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Biomedical subjects

P McCarthy

Publications and source records attributed to P McCarthy.

At least 55 records · Page 3Linked to original sources
PubMed1996

An unusual case of autoimmune hemolytic anemia with reticulocytopenia, erythroid dysplasia, and an IgG2 autoanti-U.

BACKGROUND: Autoantibodies with anti-U specificity, usually in combination with autoantibodies of other specificities, have occasionally been identified in association with autoimmune hemolytic anemia. A case of life-threatening autoimmune hemolytic anemia, characterized by several atypical features, including apparent intravascular hemolysis associated with an IgG2 anti-U, reticulocytopenia, and bone marrow dyserythropoiesis is described. CASE REPORT: A 36-year-old man with a severe case of acute-onset autoimmune hemolytic anemia was admitted to another hospital; he had a hematocrit of 15 percent, elevated bilirubin and lactate dehydrogenase, and positive direct and indirect antiglobulin tests. He received 7 units of incompatible red cells without improvement in hematocrit, and he was transferred to University Hospitals of Cleveland (OH). He was jaundiced and became syncopal in the sitting position. His serum was reddish pink; he had a hematocrit of 11.8 percent and a reticulocyte count of 2.5 percent. No spherocytes were observed in the peripheral blood smear. Shortly after admission, the hematocrit fell to 6.9 percent. He was given 3 units of "least-incompatible" red cells and was started on prednisone, with little improvement. An IgG2 autoanti-U was detected in his serum. Seven units of U- red cells were transfused over the next 4 days. The hematocrit improved to 23 percent and continued to rise without further transfusion. A bone marrow examination, initially revealing erythroid hyperplasia accompanied by dyserythropoiesis, became morphologically normal. Drug studies failed to show evidence of drug-related hemolysis. He remains well 2 years after discharge without evidence of recurrent hemolysis. CONCLUSION: Severe life-threatening autoimmune hemolytic anemia, in this instance induced by an autoanti-U, may be associated with IgG2 autoantibody and characterized by apparent intravascular hemolysis and bone marrow dyserythropoiesis. Early treatment with U- blood, in addition to steroids, may be beneficial.

Adult↗
PubMed1995

Serum neuron-specific enolase and immunohistochemical markers of neuroendocrine differentiation in lung cancer.

An enzyme immunoassay for serum neuron-specific enolase (NSE) was evaluated with respect to analytical performance and clinical utility and compared with immunohistochemical evaluation of neuroendocrine differentiation. Values obtained agreed well with values obtained using a radioimmunoassay method giving a correlation coefficient of 0.934. Analytical performance of the enzyme immunoassay was good but the diagnostic sensitivity of 82% in extensive and 67% in limited disease was insufficient for serum NSE to be of value in the diagnosis of small cell lung cancer (SCLC). Serum NSE decreased significantly in 11 of 15 patients with SCLC following institution of chemotherapy. Classification of lung cancers into SCLC and non small cell lung cancer (NSCLC) types is largely based on tumour morphology. Neuroendocrine differentiation may not be morphologically evident. Immunohistochemical staining of tumour tissue with markers of neuroendocrine differentiation, i.e. NSE (both monoclonal and polyclonal antibodies) Leu 7, Chromogranin A and P G P 9.5 was performed in both patients with SCLC and NSCLC. 38 per cent of patients with NSCLC had both raised serum NSE and positive NSE (polyclonal) immunoperoxidase staining of lung tissue. A further 35 per cent of patients showed a raised serum NSE or positive immunohistochemistry but not both. The presence of two positive immunoperoxidase markers in lung tissue has been suggested as an indicator of responsiveness to chemotherapy in NSCLC patients. A number of factors may affect immunohistochemical positivity in tissue sections and the additional use of a serum marker may better define chemotherapy responsive groups.

Adult↗
PubMed1995

Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system.

OBJECTIVE: This nonrandomized study using concurrent controls was performed to determine whether the HeartMate implantable pneumatic (IP) left ventricular assist system (LVAS) could provide sufficient hemodynamic support to allow rehabilitation of severely debilitated transplant candidates and to evaluate whether such support reduced mortality before and after transplantation. METHODS: Outcomes of 75 LVAS patients were compared with outcomes of 33 control patients (not treated with an LVAS) at 17 centers in the United States. All patients were transplant candidates who met the following hemodynamic criteria: pulmonary capillary wedge pressure > or = 20 mm Hg with a systolic blood pressure < or = 80 mm Hg or a cardiac index < or = 2.0 L/minute/m2. In addition, none of the patients met predetermined exclusion criteria. RESULTS: More LVAS patients than control patients survived to transplantation: 53 (71%) versus 12 (36%) (p = 0.001); and more LVAS patients were alive at 1 year: 48 (91%) versus 8 (67%) (p = 0.0001). The time to transplantation was longer in the group supported with the LVAS (average, 76 days; range, < 1-344 days) than in the control group (average, 12 days; range, 1-72 days). In the LVAS group, the average pump index (2.77 L/minute/m2) throughout support was 50% greater than the corresponding cardiac index (1.86 L/minute/m2) at implantation (p = 0.0001). In addition, 58% of LVAS patients with renal dysfunction survived, compared with 16% of the control patients (p < 0.001). CONCLUSIONS: The LVAS provided adequate hemodynamic support and was effective in rehabilitating patients based on improved renal, hepatic, and physical capacity assessments over time. In the LVAS group, pretransplant mortality decreased by 55%, and the probability of surviving 1 year after transplant was significantly greater than in the control group (90% vs. 67%, p = 0.03). Thus, the HeartMate IP LVAS proved safe and effective as a bridge to transplant and decreased the risk of death for patients waiting for transplantation.

Adolescent↗
PubMed1995

Allogeneic bone marrow transplantation for refractory and recurrent low-grade lymphoma: the case for aggressive management.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in recurrent low-grade lymphoma. PATIENTS AND METHODS: Between 1989 and 1994, 10 patients with chemotherapy-refractory and recurrent low-grade lymphoma were treated with myeloablative therapy and allogeneic BMT. All patients had poor prognostic features and had been extensively pretreated. RESULTS: Eight patients achieved a complete remission and none have relapsed at a median follow-up time of 816 days (range, 346 to 1,865). Two patients died of early complications. The actuarial survival and failure-free survival rates are both 80% +/- 12.6%. For surviving patients, the duration of the current remission exceeds that of any previous remission achieved. CONCLUSION: These results compare favorably with those for autologous BMT. Allogeneic BMT offers considerable promise for the treatment of patients with poor-prognosis low-grade lymphoma. Its role should be further defined in prospective studies.

Adult↗
PubMed1994

Urokinase-type plasminogen activator and outcome in Dukes' B colorectal cancer.

Urokinase-type plasminogen activator (u-PA) is a serine protease involved in cancer metastasis. Using immunohistochemical methods, we examined the relation between u-PA and long-term survival in 70 patients with Dukes' B colorectal cancer. 8-year survival was 81% in patients whose tumours demonstrated low-grade epithelial u-PA staining and 43% in those with high-grade staining (log-rank test, p = 0.01). Survival was unrelated to stromal u-PA staining. These results suggest that u-PA may be useful in the identification of patients with non-metastatic colorectal cancer at risk of tumour recurrence.

Adult↗
PubMed1994

Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease.

Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL-1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.

Adult↗
PubMed1994

Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen).

BACKGROUND: The presence of a specific cellular receptor is thought to be necessary for susceptibility to viral infection. The erythrocyte P antigen is the cellular receptor for parvovirus B19. We hypothesized that the rare persons with the p phenotype, whose erythrocytes do not have this receptor, would be naturally resistant to B19 infection, which causes erythema infectiosum. METHODS: Blood samples were collected from two populations in cross-sectional studies. We determined the P antigen phenotype of the red cells and tested plasma for anti-B19-specific antibodies. Bone marrow from donors of known P antigen phenotype was inoculated with parvovirus B19. Infectivity was measured by assays of erythroid progenitor cells, dot blot analysis, and in situ hybridization for B19 DNA, and an immunofluorescence assay for viral-capsid proteins. RESULTS: Of the 17 subjects with the p red-cell phenotype, who did not have P antigen on their erythrocytes, none (0 of 11 and 0 of 6) had serologic evidence of previous parvovirus B19 infection. In contrast, the seropositivity rates in the two control groups were 71 percent (53 of 75, P < 0.001) and 47 percent (32 of 68, P = 0.03). In vitro, bone marrow from donors with the p phenotype maintained normal erythropoiesis despite very high concentrations of virus, with no evidence of infection of erythroid progenitor cells by parvovirus B19. CONCLUSIONS: People who do not have P antigen, which is the cellular receptor for parvovirus B19, are naturally resistant to infection with this pathogen.

Adolescent↗
PubMed1994

Influence of arterial coronary bypass grafts on the mortality in coronary reoperations.

From 1988 through 1991, 1663 patients underwent a first reoperation for isolated coronary bypass grafting with 62 (3.7%) in-hospital deaths. At the primary operation, 575 patients had received at least one internal thoracic artery graft and 489 patients had at least one patent internal thoracic artery graft present at the time of reoperation. At reoperation, 1014 patients received at least one internal thoracic artery graft, 10 received an inferior epigastric graft, and 37 received a gastroepiploic graft. Of 489 patients with patent internal thoracic artery grafts at reoperation, the internal thoracic artery was damaged in 17 (3.5%); of 428 patients with a patent internal thoracic artery graft to the left anterior descending coronary artery, 14 (3.3%) had graft damage necessitating regrafting. All patients with damaged internal thoracic arteries survived. Multivariate testing of variables for their association with in-hospital mortality identified no internal thoracic artery graft at either primary surgery or reoperation (p < 0.0001), a history of congestive heart failure (p < 0.0001), advancing age (p = 0.018), female gender (p = 0.029), and emergency operation (p = 0.01) as factors linked to increased risk. Left ventricular function, left main stenosis, extent of native coronary atherosclerosis, and the interval between operations did not influence mortality. Furthermore, the presence of an atherosclerotic vein graft to the left anterior descending coronary artery a factor shown to increase in-hospital risk in previous studies did not increase risk during these years. We attribute the observation that patent internal thoracic artery and atherosclerotic vein grafts do not appear to be factors specifically increasing the risk of reoperation to the use of retrograde cardioplegic solution and increased surgical experience. The use of internal thoracic artery grafts at a primary operation does not increase the risk of a reoperation, and the use of internal thoracic artery grafts at reoperation does not increase in-hospital morbidity or mortality.

Age Factors↗
PubMed1993

A reappraisal of serial isotope bone scans in prostate cancer.

Carcinoma of the prostate is the commonest malignancy of the genitourinary tract in the male and is frequently associated with metastatic bone disease. Serial isotope bone scans for screening secondary deposits are not cost-effective. We have evaluated the serum prostate markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) as an alternative to conventional serial bone scanning in 129 patients with newly diagnosed prostate cancer over a period of 3 years. Although serum PSA did not reflect local tumour burden at presentation, it was significantly elevated in those who presented with stage D disease (p < 0.01). 45 patients presented de novo with metastatic bone deposits and a further 18 patients developed metastases during the study period. The sensitivity of PSA in detecting secondary deposits at presentation for levels in excess of 100 micrograms/l was 93.75%, the positive predictive value 95.7% and the negative predictive value for levels less than 5 micrograms/l was 90.6%. During the follow-up period the sensitivity was 94.4%, the positive predictive value 100% and the negative predictive value 100%, with a median lead time of 3 months in predicting metastases in the 18 patients with progressive disease. When compared with PAP, PSA was found to be a statistically superior marker of bone metastases both at presentation and follow-up (p < 0.05). We recommend that PAP measurements are no longer necessary and should be replaced by PSA, and that serial serum PSA estimations should determine the need for future isotope bone scans in the patient with established prostate cancer.

Acid Phosphatase↗
PubMed1993

Unilateral auto-PEEP in the recipient of a single lung transplant.

We report a patient who received a right single lung transplant (SLT) for progressive lymphangioleiomyomatosis and required reintubation for postoperative respiratory distress. She developed hemodynamic instability due to mediastinal shift from unilateral auto-PEEP with hyperinflation of the native lung. Placement of a double lumen endotracheal tube (DLET) and institution of differential lung ventilation restored equal lung inflation and hemodynamic stability.

Adult↗
PubMed1993

Omission rates of young and elderly listeners in word recognition testing.

Elderly listeners, as a group, do not perform as well as younger listeners on tests of word recognition, particularly in the presence of competing noise. It has been suggested that elderly listeners may be less willing to guess at items when they are unsure of the correct response, and as a result omit more responses. Omitting responses on word recognition tests may deflate word recognition scores. To test whether elderly listeners actually do omit more responses on word recognition tests, a group of elderly normal-hearing adults was compared to a group of young normal-hearing adults. To promote guessing, ipsilateral multitalker babble was presented at individually determined levels that approximated 50 percent performance. The subjects responded to two lists of NU6 words, and numbers of omissions were recorded. The elderly group did not omit significantly more responses to word recognition test items than the younger group. Variability was high within both groups.

Adult↗
PubMed1993

The effect of coronary reoperation on the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries.

Does coronary artery reoperation improve the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries? To examine this question, we retrospectively reviewed 1117 patients who had coronary bypass grafting and then underwent a postoperative coronary angiogram that showed a stenosis (> or = 20%) of at least one vein graft. Reoperation within 1 month of the postoperative angiogram was performed for 394 patients (REOP group) whereas 723 patients (MED group) received initial medical treatment (no reoperation or percutaneous transluminal coronary angioplasty within 1 year). Compared with the MED group, patients in the REOP group were older, more symptomatic, more likely to have left main stenosis, and had fewer patent bypass grafts (all p < 0.001). In-hospital mortality for the REOP group was 4.3%. Mean postangiogram follow-up of the entire group was 73 months. On the basis of the interval between the primary operation and the postoperative angiogram, patients were designated as having early (< 5 years) or late (> or = 5 years) saphenous vein graft stenosis. Univariate and multivariate analyses were used to identify factors influencing the survival of these subgroups. Reoperation was not identified as a variable improving the survival of patients with early vein graft stenoses. For patients with late vein graft stenoses, moderate or severe impairment of left ventricular function (p < 0.0001), advanced age (p < 0.0001), triple-vessel or left main stenosis (p = 0.0011), and stenosis in a vein graft to the left anterior descending artery (p = 0.0019) decreased survival, whereas reoperation improved survival (p = 0.0007). The improvement in survival with reoperation was particularly strong for patients with a stenotic vein graft to the left anterior descending artery. For that subset, survival was 84% and 74% for the REOP group versus 76% and 53% for the MED group at 2 and 4 years after catheterization, respectively (p = 0.004). For patients with stenotic vein grafts to the right coronary artery or circumflex coronary artery (or both), survival was 92% and 87% for the REOP group versus 89% and 78% for the MED group at 2 and 4 years after catheterization, respectively (p = 0.13). Even for patients with class I or II symptoms, reoperation prolonged survival (p = 0.002 with multivariate testing). Reoperation improves the survival of patients with late vein graft stenoses, particularly those with stenotic grafts to the left anterior descending coronary artery.

Constriction, Pathologic↗