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Biomedical subjects

J C Hebert

Publications and source records attributed to J C Hebert.

At least 19 recordsLinked to original sources

The characteristic appearance of non-alcoholic duct destructive chronic pancreatitis: a report of 2 cases.

We report 2 patients with an unusual form of chronic pancreatitis, both of whom were treated for clinical suspicion of pancreatic malignancy. The surgical specimens revealed a dense lymphoplasmacytic infiltration of the main and interlobular branches of the pancreatic duct, causing sclerosis of the duct wall, diffuse irregular lumenal narrowing, extensive parenchymal fibrosis, and organ enlargement. Neither case showed calcifications, fat necrosis, or cyst formation, features usually seen in alcoholic pancreatitis, nor was there any evidence of neoplasia. One patient had an unusual form of acalculous cholecystitis, but without cystic duct inflammation or fibrosis. Both patients recovered well from the surgical procedure and have not had any complications or relapse of their symptoms. To the best of our knowledge, these cases are representative of the recently described non-alcoholic duct destructive chronic pancreatitis, which is thought to be immune-mediated.

Adult↗

A new model for recognizing and rewarding the educational accomplishments of surgery faculty.

Faculty members' educational endeavors have generally not received adequate recognition. The Association for Surgical Education in 1993 established a task force to determine the magnitude of this problem and to create a model to address the challenges and opportunities identified. To obtain baseline information, the task force reviewed information from national sources and the literature on recognizing and rewarding faculty members for educational accomplishments. The group also developed and mailed to surgery departments at all U.S. and Canadian medical schools a questionnaire asking about the educational endeavors of the surgery faculty and their recognition for such activities. The response rate after two mailings was only 56%, but the responses reaffirmed the inadequacy of systems for rewarding and recognizing surgeon-teachers and surgeon-educators, and confirmed that the distinction between the roles of teacher and educator was rarely made. The task force created a four-tier hierarchical model based on the designations teacher, master teacher, educator, and master educator as a framework to offer appropriate recognition and rewards to the faculty, and endorsed a broad definition of educational scholarship. Criteria for various levels of achievement, ways to demonstrate and document educational contributions, appropriate support and recognition, and suggested faculty ranks were defined for these levels. The task force recommended that each surgery department have within its faculty ranks a cadre of trained teachers, a few master teachers, and at least one educator. Departments with a major commitment to education should consider supporting a master educator to serve as a resource not only for the department but also for the department's medical school and other medical schools. Although this model was created for surgery departments, it is generalizable to other disciplines.

Academic Medical Centers↗

[Severe forms of eosinophilic meningitis in infants of Mayotte. Apropos of 3 cases].

BACKGROUND: Eosinophilic meningitis caused by Angiostrongylus cantonensis is widespread in Southeast Asia and the Pacific islands. Adults develop transient meningitis with a benign course, whilst severe or fatal disease may occur in pediatric patients. CASE REPORTS: Three infant girls, aged 8 to 11 months, living on the island of Mayotte, developed fever, hypotonia, coma (2 cases), and, for one of them, seizures. Eosinophilia was detected in the peripheral blood and cerebrospinal fluid. Secondary, flaccid quadraplegia (1 case) or paraplegia (2 cases) with absence of deep tendon reflexes, urinary retention and anal incontinence were noted. Three patients had autonomic dysfunction. Computerized tomography showed enlarged ventricles and cerebral subarachnoid spaces. One patient had sequelae. Two patients could not be followed. Retrospectively, the diagnosis of angiostrongylus infection was established for two infants by a serological study. CONCLUSION: We report three new cases of infants with severe Angiostrongylus cantonensis infection in the French island of Mayotte (Comoro Islands). In this Indian Ocean area, eosinophilic meningitis seems to occur exclusively in infants and with severe radiculomyeloencephalitic forms.

Angiostrongylus cantonensis↗

Who should teach medical students surgery?

BACKGROUND: Medical schools are undergoing major curricular reform, partly in attempts to increase the number of graduates pursuing careers in the generalist disciplines. These reforms have often resulted in a shortening of the surgery clerkship, decreasing students' experiences in several domains important to the generalist. METHODS: A seven-question survey of clerkship directors of US medical schools was administered to measure the magnitude of curriculum change during the past 5 years affecting the surgery and family practice clerkships. The survey also addressed attitudes about the purpose of the surgery clerkship. RESULTS: There was an 80% (103 of 129) response rate. Between 1989 and 1994, surgery clerkships decreased on average from 11 to 10.2 weeks (P <0.05) while family practice clerkships increased from 4.2 to 6.8 weeks (P <0.05). Ninety-one percent of clerkship directors felt the primary goal of the clerkship should be to train generalists. CONCLUSIONS: The length of the surgery clerkship has decreased at several institutions. In order to ensure an appropriate educational experience for medical students, surgeons must participate actively in curriculum reform within medical schools and highlight their unique role in training generalists.

Clinical Clerkship↗

Effects of exogenous cytokines on intravascular clearance of bacteria in normal and splenectomized mice.

BACKGROUND: Pretreatment with interleukin-1 (IL-1), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) can improve alveolar macrophage bactericidal activity against pneumococci. These effects vary in eusplenic and asplenic mice. Likewise, these cytokines have been shown to improve survival after an aerosol pneumococcal challenge. Mice dying in these studies had positive blood cultures and disseminated infection. The purpose of this study was to determine the effect of cytokine pretreatment on intravascular clearance of bacteria from eusplenic and asplenic mice. METHODS: Two weeks after splenectomy or sham operation, mice were pretreated for various times with IL-1, G-CSF, or GM-CSF or their corresponding vehicles. Mice then received tail-vein injections of bacteria (0.1 mL), and quantitative blood cultures were performed 15 and 30 minutes thereafter. RESULTS: Splenectomized mice had impaired clearance of both pneumococci and Pseudomonas compared with sham-operated mice (p < 0.05). IL-1 enhanced clearance in splenectomized mice (p < 0.001) but not in sham-operated mice (p not significant). G-CSF enhanced bacterial clearance in sham-operated mice (p < 0.01) but not in splenectomized mice (p not significant). GM-CSF enhanced clearance in both groups (p < 0.001). CONCLUSION: The net effects of exogenous cytokine therapy for infections depends on the state of the host defenses at the time of therapy. These agents may be useful as adjuvants for the treatment of infections, but further study is warranted.

Animals↗

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances pulmonary defenses against pneumococcal infections after splenectomy.

BACKGROUND: Splenectomized individuals are at risk for pneumococcal sepsis. Alveolar macrophage bactericidal function is depressed after splenectomy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has pronounced effects on the number and function of macrophages. We hypothesized that GM-CSF treatment could improve alveolar macrophage bactericidal activity against pneumococci, and improve survival with pneumococcal infection. METHODS: Two weeks after splenectomy or sham operation, mice were treated with GM-CSF or saline twice daily for varying times. Alveolar macrophages were obtained by bronchopulmonary lavage, and bactericidal activity was measured. Survival was assessed after pneumococcal aerosol challenge. RESULTS: Alveolar macrophage bactericidal activity was improved with GM-CSF treatment in both eusplenic and asplenic mice (p < 0.001). GM-CSF treatment improved survival in both groups (p < 0.001). CONCLUSIONS: GM-CSF can augment alveolar macrophage function and provide protection against pneumococcal infections. It may be a useful adjuvant therapy for normal and splenectomized individuals.

Animals↗

Von Hippel-Lindau disease presenting as pancreatic neuroendocrine tumour.

A 21-year-old woman with a family history of von Hippel-Lindau disease presented with a mass in the head of the pancreas. Light microscopic features of the tumour suggested neuroendocrine differentiation and although it displayed positive immunostaining for the antigens expected in a neuroendocrine neoplasm, S-100 staining was also present. This unusual feature prompted further evaluation by routine and post-embedding protein-A gold immunoelectron microscopy, which demonstrated the presence of neuroendocrine granules. Tumour cell DNA content was normal by flow cytometry. Although this patient exhibited no other signs of von Hippel-Lindau disease, the presence of a pancreatic tumour with neuroendocrine differentiation demonstrated that she was affected. Future surveillance and genetic counselling will be influenced by this diagnosis.

Adult↗

Modifying the host response to injury. The future of trauma care.

It is beyond the scope of this article to describe all of the contributions of molecular biology to increasing our understanding of the pathophysiology of inflammation and the response to injury. This review focuses on those aspects that are clinically relevant. In addition to providing quantities of recombinant proteins, recent advances in molecular and cellular biology have provided other tools to help differentiate the pathophysiology of the host response to injury and infection. Hybridoma technology has facilitated the development of specific antibodies that are used to block the activity of a specific factor or toxin. Receptor and signal transduction biology has provided further insight into the activity and function of various factors and mediators. Studies at the level of the gene have shed light on the phylogenic relationship among various factors. Transgenic animals can be used to determine the effects of excess factor production; conversely, genetic "knockouts" are useful in determining the pathophysiology associated with the absence of a particular factor. It is clear that as our understanding of the complex interactions leading to inflammation increases, we will be able to take advantage of this knowledge to more effectively treat patients.

Cytokines↗

Dose dependency of granulocyte-macrophage colony stimulating factor for improving survival following burn wound infection.

Infections remain a serious problem following injury. Immune modulation offers an additional strategy for the treatment of infections. We evaluated the ability of a multilineage hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), to improve survival following burn injury with a superimposed burn wound infection. Groups of 12 BDF1 mice received a 15% total body surface area (TBSA) thermal injury by immersion in 100 degrees C water; 6 x 10(3) Pseudomonas was then applied to the burn wound. The GM-CSF was injected subcutaneously B.I.D. for 7 days. Mice receiving the 10-ng dose of GM-CSF had significantly improved survival compared with the controls; other doses had no significant effect on survival. Clinical trials to assess the ability of GM-CSF to reduce infectious complications following burn injury are underway and these data suggest selecting a specific dose may be critical in achieving maximal benefit.

Animals↗

Augmentation of alveolar macrophage phagocytic activity by granulocyte colony stimulating factor and interleukin-1: influence of splenectomy.

The use of cytokines and other naturally occurring substances as biopharmaceuticals for modulating the host response to trauma and infection offers new therapeutic possibilities. Cytokine pretreatment protects animals in a variety of experimental models, including splenectomized mice following pneumococcal aerosol challenge. Since splenectomy appears to affect alveolar macrophage function, we postulated that pretreatment with interleukin 1 (IL-1) and granulocyte colony stimulating factor (G-CSF) improved survival in mice following aerosol challenge of live pneumococci by activating alveolar macrophages. Alveolar macrophage bactericidal and phagocytic function was slightly, but consistently, depressed following splenectomy. Interleukin-1 and G-CSF pretreatment had pronounced effects on macrophage phagocytic and bactericidal activity, and these effects were quite different depending upon whether the mice were eusplenic or asplenic. Splenectomy augmented the effects of IL-1 on alveolar macrophage bactericidal function compared with eusplenic mice (p < 0.001), while more pronounced effects on macrophage function following G-CSF treatment were seen in mice with intact spleens (p < 0.001). The use of cytokines and other substances to modify the host response to infection has great potential. Individuals with deficits such as splenectomy will have a different net response to therapy. It is important that we be able to predict these responses accurately in most patients in order to use these substances more effectively.

Animals↗

Do general surgery residency programs adequately train surgeons to perform anorectal surgery?

The management of anorectal disease remains a major component in the practice of the general surgeon. To assess the adequacy of general surgery residencies in addressing this educational need, data were obtained from the Residency Review Committee (RRC) for surgery on the anorectal experience of all graduating residents in accredited United States programs for a recent five-year period (1987-1991). The mean number of anorectal procedures in which a resident participated throughout the residency was 30.0. This is then further subdivided by type of procedure. It is concluded that general surgery residency programs tend to provide an inadequate training experience in anorectal surgery.

Anal Canal↗

Prospective randomized study of piperacillin/tazobactam therapy of surgically treated intra-abdominal infection. The Piperacillin/Tazobactam Intra-Abdominal Infection Study Group.

A randomized prospective trial was undertaken in adult patients with serious intra-abdominal infections to determine whether a new combination of antibiotic therapy could prove as efficacious as the combination that has been widely used in practice in the recent decade (clindamycin and gentamicin). Three hundred thirty-one patients were randomized in a 2:1 ratio, with the larger number of patients being treated parenterally with piperacillin and tazobactam. The results showed that both the clinical and microbiologic performance of the piperacillin/tazobactam combination was better than that of clindamycin and gentamicin. This clinical equivalence permits overall cost savings without compromising the existing quality of antimicrobial therapy for intra-abdominal infection.

Abdomen↗

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↗

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↗

Multidisciplinary protocol for determining aminoglycoside dosage.

A protocol for determining optimal dosages of aminoglycosides early in therapy is described, and the effectiveness of the protocol is evaluated. The protocol was developed jointly by physicians and pharmacists at a 550-bed hospital to ensure that surgical patients prescribed aminoglycosides were quickly and consistently put on a safe and effective course of therapy. Physicians select an aminoglycoside and calculate a loading dose and initial maintenance dosage by using a nomogram printed on an antimicrobial order form. Nurses are trained to administer and document aminoglycoside doses accurately and to draw blood samples at the correct times. Pharmacists order serum aminoglycoside concentration assays, analyze the results, and recommend changes in dosage when necessary. To evaluate the effectiveness of the dosing protocol, the records of surgical patients treated before and after the protocol was in place were reviewed. Compared with the control group, a higher percentage of patients treated under the protocol were receiving therapeutic, nontoxic dosages of aminoglycosides within 48 hours of the start of therapy. In addition, fewer serum drug concentration tests were ordered per patient under the protocol, and the percentage of concentration determinations useful for analysis was higher. The mean duration of aminoglycoside therapy was identical before and after the protocol was instituted, and nephrotoxic reactions tended to be less common among the protocol patients. An aminoglycoside dosing protocol requiring the cooperation of pharmacists, nurses, and physicians provides a consistent, safe, and effective means of managing aminoglycoside therapy for the hospitalized patient.

Adult↗

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↗

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↗