Search PubMed⌕ Search

Biomedical subjects

J Donohue

Publications and source records attributed to J Donohue.

At least 19 recordsLinked to original sources
PubMed2000

Adjuvant bleomycin, etoposide and cisplatin in pathological stage II non-seminomatous testicular cancer. the Indiana University experience.

Two cycles of bleomycin, etoposide, and cisplatin (BEP) were evaluated as adjuvant chemotherapy for patients with pathological stage II non-seminomatous germ cell tumours. Between 1985 and 1995, 86 patients with pathological stage II non-seminomatous testicular cancer were treated with two cycles of BEP. At retroperitoneal lymph node dissection (RPLND) 49 patients (57%) had pathological stage II(A) (microscopic nodal metastases) and 37 (43%) had stage II(B) (gross nodal metastases). After RPLND, the patients received bleomycin, 30 units weekly for 8 weeks, etoposide (100 mg/m(2)) and cisplatin (20 mg/m(2)) each for 5 days every 28 days for two cycles as adjuvant chemotherapy. 4 patients were lost to follow-up. 10 patients (12%) developed granulocytopenic fever during their chemotherapy. Of the 82 evaluable patients all remained with no evidence of disease except for a single patient with a cervical nodal relapse of teratoma. This was resected and he remains disease free. Median follow-up has been 85 months (range: 42-173 months). In patients with fully resected stage II non-seminomatous germ cell tumour, two cycles of BEP were almost universally effective in preventing relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Reversible colostomy--what is the outcome?

PURPOSE: The trend toward avoidance of a colostomy at both elective and emergency large-bowel surgery is partly driven by the perceived morbidity and low closure rates of temporary stomas. The aim of this study was to examine whether significant colostomy-related morbidity remains persistently high. METHODS: To examine this, we reviewed 120 patients with a potentially reversible colostomy performed during either elective or emergency large-bowel surgery during a seven-year period. RESULTS: Forty-seven patients underwent elective and 73 patients underwent emergency colonic or colorectal resection. Fifty-eight patients had colorectal carcinoma (48.3 percent), diverticular disease accounted for 39 patients (32.5 percent), and a miscellaneous group of 23 patients (19.2 percent) made-up the remainder. Seven patients died, all in the emergency group (9.6 percent). Colostomy-related morbidity, which included stenosis, retraction, prolapse, and hernia formation, occurred in 19.2 percent of patients, with no difference between the elective (14.9 percent) and emergency (21.9 percent) groups or underlying pathologic condition. Colostomy closure was performed initially in 71 patients (59.2 percent). Highest closure rates occurred in the diverticular group (84.6 percent), followed by the colorectal carcinoma group (48.3 percent), and then the miscellaneous group (43.5 percent). One patient died undergoing colostomy closure, and complications occurred in 25 patients (35.2 percent), requiring fashioning of a second colostomy in eight patients, two of whom were closed. Final colostomy closure rate was 54.2 percent. CONCLUSIONS: This study confirms the contention that both formation and closure of defunctioning colostomies are associated with significant complications; furthermore, approximately one-half of patients will not have their colostomy closed.

Colonic Diseases↗
PubMed1995

Ambulatory care of the adult asthma patient.

Asthma is a chronic airway disorder that is a serious public health problem in many countries. Asthma affects people of all ages. It ranges from mild to severe and sometimes is fatal. Over 100 million people worldwide have asthma and the prevalence is increasing, especially in the cohort aged 1 to 14 years. Risk factors that lead to the development of asthma appear to be largely environmental and therefore potentially preventable. Lifestyle changes and exposure to allergens may be responsible for the increase in prevalence.

Adult↗
PubMed1993

Characterization of cells emerging at the time of graft failure after bone marrow transplantation from an unrelated marrow donor.

To help elucidate the mechanism responsible for graft failure (GF) following a T-cell depleted bone marrow transplant (BMT) from an unrelated donor, five patients (2 chronic myelogenous leukemia, 1 acute undifferentiated leukemia, 2 myelodysplastic syndrome) who experienced this complication were studied. All patients were HLA class I identical with their donors as determined by serology and one-dimensional isoelectric focusing (IEF); two were serologically matched with their donors for HLA class II antigens, whereas three donor-recipient pairs were serologically mismatched for one HLA-DR antigen. All patients received total body irradiation (fractionated, 1,500 rads), VP-16 (750 mg/m2), and cyclophosphamide (120 mg/kg) pre-BMT and antithymocyte globulin (15 mg/kg every other day) and methylprednisolone (2 mg/kg) post-BMT. Three patients experienced primary nonengraftment and two experienced secondary GF. Peripheral blood mononuclear cells obtained from the patients at the time of GF were studied to examine their functional and phenotypic characteristics. Emerging cells were of host origin and were found to be specifically cytotoxic to donor target cells and suppressive to the in vitro growth of donor BM, especially in the cases of primary nonengraftment. Peripheral blood mononuclear cells from these patients were expanded to form T-cell lines (TcLs). The cytotoxic activities of TcLs were tested in the presence of blocking MoAbs directed against various HLA determinants in an attempt to determine if HLA antigens expressed on donor cells were the target for cytotoxicity. The observed cytotoxic activity was blocked by antibodies to HLA-B, -C (1 patient), HLA-DR (1 patient), and HLA-DQ (1 patient). In two cases, antidonor cytotoxicity could not be blocked by MoAb directed against HLA-A, -B, -C, or -DR. Phenotypic characterization of four successfully maintained TcLs showed 100% CD3+ cells with 100% CD4+ (3 patients) or 50% CD4+/50% CD8+ (1 patient). In two of the three patients with 100% CD4+ cells, antidonor cytotoxicity was blocked by an anti-HLA class II MoAb. In contrast to our previous findings in cases of GF following T-cell-depleted HLA nonidentical family member BMT in which host T cells were CD8+ and cytotoxicity was directed against HLA class I antigens, our present study indicates host T cells emerging at the time of GF following BMT from an HLA class I IEF-identical unrelated donor can be of the CD4+ subset and seem to be capable of recognizing antigenic disparities in the HLA class II region.

Adolescent↗
PubMed1993

Sequential Tc 99m mercaptoacetyl-triglycine (MAG3) renography as an evaluator of early renal transplant function.

A prospective study was carried out to evaluate the role of sequential Tc 99m MAG3 renography in assessing transplant function in the early post-operative period. Twenty patients were included in the study. Studies were performed on all patients at intervals of 48-72 hours until discharge. There were 11 clinically diagnosed episodes of rejection, 9 of which were correctly diagnosed using MAG3 renography. Six episodes of rejection were diagnosed prior to the onset of clinical symptoms. Two patients with graft infarction were correctly diagnosed. Six patients had evidence of transient renographic abnormalities in the immediate post-operative phase which were not associated with clinical symptoms, all of these resolved spontaneously on subsequent examinations and were presumed to be related to resolving acute tubular necrosis (ATN). The perfusion index was of no discriminatory value in this study. Sequential Tc 99m MAG3 renography is highly sensitive but entirely nonspecific in the evaluation of pathology in the transplant kidney. Rejection in an uncomplicated transplant can be readily detected in many cases well in advance of clinical manifestations. This study demonstrates that Tc 99m MAG3 renography is certainly equal to Tc 99m DTPA renography or Iodine 131 renography in assessing early transplant function. However, Tc 9m MAG3 exposes the patient to considerably less radiation and the images are of superior quality.

Adolescent↗
PubMed1992

Clonal analysis of myelodysplastic syndrome: monosomy 7 is expressed in the myeloid lineage, but not in the lymphoid lineage as detected by fluorescent in situ hybridization.

Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% +/- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. Antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% +/- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% +/- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% +/- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells.

Adolescent↗
PubMed1992

Heteroconjugated antibodies enhance lymphocyte-mediated tumour cell lysis in vitro and in vivo.

Covalent linkage of an antitumour antibody specific for a tumour cell surface antigen to an antilymphocyte antibody specific for the T lymphocyte receptor complex produces a heteroconjugated antibody that can activate and redirect cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte-antitumour heteroconjugate (500A2 x 96.5) to direct the lysis of murine melanoma cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium release assay and in vivo with a tumour neutralization assay. In vitro, the addition of heteroconjugated antibody significantly increased tumour lysis by murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P less than 0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes significantly reduced the development of pulmonary metastases after intravenous tumour administration (median number of pulmonary metastases 28.5 for combined treatment versus 250 for heteroconjugate or lymphocytes alone, P less than 0.001).

Animals↗
PubMed1990

Heteroconjugate antibody-directed killing of autologous human renal carcinoma cells by in vitro-activated lymphocytes.

Tumor cell lysis can be enhanced significantly in vitro when heteroconjugate (HC) antibodies (anti-CD3 x anti-tumor mAb) are used to specifically direct lymphocyte effector cells to the tumor cell target. In order to effectively utilize HC antibodies in an immunotherapy protocol, methods must be identified for the optimum expansion, activation, and retargeting of lymphocyte-effector populations from cancer patients. In this study, we have compared the proliferative responses of different normal and renal cell carcinoma (RCC) patient lymphocyte preparations (PBL, tumor-infiltrating lymphocytes) stimulated in vitro for periods up to 12 days with a variety of growth factor combinations (anti-CD3, rIL-2, rIL-4). These activated lymphocyte preparations were then tested in vitro for their ability to kill RCC tumor cells and tumor cell lines in the presence of HC preparations (anti-CD3 mAb covalently linked to mAb reactive to different RCC tumor-associated Ag). RCC patient PBL cultured with anti-CD3 plus rIL-2 for 12 days resulted in a 3- to 160-fold expansion of effector cells. These cells, as well as tumor infiltrating lymphocytes, when retargeted with appropriate HC antibodies were capable of mediating high levels of killing of autologous tumor cells. No constitutive autologous anti-tumor cell response was detected in the absence of added HC antibodies. Of the five anti-RCC mAb tested (A6H, K29, K20, UR07, and URO 3), HC containing URO 3 x anti-CD3 and K20 x anti-CD3 elicited the highest level of tumor cell lysis by the activated lymphocyte effector cells. Together these results demonstrate that HC antibodies may be a useful imunotherapeutic reagent for directing the killing of RCC tumor cells by autologous lymphocytes.

Antibodies, Neoplasm↗
PubMed1990

The pharmacokinetics of dilevalol in renal impairment.

Dilevalol, 200 mg, was administered orally as seven daily doses to three groups of six participants, with differing degrees of renal impairment. Values of Cmax, Tmax, half-life or renal elimination did not significantly change with decreased renal function. Values of area under the plasma concentration-time curves and pre-dose concentrations tended to increase with renal impairment and there was a significant, if small, correlation between these and glomerular filtration rate. The practical clinical consequences of these results is that impairment is not likely to be associated with significant accumulation of dilevalol.

Administration, Oral↗
PubMed1989

Pharmacokinetics of amlodipine in renal impairment.

Amlodipine was administered as 14 single 5-mg oral daily doses to 27 male subjects with renal function ranging from normal to haemodialysis-dependent. Blood specimens were obtained for measurement of plasma amlodipine concentrations for 24 h following the first dose, for 168 h following the final dose and during daily administration of amlodipine. Amlodipine was well tolerated. Renal impairment had little effect on the pharmacokinetics of amlodipine. The elimination half-life was of the order of 50 h, similar to previously reported values and did not vary with renal function. Steady-state pre-dose concentrations were observed after the ninth dose. Accumulation of amlodipine was not significantly different from that expected on theoretical grounds and did not significantly change with renal function. These results suggest that once daily administration of amlodipine is suitable for all degrees of renal function and that dosage adjustment is not necessary in renal impairment.

Adult↗
PubMed1989

A longitudinal study of the contribution of dental experience to dental anxiety in children between 9 and 12 years of age.

Dental records of a group of children of both sexes were examined systematically over a period of 3 years to determine if the quantity and quality of their dental experience would be associated with increases in dental anxiety. The study was a follow-up of an earlier cross-sectional survey in which older children had demonstrated increases in dental anxiety with age. According to the evidence obtained from their dental records, the children were divided into four groups depending on their patterns of attendance (regular/irregular) and whether or not they had received invasive treatment. The results indicated that children who did not receive invasive treatment during the period under scrutiny were significantly more anxious than those who had. On the other hand, the dental anxiety of children who attended regularly and received invasive treatment did not change significantly. This applied to boys and girls alike.

Age Factors↗
PubMed1989

Enzyme immunoassay system for panel testing.

An immunoassay system based on enzyme immunoassay technology has been developed for quantitative panel testing. The system includes test card disposables, reagents, and an instrument. Patients' samples are processed semiautomatically in the instrument with minimum user intervention. The test card has multiple test areas at individual locations on a membrane solid phase so that simultaneous determinations from a single specimen are possible. Each panel also includes positive and negative reagent procedural controls. Factory-determined calibration curves for each analyte are provided in barcode form with each test kit. The reagents include a specimen dilution buffer, enzyme conjugate, and precipitogenic substrate. Up to 10 test cards at a time can be processed in random-access and continuous-access modes, with automated agitation of sample and reagents over the solid phase, temperature-controlled incubation, and membrane washing and reading, data reduction, and printout of results. The optical reader measures diffuse reflectance and features source intensity and wavelength compensation.

Chemistry, Clinical↗
PubMed1986

Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function. In patients with severe renal impairment (GFR values below 30 ml min-1 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

Adult↗