent↗
PubMed1984

Transfer of age-associated restrained tumor growth in mice by old-to-young bone marrow transplantation.

B16 melanoma and Lewis lung carcinoma grow more slowly in aged mice. Immunesenescent changes may account for this age-related difference. To test for the effect of immune deficiency on the growth of these tumors, we treated young mice with an immunosuppressive dose of radiation and then observed tumor growth. We also radiated young mice to a higher (lethal) dose and then rescued them with either young or old bone marrow transfusion. Tumors grew more slowly in radiated mice than controls and in those reconstituted with old bone marrow. These findings support the concept of immunesenescent-related reduced tumor growth.

Aging↗
PubMed1984

Recurrent hemorrhage into the pancreatic duct from a splenic artery aneurysm.

We describe a case of upper gastrointestinal hemorrhage secondary to splenic artery aneurysm-pancreatic duct fistula, with associated partial common bile duct obstruction and pancreatitis. The literature is reviewed briefly in order to stress distinctive clinical features and caveats in diagnosis. Angiography is the most definitive diagnostic study; surgical resection is curative.

Aged↗
PubMed1983

Improved survival after pneumococcus in splenectomized and nonsplenectomized mice with Corynebacterium parvum.

Splenectomy increases the susceptibility to infections with certain bacteria, particularly Streptococcus pneumoniae. Because the immunomodulator Corynebacterium parvum expands the phagocytic cell compartment and enhances reticuloendothelial function, we tested the effect of C parvum in mice challenged with aerosolized pneumococci. Mice splenectomized seven days before pneumococcal challenge and treated intraperitoneally with 700 micrograms of C parvum immediately after exposure were protected when compared with splenectomized or sham-operated saline-injected controls. Analysis of proportional hazards showed the risk of dying in order of greatest to least as follows: splenectomy/saline, sham/saline, splenectomy/C parvum and sham/C parvum. The benefits of an intact spleen and C parvum seemed to be additive in their protective effects after aerosol pneumococcal challenge. After intravenous challenge, bloodstream clearance was improved in sham-operated mice at three days after C parvum injection compared with saline-injected sham-operated controls and C parvum-injected splenectomized mice. A significant improvement in bacterial clearance did not occur until seven days after C parvum treatment in splenectomized mice. The results demonstrate the value of a nonspecific immunomodulator for enhancing the defense mechanisms of both normal and splenectomized animals.

Adjuvants, Immunologic↗