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Biomedical subjects

S McCabe

Publications and source records attributed to S McCabe.

At least 37 records · Page 2Linked to original sources

Immunological effects of insulin-like growth factor-I--enhancement of immunoglobulin synthesis.

In addition to its activity as a metabolic hormone and a regulator of somatic growth, insulin-like growth factor-I (IGF-I) has cytokine-like activities on lymphoid cells. A 14-day infusion of recombinant human (rh)IGF-I increased lymphocyte numbers in all the peripheral lymphoid organs examined. This increase was apparent for up to 3 weeks following cessation of hormone treatment. A second administration of rhIGF-I, given when the lymphocyte numbers in the rhIGF-I-treated mice had returned to control values, resulted in similar increases in the peripheral T and B cell populations. This increase in lymphocyte numbers had functional significance, since rhIGF-I-treated mice produced elevated antibody titres following primary or secondary antigen challenge compared with controls. In addition, when rhIGF-I-treated mice were immunized with a suboptimal dose of antigen they produced antibody titres which were equivalent to those generated by immunization with optimal doses of antigen. When examined in vitro, addition of rhIGF-I alone to cultures of splenocytes from antigen-primed mice stimulated immunoglobulin synthesis. These studies suggest that IGF-I produced locally by thymic and bone marrow stromal cells may be a natural component of B and T cell lymphopoiesis.

Animals↗

Opioid-induced stimulation of fetal respiratory activity by [D-Ala2]deltorphin I.

[D-Ala2]deltorphin I effects on fetal respiratory activity was characterized to determine the role delta-opioid receptors play in modulating fetal respiratory activity. [D-Ala2]deltorphin I, infused at 0.3 or 100 micrograms/h, intracerebroventricularly (i.c.v.), stimulated fetal respiratory activity without changing blood pH, PCO2 or PO2. Stimulation by 0.3 micrograms/h, but not 100 micrograms/h, was blocked by i.c.v. infusion of the delta-opioid receptor antagonist, naltrindole. Stimulation by 100 micrograms/h was blocked by the mu 1-opioid receptor antagonist naloxonazine. These data suggest stimulation of fetal respiratory activity by 0.3 micrograms/h [D-Ala2]deltorphin I are mediated specifically through delta-opioid receptors; while [D-Ala2]deltorphin I at 100 micrograms/h is no longer selective for the delta-opioid receptor, and the stimulation may be mediated through the mu 1-opioid receptor.

Animals↗

An evaluation of rapid exchange and simultaneous grip tests.

The usefulness of the rapid exchange grip test and a modification of this test, the rapid simultaneous grip test, in detecting submaximal grip efforts was evaluated. Uninjured subjects giving maximal or submaximal grip efforts were tested at grip rates of 80 and 100 repetitions per minute. Rapid exchange grip at 80 repetitions per minute yielded a sensitivity of 86% and a specificity of 97%. Rapid simultaneous grip at 80 repetitions per minute yielded a sensitivity of 81% and a specificity of 93%. Poorer sensitivities and specificities resulted when a clinical population of patients was tested. Patients who were not giving maximal efforts tended not to comply with the test protocol. The rapid exchange and rapid simultaneous grip tests do assist in detecting submaximal grip efforts; limits to these tests are emphasized.

Adolescent↗

Recipient vessels in head and neck microsurgery: radiation effect and vessel access.

Historical cohort analysis compared free-flap survival rates in 226 irradiated and 108 nonirradiated head and neck reconstructions. The failure rate for the irradiated flaps (3.5 percent) did not differ significantly from that for the nonirradiated group (2.9 percent). A case-control study of the failed irradiated flaps revealed infection and lag time between radiotherapy and surgery as the only factors significantly associated with free flap failure. Salvage techniques (vein grafting, cephalic transposition, and Corlett looping) for recruiting recipient vessels into radically ablated head and neck beds are reviewed.

Adult↗

Role of mu 1- and delta-opioid receptors in modulation of fetal EEG and respiratory activity.

Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu 1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu 1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2,D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu 1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu 1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu 1-opioid receptors in the regulation of respiratory timing and EEG activity.

Animals↗

Insulin-like growth factor-1 stimulation of lymphopoiesis.

We show that treatment of adult mice with recombinant human insulin-like growth factor 1 (rhIGF-1) induces striking modifications in lymphocyte number and function. 9-mo-old male mice received rhIGF-1 (4 mg/kg per d) or its excipient by subcutaneous infusion from osmotic minipumps for 7 or 14 d. Mice were weighed daily and bled at sacrifice; the spleen and thymus were harvested and single cell suspensions were made for analysis of cell phenotype and cell number. The responses of splenocytes to mitogens (concanavalin A, lipopolysaccharide, and pokeweed mitogen), alloantigens and dinitrophenyl ovalbumin were measured. After either 7 or 14 d of treatment, rhIGF-1 had an overall whole-body anabolic effect, resulting in increased body and organ weights with prominent increases in the weight of the spleen and thymus. Furthermore, the rhIGF-1 treated mice were normoglycemic but had reduced blood urea nitrogens, again reflecting the anabolic activity of rhIGF-1. The increased spleen and thymus weights were associated with a large increase in the number of lymphocytes in both organs. In addition to an increase in T cells, specifically CD4+ T cells, a dramatic increase in splenic B cells was also observed. This increase was accompanied by an enhanced responsiveness to dinitrophenyl ovalbumin resulting in increased immunoglobulin production. However, despite the increases in cellularity, there was a decrease in the in vitro responses of spleen cells to mitogens after 7 d of rhIGF-1 treatment. In contrast, treatment with rhIGF-1 for 14 d increased both the cell number and mitogenic responses of splenocytes suggesting that some time is required for the cells populating the peripheral organs to gain mitogenic responsiveness. It is clear from these data that rhIGF-1, at doses that have whole-body anabolic activity, can expand cell number in lymphoid tissue in a normal adult mouse. These dual effects of rhIGF-1, of increasing lymphocyte number and activity, indicate that, in a normal adult animal, rhIGF-1 can cause major changes in lymphoid tissues that are of potential benefit to the functioning of the immune system.

Animals↗

The counterpart relationship: a model for clinical nurse specialists in international nursing practice.

The proposed counterpart relationship model can be an effective tool in blending role functions to provide culturally sensitive nursing care in international settings. The authors explore their experience in developing a counterpart relationship where the CNS enters into a mutually collaborative relationship with a host counterpart from a cultural base different from the CNS's. The goal is to improve the level of health care provided to a specific cultural group and to transition the responsibilities of the CNS to the host counterpart.

Global Health↗

Verification of the pressure provocative test in carpal tunnel syndrome.

Three provocative tests (pressure, Phalen's test, and Tinel's sign) were studied in 30 patients with carpal tunnel syndrome and 30 control subjects. The pressure provocative test had a sensitivity of 100%. In contrast, Phalen's test was 88% sensitive and Tinel's sign only 67% sensitive. The pressure provocative test is a sensitive indicator of median nerve compression at the wrist with a faster reaction time than Phalen's test (mean time of 9 seconds vs 30 seconds). It is an appropriate provocative test in patients with stiff or painful wrists when wrist flexion is restricted.

Adult↗

Central opioid modulation of breathing dynamics in the fetal lamb: effects of [D-Pen2,D-Pen5]-enkephalin and partial antagonism by naltrindole.

The effects of opiates on fetal breathing movements (FBM) have been shown to be complicated, with stimulation at low doses and suppression at higher doses. Recent studies have shown that morphine-induced stimulation of FBM can be blocked by naloxonazine (NALZ), suggesting action at the mu 1 opioid receptor. To examine the role of delta receptors in modulating FBM, the effects of [D-Pen2,D-Pen5]-enkephalin (DPDPE) on breathing dynamics were studied in fetal lambs with chronically implanted diaphragmatic electromyographic electrodes. DPDPE given i.c.v. (4.6-465 nmol/hr) caused significant time and dose-related increases in the number of breaths/hr and the incidence of fetal breathing movements, without significant changes in blood pH, PCO2 or PO2. Higher doses resulted in an attenuation of the responses, with a significant decrease in breaths/hr at 465 nmol/hr. DPDPE also induced a much more continuous and regular breathing pattern. All DPDPE effects were completely abolished by pretreatment with i.v. naloxone, but were unaffected by naloxonazine pretreatment. Naltrindole did not alter the effects of DPDPE on breath number or incidence of FBM, but blocked the effects on continuity and regularity of the breathing pattern. These results demonstrate that DPDPE stimulates breathing activity as well as alters breathing dynamics in the fetal lamb. The differential sensitivity of these two actions to naltrindole suggest that they may be mediated by different delta receptor subtypes, and that the mu 1 receptor is not involved.

Analgesics↗

Internal neurolysis fails to improve the results of primary carpal tunnel decompression.

This prospective, randomized study compares two treatment methods in patients with primary carpal tunnel syndrome. Decompression of the transverse carpal ligament was done in thirty-two hands (thirty patients) and decompression of the transverse carpal ligament with the addition of an internal neurolysis of the median nerve was done in thirty-one hands (twenty-nine patients). Relief of symptoms was described in eighty-eight percent of the patients with carpal ligament release and eighty-one percent of patients with carpal ligament release plus internal neurolysis. Improvement in hand sensibility testing, in thenar muscle strength, and atrophy was noted in both treatment groups with no statistical difference between groups. The addition of an internal neurolysis to division of the transverse carpal ligament does not add significant improvement in the sensory or motor outcome of patients with primary carpal tunnel syndrome.

Carpal Tunnel Syndrome↗

Genomic cloning and heterologous expression of human differentiation-stimulating factor.

Differentiation-stimulating factor (D-factor) purified from mouse Ehrlich ascites cells was sequenced partially and found to be almost identical to leukemia inhibitory factor (LIF) from mouse Krebs II ascites cells. In comparison to LIF, D-factor had an additional amino-terminal serine residue. Using synthetic oligonucleotide probes designed from the murine D-factor sequence, we cloned the human gene encoding D-factor. A partial D-factor cDNA was cloned from COS-1 cells transfected with the human D-factor gene under the control of a heterologous promoter. We used this cDNA to construct a vector for direct expression of the protein in Escherichia coli. A mammalian cell expression vector was constructed using the signal sequence of interferon-alpha A linked to the D-factor cDNA. Both forms of recombinant human D-factor were active on the murine myeloid leukemia cell line M1 in a dose- and time-dependent manner for the inhibition of [3H]thymidine incorporation, and also induced phagocytosis, Fc receptor expression, and prostaglandin E2 synthesis by M1 cells.

Amino Acid Sequence↗

Direct in vivo observations of embolic events in the microcirculation distal to a small-vessel anastomosis.

This study was done to determine whether microemboli are produced by an arterial anastomosis. Direct in vivo observations were made in an isolated microcirculatory bed lying directly downstream from a newly made anastomosis. The tissue used was the isolated rat cremaster muscle, a new experimental model. The vessel anastomosed was the external iliac artery. Following anastomosis, microemboli were clearly observed in eight of eight animals during the first 30 minutes after clamp release. Embolic events were sometimes of impressive magnitude and in one case were associated with cessation of blood flow throughout the preparation. No microemboli were observed in eight of eight animals subjected only to dissection of the cremaster, nor were any observed in eight of eight animals in which the isolated cremaster was subjected only to 2 hours of clamp ischemia. These findings may be significant in explaining perturbations to blood flow following free-tissue transfer and instances of partial tissue necrosis following apparently successful arterial repair. These findings also identify an important factor (microemboli) to be considered in research on reperfusion injury.

Animals↗

Second toe transfer for thumb reconstruction in multiple digit amputations including thumb and basal joint.

Amputation of the thumb, including the basal joint, is a disabling injury that leaves limited reconstructive options. Three cases of multiple digit amputation including the thumb and basal joint are presented in which a second toe transfer was used to reconstruct the thumb. All patients have functional pinch with an average pinch strength of 27% of the opposite uninjured extremity. The average grip strength for two patients is 44% of the opposite hand. Average motion of the transfer at the MP, PIP, and DIP is 25 degrees, 37 degrees, and 9 degrees, respectively. Adduction and abduction are obtained, the degree depending on the site of proximal bony fixation. No patient has morbidity at the donor site and all are happy with their reconstruction. In selected cases we feel second toe transfer is an excellent choice to reconstruct the thumb amputated at a proximal level.

Adult↗

Validation of a prognostic score in critically ill patients undergoing transport.

Fifty consecutive critically ill patients transported between hospitals by a mobile intensive care team were assessed prospectively using a modification of the acute physiology and chronic health evaluation (APACHE II) sickness scoring system. Assessments were made before and after resuscitation, on return to base, and after 24 hours of intensive care. No patient died during transport. Twenty two patients died subsequently in hospital and 28 survived to return home. The mean score for the non-survivors before resuscitation was 21.7 and for the survivors 12.2 (p less than 0.0005). Among the non-survivors there was a significant fall in score with resuscitation but this did not alter their subsequent outcome. Neither group deteriorated during transport. The sickness score is a powerful method for determining prognosis, and employed longitudinally it may be useful in the assessment of treatment. It has important implications for the administration and organisation of regional intensive care services.

Adult↗