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Biomedical subjects

K McCarthy

Publications and source records attributed to K McCarthy.

At least 73 records · Page 4Linked to original sources
PubMed1995

Evaluation of recombinant human factor IX: pharmacokinetic studies in the rat and the dog.

The pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine, a purified human plasma-derived factor IX, after single 100 IU/kg i.v. doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine were 4-5 micrograms/ml. The mean plasma half-lives were 13.2 +/- 1.6 h for rhFIX and 13.3 +/- 1.6 h for Mononine. Dogs also received rhFIX (40 IU/kg i.v., daily) for 28 days or Mononine (40 IU/kg i.v. daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine (40 IU/kg) dogs.

Animals↗
PubMed1995

Spirometry for the primary care physician.

The clinician wishing to employ a spirometer in the office must be aware of the equipment available and the current standards for validating and maintaining such equipment. Indications for spirometry are fairly frequent in general medical practice for both diagnosis, response to therapy, and for risk assessment prior to surgery. The criteria for characterizing a spirogram as normal, obstructive or restrictive, are well defined. The information obtained may be very helpful to point to additional specific diagnostic studies or to outline a specific treatment plan.

Family Practice↗
PubMed1994

Clonal analysis of three morphologically distinct lymphomas occurring in the same patient.

AIMS: To determine whether three morphologically distinct lymphomas (mucosa associated lymphoid tissue (MALT) lymphoma, monocytoid B cell lymphoma, and large cell anaplastic lymphoma), which occurred in the same patient, were in fact three morphological variants of the same lymphoproliferative process. METHODS: Previously described methods of clonal analysis using the polymerase chain reaction (PCR) were used to determine the pattern of rearrangements of the immunoglobulin heavy chain gene and the T cell receptor beta and T cell receptor gamma chain genes in the three lymphomas. RESULTS: All three morphological entities had identical patterns of gene rearrangements. CONCLUSIONS: This finding confirms the association between MALT lymphoma and monocytoid B cell lymphoma, and also provides evidence that large cell anaplastic lymphoma may not only arise de novo but may also be an end stage morphological picture in lymphoma progression.

Colonic Neoplasms↗
PubMed1994

Endometrial polyps, hyperplasia, and carcinoma in postmenopausal women: differentiation with endovaginal sonography.

PURPOSE: To characterize endometrial polyps, hyperplasia, and carcinoma with endovaginal ultrasound in postmenopausal women. MATERIALS AND METHODS: Seventy-three postmenopausal women with abnormally thick endometria on endovaginal sonograms were retrospectively identified. The endometrial appearance was characterized as hyperechoic, containing cystic spaces, or heterogeneous. The final study group consisted of 68 women, in whom the pathologic and sonographic findings were correlated. RESULTS: Thirty sonograms showed hyperechoic endometria in women with hyperplasia (n = 8), polyps (n = 4), polyps and hyperplasia (n = 2), or atrophy, proliferative change, mild atypia, or normal endometria (n = 16); 27 sonograms showed cystic spaces in women with polyps (n = 21), carcinoma (n = 1), polyps and hyperplasia (n = 2), or atrophy (n = 3); and 11 sonograms showed heterogeneous endometria in women with endometrial carcinoma (n = 7), atrophy (n = 2), proliferative endometrium (n = 1), or secretory endometrium (n = 1). Cystic spaces were predictive of polyps (P = 1.19 x 10(-10)). CONCLUSION: Endovaginal sonography may be useful for differentiation of endometrial polyps, hyperplasia, and carcinoma.

Aged↗
PubMed1994

Topoisomerase II mediated DNA lesions induced by acridine-4-carboxamide and 2-(4-pyridyl)quinoline-8-carboxamide.

Acridine-4-carboxamide and 2-(4-pyridyl)quinoline-8-carboxamide represent a new generation of antitumor intercalators related to amsacrine (m-AMSA), a classic topoisomerase II-targeted drug. We examined the ability of these tricyclic carboxamides to induce DNA lesions that reflect the stabilization of topoisomerase II cleavage complexes. DNA-protein cross-links (DPC) and DNA double-strand breaks (DSB) were assessed in mouse fibrosarcoma cells (line 935.1). DPC were rapidly formed and readily reversible. A bell-shape concentration dependence suggested a self-inhibition of DPC at higher drug levels. In isolated nuclei, DPC formation by 2-(4-pyridyl)quinoline-8-carboxamide required ATP and was inhibited by novobiocin, a topoisomerase II inhibitor. Acridine-4-carboxamide and 2-(4-pyridyl)quinoline-8-carboxamide were also potent inducers of DSB. In contrast to DPC, however, DNA breaks continued to increase with drug concentration. These DSB were masked (presumably by non-covalently associated proteins) when analyzed by nucleoid sedimentation. Thus, while both DPC and DSB seemed to be topoisomerase mediated, at least some DSB appeared to lack the enzyme bound covalently. DNA lesions by tricyclic carboxamides occurred, in general, at drug concentrations comparable to those needed to inhibit cell survival. Also, the tricyclic carboxamides inhibited the catalytic activity of isolated topoisomerase II. The results indicate that tricyclic carboxamides interfere with the action of topoisomerase II. However, the mechanisms of enzyme inhibition by these drugs differ from the classical trapping of topoisomerase in covalent cleavage complex m-AMSA.

Acridines↗
PubMed1993

Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice.

The effects of recombinant human interleukin-11 (rhIL-11) on in vivo mouse megakaryocytopoeisis were examined. Normal C57Bl/6 mice and splenectomized C57Bl/6 mice were treated for 7 days with 150 micrograms/kg rhIL-11 administered subcutaneously. In normal mice, peripheral platelet counts were elevated compared with vehicle-treated controls after 3 days of rhIL-11 treatment and remained elevated until day 10. Splenectomized mice treated with rhIL-11 showed elevated peripheral platelet counts that were similar in magnitude to normal rhIL-11-treated mice. However, on day 10 the platelet counts in rhIL-11-treated, splenectomized mice were no longer elevated. Analysis of bone marrow megakaryocyte ploidy by two-color flow cytometry showed an increase, relative to controls, in the percentage of 32N megakaryocytes in both normal and splenectomized animals treated with rhIL-11. In normal mice, the number of spleen megakaryocyte colony-forming cells (MEG-CFC) were increased twofold to threefold relative to controls after 3 and 7 days of rhIL-11 treatment, whereas the number of bone marrow MEG-CFC were increased only on day 7. The number of MEG-CFC in the bone marrow of rhIL-11-treated, splenectomized mice was increased twofold compared with controls on both days 3 and 7 of the study. These data show that in vivo treatment of normal or splenectomized mice with rhIL-11 increased megakaryocyte progenitors, stimulated endoreplication of bone marrow megakaryocytes, and increased peripheral platelet counts. In addition, results in splenectomized mice showed that splenic hematopoiesis was not essential for the observed increases in peripheral platelets in response to rhIL-11 administration.

Animals↗
PubMed1993

HIV infection in women.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed1993

Trial of standard versus modified expiration to achieve end-of-test spirometry criteria.

To assess whether satisfying American Thoracic Society (ATS) end-of-test spirometry criteria can be enhanced by modifying the patient's expiratory technique, we conducted a cross-over trial of two expiratory techniques in 48 patients with a range of pulmonary functions (Group 1, n = 12: FEV1/FVC < 0.45; Group 2, n = 11: FEV1/FVC, 0.45 to 0.60; Group 3, n = 16: FEV1/FVC, 0.61 to 0.74; Group 4, n = 9: FEV1/FVC > or = 0.75). After randomizing the order of testing, each patient performed three exhalations using a "standard" forced expiratory maneuver and a modified expiratory technique consisting of an initial maximal expiratory effort followed by a "relaxed expiration" for as long as possible. Patients initiated "relaxed expiration" when instructed by the supervising technician, who issued the instruction to relax when expiratory airflow fell to < or = 200 ml/s (as determined by flow-volume loop analysis). ATS end-of-test criteria were satisfied significantly more often using the modified expiratory technique (58.3% of testing sessions) than using the standard technique (18.7% of sessions, p = 0.001) because of prolongation of the forced expiratory time (FET) with the modified technique in all patient groups. In the 38 patients with FEV1/FVC < or = 0.75, the largest FVC and FET rose significantly using the modified expiratory technique, without compromising the largest FEV1 in any group. In patients with FEV1/FVC > or = 0.75, FET increased without concomitant changes in FVC or FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effectiveness of combined induction chemotherapy and radiotherapy in advanced nasopharyngeal carcinoma.

PURPOSE: This prospective trial was conducted with the goal of achieving an improvement in both overall and progression-free survival in previously untreated patients with stage IV nasopharyngeal carcinoma who received an induction chemotherapy regimen of fluorouracil (5-FU) and cisplatin followed by radiotherapy. PATIENTS AND METHODS: From January 1985 to January 1990, 47 patients with T1-4N2-3M0 squamous cell carcinoma of the nasopharynx were treated at The University of Texas M.D. Anderson Cancer Center with two to three cycles of 5-FU (1,000 mg/m2 continuous infusion per day x 5 days) plus cisplatin (100 mg/m2 continuous infusion on day 1 only) followed by radiotherapy using the conventional time/dose schedule. RESULTS: The response rate to chemotherapy was 93.2% (20.5% complete response [CR]; 72.7% partial response [PR]), and the overall CR rate after radiotherapy was 86%. With a median follow-up period of 53 months, the 2-, 4-, and 6-year survival rates were 80%, 71.6%, and 67.4%; the overall treatment failure rate was 27%. Treatment was well tolerated and without significant acute or chronic toxic effects. CONCLUSION: The results of this prospective study demonstrate that 5-FU plus cisplatin followed by radiotherapy can induce a durable remission in a high proportion of patients with poor-prognosis stage IV nasopharyngeal carcinoma.

Adolescent↗
PubMed1993

Physician-ordered respiratory care vs physician-ordered use of a respiratory therapy consult service: early experience at The Cleveland Clinic Foundation.

BACKGROUND: Accumulative evidence suggests that respiratory care is frequently misallocated. We report the results of a pilot study of a delivery system aimed at correcting such misallocation. METHODS: The delivery system (Respiratory Therapy Consult Service, or RTCS) allows respiratory therapists (when requested by the case-managing physician) to determine respiratory care, with decisions guided by algorithm (ie, Consult patients). In the pilot study, Therapist Evaluators responded to requests for Consults on two study wards. All staff therapists participated in implementing Evaluator-determined treatment. STUDY DESIGN: We evaluated 38 patients (20 of whom were Consult patients) randomly selected from a total of 82 patients undergoing abdominal surgery during the study period. RESULTS: Consult patients were significantly older than non-Consult patients, more likely to be heavy smokers (67 vs 43%), and sicker as suggested by a higher Triage Score. Consult patients received more types and more total respiratory care services, demonstrated a trend toward longer stay, and had significantly higher respiratory therapy charges. CONCLUSION: Our experience shows that a consult program can be successfully implemented in a large, tertiary care institution with widespread physician and nursing support. Whether the RTCS fulfills its goal of ameliorating misallocation of respiratory care has yet to be proven and awaits the completion of other studies currently under way.

Abdomen↗
PubMed1993

FcR+/- subsets of Ia+ pulmonary dendritic cells in the rat display differences in their abilities to provide accessory co-stimulation for naive (OX-22+) and sensitized (OX-22-) T cells.

A substantial body of evidence indicates that the primary sensitization of naive T cells to inhaled antigens occurs in the regional lymph nodes, whereas secondary responses may be generated directly within lung tissue. Ia+ pulmonary dendritic cells are widely distributed within the rat lung where they can participate in the induction of the immune response to inhaled antigens. Recently, two subsets of Ia+ pulmonary dendritic cells have been distinguished based on their expression of Fc receptors (FcR), but little is known concerning their abilities to support the responses of naive or sensitized T cells. In order to address this question, pulmonary FcR+/- dendritic cells have been purified from enzymatic digests of Lewis rat lungs, based on their differential binding to heat-aggregated immunoglobulin. The FcR+/- dendritic cell subsets differed with respect to their light microscopic appearance and in their expression of non-specific esterase. Only the FcR+ subset was able to phagocytize latex beads and showed intracellular phagolysosomes by electron microscopy. Both of the FcR+/- subsets rapidly formed clusters with naive (OX-22+) and sensitized (OX-22-) T cells. However, the clusters yielded by the FcR+ subset were substantially smaller, possibly reflecting their diminished surface membrane expression of the intercellular adhesion molecule-1. The FcR+/- subsets were capable of presenting soluble and particulate antigens to OX-22- T cells. FcR+ cells were less effective than FcR- cells in promoting the proliferative response of OX-22+ T cells to concanavalin A and in the primary mixed leukocyte reaction. We conclude that the FcR+/- pulmonary dendritic cells differ in their abilities to support the responses of naive and sensitized T lymphocytes. This observation may have significance for how primary and secondary pulmonary cell-mediated immune responses are generated.

Animals↗
PubMed1992

Lymphomas of the cervix and upper vagina: a report of five cases and a review of the literature.

Five cases of non-Hodgkin's lymphoma of the cervix or upper vagina presenting over the last 20 years are described. The international literature has been reviewed for similar cases and a further 72 found. In 37 of these cases the pathology had been described according to one of the modern lymphoma classifications and details of clinical presentation, staging, treatment, and outcome were adequately described. The management and outcome of these patients have been critically reviewed and recommendations for the management of patients presenting with this disease have been made.

Adult↗
PubMed1992

Occupational exposure to 1,6-hexamethylene diisocyanate-based polyisocyanates in the state of Oregon, 1980-1990.

Monitoring of exposure to 1,6-hexamethylene (HDI) monomers and HDI polyisocyanates in Oregon was initiated in 1980 and covered primarily spray painting and related activities. A total of 562 air samples were collected from 60 workplaces during the years 1980-1990 and analyzed for HDI and HDI polyisocyanate content. Of the total, only a small fraction (6%) of the samples exceeded the state of Oregon permissible exposure limit (PEL) of 0.02 ppm for HDI monomer; however, a much higher number (42%) of the samples exceeded the Oregon PEL of 1 mg/m3 for HDI polyisocyanates. Spray finishing operations were divided into three categories: continuous industrial spraying, auto body repair shops, and intermittent spray operations of large objects. The highest exposures among all three categories for both HDI and HDI polyisocyanates were measured during spray finishing. The geometric mean for HDI in the industrial spray operations was 0.001 ppm and for HDI polyisocyanates was 3.78 mg/m3. Frequently, the peak exposures exceeded the Oregon PEL for polyisocyanates, reaching as high as 12.2 mg/m3. In auto body shops, the mean for HDI was 0.002 ppm and for HDI polyisocyanates was 1.60 mg/m3 with peak concentrations of 0.049 ppm for HDI and 18.4 mg/m3 for HDI polyisocyanates. In the third category of spray finishing of large objects, the geometric means for three subcategories ranged from 0.001 to 0.017 ppm for HDI with a peak concentration of 0.069 ppm. The geometric means for HDI polyisocyanates ranged from 2.09 to 15.9 mg/m3 with a peak of 29.5 mg/m3. In all the surveys, the ventilation facilities and personal protective equipment were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyanates↗
PubMed1992

Stimulation of the P2Y purinergic receptor on type 1 astroglia results in inositol phosphate formation and calcium mobilization.

Cultured astroglia express purinergic receptors that initiate phosphoinositide metabolism and calcium mobilization. Experiments were conducted to characterize the purinergic receptor subtype on type 1 astroglia responsible for stimulation these second-messenger systems. Inositol phosphate (IP) accumulation and calcium mobilization were measured after stimulation with ATP or purinergic receptor subtype-selective ATP analogues. ATP (10(-5) M) increased IP accumulation severalfold. Dose-effect assays monitoring astroglial IP accumulation revealed the order of potency that defines the P2Y receptor: 2-methylthioadenosine 5'-triphosphate greater than ATP greater than alpha beta-methyleneadenosine 5'-triphosphate greater than beta gamma-methyleneadenosine 5'-triphosphate. The influence of ATP on intracellular calcium levels in individual type 1 astroglia was examined using the calcium indicator dye, fura-2. Dose-effect experiments indicated that ATP was equally potent for generating inositol phosphates and increasing cellular calcium. The most prevalent response (87% of total responses) to ATP consisted of a rapid increase in calcium to a peak level that was approximately five times greater than the prestimulation level. This peak was followed by a decline to a plateau level that was significantly above baseline. This plateau phase of the calcium increase was maintained for at least 5 min in the presence of ATP and was dependent on external calcium. Many (23%) astroglia exhibited spontaneous calcium oscillations whose frequency and magnitude increased after the addition of 10(-5) M ATP. Immunocytochemical staining indicated that the responses occurred in glial fibrillary acidic protein positive cells. We conclude that type 1 astroglia express the P2Y purinergic receptor which regulates IP production and calcium mobilization.

Adenosine Triphosphate↗
PubMed1992

A prospective study of the effectiveness of brief professionally-led support groups for infertility patients.

OBJECTIVE: This study prospectively evaluates the effectiveness and patient acceptability of professionally-led support groups in alleviating psychologic distress in infertility patients. METHOD: Sixty-four consecutive patients in a university hospital infertility program were administered a battery of psychologic tests before and after attendance at an 8 weekly session support group. The comparison group consisted of 35 consecutive infertility referrals to the same unit who were not initially offered the support group and were similarly tested over an 8 week period. RESULTS: Support group patients had significantly greater (p less than or equal to 0.01) entry than exit scores on several measures of psychologic distress and depression (the Beck Depression Inventory, the Hamilton Rating Scale for Depression, and the Global Severity Index, Anxiety, Depression, Hostility and Obsessive Compulsive Subscales of the Brief Symptom Inventory). The Avoidance Coping Style on the Moos Coping Responses Inventory was correlated with a higher Global Severity Index (p less than or equal to 0.01). Comparison group patients had similar psychometric scores to the support group patients at entry but showed no change over 8 weeks. Attenders expressed a high rate of satisfaction with the support group. CONCLUSIONS: Professionally-led support groups are a highly acceptable and effective intervention in self-referred patients in alleviating psychological distress related to infertility.

Adaptation, Psychological↗
PubMed1991

Growth of human immunodeficiency virus I in cultured cells in the absence of the CD4 antigen.

The ability of a variety of epithelial, embryonal, placental, and neuronal cells to express the CD4 antigen and to be infected by human immunodeficiency virus 1 (HIV-1) was examined. Only two (IMR-32 and HeLa-T4) expressed CD4 detectable by indirect immunofluorescence, and both were infectable by HIV-1. Two others, a human laryngeal carcinoma (HEp-2) and human colonic carcinoma (HT-29), did not express CD4 antigen but were infectable by HIV-1. Infection of the HEp-2 cells was detectable four months (and 20 serial passages) later. Infection of HEp-2 cells was not inhibited by anti CD4 monoclonal antibody but was by the lectin concanavalin A. These results suggest the presence of a receptor other than CD4 can be involved in HIV-1 infection.

Animals↗
PubMed1991

Reducing disinfectant wastage.

In order to lower departmental costs in an ophthalmological outpatient department by reducing wastage, the stability of available chlorine at levels of 280 ppm and 560 ppm in litre solutions of sodium dichloroisocyanurate was investigated over a three-week period. There was no significant decay in available chlorine at these levels in solutions kept at 20 degrees C. Sodium dichloroisocyanurate may be prepared on a weekly instead of a daily basis with an annual saving of 1200 pounds to 1400 pounds.

Chlorine↗