Hanseniasis and whole body hyperthermia.
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Biomedical subjects
Publications and source records attributed to R D Pearson.
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The effect on subsequent larval survival of infesting sheep repeatedly with larvae of Lucilia cuprina was assayed in vivo and in vitro. One in vivo assay technique, in which implanted larvae were grown to third instar, indicated a significant reduction in larval survival; another in vivo technique, in which larvae were allowed to develop to second instar in small aluminium rings attached to the sheep, indicated no reduction in larval growth or survival. Larvae of Lucilia cuprina grown in vitro on media containing sera from previously infested sheep were significantly retarded in growth after 20 h compared with controls; no difference was detected when larvae were allowed to develop to pupation on two changes of the same media. No significant differences in survival of larvae either to 20 h or to pupation were obtained between the two treatments. ELISA antibody levels against crude soluble larval material were significantly higher for sera from infested sheep than for control sera, and the regression of antibody level on mean larval weight obtained after 20 h growth in vitro was significant. The immunoglobulin fraction isolated from sera of infested sheep significantly retarded larval growth when incorporated with normal serum in growth media. These results are consistent with an effect of specific anti-larval antibody produced by sheep in response to infestation.
We identified characteristics of items causing sharp object injuries in hospital personnel during a 10-month interval. Sharp objects were defined as items that were not hollow-bore needles, that cause lacerations or puncture wounds. Workers reporting sharp object injuries were interviewed to determine what items caused injury and the circumstances of their injuries. Of 89 incidents, 51% were surgical instrument injuries, 19% were lancet injuries, 16% were glass injuries, and 15% were caused by other sharp items. A frequent feature of sharp objects causing injuries was the necessity of disengaging a disposable sharp item from a reusable holder. The application of manual force to fragile glass items also caused many injuries. Opportunities for safer product design and improved materials are discussed to reduce this common occupational hazard.
Two very large bodies of information seem to overlap, one being the epidemiological and pathological studies on sudden infant death syndrome (SIDS), the other being the research on hibernation. Until now, these two phenomena have been studied independently; however, it will be argued here that the role of the pineal gland, that of brown adipose tissue (BAT) and sleep patterns in both endothermic hibernating mammals and those babies presenting as SIDS provide clues and support for the hypothesis that SIDS is pathoplastic to the hibernatory response.
A major factor in the introduction of new products designed to decrease the risk of needlesticks to healthcare workers (HCWs) is whether the increased expense of a safer device is offset by the savings of preventing needlesticks. The itemized costs of needlestick injuries associated with six major needled devices were estimated and compared to the cost of the devices causing the injuries, based on 1988 dollars. Included was the cost of treatment, prophylaxis and employee health department personnel time. The average cost of needlestick injury was $405, with a narrow range of $390 to $456 for different devices. As a percent of the cost of the devices, needlesticks cost as little as 10% of the cost of the device, for the intravenous (IV) catheter, to as much as 457%, for needles used to connect IV lines. On the average, needlesticks cost 36% of the devices' cost. These data may be used to weigh the potential economic benefits of safer needle technology or other strategies intended to reduce the incidence of needlesticks.
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Domestic dogs are considered to be a major reservoir of Leishmania donovani chagasi in northeast Brazil, and the elimination of infected dogs is an important part of the control program. We assessed 2 serological methods, IFA and ELISA. Of 405 dogs, 8% were positive by IFA obtained from blood collected by drying onto filter paper followed by elution, 17% were positive by IFA performed using sera, and 38% were positive by ELISA on the same sera. Thirty-five dogs, seropositive by 1 or more of the above tests, were killed and touch preparations were made of liver, spleen, and mesenteric lymph nodes. Samples were cultured in enriched NNN media. The ELISA recognized all dogs with proven infection; IFA detected 10 of 12. Eleven dogs were positive by touch preparations and 7 by culture. In addition, kDNA hybridization was undertaken with probes to L. donovani chagasi, L. braziliensis ssp., and L. mexicana amazonensis. Positive results were obtained from tissue in 19 instances, but 10 culture positive specimens were not recognized.
Leishmania donovani, an intracellular pathogen in vertebrates, is found as an amastigote within cells of reticuloendothelial origin. The spleens of experimentally infected Syrian hamsters are frequently used as a source of amastigotes for studies of host-parasite interactions, but amastigotes isolated from hamster spleens have been found to have surface-bound host immunoglobulins, which may confound interpretation of such studies.
Wasting and secretion of the catabolic cytokines tumor necrosis factor (TNF)/cachectin and interleukin 1 (IL-1) were assessed in weanling Syrian hamsters infected with Leishmania donovani amastigotes. Whereas the mean weight of uninfected animals increased progressively over 9 weeks, the mean weight of infected animals plateaued at 4-6 weeks and then decreased progressively until death. Splenic mononuclear cells from control hamsters produced 11.3 +/- 8.3 (SD) ng TNF/10(6) mononuclear cells/24 hr. TNF secretion in infected animals was greater than the mean +/- 2 SD of controls in 1 of 3 hamsters at 2 weeks post-infection and in 8 of 9 hamsters at weeks 4-8. The mean TNF secreted by infected animals studied at weeks 4-8 was 371 (range 28-800) ng TNF/10(6) mononuclear cells/24 hr (P = 0.005). Control hamsters produced 7.7 +/- 2.7 pg IL-1/10(6) mononuclear cells/24 hr. At 2 weeks, mononuclear cells from 2 of 3 infected animals secreted amounts of IL-1 greater than the mean +/- 2 SD of controls. All of 8 infected hamsters secreted increased amounts of IL-1 at 4-8 weeks. The mean was 164 (range 17-370) pg IL-1/10(6) mononuclear cells/24 hr (P = 0.002). In comparison to infected animals, mononuclear cells from control hamsters incubated with lipopolysaccharide, 10 micrograms/ml, produced 172.5 ng TNF and 44.6 pg of IL-1/10(6) mononuclear cells/24 hr. The effect of visceral leishmaniasis on food intake was assessed in a separate group of animals housed individually in metabolic cages. Significant reductions in weight and food intake were first observed at 2 and 3 weeks of infection, respectively. By 5 weeks, the food intake of infected animals was 46% that of controls. Syrian hamsters infected with L. donovani provide an excellent model with which to study the mechanism of wasting.
Leishmania donovani produces progressive wasting and ultimately fatal visceral leishmaniasis in Syrian hamsters and provides an excellent model of progressive disease in humans. Experimentally infected hamsters were used to investigate the development of nonspecific immune suppression during visceral leishmaniasis and its association with humoral factors and wasting. At 2 wk all infected hamsters had developed antibody against a 59-kDa parasite antigen not recognized by sera of control hamsters. By 4 wk, strong antibody responses were noted against antigens of 26, 35, 46, 69, 107, and 120 kDa. No additional antigen was recognized at 6 or 8 wk or in hamsters treated with high doses of a pentavalent antimonial (stibogluconate sodium, 100 mg/kg/day for 5 days). Weight loss was first noted in infected hamsters at 8 wk. No difference in splenic lymphocyte proliferation in response to concanavalin A (Con A) was noted at 2 wk, but by 6 wk infected animals had only 20% of the Con A response of controls, and by 8 wk only 13%. Furthermore, incubation of splenic lymphocytes from uninfected control animals with 5% fetal calf serum and 5% serum from infected hamsters obtained at 4, 6, or 8 wk suppressed Con A responses by 50%, 99%, and 100%, respectively. Spleen cells from drug-treated animals exhibited no suppression of Con A responses when incubated with 5% autologous serum, but there was profound suppression when they were incubated with 5% autologous serum obtained during the acute phase of infection. Humoral factors, but not wasting, contributed to the suppression of lymphocyte responses.
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Cattle have been vaccinated against Boophilus microplus with antigens derived from partially fed female ticks. The immune response of the host lyses the gut cells of adult ticks, causing a reduction in the number, weight and reproductive capacity of engorging ticks. This response is different from the immunity that cattle acquire after repeated tick infestation. Evidence is presented that the antigens used in vaccination are located on the plasma membrane of the gut cells and it is unlikely that these antigens are secreted into the host during feeding. Vaccination using such 'concealed' antigens may not encounter the mechanisms of immune evasion that parasites usually demonstrate. In-vitro assays suggest that vaccination immunity is not dependent on the need to stimulate cell-mediated responses. Immunoglobulin G alone, or with the aid of complement, is enough to damage tick gut. The normal function of the one protein antigen isolated so far is unknown but we speculate that it serves some vital function on the cell plasma membrane.
The prognosis of juvenile rheumatoid arthritis (JRA) is generally good, although premature death occurs in a subset of children. Secondary infections, chronic amyloidosis, and heart disease have been reported as common causes. Our experience indicates that JRA can also herald the development of a severe immune enteropathy. In the case presented, typical JRA was followed by fulminant hepatitis; skin rashes; recurrent, severe, watery diarrhea; malabsorption; and ultimately death. Biopsies of the small bowel exposed to the patient's serum revealed deposition of complement and immunoglobulins in the epithelium. Although not widely appreciated, JRA can herald a multisystem syndrome characterized by severe immune enteropathy.
Serum from healthy, nonimmune humans contained immunoglobulin M (IgM) antibodies that agglutinated Leishmania donovani promastigotes, activated complement, and enhanced promastigote ingestion by human monocytes. The findings indicate that IgM antibodies have the capacity to affect the initial interaction of L. donovani promastigotes with human host defenses.
BALB/cJ mice, which are homozygous for Lshs on chromosone 1, are genetically susceptible to Leishmania donovani (S3), but spontaneously reduce their parasite burdens late in the course of infection. Spleens from chronically infected mice (5 to 8 mo) were found to have T cells that responded to leishmanial Ag by proliferating and secreting immune IFN. An IFN-secreting T cell line derived from the spleen of a chronically infected mouse, after boosting with leishmanial Ag and treatment with Pentostam to kill residual parasites, was able to activate macrophages to kill amastigotes in vitro. Furthermore, after adoptive transfer of this cell line, naive BALB/cJ mice challenged with amastigotes demonstrated a 42-fold reduction in parasite burden compared to controls. Four of five clones derived from the protective T cell line secreted IFN and proliferated between days 7 and 14 after Ag stimulation. All clones were Ly1+2-, L3T4+. Another T cell line, which had Ly1+2-, L3T4+ phenotype, was derived from the lymph nodes of s.c. immunized, uninfected mice. It multipled but never produced IFN in response to leishmanial Ag and failed to protect macrophages against L. donovani infection in vitro or in vivo. This nonprotective T cell line and the fifth clone from the protective line, which also did not secrete IFN, proliferated between days 2 and 7 after Ag stimulation. In summary, leishmania-responsive helper/inducer T cells, which produced IFN but were slow to proliferate in response to Ag in vitro and which were able to activate macrophages to reduce amastigotes in vitro and in vivo, are present in chronically infected BALB/cJ mice and may mediate the decrease in parasite burden during chronic infection.
We identified characteristics of devices that caused needle-stick injuries in a university hospital over a 10-month period. Hospital employees who reported needle sticks were interviewed about the types of devices causing injury and the circumstances of the injuries. Of 326 injuries studied, disposable syringes accounted for 35 percent, intravenous tubing and needle assemblies for 26 percent, prefilled cartridge syringes for 12 percent, winged steel-needle intravenous sets for 7 percent, phlebotomy needles for 5 percent, intravenous catheter stylets for 2 percent, and other devices for 13 percent. When the data were corrected for the number of each type of device purchased, disposable syringes had the lowest rate of needle sticks (6.9 per 100,000 syringes purchased). Devices that required disassembly had rates of injury of up to 5.3 times the rate for disposable syringes. One third of the injuries were related to recapping. Competing hazards were often cited as reasons for recapping. They included the risk of disassembling a device with an uncapped, contaminated needle and the difficulty of safely carrying several uncapped items to a disposal box in a single trip. New designs could provide safer methods for covering contaminated needles. Devices should be designed so that the worker's hands remain behind the needle as it is covered, the needle should be covered before disassembly of the device, and the needle should remain covered after disposal. Such improvements could reduce the incentives for recapping needles and lower the risk of needle-stick injuries among health care workers.