Canine pancreas and kidney transplantation following total-lymphoid irradiation

The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification.     

HYPOTHERMIA AND SEVERE TRAUMA

During the period from May 1992 until April 1993, 108 patients were admitted to Liverpool Hospital with Injury Severity Scores (ISS) > 15. Temperatures had been recorded in 100. Of these, 17 had a core temperature of less than 35°C documented within 24 h of arrival. The hypothermic group presented with more severe injuries and contained a disproportionate number of females. Hypothermia was found to be more common in the winter months, but it was not associated with a delay in reaching hospital from the time of injury. When injuries were ranked by ISS, both hypothermic and normothermic patients were equally likely to have received a blood transfusion; however, the mean number of units of packed cells transfused was greater for the hypothermic group with ISS < 41 than for the similarly injured normothermic group. Two patients in the hypothermic group had sustained bums, and both of these were hypothennic on arrival. All of the hypothermic patients who required surgery developed hypothermia in the operating theatre.     

The management of injuries--a review of deaths in hospital

A prospective review was undertaken of the management of 111 consecutive patients who died in hospital after admission for treatment of injuries. A standard set of data relating to each patient was reviewed by each member of a trauma death audit committee and then by the whole committee. Autopsy reports were available on all patients. Conclusions were drawn concerning defective aspects of patient management and possible avoidance of each death. Injury severity was assessed using the Trauma Score (TS) and Injury Severity Score (ISS). The possibly avoidable death (PAD) rate was 17%. The most common defects in management were related to inadequate fluid resuscitation and delays in definitive management. The greatest contributions to the PAD rate were from inadequate fluid resuscitation, delays and inadequate perception of the severity of injuries or significance of clinical deterioration. Increasing age was related to a higher frequency of PAD. PAD rate in the presence of severe head injury was 8%, but was 63% in the absence of a severe head injury. It is concluded that review of all trauma deaths is an achievable, beneficial and essential part of a hospital-based integrated trauma service. TS and ISS are not sufficiently sensitive to justify their use in selecting deaths for review. Improved blood volume replacement, earlier and more direct management and supervision by senior specialist staff, and elimination of causes of delay in patient management should all decrease the death rate from injuries particularly in patients without severe head injury.     

Ultrastructural aspects ofTrypanosoma (Megatrypanum) freitasi in co-cultivation with mammalian cells

Cultures ofTrypanosoma (Megatrypanum) freitasi with L929 mouse fibroblasts at 27.5°C were examined by scanning and transmission electron microscopy in an attempt to clarify the processes of colony formation by the epimastigotes and of their attachment to substrata. It was seen that the flagellates occupy intercellular spaces and do not associate with intact fibroblasts. As the trypanosome population increases, ever larger portions of the substratum are cleared of fibroblasts and occupied by conglomerates of epimastigote colonies consisting of about a dozen organisms that attach to the substratum by their anterior extremities and form pyramidal clusters. Attachment of the epimastigotes involves the flagellar membrane, which becomes extraordinarily enlarged and assumes various aspects of broad sheets, filaments and loops over the substratum or along the flagellum, which exhibits a shortened axoneme. Desmosome or hemidesmosome plaques are present when the attachment takes place between membranes or between the membrane and the substratum.Supported by grants from CNPq and FINEP     

Three Evaluation Methods of a Community Health Advocate Program

The title Community Health Advocate (CHA) is one of thirty or more titles used throughout the world for an indigenous outreach worker who is trusted and respected in his or her community and who serves as a bridge between peers and health professionals. In 1992, the Center for Healthy Communities in Dayton, Ohio developed a program to train as Advocates people indigenous to the communities in which they would be working. Since the first CHAs began work in January 1993, the effectiveness of the program has been evaluated from three perspectives: the Community Health Advocates, the managers directors of the community sites at which the CHAs work, and the clients with whom the CHAs work. Advocates indicated that the training program adequately prepared them for their roles and functions. They also identified systematic frustrations and barriers that made it more difficult for them to perform their job. Community site directors and community leaders indicated that the CHAs were considered a positive force in meeting client needs and facilitating independence, and were very effective in outreach and coordination of resources. A survey of CHA clients revealed an overwhelmingly positive response to the Advocate's work, validating the belief that CHAs can fill an important niche in the health care community. The three evaluation processes described in this paper helped to document the need for and the effectiveness of this program and can serve as a model for similar programs.     

Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation

In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells.     

Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP)

The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.      

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

Effects of prior polysaccharide vaccination on magnitude, duration, and quality of immune responses to and safety profile of a meningococcal serogroup C tetanus toxoid conjugate vaccination in adults

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naive adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naive to meningococcal vaccination, and 40 had previously received > or =1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of > or =8 or > or =128 were similar (P > 0.46); >94% of subjects achieved titers of > or =128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naive (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naive and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.