Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 73 records · Page 4Linked to original sources

PubMed1993

The role of diagnostic laparoscopy in the management of trauma patients: a preliminary assessment.

This study evaluated the role and advantages of diagnostic laparoscopy (DL) compared with diagnostic peritoneal lavage (DPL) in 75 trauma patients who were prospectively studied with DL followed by DPL. Of these, 59 patients had blunt injuries and 16 stab wounds. Seventy patients (93%) had the procedures performed in the emergency department (ED); 41 (59%) of these were awake and under local anesthesia. Forty-two patients had negative DPL and DL results with no subsequent sequelae. Twenty-three patients had negative DPL results and abnormal DL results. Of these, 20 were managed nonsurgically, and three (DPL < 10,000 RBC) underwent surgery based solely on DL findings of diaphragmatic lacerations from stab wounds. These were repaired. All 23 had an uneventful course. Three patients had positive DPL and insignificant DL findings. Laparotomy and DL findings correlated. A splenectomy for iatrogenic injury unrelated to DL and two nontherapeutic laparotomies were performed. Seven patients demonstrated both positive DPL and significant DL findings, and all had therapeutic laparotomies. Management based on DL rather than DPL would potentially have improved care in 8% of cases (6 of 75). Reliance on DL improved care in 19% (3 of 16) of patients with stab wounds and possibly could have in 3% (2 of 59) of those with blunt injuries. Management using DL would have potentially improved care in 30% (3 of 10) of patients with positive DPL findings and 5% (3 of 65) with negative DPL findings. Diagnostic laparoscopy can be performed safely in stable patients under local anesthesia in the ED. It offers no advantage over DPL as a primary assessment tool in blunt trauma. It does have advantages in the management of stab wounds. Diagnostic laparoscopy has a role in redefining DPL criteria for laparotomy and, in selected patients, as an adjunct to DPL, allowing further diagnosis and potentially the treatment of injuries without laparotomy.

Abdominal Injuries↗

PubMed1993

Evaluation of PDGF-BB, PDGF-AA, bFGF, IL-1, and EGF dose responses in polyvinyl alcohol sponge implants assessed by a rapid histologic method.

Polyvinyl alcohol sponge implants were used in rats, mice, and guinea pigs to determine dose responses of growth factors. Eight differently treated sponges per rat or guinea pig (4/mouse) were injected with test material on alternate days and evaluated at day 8. Much of the observed response occurred in and around the capsule and was manifest as densely cellular granulation tissue. Including this capsular response in a single histologic slide ranking system provided a more sensitive and faster method of assessing growth factor effects than measurement of connective tissue ingrowth alone. Clear dose responsive effects were seen with recombinant human PDGF-BB, PDGF-AA, bFGF, and IL-1 beta, while EGF gave a lesser response. Lipopolysaccharide did not affect the connective tissue response, alone or in combination with PDGF-BB. PDGF-BB was tested in each species, and the dose response characteristics were qualitatively and quantitatively similar across species.

Animals↗

PubMed1993

Bone marrow toxicity by silver sulfadiazine.

The effect of silver sulfadiazine (SSD) on the production of granulocytes and macrophages was studied in a murine model of cutaneous injury. Application of SSD daily to mice receiving a 10 percent full-thickness total body surface area burn injury failed to demonstrate consistent suppression of the bone marrow at one, four or seven days postinjury. Mice undergoing a 10 percent full-thickness skin excision (SE) and daily SSD application (SE plus SSD) had a near 50 percent reduction in total peripheral blood leukocyte counts in comparison with a control group and untreated mice that were skin-excised (SE-U) (p < 0.03) to 0.002) on day one postinjury and maintained this reduction compared with SE-U at days four and seven postinjury. The absolute number of granulocytes in SE plus SSD was only 10 percent of control or SE-U (p < 0.04 to 0.002) at day one postinjury and remained less than SE-U at four and seven days postinjury. Femoral bone marrow assay of granulocyte-macrophage progenitor cells (GM-CFC) revealed a marked reduction in nucleated bone marrow cells for SE plus SSD compared with respect to control at days one and seven and SE-U at days four and seven (p < 0.02 to 0.001). GM-CFC were significantly depressed in SE plus SSD on day one compared with C and SE-U and day four compared with SE-U (p < 0.01 to 0.001), but returned to control values by day seven. When SSD (0.5 to 500.0 micrograms per milliliter) was added to culture plates containing maximally stimulated normal murine or human bone marrow cells, the colony count was depressed in a dose-dependent manner. In vitro SSD is directly cytotoxic to myelopoietic tissue, and in vivo, alters the myeloid cell compartment. These observations in combination may explain the transient leukopenia frequently observed in patients receiving topical chemoprophylaxis with SSD.

Animals↗

PubMed1993

Fetal wound healing.

Multiple distinctions concerning the adult and fetal wound healing processes exist. In the fetus, a minimal inflammatory response to wounding is seen with a marked deposition of glycosaminoglycans, particularly hyaluronic acid. Collagen seems to be present in small amounts and is rapidly and efficiently organized into structural nonscarred tissue components, a process that seems to be uniquely influenced by the ECM and its components. The exact mechanisms of control of growth, development and healing in the fetus are unclear, although a transition from fetal to adult processes takes place in utero. Furthermore, some processes may, in part, transiently reappear in healing wound found in adults. Clearly, there is a vast horizon for future investigation. The concept of fetal surgical treatment has become a reality. Many observations made in this field may well be applied in future attempts to prevent pathologic healing, and may even yield wounds far superior to the predicted "normal" results we see today. The future of wound manipulations may involve the crafting of complex matrices interwoven with a variety of cytokinetic agents, which could result in a healed wound or regenerated tissue that is mechanically and functionally equivalent to adjacent unwounded tissue. Furthermore, if the secrets of fetal healing can be revealed, areas of clinical intervention may be expanded to aid in controlling other abnormal patterns of tissue growth observed in clinical medicine as well.

Animals↗

PubMed1992

Interleukin 1 beta improves survival following cecal ligation and puncture.

Despite antibiotic therapy intra-abdominal sepsis following major surgery is a significant cause of mortality. We sought to determine if interleukin-1 beta (IL-1) could improve survival in a murine model of intra-abdominal infection. Groups of 10 BDF1 mice received a single subcutaneous (sc) injection of recombinant human IL-1 beta 24 hr prior to cecal ligation and puncture (CLP) and were assessed twice daily for survival. Mice that received a single injection of IL-1 beta 24 hr prior to CLP had a dose-dependent improval in survival compared to controls. The beneficial effect of IL-1 treatment may have been related to its ability to stimulate myelopiesis. The addition of indomethacin, in an effort to limit possible toxicity of IL-1, did not further improve survival. Appropriate timing of specific immunomodulators may provide an additional strategy for the treatment of infections.

Abdomen↗

PubMed1992

Intoxication and injury.

The relationship between alcohol use and injury severity was investigated in trauma patients admitted to a tertiary referral hospital during a 23-month period. Admission blood alcohol levels (BALs) were obtained on 427 trauma patients, who were stratified into three groups: those with no measurable blood alcohol, those within the legal limit of 100 mg/dL, and those over the legal limit or intoxicated. The no-alcohol group had significantly lower injury severity than the other two groups (p less than 0.001). Even when the BAL was well within the legal limit, injuries suffered by those in the alcohol-positive groups were more severe than those in the no-alcohol group. Confirmatory evidence of the effect of alcohol on injury severity was reflected by a 2.3% mortality in alcohol-negative patients compared with a 13.3% death rate in alcohol-positive patients (p less than 0.0001). To assess the potentially confounding effect of alcohol on injury scoring accuracy, we examined the change in Glasgow Coma Scale (GCS) scores following admission. No significant differences were found when admission GCS values were compared with GCS determinations made 24 hours following admission by separate observers. To correct for any potential bias as a tertiary referral center, repeat analysis with exclusion of transferred patients was done with essentially no change in results. Our data revealed a highly significant relationship between alcohol use, degree of injury, and resource consumption.

Adult↗

PubMed1992

Tumor necrosis factor and cardiac function.

The direct effect of tumor necrosis factor (TNF), a product of activated macrophages, on myocardial performance was determined using an isolated papillary muscle technique and a modified Langendorff preparation. Papillary muscle was obtained from male adult rats 4-5 hours after they received either 100 ng/kg TNF (group A), or 100 micrograms/kg TNF (group B) or saline (control). Group B animals exhibited significantly greater peak tension development and velocity of contraction compared with controls (p less than 0.05). In group A animals these variables were not significantly different from those of the controls (p greater than 0.05). Electrophysiologic measurements revealed a significant decrease in resting membrane potential in both group A and group B animals compared with the controls (p less than 0.05). Whole hearts perfused with serum from animals treated with TNF 18-22 hours earlier exhibited significant impairment of contractility, decreased rate of systolic pressure development, and decreased rate of relaxation compared with the controls (p less than 0.05). Coronary flow and myocardial water content were similar for both groups of perfused hearts. These data suggest that tumor necrosis factor stimulates an early beneficial effect on myocardial function, which 18-22 hours later is associated with impairment of myocardial performance. This effect appears to be serum transferable.

Action Potentials↗

PubMed1992

Predictors of blinding or serious eye injury in blunt trauma.

Multivariate analysis was used to identify factors predicting injury and visual outcome in 94 blunt trauma patients evaluated for eye injuries among 6700 admissions to a level I trauma center over a 29-month period. Patients with penetrating eye injuries were excluded from this review. Eye injury was detected in 93% or 87 of the patients evaluated. Seven percent of eye injuries resulted in blindness, 22% were serious (visual acuity between 20/40 and 20/200 or eye injury requiring surgery), and 71% were temporary (final visual acuity of 20/40 or better). The presence of an afferent pupillary defect or a nonreactive pupil was the most important factor in predicting the severity of eye injury (p = 0.0023), followed by facial fractures (p = 0.0084), and no eye opening or eye opening to pain within the Glasgow Coma Scale (p = 0.02). Eye injury is an infrequent complication of blunt trauma. Appropriate consultation for evaluation of this problem can be obtained based on findings from the initial history and screening physical examination.

Adolescent↗

PubMed1992

The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state.

The effect of burn wound size on the activation of fibrinolysis, coagulation, and contact factors was analyzed in 60 thermal injury patients. Blood samples from 47 male patients and 13 female patients, (average age 37 years; range 1.5-70 years) were collected within the first 36 hours and at 5-7 days following injury. The patient population was categorized by percentage of burn (second degree and/or third degree): less than 20%, n = 22; 20%-40%, n = 18; greater than 40%, n = 20. The average percentage of burn was 32% (range, 4%-95%). The mechanism of injury was by flame (25), explosion and flame (19), scald (12), electric (3), or chemicals (1). An associated inhalation injury was present in 12 patients. The overall mortality rate was 13% (8). Sepsis or serious infection occurred in 23% (14) of the patients. On admission, 83% of the patients had normal prothrombin times (PT) and activated partial thromboplastin times (APTT). However, specific hemostatic variables showed marked changes. Admission hemostatic markers that correlated with the severity of injury were: tissue-plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (D-di), plasminogen (Plg), proteins C and S (PrC and PrS), antithrombin III (ATIII), thrombin-antithrombin complex (TAT), kallikrein (Kal:c), kinin (Kin), C1 esterase inhibitor (C1Inh), and factor VII clotting and antigen (FVII:c, FVII:ag). These data suggest that during the early course following burn injury, thrombogenicity is increased (TAT increases) because of a decrease in ATIII, PrC, and PrS; and fibrinolysis activation (D-di increases) occurs via an increase in tPA with a p value increase in PAI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Routine pelvic x-ray studies in awake blunt trauma patients: a sensible policy?

To evaluate the usefulness of routine pelvic x-ray films in the resuscitation of blunt trauma victims, 1395 patients were prospectively evaluated over a 13-month period. Of these, 810 (58%) were awake with Glasgow Coma Scale scores greater than or equal to 13 and were enrolled into the study. A history, with directed questions regarding pelvic pain, a clinical examination of the pelvis, and an anterior-posterior pelvic x-ray film (APPX) were obtained for each patient. Thirty-nine patients (5%) had fractures identified on the x-ray films. Of these patients with radiographically identified fractures, 34 (87%) complained of pain and had positive results on clinical examination, two (5%) either complained of pain or had positive results on examination and three (8%) had neither complaint of pain nor positive examination results. Of the 771 patients without fractures 743 (96%) lacked pain complaints or positive examination results. The likelihood of fracture was greatest in patients with complaints of pain and positive examination results (65%) followed by patients with either complaint of pain or positive examination results (16%). Only three (0.4%) of the 743 patients having no complaints of pain and a negative clinical examination had fractures diagnosed roentgenographically. These were minor fractures that did not affect the clinical course. Total charges incurred to diagnose pelvic fractures in this low-yield patient group were $88,028. We conclude that the practice of obtaining a screening APPX is not necessary or cost-effective in the management of awake blunt trauma patients who do not complain of pain and who have normal pelvic physical examination results.

Adolescent↗

PubMed1992

Treatment of intra-abdominal infection with granulocyte colony-stimulating factor.

Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Fractures in the under-3-year-old age cohort.

One hundred twenty-four urban children under 3 years of age admitted for fractures were retrospectively reviewed to determine the frequency of accidental and nonaccidental causes in this population. The fractures were categorized according to their mechanisms: motor-vehicle passenger or pedestrian accident, other accidents, or child abuse. There were no differences in the frequency of fractures by race, date of birth, or season in which the injury occurred. Skull fractures were most frequent (62%), followed by femur fractures (11%). There was a 26% increase in fractures between 1987 and 1989, especially in the non-motor vehicle cohort. Caretaker ignorance and/or carelessness was a common cause of fractures in the infant and toddler age group. Injuries were still occurring in spite of infant care seat use. The American public must be educated in preventive medicine and safety to decrease the senseless morbidity of our greatest resource.

Accidents↗

PubMed1991

The epidemiologic features of nosocomial infections in patients with trauma.

Sepsis is a major cause of morbidity and mortality in patients with trauma. To elucidate factors that might lead to infection, we studied the epidemiologic characteristics of nosocomial infections in our patient population with trauma. During a 3.5-year period, 2496 patients were entered into our hospital trauma registry and cross-matched with hospital infection control surveillance information. Two hundred twenty-nine patients with trauma and nosocomial infections were identified (9.2%), a figure that was nearly twice the nosocomial infection rate for the general hospital population. The majority of those infected were either orthopedic (51%), general surgical (25%), or neurosurgical (13%) patients. The most common sites of first infection were urinary tract (61%) or respiratory system (14%). Patients developing nosocomial infections were significantly older and had a higher Injury Severity Score than those who did not. Injury site was related to risk of infection with injuries of the spine, chest, and extremity showing the most significant relationship. The length of stay as well as hospital charges were significantly related to the occurrence of infectious complications. By determining the patient with trauma at risk for infection, treatment strategies can be designed to minimize septic complications.

Accidents↗

PubMed1991

The effect of granulocyte colony-stimulating factor (G-CSF) upon burn-induced defective neutrophil chemotaxis.

Severe thermal injury results in impairment of granulocyte production and function. The ability to improve the functional capacity of neutrophils could contribute to a reduced morbidity and mortality from sepsis following thermal injury. Previous studies from this laboratory have shown that rhG-CSF increases the number of femoral marrow granulocyte progenitor cells and circulating neutrophils as well as the survival rate following burn wound infection. The studies reported here examine the effect of in-vivo administration of rhG-CSF on neutrophil chemotaxis following a burn injury and also following superimposed Pseudomonas burn wound sepsis in mice. Casein-elicited peritoneal neutrophils were harvested 72 hours after burn injury and 24 hours after infection. Chemotaxis was assessed using microchemotaxis chambers and 10(-5) M fMet-Phe as a chemoattractant. The number of neutrophils that migrated into the filter was used as an index of directed chemotaxis. Burn injury resulted in depressed chemotaxis compared with sham or sham/G-CSF-treated animals (p less than 0.05). Administration of rhG-CSF to burned animals resulted in a level of neutrophil chemotaxis comparable with that in control animals. The presence of a burn wound infection caused no further impairment of chemotaxis. Administration of rhG-CSF to animals with a burn wound infection resulted in improved chemotaxis compared with sham, burned, and burned/infected animals. The beneficial effect of G-CSF following burn wound infections from this and previous studies appears to be a combination of expanded numbers of myeloid elements and preservation of their function.

Analysis of Variance↗

PubMed1990

The differential effect of corticosteroids on wound disruption strength in mice.

The detrimental role of corticosteroids on wound healing is well recognized. This study examined the effect of equipotent anti-inflammatory doses of dexamethasone sodium phosphate, methylprednisolone sodium succinate, or hydrocortisone sodium succinate on wound healing in mice. Mice were injected daily for 12 days; the mice were wounded on day 3 of steroid injection, with wound analysis done on day 10 after wounding. Dexamethasone and hydrocortisone significantly impaired wound healing, as assessed by wound disruption strength when compared with controls or methylprednisolone. Dexamethasone and hydrocortisone both displayed dose-dependent relationships for impairment of healing, while over comparative doses, methylprednisolone failed to affect healing significantly. Regression analysis revealed nearly identical curves for hydrocortisone and dexamethasone that differed significantly from that of methylprednisolone. Our observations suggested that these preparations possessed a differential effect on the healing wound that should be considered to minimize postsurgical or traumatic wound-healing problems.

Animals↗

PubMed1990

The effect of interleukin 1 alpha on survival in a murine model of burn wound sepsis.

We examined the effects of human recombinant interleukin 1 alpha (IL-1 alpha) in a murine model of burn wound sepsis. The BDF1 male mice received a 15% burn injury, followed by burn wound inoculation with Pseudomonas aeruginosa. Improvement in survival was noted in the mice that received a single injection of 100 or 1000 ng of IL-1 alpha in comparison with the control animals (IL-1 alpha, 100 ng vs control, 60% vs 13%; IL-1 alpha, 1000 ng vs control, 40% vs 0%). The animals that received 1 ng twice daily for 7 days had improved survival in comparison with the controls (IL-1 alpha vs control, 70.8% vs 20.8%). The animals that received a single injection of 1000 ng after a bacterial challenge with 10(4) P aeruginosa of IL-1 alpha had fewer positive blood cultures at 48 hours compared with the controls (57% vs 89%). In addition, the animals that received 100 ng of IL-1 alpha had significantly increased absolute neutrophil counts at 6, 24, and 48 hours after thermal injury and bacterial challenge with 10(3) colony-forming units of P aeruginosa. The use of cytokines to modulate the host response to injury or infection may lead to additional strategies to improve the outcome following burn injury.

Animals↗

PubMed1990

Protective effect of recombinant human granulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice.

Granulocyte colony-stimulating factor stimulates the proliferation and differentiation of progenitor cells committed to the neutrophil lineage, and it has been shown to improve survival to bacterial challenge in neutropenic mice. We studied recombinant human granulocyte colony-stimulating factor (rhG-CSF), cloned from bladder cell carcinoma line 5637, in a nonneutropenic infection model of Streptococcus pneumoniae pulmonary infection in splenectomized and sham-operated control mice. The rhG-CSF improved survival in the splenectomized mice but not in the sham-operated mice. Circulating leukocyte counts were greatest for the rhG-CSF-treated splenectomized mice compared with all other groups, presumably due to a loss of splenic sequestration. Clearance of live pneumococci from mouse lung pairs was impaired after splenectomy. The rhG-CSF improved lung clearance in both splenectomized and sham-operated mice compared with saline solution-treated controls. The number of live pneumococci recovered from tracheobronchial lymph nodes at 24 hours after aerosol challenge was greatest in the splenectomized mice vs sham-operated mice. Decreased numbers of viable pneumococci were recovered from tracheobronchial lymph nodes from the rhG-CSF-treated splenectomized mice and the sham-operated mice vs saline solution-treated controls. The rhG-CSF may be a useful adjuvant for treating infections in individuals with immunologic dysfunctions other than neutropenia.

Animals↗

PubMed1990

Tumor necrosis factor and wound healing.

Tumor necrosis factor alpha (TNF), 1 to 500 ng in saline (PBS) or collagen, was applied to the wounds of normal and Adriamycin-impaired mice and wound disruption strength (WDS) and histology were examined. Also wounded mice were administered TNF 25 to 75 micrograms/kg IP daily and WDS was determined. Wound histology was examined 6 months after wounding and local TNF application. Local TNF 5 to 500 ng in PBS did not significantly affect WDS. Local TNF 5 to 50 ng in collagen increased WDS 33% to 65% in Adriamycin-impaired animals (p = 0.05 to p less than 0.02). Local TNF 50 to 500 ng in collagen increased WDS 23% to 49% in normal animals (p = 0.08 to p less than 0.01). Adriamycin-impaired animals demonstrated improved wound histology with local TNF in collagen. Systemic TNF did not significantly affect WDS. Local TNF in collagen did not induce histologic pathology at 6 months. TNF may modulate macrophage function and local TNF in collagen can improve WDS in normal and Adriamycin-impaired animals.

Administration, Topical↗