Biomedical subjects
D Mitchell
Publications and source records attributed to D Mitchell.
Epstein-Barr viral genome in lymph nodes from patients with Hodgkin's disease may not be specific to Reed-Sternberg cells.
A possible etiologic role for Epstein-Barr virus (EBV) in Hodgkin's disease (HD) was investigated by probing for EBV genome in 52 biopsy specimens involved with HD and 43 hyperplastic lymph node specimens. Using dot-blot hybridization (Bam HIW probe), Southern blot hybridization (Xho I probe), and polymerase chain reaction analyses, 27%, 27%, and 58% of the nodes with HD were positive for EBV genome, respectively, as compared to 16%, 14%, and 43% in the hyperplastic lymph nodes. Clonal and nonclonal episomal EBV and linear replicating EBV genome were present in both conditions. Immunoglobulin heavy chain gene rearrangements were found in two clonal and two nonclonal EBV-positive HD cases, but not in the lymphoid hyperplasia cases. These findings and other recent reports showing EBV genome in benign lymphoid cells by in situ hybridization in Hodgkin's disease suggest that the characteristics of EBV infection in HD could be explained by the reactive cellular milieu, especially in the setting of defective immunity. The identification of EBV genome in Reed-Sternberg cells may, therefore, be a nonspecific phenomenon.
Prevention of thromboembolic disease following total knee arthroplasty. Epidural versus general anesthesia.
Seventy-two patients were randomized into a prospective clinical trial to evaluate the effects of epidural (EA) versus general anesthesia (GA) on the incidence of thromboembolic disease (TED) following total knee arthroplasty (TKA). Males received aspirin 650 mg po bid and females low-dose warfarin daily to maintain the prothrombin time at 15 to 16 seconds for pharmacologic prophylaxis against TED. Thirty-four patients had EA and 38 GA for their primary TKA. Contrast venography and ventilation-perfusion scanning were performed on the sixth, seventh, and eighth postoperative days, and these were interpreted in a blinded fashion. The mean age of the 45 males and 27 females was 64 years (range, 42-84 years). There were no significant differences between the two groups with respect to hematocrit, operative time, blood loss, number of units transfused, or hospital stay. Twelve of the 34 patients (35%) receiving an EA and 10 of the 38 patients (26%) receiving GA developed TED, an overall incidence of 31% (p greater than 0.05) Fifty-three percent of the clots were located in the popliteal vein above the trifurcation or more proximal. However, the incidence of proximal vein thrombosis was significantly less in patients receiving an EA (46%) rather than a GA (64%). The incidence and distribution of clots was not affected by the type of pharmacologic prophylaxis, gender, or use of methylmethacrylate. Ten percent of the patients had a positive scan by strict criteria and were thought to have a pulmonary embolism (PE). In patients with a femoral vein clot, the incidence of PE was 67%. One bleeding complication occurred in a patient who took double the appropriate warfarin dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Current and future trends in state-operated mental retardation institutions in the United States.
Results of a national study of state-operated institutional care in the United States were presented. The relations among census reduction, staffing level, and resident cost were explored. Resident cost escalated dramatically in recent years, primarily because staffing levels in the states remained relatively stable, whereas the institutional census continued to decline. Econometric projections suggest that by the year 2000, the institutional census will fall below 55,000 persons, cost per resident will rise to more than $113,000 per year, and 28 to 51 institutions will close.
Intrathecal N-methyl-D-aspartate induces hyperexcitability in rat dorsal horn convergent neurones.
We have investigated the effects of intrathecal (i.t.) N-methyl-D-aspartate (NMDA) and an NMDA antagonist D-2-amino-5-phosphonovalerate (APV) on spontaneous and evoked activity in rat dorsal horn convergent neurones. Extracellular recordings were made from 54 convergent neurones located in both the superficial and deep dorsal horn. NMDA induced a dose-dependent increase in the spontaneous firing rate of convergent neurones, with 1 microM and 1 mM NMDA producing firing rates significantly greater than i.t. saline. In addition, NMDA induced hyperexcitability to subsequent noxious mechanical stimuli at 1 microM and 1 mM, and to innocuous stimuli at 1 mM. The NMDA-induced spontaneous hyperexcitability was reversed by pretreatment with 1 microM APV i.t. Diffuse noxious inhibitory controls (DNIC) applied to areas of the body remote from the receptive field also inhibited the NMDA-induced effects. There was no difference between the responses of superficial and deep dorsal horn neurones, suggesting a uniform excitatory action of NMDA on convergent neurones. Our results support a role for the NMDA receptor in mediating a central component of hyperalgesia, at the level of the spinal cord dorsal horn.
N-methyl-D-aspartate receptors mediate responses of rat dorsal horn neurones to hindlimb ischemia.
We have investigated the role of NMDA receptors in the rat dorsal horn in mediating neuronal responses to noxious hindlimb ischemia, induced by acute occlusion of the femoral artery, as well as in the hyperalgesia evident when noxious mechanical stimuli were applied to the ischemic limb. Two specific NMDA antagonists, D-2-amino-5-phosphonovalerate (APV) and ketamine hydrochloride were applied intrathecally directly on to the spinal cord, in enflurane-anaesthetised rats. Both APV (1 microM and 100 microM) and ketamine (1 mM and 100 mM) inhibited the increase of dorsal horn neuronal firing rate induced by ischemia, but did not alter the neuronal response to noxious pinching or innocuous brushing of the receptive field. Both agents, however, abolished the hyperalgesia to noxious pinching induced by ischemia. Our results support the hypothesis that the excitatory amino acids are involved in the transmission of nociceptive information in the spinal dorsal horn, and also favour a central mechanism for hyperalgesia at the spinal level, possibly also mediated by the NMDA receptor.
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Selective brain cooling after bilateral superior cervical sympathectomy in sheep (Ovis aries).
We have investigated the role of the sympathetic innervation of the vasculature of the head in the control of selective brain cooling of sheep, during exposure to high and low ambient temperatures and during endotoxin-induced fever. Bilateral removal of the superior cervical ganglia resulted in a significant reduction of hypothalamic temperature during all procedures. Respiratory rate was also depressed by the sympathectomy, apparently mainly as a result of a decrease in nasal airway patency. Rectal temperature changes after sympathectomy were dependent on the experimental conditions, and the rectal - hypothalamic temperature difference was enhanced during heat exposure and fever. Our results support the contention that sympathetically mediated changes in nasal blood flow and in venous return from the nasal cavity, via the angularis oculi and facial veins, may be involved in the control of selective brain cooling in sheep.
Synthesis of research on the costs of institutional and community-based care.
Cost studies in the long-term care field are reviewed, with emphasis on those relating to people with developmental disabilities. Studies frequently stressed the cost-effectiveness of community programs but often had significant methodological problems. Among the predominant findings in the literature were: 1) the generally lower average costs per client in community programs versus institutional programs; 2) unexplained wide cost ranges in similar community programs; and 3) significant cost shifts among federal, state, and local governments associated with deinstitutionalization initiatives. The implications of these findings for public officials and the advocacy community are discussed.
Selection of antihypertensive therapy.
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What information should the multiple birth family receive before, during and after the birth?
Advances in the management of the multiple pregnancy and delivery must be accompanied by corresponding improvements in service access outside key centres and especially in the information families receive about what may happen during or after the pregnancy. A major review of birthing services in Victoria has focussed attention on four areas where the quality of information is often inadequate. 1) Prepregnancy and the standard of counselling about the incidence of multiples as a result of fertility drugs and in vitro fertilization procedures and about problems which may accompany a multiple birth. 2) Antenatal: At what stage of the pregnancy should parents be told of the multiple pregnancy and how should monitoring of the mother and procedures such as bedrest take into account what are often conflicting demands within the family? 3) Perinatal: Families are frequently illprepared for a cesarean delivery and for the procedures for premature multiples. The problem is often compounded by separation of the mother from one or both twins. While bereavement services are improving, much still needs to be learned about handling congenital abnormalities in one or more multiples. 4) Postnatal: Irrespective of the level of prenatal advice, families greatly underestimate the workload with multiples. The resulting stress contributes to the incidence of postnatal depression, child abuse and divorce now being reported from multiple birth families. Some suggestions are made from social psychology and genetic counselling about how families can best handle risk information to achieve the goal of neither under- nor overestimating the risks at these different stages of the multiple pregnancy.
Memory factors in age-related differences in simple reasoning.
Adults in their 50s were compared with adults in their late teens or 20s in the accuracy of relatively simple reasoning decisions involving varying amounts of information. Because the magnitude of the age differences in decision accuracy was independent of the amount of information relevant to the decision, it was suggested that adults in their 20s and 50s do not differ in the effectiveness of integrating information across multiple premises. However, the 2 groups differed in the accuracy of trials involving only a single relevant premise, and thus it was inferred that 1 factor contributing to reasoning differences within the age range from 20 to 60 may be a failure to encode, or retain, relevant information.
Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity.
Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the clones recognize MBP peptide 1-9 in the context of I-Au. A strong positive correlation was found between levels of lymphotoxin (LT) and tumor necrosis factor alpha (TNF-alpha) mRNA and biological activity on L929 cells and their capacity to induce paralysis, the clinical hallmark of experimental allergic encephalomyelitis (EAE). No correlation was found between interleukin-2 or gamma interferon production and encephalitogenicity. LT and/or TNF-alpha may play a central role in the pathogenesis of EAE.
Observations on the morphology of pronuclei and nucleoli in human zygotes and implications for cryopreservation.
The effects of cryopreservation on human zygotes at various stages between the appearance of pronuclei and their close association were investigated. Pronuclear zygotes (n = 233) from 101 patients were frozen using propanediol 21-35 h following egg collection. The incidence of implantation of thawed pronuclear zygotes frozen 29-35 h following oocyte collection was significantly higher than that of younger pronuclear zygotes (28 versus 10%, respectively). Zygote age did not affect cell survival following cryostorage. The diameter and association of pronuclei and the number and distribution of nucleoli were determined from video tape recordings of 140 fresh zygotes. Pronuclear migration continued after pronuclear enlargement. The number of nucleoli remained constant during pronuclear migration, but their random distribution within the pronucleus diminished. Strongly adhered pronuclei had significantly more aligned nucleoli on adjacent sides than pronuclei which were still visually separated by ooplasm. This equatorial distribution of nucleoli was noted in the majority of zygotes older than 26 h. The findings suggest that zygote cryopreservation should be initiated when pronuclear migration is completed. This moment can be determined accurately by studying pronuclear association and nucleolar alignment.
Detection of HIV-1 in human lung macrophages using the polymerase chain reaction.
We have used the polymerase chain reaction to investigate HIV-1 infection of lung macrophages from 44 AIDS patients with pneumonia. Proviral HIV-1 DNA was detected in the lung macrophages of 47% (21 of 44) of patients tested; 32% (seven of 21) of the patients had Pneumocystis carinii pneumonia (PCP), and 56% (11 of 21) had pneumonia caused by other aetiological agents. Matched peripheral blood specimens were obtained from 22 patients in this study, and HIV-1-specific DNA was detected in 100% (22 out of 22) of non-adherent white cell preparations tested. HIV was detected in blood monocytes of 11 out of 22 patients (50%), and a virus signal was also found in the lung macrophages of eight of these patients. Our results indicate that PCP does not predispose lung macrophages to HIV-1, nor does HIV-1 infection of lung macrophages increase the probability of contracting PCP.
Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate.
The serum level of the aminoterminal peptide of type III procollagen (P3NP) was measured in 51 psoriatic patients on long-term, once weekly, low-dose methotrexate and in a control group of patients with extensive psoriasis who had never had systemic treatment. Serum P3NP levels were normal in all control patients, but were elevated in the majority of methotrexate-treated patients, even those with normal or non-specific liver histology. Although the highest P3NP values were found in the groups of patients with fibrosis and cirrhosis, isolated P3NP measurements did not discriminate between individuals with and without significant liver pathology. Neither standard nor dynamic liver function tests were able to identify patients with significant liver damage and in most cases results were in the normal range.
Identification of genes affecting production of the adhesion organelle of Caulobacter crescentus CB2.
Transposon (Tn5) mutagenesis was used to identify regions in the genome involved with production, regulation, or attachment to the cell surface of the adhesive holdfast of the freshwater bacterium Caulobacter crescentus CB2. A total of 12,000 independently selected transposon insertion mutants were screened for defects in adhesion to cellulose acetate; 77 mutants were detected and examined by Southern blot hybridization mapping methods and pulsed-field gel electrophoresis. Ten unique sites of Tn5 insertion affecting holdfast function were identified that were clustered in four regions of the genome. Representative mutants of the 10 Tn5 insertion sites were examined by a variety of methods for differences in their phenotype leading to the loss of adhesiveness. Four phenotypes were identified: no holdfast production, production of a smaller or an altered holdfast, production of a holdfast that was unable to remain attached to the cell, and a fourth category in which a possible alteration of the stalk was related to impaired adhesion of the cell. With the possible exception of the last class, no pleiotropic mutants (those with multiple defects in the polar region of the cell) were detected among the adhesion-defective mutants. This was unexpected, since holdfast deficiency is often a characteristic of pleiotropic mutants obtained when selecting for loss of other polar structures. Overall, the evidence suggests that we have identified regions containing structural genes for the holdfast, genes involved with proper attachment or positioning on the caulobacter surface, and possibly regions that regulate the levels of holdfast production.
Comment: oral cephalosporins.
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