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Biomedical subjects

A M Johnson

Publications and source records attributed to A M Johnson.

At least 343 records · Page 19Linked to original sources

Cardiac surgery in Wessex.

The results of 3000 consecutive operations using cardio-pulmonary bypass show that the overall early mortality was 6.1%, dropping from 8.9% in the first 1000 to 4.4% in the third 1000. Operations for valve disease have been the most common, the early mortality for aortic valve replacement being 3.1% and for mitral valve replacement 2.9%. Combined aortic and mitral valve replacement had an early mortality of 4.4%. The number of patients undergoing isolated coronary artery bypass grafting has increased from 59 in the first 1000 to 292 in the third 1000 operations, with an overall early mortality of 1.3%. Six hundred and ninety seven patients underwent surgery for congenital heart disease with an overall early mortality of 10.9% (7.5% in the last 2000 cases). The patients have been followed up from one to 8.5 years. A high proportion have returned to work and enjoy a normal life. At the time of review, 87% of the 3000 patients were alive. Long waiting times for outpatient and inpatient care indicate underprovision of facilities relative to regional demand.

Adolescent↗

Pancreatitis with arthropathy and subcutaneous fat necrosis. Evidence for the pathogenicity of lipolytic enzymes.

The occurrence of peripheral fat necrosis in exceptional cases of pancreatic disease is not well understood. We report studies on such a patient with arthropathy and subcutaneous nodules. Examination of serial serum samples demonstrated striking elevations of the pancreatic enzymes phospholipase A, 3-3.4 units/ml (normal 0.17-0.41); lipase, 7-39 Sigma-Tietz units/ml (normal less than 1); immunoreactive trypsin, 912-3,207 ng/ml (normal 12-41). The distinguishing characteristic of the patient's synovial fluid was a marked elevation of hydrolized fatty acids (680 mg/dl versus 19 +/- 19 in control inflammatory joint fluids). Synovial fluid fatty acid distribution was identical to values for tissue fat. In contrast, serum fatty acid levels and distribution were normal. No associated proteinase inhibitor or significant immunologic abnormality was detected. Certain properties of adipose cells and lipolytic enzymes may help explain the characteristically selective necrosis of fat cells observed in this syndrome.

Fat Necrosis↗

Ultrastructural and biochemical studies on the immunohistochemistry of Toxoplasma gondii antigens using monoclonal antibodies.

To determine the cellular distribution of Toxoplasma antigens, RH strain tachyzoites were incubated with either one of three monoclonal antibodies (FMC 19, FMC 20, FMC 22) to T. gondii, or one of two controls (the murine myeloma protein MOPC 21, or phosphate buffered saline), and then incubated with peroxidase-labelled goat-antimouse IgG. Diaminobenzidine was added as substrate and electron microscopy was used to localize the reaction. All three antibodies bound to the entire periphery of the tachyzoite surface membrane. To ascertain the chemical composition of the antigens against which seven monoclonal antibodies (FMC 18, FMC 19, FMC 20, FMC 22, FMC 23, 2G11, 3E6) to T. gondii reacted, untreated, pronase-treated, or periodate-treated tachyzoites were incubated with the antibodies or MOPC 21, and then with [125I]-Protein A. The pronase-treated tachyzoites showed reduced binding for six of the antibodies, compared with the reduction in binding of MOPC 21 with the pronase-treated parasites. The periodate-treated tachyzoites had reduced binding for FMC 18 only. The results of these experiments confirm that most Toxoplasma surface antigens are protein in nature, and are consistent with the hypothesis that at least one cytoplasmic antigen is secreted onto the parasite cell surface.

Animals↗

Valve surgery in patients over the age of sixty-five.

Two hundred one patients over the age of 65 underwent valvular heart surgery with a hospital mortality of 5.5% and a late mortality of 18.4%. One hundred forty-one patients underwent isolated valve replacement (90 AVR, 51 MVR) with a hospital mortality of 1.5% (AVR 1%, MVR 2%). Multiple procedures carried a significantly higher hospital mortality (16%). Analysis of hospital and late deaths does not suggest that age alone should be accepted as a decisive factor in selection for surgery. There is a significantly higher late mortality in those who have had MVR (30%) compared with those having had AVR (14.6%). The importance of associated coronary artery disease as a risk factor has not been defined, but there is some evidence to suggest it is more important in this respect when found in association with mitral valve rather than aortic valve disease. An improved quality of life postoperatively was evident in the majority of survivors.

Age Factors↗

Elevated maternal serum alpha-fetoprotein, second-trimester oligohydramnios, and pregnancy outcome.

Although the primary purpose of maternal serum alpha-fetoprotein (AFP) screening is to detect open neural tube defects, the technique is of value in the diagnosis of other fetal abnormalities. Six patients from the Alpha-Fetoprotein Screening Program, Perinatal Region IV, were found to have twice elevated maternal serum AFP levels associated with severe early second-trimester oligohydramnios. Five of the fetuses were found to have urinary tract abnormalities. The source of the elevated maternal serum AFP is not clear. Pregnancy prognosis appears poor. These cases should be thoroughly studied so that patients may be accurately informed of the recurrence risk.

Amniotic Fluid↗

Monoclonal antibodies to Toxoplasma cell membrane surface antigens protect mice from toxoplasmosis.

Groups of mice were given an intraperitoneal injection of one of six monoclonal antibodies to Toxoplasma gondii, a mixture of equal amounts of five monoclonal antibodies to T. gondii, or the murine myeloma protein MOPC 21, and challenged with either a highly virulent or moderately virulent parasite strain. Two monoclonal antibodies (FMC 19 and FMC 22) conferred total protection against the moderately virulent challenge, with all mice surviving, whereas 90% of control mice died. FMC 19 and FMC 22 also conferred significant protection against the highly virulent challenge as indicated by a prolonged mean time to death (MTD) of immunized compared with control groups of mice. One monoclonal antibody (FMC 23) and the mixture of five antibodies gave significant protection against the moderately virulent challenge only. Passive immunization with dilutions of FMC 22 antibody indicated that the lowest serum titer needed to confer significant protection to mice against a moderately virulent Toxoplasma challenge was 1/640. Mice challenged with highly virulent tachyzoites that had been preincubated with FMC 22 had a significantly longer MTD than mice challenged with highly virulent tachyzoites that had been preincubated with MOPC 21 or phosphate buffered saline, pH 7.2 (PBS). Immunoprecipitation and autoradiography of radiolabeled tachyzoites confirmed that FMC 19 was directed against a 35,000 molecular weight (mol. wt.) antigen and FMC 22 was directed against a 14,000 mol. wt. fraction. The potential for use of single antigens as protective immunogens in preventing toxoplasmosis is raised.

Animals↗

Molecular weight analysis of soluble antigens from Toxoplasma gondii.

Ultrasonicated Toxoplasma gondii (RH strain) tachyzoites were fractionated into a water-soluble and a deoxycholate-soluble fraction. Polyclonal immune mouse serum was prepared by challenging chronically-infected mice with viable RH strain tachyzoites. The parasite fractions were labelled with 125I, and the radio-labelled antigens were precipitated by the immune mouse serum or a monoclonal anti-Toxoplasma antibody (FMC 20), that reacts only in the indirect hemagglutination antibody test. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of the immunoprecipitates showed that the water-soluble fraction contained 10 antigenic polypeptides, and the deoxycholate-soluble fraction contained seven antigenic peptides. The FMC 20 reacted against a 98,000-dalton antigen that was present in the water-soluble fraction only.

Animals↗

Acquired ventricular septal defect.

The past 9 years' experience with ventricular septal rupture complicating myocardial infarction has been reviewed. Thirty-six patients were treated surgically, with 10 early deaths (28%) and one late death, for an 8 year actuarial survival rate of 63%. The mortality was highest for those defects which followed inferior infarction, 38% compared with 13% following anterior infarction. The infarction-operation interval also greatly influenced mortality; under 2 weeks, 43%; over 2 weeks, 18%. Concomitant coronary artery bypass grafts (13 patients) or left ventricular aneurysmectomy (14 patients) did not carry an increased mortality. Of 17 patients who presented with cardiogenic shock, eight died (47%). The intra-aortic balloon pump (IABP) was used in 16 patients (44%) and helped greatly in the management of the critically ill. With an estimated 17 acquired septal defects occurring each year in persons under 65 years of age in Wessex, awareness of this complication and of the favorable outcome of operation is essential among those who treat the aftereffects of myocardial infarction.

Aged↗

Genetic predictors of patient response and side effects in the treatment of rheumatoid arthritis with a high dose nonsteroidal antiinflammatory drug regimen.

Clinical, laboratory, genetic, and radiologic studies were evaluated for 18 patients with rheumatoid arthritis who were treated for a mean of 16.6 months with a regimen involving supplementary aspirin and piroxicam, an investigational, nonsteroidal antiinflammatory agent. Although improvement in disease activity was seen, progression was evident on successive radiographs. Disease activity was not associated with the presence of any of the genetic markers. Peptic ulcers developed in 33% of patients, all of whom had type O blood. ABO blood typing may therefore be useful in patients with rheumatoid arthritis before consideration of therapy with potentially ulcerogenic drugs.

Adult↗

Nonparametric joint estimators for disease resistance and survival functions in survival/sacrifice experiments.

The nonparametric estimators proposed in this paper simultaneously estimate the disease resistance function, S(t), for the distribution of time to occurrence of disease, and the survival function, P(t), for the distribution of time to death caused by the disease. The estimators are applicable to animal survival data when the disease of interest is irreversible and the cause of death of each animal can be determined. Diseases need not be classified as universally lethal or universally nonlethal, and time to occurrence of the disease of interest need not be observable directly. It is shown that the proposed estimators are maximum likelihood estimators under the condition that S(t)/P(t) is monotonically decreasing. Application of the derived estimators is illustrated with experimental survival/sacrifice data, and results of a simulation study of the estimators' performance are reported.

Animals↗

Maternal serum alpha-fetoprotein screening: a report of the Forsyth County project.

A pilot screening program for the prenatal detection of neural tube defects has been conducted in Forsyth County, North Carolina. During the first 2 years of the program, 3,476 women were screened by quantitating levels of maternal serum alpha fetoprotein. Three neural tube defects and one case of multiple congenital anomalies with severe gastroschisis were detected as a result of the screening program. Outcome of pregnancy has been monitored in this group of women and no false negatives have been reported. No false positive amniotic fluid alpha-fetoprotein values were observed and no normal fetuses were aborted. Data gathered from this screening program again document the validity of maternal serum screening. The method of implementing a program for the prenatal decision of neural tube defects in urban areas is discussed.

Amniotic Fluid↗

Hybridomas secreting monoclonal antibody to Toxoplasma gondii.

Six hybridomas that secrete monoclonal antibody to Toxoplasma gondii have been developed. Four of these secrete antibody of the IgG1 subclass, one secretes antibody of the IgG2a subclass and the remaining hybridoma secretes antibody of IgG3 subclass. One IgG1 subclass antibody reacts only in the indirect haemagglutination antibody test (IHAT), four (3 IgG1 and 1 IgG2a) react only in the indirect immunofluorescence antibody test (IFAT), and the IgG3 antibody reacts in both the IHAT and IFAT.

Animals↗

Analysis of animal weight gains in chronic toxicity studies.

The growth pattern of an animal or group of animals during a chronic toxicity study can be used in a a number of ways. Perhaps the most important uses are for prediction of future weights and as evidence of toxic effects. In this paper a model for animal weight gain is constructed and analyzed. Tests and interval estimates are constructed for comparison of growth patterns. It is shown that the asymptotic weight limit of a growth curve is a parameter with which meaningful inferences may be made. Finally, the model is applied to experimental data collected at the National Center for Toxicological Research.

Animals↗