Search PubMed⌕ Search

Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 163 records · Page 9Linked to original sources

Lymphoedema/hypercalcaemia syndrome mediated by parathyroid-hormone-related protein.

A 24-year-old woman presented with a cryptogenic, hypercalcaemic syndrome with metastatic pulmonary calcification and leg and massive breast enlargement and bilateral chylous pleural effusions compatible with a generalised lymphatic abnormality. The patient's serum parathyroid hormone-related protein concentration was very high at a time when she was significantly hypercalcaemic, implying that the hypercalcaemia was mediated by this protein.

Adult↗

Nongenital pelvic leiomyosarcoma metastatic to the heart.

A patient who had a 5-year history of a low-grade nongenital pelvic leiomyosarcoma was evaluated for worsening dyspnea, hypertension, and jugular venous distension. An echocardiogram revealed a large right atrial mass. At surgical exploration, metastatic leiomyosarcoma was found within the inferior vena cava extending from below the renal veins up into the right atrium. Using cardiopulmonary bypass with profound hypothermia and circulatory arrest, the inferior vena cava was opened below the renal veins, and the tumor was transected. That portion of the tumor above this transection was then extracted through a right atriotomy. Resection of the pelvic tumor was not thought to be feasible. The patient remains asymptomatic with stable pelvic tumor 1 year after the procedure.

Female↗

A revised rotarod procedure for measuring the effect of antinociceptive drugs on motor function in the rat.

Tests of putative antinociceptive agents that rely on a motor response of an experimental animal to a noxious stimulus will give false positive results, and may be unethical, if the agent compromises motor function. We report a procedure for measuring potential effects of antinociceptive agents on motor function in the trained rat, using an 80 mm diameter rotarod. Rats were selected for ability to exercise on the rotarod and trained to increasing speeds. In test trials, we measured the time that trained rats could stay on the rod, rotating at 25 rpm, with a cut off at 60 min. Morphine administration decreased rotarod performance significantly at doses of 5.0 mg/kg (P less than 0.05, n = 10) and 7.5 mg/kg (P less than 0.005, n = 10). We also assessed the response to a noxious thermal stimulus by measuring tail flick latency following tail immersion in water at 49 degrees C. A significant dose-dependent increase in tail flick latency was found for dosages of morphine between 2.5 mg/kg and 7.5 mg/kg (P less than 0.005, n = 10). Our rotarod procedure, which incorporates selection, training, and a 60 min trial, provides a sensitive and consistent means of assessing motor function. Our results, implying that morphine indeed compromises motor function in rats at doses at which it is antinociceptive, confirm the necessity for investigating the motor effects of any putative antinociceptive agent.

Analgesics↗

Effects of alpha-melanocyte stimulating hormone on fever caused by endotoxin in rabbits.

1. We measured the effect of intravenous and intracerebroventricular injections of alpha-melanocyte stimulating hormone (alpha-MSH) on changes in body temperature and serum iron concentration following i.v. injection of endotoxin in rabbits. 2. Intravenous alpha-MSH (2.5 micrograms) significantly reduced both phases of endotoxin fever and attenuated the fall in serum iron concentration which follows endotoxin injection. 3. Intracerebroventricular alpha-MSH (200 ng) reduced only the second phase of the fever and had no effect on the fall in the serum iron concentrations. 4. We conclude that alpha-MSH, in doses that are known to inhibit endogenous pyrogen fever, inhibits the fever induced by endotoxin in rabbits, probably by blocking the actions of endogenous pyrogens mediating the endotoxin fever.

Animals↗

Cerebrospinal fluid angiotensin converting enzyme levels in the diagnosis of neurosarcoidosis.

Cerebrospinal fluid angiotensin converting enzyme (CSF-ACE) level was measured in two patients considered to have neurosarcoidosis, three patients with possible neurosarcoidosis and in 38 control patients suffering from prolapsed intervertebral discs. Both neurosarcoidosis patients had elevated levels (1.8 and 5.4 mumol/l/min) while the possible neurosarcoidosis patients had values similar to the control patients (mean 0.59 +/- 0.42 mumol/l/min). We suggest that CSF-ACE values may be of use in some patients as a diagnostic test for neurosarcoidosis and provide a reference range of normal controls.

Adult↗

Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-gamma.

Some investigators have proposed myoblast transfer as a potential therapy for the treatment of Duchenne muscular dystrophy. Little is known about the immunobiology of myoblast transplantation. Transplantation rejection is mediated to a large extent by CD8+ T cells, which recognize alloantigens encoded by class I HLA genes, and by CD4+ T cells, which recognize alloantigens encoded by class II HLA genes. Gamma interferon (IFN-gamma) is a potent inducer of HLA class II molecules as well as beta 2-microglobulin, which is co-expressed with HLA class I. IFN-gamma may be a critical cytokine involved in graft rejection. We purified human myoblasts by flow cytometry and incubated them in vitro for varying time periods with recombinant human IFN-gamma. The inducibility of HLA-DR and -DP molecules raises a note of caution concerning possible rejection phenomenon which might occur following myoblast transplantation.

Cells, Cultured↗

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.

Gene Rearrangement↗

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)

Adult↗

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.

Budgets↗

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.

2-Amino-5-phosphonovalerate↗

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.

Animals↗

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.

Animals↗

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.

Community Mental Health Services↗

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.

Adaptation, Psychological↗