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Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 127 records · Page 7Linked to original sources
PubMed1983

Effects of protein-calorie malnutrition and refeeding on fluorouracil toxicity.

Mice were used to study the effects of protein-calorie malnutrition and its reversal on granulocyte-macrophage production and fluorouracil's toxic effect on bone marrow. An in vitro quantitative clonal culture technique for bone marrow granulocyte-macrophage progenitor cells (GM-CFC) was used. Animals on a protein-free but otherwise complete diet for ten days had a significant contraction in total marrow cellularity and GM-CFC numbers paralleling the animal's weight loss. The acute toxic effect of fluorouracil on bone marrow was not increased in protein-deprived animals. On refeeding, there was a biphasic response in the degree of toxic effect on marrow. Animals refed for one day had significantly increased fluorouracil-related marrow abnormalities. However, animals refed for four days, when marrows were repleted, were partially protected from the drug's cytotoxic effects. The increased sensitivity in mice refed for one day was related to more GM-CFC in active DNA synthesis.

Animals↗
PubMed1983

Lack of protection by pneumococcal vaccine after splenectomy in mice challenged with aerosolized pneumococci.

The efficacy of pneumococcal vaccine given after splenectomy lacks experimental validation. Adult CD-1 male mice that received type III pneumococcal capsular polysaccharide vaccine 1 microgram IP, 48 hours postsplenectomy and 7 days before challenge with aerosolized type III Streptococcus pneumoniae had a significantly higher mortality (96%) compared to immunized controls (64%) (p less than 0.002). The vaccine protected immunized sham-operated mice compared to unimmunized controls (p less than 0.015). Mice immunized 7 days before splenectomy were equally protected when compared to immunized sham-operated mice (p = NS). All deaths were secondary to culture-proven pneumococcal infection. These findings corroborate previous experimental and clinical studies demonstrating an impaired immunologic response and increased susceptibility to infection in asplenic individuals. Pneumococcal vaccines should be given before nonemergent splenectomy. Alternatives to splenectomy should be considered for patients with traumatized spleens where possible.

Aerosols↗
PubMed1983

Hematopoietic toxicity by cimetidine. Reexamination using the antimetabolite azathioprine.

By using an in vitro quantitative clonal culture technique for bone marrow granulocyte/macrophage progenitor cells (GM-CFC), we studied the effects of cimetidine alone and cimetidine plus azathioprine on bone marrow toxicity in C57BL/6 mice. Femoral bone marrow showed no effect of cimetidine in doses from 31.25 to 500 mg/kg on either marrow cellularity or the number of GM-CFC. Cimetidine pretreatment with single doses of 62.5 mg/kg or 250 mg/kg had no effect on the bone marrow suppression of azathioprine at 100 mg/kg. Chronic cimetidine pretreatment at 62.5 mg/kg daily for 7 days also had no effects on the single-dose azathioprine toxicity. Cimetidine given either before or after azathioprine had no effect on the rate or final level of recovery of GM-CFC in the marrow after depletion by azathioprine. Cimetidine in vitro at doses of 3.1 to 200 micrograms/ml caused no alteration in the proliferative response of the GM-CFC. Analysis of the serum colony-stimulating activity 1 to 24 hr following doses of cimetidine of either 12.5 mg/kg or 31 mg/kg caused no change in the serum colony-stimulating activity. We could find no evidence that at clinically relevant doses, cimetidine increased the hematopoietic toxicity of the azathioprine or altered the rate of bone marrow recovery after azathioprine depletion.

Animals↗
PubMed1982

Intestinal intubation in acute, mechanical small-bowel obstruction.

A review of 100 consecutive patients admitted with simple, mechanical small-bowel obstruction secondary to adhesions and treated for at least 24 hours with nonoperative intestinal intubation showed that of 76 patients admitted with partial small-bowel obstruction, 49 (65%) were successfully treated without operation. Of those with complete small-bowel obstruction (CSBO), 18 of 24 (75%) subsequently required surgical intervention; however, six of 24 (25%) were safely treated by nonoperative intubation. The 24-hour delay in surgery for CSBO did not increase morbidity or mortality in the 18 requiring operations. Major indications for surgical intervention were suspected strangulated obstruction or persistent obstruction, which frequently was associated with unsuccessful tube passage. Administration of antibiotics preoperatively was associated with a significant reduction in wound infections in patients requiring resection or enterotomy.

Acute Disease↗
PubMed1982

Effect of disulfiram (tetraethylthiuram disulfide) amd diethyldithiocarbamate on the bladder toxicity and antitumor activity of cyclophosphamide in mice.

Cyclophosphamide is the most commonly prescribed alkylating agent in clinical medicine. The usefulness of cyclophosphamide is often limited, however, by its propensity to cause hemorrhagic cystitis especially in children or patients receiving concomitant radiotherapy. Administration i.p. of cyclophosphamide at doses of 100 mg/kg or more to mice produced a significant increase in urinary bladder weight within 48 hr of treatment. The present studies demonstrate that disulfiram prevented cyclophosphamide-induced bladder damage when administered p.o. within 1 hr of cyclophosphamide treatment. Diethyldithiocarbamate, a sulfhydryl-containing metabolite of disulfiram, had identical uroprotective activity. Unlike disulfiram, diethyldithiocarbamate was effective only when administered 2 to 4 hr after cyclophosphamide. Disulfiram augmented slightly the antitumor activity of cyclophosphamide against L1210 murine leukemia in vivo when administered 30 min prior to cyclophosphamide. In contrast, diethyldithiocarbamate had no effect on the antitumor activity of cyclophosphamide when administered 4 hr after cyclophosphamide.

Animals↗
PubMed1981

Systemic amyloidosis involving two renal transplants.

Two patients with primary amyloidosis, each of whom had received a renal transplant for chronic renal failure, developed amyloid in their allografts. In one patient amyloid was present primarily in glomeruli and to a lesser extent in the interstitial tissue. This patient developed renal failure necessitating retransplantation. In the second patient amyloid was seen in the interstitium and interlobular blood vessels. Minimal amyloid was present in the glomeruli. This patient died of cardiac amyloidosis with good graft function at the time of death. Of the several patients recorded in the literature with amyloid in renal allografts, our first patient is the only one to exhibit glomerular amyloid and failure of the graft. Amyloid in areas other than the glomerulus does not appear to be incompatible with satisfactory graft function.

Amyloid↗
PubMed1979

Effect of ureteral ligation and nephrectomy on granulocyte-macrophage progenitor cells and azathioprine toxicity.

Using an in vitro quantitative clonal culture technique of bone marrow granulocyte-macrophage progenitor cells (colony-forming units culture (CFU-c)), we studied the hematopoietic toxicity of azathioprine after unilateral and bilateral ureteral ligation, unilateral and bilateral nephrectomy, and splenectomy in C57BL/6 mice. Analysis of femoral bone marrow 18 hr after i.p. injection of azathioprine (300 mg/m2) revealed increased CFU-c toxicity in comparison to controls as follows: (1) bilateral ureteral ligation, P less than 0.01; (2) bilateral nephrectomy, P less than 0.01; (3) unilateral ureteral ligation, P greater than 0.05 less than 0.1; (4) unilateral nephrectomy, P, not significant; and (5) splenectomy, P, not significant. Extrapolation from a dose-response curve for the toxicity of azathioprine on the bone marrow CFU-c indicated that bilateral ureteral ligation and bilateral nephrectomy had the effect of a 25 to 50% increase in the azathioprine dose. After bilateral ureteral ligation, serum granulocyte-macrophage colony-stimulating factor levels were increased and in vitro tritiated thymidine suicide studies showed an increased proliferative rate of the CFU-c. Since azathioprine is a predominantly cell cycle-specific agent, we suggest that increased sensitivity to azathioprine is related to the increased proliferative rate of the CFU-c. The findings provide a rationale for a clinical policy of azathioprine reduction when there is depressed renal function.

Animals↗
PubMedDate not supplied

Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1.

Previous studies suggest that normal wound repair requires the regulated production of monocyte and macrophage chemoattractants. The current study examines the role of monocyte chemoattractant protein-1 (MCP-1) in coordinating monocyte recruitment into sites of injury. MCP-1 protein was detected in both incisional and excisional murine wounds, with a peak concentration occurring slightly before maximum macrophage infiltration. Compared to wounds treated with control antibody, wounds treated with a neutralizing monoclonal anti-MCP-1 antibody contained significantly fewer macrophages (8.2 +/- 0.9 vs. 14 +/- 1.7 macrophages per high power field, p < 0.05). Conversely, the addition of recombinant MCP-1 to wounds resulted in a substantial increase in the number of macrophages (107% to 124% increase over untreated wounds, p < 0.01). Because macrophages promote wound healing, the effect of recombinant MCP-1 on the wound healing process was examined. Incisional wounds (n = 12) were either left untreated or treated with vehicle alone, 5 ng recombinant MCP-1 in vehicle, or 50 ng recombinant MCP-1 in vehicle. Wound disruption strength was determined on days 7, 14, 21, and 28 for each group. Wounds treated with MCP-1 exhibited a slight increase in wound disruption strength at nearly all time points but this increase did not reach statistical significance. Addition of 100 ng of MCP-1 to excisional wounds did not have any significant effect on wound reepithelialization. Taken together, the results show that MCP-1 is produced within wounds at physiologic concentrations, and is an important positive regulator of macrophage recruitment into sites of injury. Addition of exogenous MCP-1 to wounds of normal mice yields only modest enhancement of the repair process.

Animals↗
PubMedDate not supplied

Bone marrow stem cell and progenitor response to injury.

Hematopoietic stem cells represent a long term reservoir of cells to populate blood with multiple formed cells. These hematopoietic stem cells proliferate and mature into lymphoid, erythroid, and myeloid precursor cells, with the balance of these cell populations modulated by major thermal injury, with or without sepsis. Recent studies indicate that thermal injury shifts this balance to favor the monocyte/macrophage lineage at the expense of neutrophil production. The mechanisms for these changes are now being elucidated with the results of clinical importance, because understanding the dynamics of the different precursor pools could be used to identify patients at greater risk for systemic inflammatory sequelae following major thermal injury.

Burns↗
PubMedDate not supplied

hsp70, hsp32, and grp78 are increased in thermally injured skin with and without antithrombin(human) concentrate infusion.

An acquired deficiency of antithrombin (AT), an anti-inflammatory protein, develops in patients with thermal injuries. Skin thermotolerance is regulated by heat shock protein (hsp) genes. hsp70, hsp32, hsp27, and glucose-regulated protein78 (grp78) were studied in burned and unburned human skin to determine whether correction of the AT deficiency modulated the intensity of expression of these proteins. Fifty-four human skin samples were prepared by Western blot analysis: 11 unburned and 22 burned control skin samples and 7 unburned and 14 burned skin samples from patients treated with AT(Human), or AT(H). The intensity of hsp32 expression in burned AT(H)-treated skin (P < .001) and in burned control skin (P < .01) was significantly increased compared with unburned control skin. The intensity of expression of hsp70 was statistically significant in burned AT(H)-treated skin compared with unburned control skin (P < .02), as was that of grp78 (P < .01). Thermally injured skin with or without AT(H) treatment had an increased expression of hsp70, hsp32, and grp78 compared with unburned control skin.

Adolescent↗
PubMedDate not supplied

Comparative analysis of bedside and operating room tracheostomies in critically ill patients with burns.

The objective of this study was to demonstrate that bedside burn intensive care unit tracheostomy is a safe and cost-effective procedure and has advantages over operating room tracheostomy. The charts of all patients who underwent tracheostomies in the burn unit between January 1990 and September 1993 were reviewed retrospectively. All tracheostomies were performed by residents in their second to fourth postgraduate years. The identical operating room technique was used for all bedside procedures including complete instrument tray, electrocautery, and adequate lighting. Standard tracheostomies were routinely performed at the bedside instead of the operating room in an attempt to deal with an increasing number of critically ill patients with burns requiring operating room surgical procedures. No patient-specific criteria were used to determine whether bedside or operating room tracheostomy would be performed. Charges for bedside intensive care unit and operating room tracheostomy were compared. Group t test and chi-square analysis were used with significance set at p < 0.05. Forty-three tracheostomies were performed in the 45-month period reviewed. Twenty-five tracheostomies performed in the operating room were compared with the 18 tracheostomies performed at the bedside in the burn intensive care unit. No statistical difference existed in age, sex, mean total body surface area percent burned, mean inspired oxygen, mean positive end expiratory pressure, mean pretracheostomy intubated days, presence of inhalation injury, or complication rate between groups. The average combined cost for operating room and anesthesia was $1740 per tracheostomy performed in the operating room. No charge was given to the patient for a bedside tracheostomy apart from the surgeon's fee and tracheostomy tube.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Accelerated healing and reduced need for grafting in pediatric patients with burns treated with arginine-glycine-aspartic acid peptide matrix. RGD Study Group.

Arginine-glycine-aspartic acid (RGD) peptide matrix is designed to promote dermal healing by providing a molecular scaffold that facilitates cell ingrowth and establishment of normal tissue architecture. This study investigated the effectiveness and safety of RGD peptide matrix in the treatment of partial-thickness scald burns in pediatric patients. Either topical RGD peptide matrix or control treatment with silver sulfadiazine was applied to matched burn sites daily for up to 21 days. With RGD peptide matrix application under synthetic occlusive dressing, the incidence of healing was nearly threefold higher, average time to healing 2.5 days shorter (regression estimation), extent burn closure at all treated sites 37% greater, and number of needed grafting procedures fourfold lower compared with control treatment. All these differences were statistically significant. RGD peptide matrix was well tolerated. RGD peptide matrix promoted and accelerated healing in this study and thus may be able to reduce morbidity and treatment costs of partial-thickness burns in pediatric patients.

Administration, Topical↗
PubMedDate not supplied

Preparation for burn center verification.

Today's managed care environment has challenged health care institutions to deliver quality cost-effective health care. In the burn community the American Burn Association/American College of Surgeons Burn Center Verification has become an increasingly sought after quality credential. Essential to successful completion of the verification process is the identification of key components that must be in place before an application is submitted. These components must be well documented and present in the application and during the site visit. Adequate burn team preparation is a significant contributor to successful verification. In addition, the process necessitates self-examination and acquires the benefits of validating current practices and identifying opportunities for improved patient care and efficient operation. This article details the preparation process undertaken by one burn center before its successful verification.

Burn Units↗
PubMedDate not supplied

Postburn edema and related changes in interleukin-2, leukocytes, platelet activation, endothelin-1, and C1 esterase inhibitor.

Interleukin-2 (IL-2) promotes multisystem organ edema, lung neutrophil sequestration, and platelet activation through alterations in the microvascular barriers and permeability. IL-2, complement, platelet, and vascular endothelial activation were evaluated in 60 patients. One-factor analysis of variance indicated a significantly increased absolute neutrophil count on day 1 (p < 0.0001) and decreased C1Inh, p = 0.0001, with elevated IL-2 levels in the 20% to 40% group (p = 0.008). Endothelin-1 levels were significantly increased in the 20% to 40% total body surface area group on day 5. The absolute neutrophil count was significantly reduced in both groups, and C1Inh rose to near normal levels by day 5. No significant elevations of 6-keto prostaglandin F1 alpha were observed on day 1 or day 5 in the < 40% total body surface area group; however, these levels were significantly elevated on day 1 in the > 40% total body surface area group. Thromboxane B2 and platelet factor 4 were significantly elevated in all groups (p = 0.001) on days 1 and 5. Regression analysis implicated infection as a significant contributor to the IL-2 variations (r2 = 0.61), with inhalation injury minimally affecting IL-2 plasma levels (r2 = 0.09). Generalized edema increased with increasing burn wound size in parallel with elevated IL-2 and endothelin-1 levels, reduced C1Inh levels, and leukocytosis in the first week after thermal injury. These data suggest that there are dynamic interactions among the endothelium, cytokine stimulation, leukocytosis, complement, and platelet activation in promoting the microvascular permeability.

Adolescent↗
PubMedDate not supplied

A conservative thermal injury treatment protocol for the appropriate Jehovah's Witness candidate.

The Jehovah's Witness (JW) members abstain from receiving blood transfusions or blood product infusions because these treatments are considered an extension of life. A JW who incurs significant thermal injury requires a protocol defining good clinical practices in life-threatening predicaments acceptable to JW members to avoid legal proceedings. Assessment of religious commitment, competency, family resources, and respect for the patient's refusal of treatments is required. Detailed documentation of the patient's position is necessary. Medical management should include standard critical care measures, blood conservation, restricted laboratory work, utilization of pediatric blood collection tubes, nonblood plasma expanders, erythropoietin administration, iron supplements, and aggressive nutritional support with appropriate surgical conservation measures during skin grafting procedures. With conservative management, a positive outcome can be attained without recourse to the legal system.

Blood Substitutes↗