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Biomedical subjects

J C Hebert

Publications and source records attributed to J C Hebert.

At least 37 records · Page 2Linked to original sources

Pneumococcal vaccine improves pulmonary clearance of live pneumococci after splenectomy.

The efficacy of pneumococcal capsular polysaccharide vaccines after splenectomy to decrease the incidence of postsplenectomy pneumococcal sepsis is controversial. We examined the effect of pneumococcal vaccine on clearance of live pneumococci from lungs of splenectomized and sham-operated mice following an aerosol challenge of pneumococci. Splenectomy impaired clearance of pneumococci from mouse lungs and allowed for increased translocation of pneumococci to tracheobronchial lymph nodes compared to shams (P less than 0.01). Pneumococcal vaccine improved lung clearance in both splenectomized and sham-operated mice compared to saline controls (P less than 0.01), but the number of live pneumococci recovered from lung pairs was greater in splenectomized mice compared to shams (P less than 0.01). Pneumococcal vaccination facilitated earlier translocation of pneumococci to tracheobronchial lymph nodes, and probably promoted bactericidal activity in these nodes, in both splenectomized and sham-operated mice. Survival in splenectomized mice was improved by vaccination, but remained significantly less than that in saline-treated sham-operated mice (P less than 0.0009). The data show that pneumococcal vaccine can improve lung antipneumococcal defenses in splenectomized mice, but not to the same degree as in mice retaining their spleens. Pneumococcal vaccine should be given after splenectomy, but surgeons should caution patients that it may be less effective than when given to individuals with intact spleens or before elective surgery.

Animals↗

Serum antibody responses to pneumococcal vaccine after splenic autotransplantation.

Immunization with pneumococcal capsular polysaccharide vaccines is advocated after splenectomy; however, experimental and clinical data suggest an impaired antibody response in splenectomized individuals. This study examined the value of splenic autotransplantation at various sites in augmenting the antibody response to Type III pneumococcal capsular polysaccharide in mice immunized 3 months after operation. Splenectomy resulted in impaired antibody responses compared to sham-operated mice (p less than 0.001) using an enzyme-linked immunosorbent assay. Mice with intraperitoneal splenic autotransplants, but not mice with subcutaneous or intramuscular transplants, had greater antibody responses compared to splenectomized mice (p less than 0.05). Antibody responses were elevated only in mice autotransplanted with 50% or more of the original splenic mass. Since autotransplantation of splenic tissue augments the antibody response to pneumococcal capsular polysaccharides, the combination of splenic autotransplantation and pneumococcal vaccination may confer more protection than either modality alone in individuals who must undergo splenectomy.

Animals↗

Pulmonary antipneumococcal defenses after hemisplenectomy.

Conservative splenic surgery such as partial splenectomy is advocated for splenic injuries, since splenectomy predisposes individuals to overwhelming sepsis with encapsulated organisms, of which Streptococcus pneumoniae is the most frequently isolated. The respiratory route is argued to be the most likely portal of entry of pneumococci; however, little data exist on the interaction of the spleen and pulmonary defense mechanisms against pneumococcal invasion. We studied the effect of splenectomy, 50% splenectomy (hemisplenectomy), 25% splenectomy, and sham operation on in vivo clearance of live pneumococci from the lungs of male CD-1 mice following an aerosol challenge of pneumococci. Splenectomy impaired pneumococcal clearance from mouse lung pairs and allowed for increased translocation of live pneumococci to tracheobronchial lymph nodes compared to sham-operated controls. Preservation of splenic mass by partial splenectomy improved lung clearance and allowed for fewer bacteria to be cultured from tracheobronchial lymph nodes compared to splenectomized animals. Clearance of live pneumococci from the lungs and survival were directly proportional to the amount of splenic tissue remaining. Splenic factors probably exist which regulate reticuloendothelial cell function throughout the host. Maintaining adequate splenic mass, therefore, is an important consideration when operating for splenic trauma.

Animals↗

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↗

Chylothorax following fracture of the thoracolumbar spine.

Chylothorax is an uncommon occurrence seen most frequently in patients with malignancy. We report a case of chylothorax following fracture-dislocation of the thoracolumbar spine, the ninth reported case in the English literature. Seven cases of chylothorax were identified in a 12-year period at our institution. A total 925 patients sustained fractures of the thoracic or lumbar spine during this period, and this was the only case associated with chylothorax. We have reviewed the literature, and recommend conservative management utilizing closed thoracotomy drainage and total parenteral nutrition for at least 2 weeks. If chyle flow has not diminished by that time then thoracic duct ligation should be considered.

Adolescent↗

Immunization with heat-killed pneumococci, but not pneumococcal capsular polysaccharides, improves survival in splenectomized mice.

Immunization with pneumococcal capsular polysaccharides (pn PS) is advocated after splenectomy to decrease the risk of overwhelming sepsis. The clinical and experimental evidence for the benefit of immunization after splenectomy is controversial. Various reports in the literature have claimed a benefit of immunization after splenectomy, but careful review of methodologies reveals that heat-killed pneumococci (pn) were used to immunize the experimental animals. Since we have not been able to protect splenectomized (splx) mice by immunization with pn PS, we compared survival after live pneumococcal aerosol challenge and antibody (Ab) responses in splx and sham splx mice immunized with either pn PS or heat-killed pn. Immunization with either heat-killed type 3 pn or pn type 3 PS improved survival in sham-splx mice compared to saline controls (p less than 0.001). Only immunization with heat-killed type 3 pn improved survival in splx mice (p less than 0.001), while pn PS had no effect on survival compared to saline splx controls. Ab responses to pn type 3 PS measured by enzyme linked immunosorbent assay were depressed in splx mice compared to sham-splx mice regardless of the method of immunization. Sham-splx mice immunized with heat-killed pn had higher Ab levels compared to mice vaccinated with pn PS (p less than 0.001) suggesting an adjuvant effect in sham-splx mice. The data suggest that immunization with pn PS may not be beneficial to a splx host. Improved survival after immunization with heat-killed bacteria in splx mice may be related to Ab responses to antigens other than the capsular polysaccharide.

Animals↗

Post-traumatic upper airway obstruction secondary to a lingual artery hematoma.

An accident victim presented with maxillofacial trauma complicating a head injury. After the airway was secured by tracheostomy, surgical exploration revealed a lingual artery hematoma. This case illustrates the progressive airway occlusion seen with this disorder and the importance of repeated oral examinations.

Adult↗

Reiter's syndrome and recurrent peritonitis after appendectomy.

A 15-year-old male adolescent underwent an appendectomy for acute gangrenous appendicitis. One week after surgery, he underwent an exploratory laparotomy that revealed two pericecal abscesses, which were drained. Two weeks later, he had diffuse peritonitis and underwent another laparotomy, which revealed a sterile fibrinous peritonitis. Oligoarticular inflammatory arthritis, urethritis, and recurrent peritonitis subsequently developed. He was found to be positive for HLA-B27 antigens. This case report illustrates that reactive arthritis (Reiter's syndrome) may develop after peritoneal infections. It also raises the possibility that the inflammatory process, which involves other serosal surfaces in Reiter's syndrome, may affect the peritoneum.

Abscess↗

Juvenile polyp with intramucosal carcinoma.

Intramucosal carcinoma arising in an otherwise typical juvenile polyp is reported. Adenomatous change and carcinoma in situ have been previously documented in patients with the multiple juvenile polyposis syndrome. The syndrome was not present in this case. Although rare, juvenile polyps (both in solitary and multiple forms) are a potential site of malignant change.

Adult↗

The age-related decline in antibody response is transferred by old to young bone marrow transplantation.

The immune response declines with age. This decline correlates with thymic involution and involves primarily a loss in T-cell function, whereas humoral immunity is more variably affected. In the current experiments we have measured immunoglobulin synthesis in vitro after mitogen stimulation, and specific antibody response after vaccination. We found that the response to pokeweed mitogen by non-specific immunoglobulin production, and the response to vaccine was shown to be transferred to lethally irradiated young mice by old to young bone marrow transplantation. Both pokeweed mitogen and tetanus toxoid require T-cell help for optimal response, and, therefore, our observations are in accordance with the age-associated decline in T-cell immunity. The finding that young hosts transplanted with old bone marrow produce less antibody than young hosts transplanted with young bone marrow highlights the importance of the decline in cellular function with age.

Aging↗

Preparation and release characteristics of tobramycin-impregnated polymethylmethacrylate beads.

Preparation of tobramycin-impregnated polymethylmethacrylate (PMMA) bone cement beads and release of tobramycin from the beads in vitro and after implantation in a patient are described. Tobramycin sulfate powder 1.2 g was mixed with Palacos PMMA bone cement 40 g in a custom-made mold to produce 25 beads containing 3.26 mg tobramycin (as the sulfate salt) per bead. Chains of the beads, strung on stainless-steel suture, were sterilized with ethylene oxide. Three single beads were each placed in multiple-electrolyte solution (pH 7.4); the solution was removed and replaced with fresh solution every 24 hours for 28 days. The tobramycin content of each day's solution was determined by fluorescence polarization immunoassay. After day 28, solution was removed weekly for assay until day 84. Tobramycin concentrations were measured in drainage from the surgical wound after six chains of tobramycin-PMMA bone cement beads were implanted in the right acetabulum and femur of a patient whose hip prosthesis had been removed because of infection. Tobramycin concentrations in the dissolution medium averaged 34.3 micrograms/mL initially, and 7.5 micrograms/mL on day 2, gradually decreasing to 0.6 microgram/mL on day 28. Release of tobramycin followed a predictable pattern, and variation among samples was small. Over 12 weeks, less than 20% of the theoretically available tobramycin from a single bead was released. Tobramycin concentration in wound drainage was 90.0 micrograms/mL during the first 24 hours after surgery, while serum tobramycin concentrations were less than 0.5 microgram/mL. Extemporaneously prepared beads of bone cement are effective for delivering high concentrations of tobramycin to an infection site.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Cements↗

Effect of thymosin alpha one on specific antibody response and susceptibility to infection in young and aged mice.

The antibody response to a variety of antigens has been shown to diminish with age. We investigated the capacity for Thymosin Alpha One (T alpha 1) treatment to augment antibody production in tetanus toxoid (TT) and pneumococcal capsular polysaccharide (PN) inoculated young and old mice. We also measured survival of these immunized mice after aerosol exposure to Streptococcus pneumoniae. As predicted antibody response to TT, but not PN, was significantly reduced in the old animals and T alpha 1 augmented antitetanus antibody in both young and old mice. T alpha 1 did not have an effect on anti pneumococcal antibody production. All mice that had received PN did have an antibody response, yet survival after exposure to the organism was strikingly less in the old animals. Our data support the contention that antibody response to T-dependent antigens (such as tetanus toxoid) falls with aging but can be reconstituted somewhat by thymic factors. Furthermore, for T-independent antigen (such as pneumococcal capsular antigens) the age-related changes are less evident. In the latter situation, the presence of a brisk antibody response after vaccination was not sufficient to prevent pneumonia and death in old animals.

Aerosols↗

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↗

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↗

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↗

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↗