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Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 91 records · Page 5Linked to original sources

Injuries during woodworking, home repairs, and construction.

Study was made of 495 consecutive primary care patients treated for woodworking, home repair, and wood-related construction injuries. Mean AIS was 1.2, and 6% were hospitalized. Estimated annual injury rate involving such activities is 3.3/1,000 residents. Fifty-eight per cent of injuries occurred at work. Overall, where complete data are available, 30% of injuries involved use of power equipment, with injury usually resulting from direct contact with the equipment. The lone exception was portable circular or "Skill" saws, with a large proportion of eye injuries from ejected sawdust. Use of non-power equipment was involved in 21% of injuries, and falls from ladders or other elevations 14%. Mean days of complete or partial disability for work, home, and recreational activities were 11.8, 10.4, and 13.3, with 79% of work disability occurring to persons who had not been hospitalized.

Absenteeism↗

Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment.

We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) given after the administration of 5-fluorouracil (5-FU) results in augmented hematopoietic recovery as evidenced by increased white blood cell and neutrophil counts. Mice receiving GM-CSF following 5-FU administration were observed to have a marked elevation in splenic granulocyte-macrophage colony-forming cells (GM-CFC) and a decrease in the femoral bone marrow GM-CFC. Because GM-CSF has been shown to increase prostaglandin synthesis and prostaglandins are thought to provide a negative feedback signal to down-regulate myelopoiesis, we sought to determine if the cyclooxygenase inhibitor, indomethacin, could prevent the reduction in the number of femoral bone marrow GM-CFC seen when GM-CSF was administered following 5-FU. Groups of mice received a single 60 mg/kg i.p. injection of 5-FU followed 24 h later by twice-daily injections of 1 micrograms GM-CSF and daily injections of 3, 5, or 6 mg/kg indomethacin; the hematopoietic assays were performed on day 7 following 5-FU. Compared to those animals that received GM-CSF alone following 5-FU, mice receiving 5 mg/kg indomethacin plus GM-CSF following 5-FU had increased numbers of GM-CFC in their bone marrow (3923 +/- 634 vs 971 +/- 138; p less than 0.001) as well as increased neutrophil counts (18,995 +/- 2872 vs 11,497 +/- 2476; p less than 0.01). Indomethacin alone was, in part, capable of facilitating hematopoietic recovery following 5-FU administration, but not to the extent seen when used in combination with GM-CSF. Prostaglandin inhibitors may have a role in combination with hematopoietic growth factors in accelerating hematopoietic recovery following cytoreductive chemotherapy.

Animals↗

Practical evaluation of trauma deaths.

The TRISS method of auditing trauma deaths necessitates audit of patients with minor injuries who die of their underlying medical problems. Using an anatomic definition of injury as a criterion for audit, as suggested by Wesson et al. at the Hospital for Sick Children in Toronto, excludes patients with minor injuries but necessitates audit of patients who expired due to systems problems rather than in-hospital patient care. We propose combining the TRISS and Toronto methods in order to identify the deaths truly appropriate for detailed review of hospital care. Fifty-four trauma deaths over a 22-month period were audited and categorized as frankly preventable, potentially salvageable, or nonpreventable. Considering only in-hospital care, the deaths designated as potentially salvageable by audit were likely to be identified by both TRISS and Toronto, while deaths targeted by only one system were more likely to be nonpreventable by audit. The predictive value of this combination of methods (84.6%) was better than Toronto (52.4%) or TRISS (54.5%) using audit results as the standard for comparison. This simple computerized method may serve as a practical and inexpensive method of targeting deaths for in-depth review.

Adolescent↗

The beneficial effect of granulocyte colony-stimulating factor (G-CSF) in combination with gentamicin on survival after Pseudomonas burn wound infection.

Inadequate granulopoiesis and decreased granulocyte function are thought to play a significant role in the burned victim's susceptibility to infection. In an attempt to determine whether the regulatory granulopoietic growth factor G-CSF could favorably affect survival when used in combination with antibiotics, we examined survival in a murine model of Pseudomonas aeruginosa burn wound infection. One hundred twenty male BDF1 mice received a 15% total body surface area burn and were randomized to one of five treatment groups: (1) burn only, (2) burn + infection, (3) burn + infection + G-CSF, (4) burn + infection + gentamicin, and (5) burn + infection + G-CSF + gentamicin. Infected mice received a 10(3) colony-forming units topical inoculum of Pseudomonas to the wound immediately postburn. Gentamicin animals received 6.0 mg/kg intraperitoneal gentamicin as a single dose immediately postburn. G-CSF was administered as 100 ng twice daily for 7 days. All treatment groups showed improved survival compared with the burn + infection group, which showed 100% mortality by day 9 (p less than 0.001 all groups; Cox-Mantel statistic). Group 5 (burn + infection + G-CSF + gentamicin) exhibited improved survival as compared with either group 3 (burn + infection + G-CSF, p = 0.054) or group 4 (burn + infection + gentamicin, p = 0.007). The use of hematopoietic growth stimulants in combination with antibiotic therapy may result in improved outcome after burn injury, and it suggests new treatment options in the management of postburn infectious complications.

Animals↗

Predicting hospital charges for trauma care.

Diagnosis related groups (DRGs) have sharply decreased the amount of compensation hospitals can expect for providing trauma care. A total of 637 patients admitted for acute traumatic injuries between Oct 1, 1985, and July 30, 1986, had their DRG classifications, Injury Severity Scores, trauma scores, and ages compared with hospital charges in an attempt to identify factors that could be used to accurately predict hospital charges. The best prediction of charges was obtained when DRG assignment was combined with Injury Severity Scores and age. When the equation obtained by this approach was applied to a separate population of 301 patients, the average difference between the actual charge and that predicted was $38 and would have led to a 33-fold decrease in money lost by the hospital. Altering the DRG payment schedule as proposed would allow hospitals to be fairly compensated for the care of trauma patients.

Adolescent↗

Recombinant human granulocyte colony-stimulating factor and Pseudomonas burn wound sepsis.

Multiple immune defects have been demonstrated following thermal injury, including defective granulocyte production and function. Recombinant human granulocyte colony-stimulating factor (rhGCSF) is a regulator of the myelopoietic system. The effect of rhGCSF administration on survival and on the myelopoietic system in a murine model of Pseudomonas burn wound sepsis was investigated. Male BDF1 mice that underwent a 15% total body surface area burn injury and burn wound seeding with 1 x 10(8) Pseudomonas aeruginosa organisms demonstrated an improved mean survival time with the subcutaneous administration of 100 ng of rhGCSF twice a day. Mice that underwent a similar thermal injury and burn wound seeding with 3 x 10(7) P aeruginosa organisms demonstrated an augmented myelopoietic response through the administration of rhGCSF, as represented by significantly increased white blood cell count, neutrophil count, splenic weight, femoral marrow cellularity, and femoral marrow granulocyte-macrophage colony-forming cell count. Myelopoietic augmentation through rhGCSF administration may serve to decrease the morbidity of septic events following thermal injury.

Animals↗

Recombinant granulocyte-macrophage colony-stimulating factor improves hematopoietic recovery after 5-fluorouracil.

Antitumor chemotherapy is often limited by hematopoietic toxicity. In an attempt to determine if it is possible to attenuate the myelosuppressive effects of chemotherapy, we administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), a multilineage hematopoietic growth factor, to mice receiving 5-fluorouracil (5-FU). Mice receiving injection of 5-FU followed 24 hr later by a single 1-microgram injection of rmGM-CSF had significantly increased femoral bone marrow granulocyte-macrophage colony-forming cells (GM-CFC) 48 hr after 5-FU injection compared to animals receiving 5-FU alone. Animals receiving rmGM-CSF twice daily beginning 24 hr after 5-FU had significantly elevated white blood cell counts and increased granulocyte and monocyte counts at Day 7 following 5-FU injection, compared to those of 5-FU animals. The total reserve of GM-CFC was also expanded initially in the femoral marrow and later in the spleen of animals receiving rmGM-CSF following 5-FU. A means of accelerating bone marrow recovery and restoration circulating granulocytes and monocytes could allow more frequent doses of chemotherapy to be administered or shorten the time period that patients are leukopenic.

Animals↗

Nutritional modulation of tumor growth.

The relationship between tumor and host tissue proliferation as a function of protein calorie deficiency followed by balanced nutritional repletion was examined in a series of C3H female mice with MA16/C tumors. Tumor and host tissue DNA synthesis was determined in animals with subcutaneously implanted tumors who were randomized to either regular diet (RD) or a totally protein-free diet (PFD) for 5 days followed by refeeding for 4, 8, 12, 24, 36, 48, or 72 hr. Animals maintained on a protein-free diet demonstrated a decrease in DNA synthetic activity in both tumor and host tissues. Following refeeding of a regular diet to animals fed the protein-free diet, resumption of DNA synthesis in tumor preceded that of liver and was greatest by four hours of refeeding. In the liver, return of DNA synthetic activity was delayed but exceeded control levels by 36 hr. Compared to our previous studies examining the effects of starvation, we found that an isocaloric protein-free diet caused a smaller decrease in tumor DNA synthetic activity and an earlier resumption in tumor proliferation with the reinstitution of a normal protein diet. These studies suggest a nutrient-specific response for tumor and host tissues with nutritional deprivation and refeeding.

Animal Nutritional Physiological Phenomena↗

Do nutritional alterations contribute to adriamycin-induced impaired wound healing?

Adriamycin-impaired wound healing in mice was found to be related to the degree of weight loss which in turn was dependent on the dose given. Treated animals had an initial decrease in food consumption that correlated with initial weight loss. After approximately 7 days, food consumption returned to normal but the weight loss persisted. Both Adriamycin-treated mice and animals pair fed the amount of food consumed by drug-treated mice had wounds significantly weaker than control animals at 7 and 11 days. The Adriamycin-treated animals had 11-day wound strengths equal to or weaker than the pair fed group. By Day 14, the pair fed animals had wounds similar to those of controls but the Adriamycin-treated animals remained significantly weaker than the other groups. We feel that initially Adriamycin produces a short-term nutritional deficit that contributes to early wound healing impairment. Later, the toxicity of the drug predominates in altering wound repair.

Animals↗

Effects of fluid resuscitation on cardiac dysfunction following thermal injury.

To test the hypothesis that low cardiac output in burns is secondary to hypovolemia, the effects of resuscitation on isovolumic contracting rat heart following a full-thickness burn were studied. Sprague-Dawley rats were randomly assigned into three groups: (1) Sham burn, (2) 30% body surface area burn nonresuscitated, (3) 30% body surface area burn with 15 cc Ringer's lactate/180 g body wt ip at the time of burn resuscitated. Twenty hours postburn, the hearts were mounted on a Lagendorff perfusion apparatus. A balloon-tipped catheter placed in the left ventricle measured pressure and dp/dt. Coronary flow was determined. Myocardial samples for ATP and water were obtained. Left ventricular function was evaluated by recording peak systolic pressure, end diastolic pressure, and maximum +/- dp/dt while balloon volume was increased to 0.3 cc. Results are with end diastolic volume constant at 0.15 cc. Compared to sham burn, burn nonresuscitated generated lower peak systolic pressure +/- dp/dt and higher end diastolic pressure while hearts from burn resuscitated generated the same as sham burn. Coronary flow and tissue water content was similar in all. ATP content was lower in burn nonresuscitated. Our data support that impaired systolic and diastolic function in burn nonresuscitated hearts is associated with lower ATP levels not seen in burn resuscitated and reperfusion of burn nonresuscitated hearts does not reverse the myocardial depressant effect.

Adenosine Triphosphate↗

Vascular reactivity following thermal injury.

Major thermal injury is associated with alterations in both pulmonary and systemic vascular resistance. Pulmonary artery hypertension may lead to right heart dysfunction and pulmonary insufficiency. The effect of thermal injury on vascular reactivity is unknown. Increases in circulating vasoactive substances, as well as alterations in vascular smooth muscle receptor activity, have been hypothesized to occur following thermal injury. We have studied aorta and pulmonary artery vascular sensitivity to five agonists in a 35% full-thickness thermal injury rat model. Vascular reactivity was normal to agonists that constrict vascular smooth muscle via receptor-mediated calcium influx. Unresuscitated and resuscitated burn injury resulted in a decrease in peak tension development to prostaglandin F2 alpha (PGF2 alpha) and potassium, agonists whose effects are mediated via membrane depolarization. Fluid resuscitation synchronous with burning did not alter peak tension development in agonists whose actions were mediated via receptor mechanisms. Peak tension development in resuscitated animals to agonists that affect contraction by depolarization remained deficient. To rule out simple blood loss as the etiology for these changes, the experiment was repeated in rats sustaining an acute 25% blood volume loss. Simple hypovolemia induced no changes in aortic or pulmonary vascular sensitivity. We hypothesize that thermal injury may result in a depolarization of vascular smooth muscle membranes altering voltage-dependent calcium channels.

Animals↗

Jejunal ulceration and stricture due to wax-matrix potassium chloride tablets and amitriptyline.

A 68-year-old woman presented with abdominal distention of several weeks duration and an acute small bowel obstruction. For several years she had been prescribed amitriptyline 150 mg/d, L-thyroxine 100 micrograms/d, and digoxin 0.25 mg/d. For the previous year she had been taking hydrochlorothiazide 50 mg/d and wax-matrix KCl 20 mEq/d for hypertension. At surgery a "napkin-ring" stricture of the midjejunum was found. It had microscopic features consistent with KCl local toxicity. It is speculated that delayed gastrointestinal motility secondary to amitriptyline predisposed this patient to wax-matrix KCl toxicity and that this potential side effect be considered when prescribing wax-matrix KCl.

Aged↗

Immunomodulators and wound healing.

The synthetic immunomodulators muramyl dipeptide (MDP), thymopoietin pentapeptide (TP5), and CP-46,665 were examined for their effects on wound healing in mice. We found no differences in wound disruption strength between immunomodulator-treated animals and saline controls on days 11, 14, and 21. The only exception was with high-dose CP-46,665, which produced weakened wounds on day 14 (p less than 0.05) and 21 (p less than 0.01). CP-46,665 was further studied by injecting high and low doses 48 hours before or after wounding. No differences were seen for these groups compared to controls at 11 and 21 days. Finally, to simulate a common clinical situation, mice were subjected to a 10% total body surface area (TBSA) burn to the right paraspinal region. Twenty-four hours later, a left paraspinal incision was performed with simultaneous injection of saline, Corynebacterium parvum (C. parvum), or low-dose TP-5, MDP, or CP-46,665. At 11 days, no detriment in wound healing was found for burned control or any of the immunomodulator-treated animals except in the C. parvum-treated mice, with significantly weakened skin strips (p less than 0.001). While C. parvum may be detrimental to wound healing, the synthetic modulators tested appear to have little effect on wound healing.

Acetylmuramyl-Alanyl-Isoglutamine↗

Splenic arteriovenous fistula.

We present a case of a splenic arteriovenous fistula (AVF) occurring postsplenectomy. The splenectomy was performed as a result of severe blunt abdominal trauma. The fistula was discovered in the postoperative period and controlled with intravascular coils. Splenic AVF are usually due to rupture of a pre-existing splenic artery aneurysm, post-traumatic, or iatrogenic. Diagnosis and treatment of a splenic AVF are necessary to prevent the development of hepatosclerosis and esophageal varices.

Adult↗

Is impaired wound healing caused by infection or nutritional depletion?

Since infection and malnutrition both impair wound repair, we examined the interactions of an intra-abdominal abscess and its nutritional alterations on wound healing. Mice subjected to a left paraspinal incision then underwent either cecal ligation and puncture (CLP) or sham operation (sham). Abscesses and an early decrease in food intake developed in all CLP mice, but the animals resumed normal food consumption by day 7. The CLP animals had an initial 20% weight loss; however, by day 11 they had a gradual return toward control weight. Fresh and formalin-fixed wound disruption strengths determined on days 7 through 35 revealed a significant weakness in CLP animals. To examine the role of nutritional intake, an additional set of experiments were performed with the following groups: CLP, sham, no operation (control), or sham operation with pair-feeding an amount equal to that consumed by the CLP group to reproduce only the nutritional deficit (sham/dep). At 7 and 11 days, fresh wound-disruption strengths of both CLP and sham/dep animals were significantly weaker than those of control or sham animals. A defect in formalin-fixed healing also existed for sham/dep mice at day 11. These findings suggest that short-term reduction in nutrient intake as a result of infection may be a major determinant of impaired wound healing.

Abscess↗