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Biomedical subjects

R John

Publications and source records attributed to R John.

At least 55 records · Page 3Linked to original sources
PubMed2000

Postpartum thyroiditis and long-term thyroid status: prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity.

Postpartum thyroid dysfunction (PPTD) occurs in 5% of women, with hypothyroidism developing in 23% of these after 3-5 yr. We have determined the prognostic significance of thyroid peroxidase antibody (TPOAb), thyroid ultrasound morphology (U/S), human leukocyte antigen haplotype, and postpartum thyroid status on the development of thyroid dysfunction 77-81 months after PPTD. Ninety-eight TPOAb-positive [48 who had developed PPTD (group 1) and 50 without PPTD (group 2)] and 70 TPOAb-negative (group 3) women (derived from 145 TPOAb-positive and 229 TPOAb-negative cohorts at the index pregnancy), with comparable ages, parity, pregnancies after index pregnancy, and follow-up duration, were studied. Thyroid dysfunction occurred in 46% of group 1 vs. 4% of group 2 (P<0.001) and 24.5% of groups 1 and 2 vs. 1.4% of group 3 (P<0.001). Factors predictive of thyroid dysfunction included a hypothyroid form of PPTD, TSH more than 20 mU/L, and higher TPOAb levels (213.8 kIU/L in group 1 vs. 131.8 kIU/L in group 2; P<0.002) during the postpartum period. Although TPOAb was higher in group 1 than in group 2 at follow-up (166 vs. 97.7 kIU/L; P<0.03), there was no significant fall in TPOAb levels within either group during the period of follow-up. The prevalence of ultrasound hypoechogenicity was higher in group 1 than in group 2 at follow-up (76% vs. 52%; P<0.006), but U/S improved in 62.5% of group 1 during the period of follow-up. Human leukocyte antigen DR10 was lower in those who developed late thyroid dysfunction. These data, representing the longest follow-up of PPTD women, clearly show that the hypothyroid form of PPTD, high TPOAb levels, and a hypoechogenic U/S pattern lead to a high risk (relative risk, 32) of long term thyroid dysfunction. This compares with a relative risk of 12.9 for TPOAb- and PPTD-positive women, who remained euthyroid at the end of the first postpartum year, and 2.8 for TPOAb-positive but PPTD-negative women, all compared to TPOAb-negative women. Therefore, long term surveillance of TPOAb- and PPTD-positive women (group 1) is indicated.

Adult↗
PubMed2000

Augmentation of central arterial pressure in mild primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown increased pulse pressure to be a powerful predictor of cardiovascular events. As increases in pulse pressure are due largely to arterial stiffening, we measured arterial stiffness in 21 subjects with PHPT (18 women and 3 men; 46-71 yr old) and 21 age- and sex-matched healthy controls using pulse wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and augmentation index, a measure of vessel stiffness. Metabolic parameters were also measured. The serum calcium level among PHPT subjects was (mean +/- SD) 2.74+/-0.14 mmol/L. pulse wave analysis showed that both augmentation and the augmentation index were significantly higher in the PHPT group vs. controls [16+/-5 vs. 10+/-4 mm Hg (P < 0.001) and 36+/-9% vs. 25+/-6% (P < 0.001)] despite comparable brachial systolic pressures between groups (136+/-13 vs. 134+/-18 mm Hg). Patients with PHPT had higher fasting serum insulin levels [median (range), 15.8 (7.4-39.4) vs. 11.6 (5.1-23) mU/L; P < 0.05] and triglyceride (1.6+/-0.6 vs. 1.2+/-0.4 mmol/L; P < 0.05), but lower high density lipoprotein cholesterol (1.4+/-0.4 vs. 1.6+/-0.3 mmol/L; P < 0.05). These data indicate that subjects with mild PHPT (calcium, <3.0 mmol/L) have increased arterial stiffness, as evidenced by higher augmentation of central aortic pressures. Enhanced vessel stiffness may arise from a combination of structural and functional vascular changes due to hypercalcemia and/or metabolic abnormalities. Increased vascular stiffness in subjects with PHPT may account in part for the increased cardiovascular risk in this group.

Aged↗
PubMed2000

Comparative multicentre study of a panel of thyroid tests using different automated immunoassay platforms and specimens at high risk of antibody interference.

The introduction of automation for immunoassays in recent years has brought about important and evident improvements in assay precision. Increasing standardization and comparability between platforms should enable the development of clinical guidelines and diagnostic algorithms for appropriate clinical decision making. A continuing source of variation between different automated immunoassay platforms is the sporadic effect of interfering antibodies or substances, thus causing aberrant results not supporting the patient's clinical status. The aim of this study was to describe current thyroid panel variation between automated immunoassay platforms including population specimens at risk of antibody interference. A multisite design with laboratories in three different countries using four different automated immunoassay platforms (Roche-Boehringer Mannheim Elecsys (Italy), Roche-Boehringer Mannheim ES300 (Wales), Bayer Immuno 1 and the Bayer ACS:180 evaluated the thyroid panel of thyrotropin (TSH), triiodothyromine (T3), free thyroxine (FT4) and free triiodothyronine (FT3). A common set of 158 randomly selected patient samples of non-thyroid and thyroid disorders, with and without treatment, was tested. Included were 62 patient samples at risk for endogenous antibody interference with high antimicrosomal antibody, anti-TSH receptor antibody and increased rheumatoid factor sub-populations. Across all controls and between platforms, precision measurements were comparable and varied between 0.7% and 12.8% for TSH, 2.8% and 13% for FT4, 1.8% and 10.5% for FT3 and 3.1% and 16% for T3 assay. Acceptable correlation and reproducibility were found between the three Bayer Immuno 1 platforms at each country's site with all four thyroid panel assays demonstrating r-values of 0.989 to 1.000 and slopes of 0.915 to 1.078. Comparisons between the different platforms showed acceptable correlation for all thyroid panel assays. Specimens containing rheumatoid factor were associated with a significantly increased variation between systems for the FT4 and FT3 assays (p < 0.01). This effect did not appear to be selective for a given platform. For specimens with raised autoimmune antibodies and therefore at risk of assay antibody interference, no variation could be observed between the platforms.

Antibodies↗
PubMed2000

The diagnosis and management of aortic dissection occurring years after open heart surgery.

Aortic dissection occurring after open heart surgery is an uncommon but well recognized complication. Unfortunately, it is associated with a high morbidity and mortality. Pre-existing aortic wall pathology, intraoperative aortic manipulations and hypertension are known to predispose to the development of this condition. We report a case of aortic dissection occurring 2 years after coronary artery bypass surgery and complicated by acute saphenous vein graft occlusion and severe mitral insufficiency. We review the diagnosis and management of this complication.

Aged↗
PubMed1999

Quantitative changes in T-cell populations after left ventricular assist device implantation: relationship to T-cell apoptosis and soluble CD95.

BACKGROUND: Left ventricular assist devices (LVADs) are currently being evaluated as permanent therapy for end-stage heart failure. Because life-threatening infections limit successful long-term device implantation, we investigated the relationship between quantitative T-cell defects in LVAD recipients and CD95-mediated T-cell apoptosis. METHODS AND RESULTS: Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management. Fluorochrome-labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recipients had a relative lymphopenia and reduction in CD4 T-cell levels compared with NYHA class IV heart failure controls. These observations were confirmed in a longitudinal study in LVAD recipients, which showed that device implantation was accompanied by progressive and sustained reductions in circulating CD4 T-cell levels. These abnormalities in LVAD recipients were accompanied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2-fold greater for CD4 T cells than for CD8 T cells. CONCLUSIONS: These results suggest that the reduction in CD4 T-cell levels accompanying LVAD implantation is a consequence of an augmented pathway of CD95-mediated apoptosis. The clinical consequences of these abnormalities may include increased prevalence of systemic infections.

Apoptosis↗
PubMed1999

Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients.

BACKGROUND: Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity. METHODS AND RESULTS: Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student's t test. Prolongation in transplant waiting time was related to serum IgG anti-HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency. CONCLUSIONS: These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.

Graft Rejection↗
PubMed1999

Vasopressin deficiency and pressor hypersensitivity in hemodynamically unstable organ donors.

BACKGROUND: Solid organ donors often develop hypotension due to vasodilation, and recently we observed that a variety of vasodilatory states are characterized by vasopressin deficiency and hypersensitivity. Thus, we investigated the prevalence of vasopressin deficiency in hypotensive solid organ donors without clinical evidence of diabetes insipidus; we also investigated the vasopressor effect of vasopressin replacement in hypotensive donors. METHODS AND RESULTS: Fifty organ donors were evaluated for hemodynamic instability, (mean arterial pressure [MAP]</= 70 mm Hg despite the use of catecholamine vasopressors), and in those unstable donors who were not already receiving exogenous vasopressin, low-dose vasopressin was administered as a continuous infusion (0. 04 to 0.1 U/min). MAP, catecholamine requirements, serum vasopressin, and serum osmolality were obtained before and after vasopressin administration. Ten patients meeting the enrollment criteria received vasopressin and MAP increased from 72.2+/-3.5 to 89.8+/-4.2 mm Hg, (P<0.05), allowing for complete discontinuation of catecholamine pressors in 4 (40%) patients and a decrement in pressor dose in 4 (40%). Plasma vasopressin levels (2.9+/-0.8 pg/mL) were low for the degree of hypotension. CONCLUSIONS: Hemodynamically unstable organ donors without clinically apparent diabetes insipidus display a defect in the baroreflex-mediated secretion of vasopressin. In these patients, low-dose vasopressin significantly increases blood pressure with a pressor response sufficient to reduce catecholamine administration.

Adolescent↗
PubMed1999

Induction of swine major histocompatibility complex class I molecules on porcine endothelium by tumor necrosis factor-alpha reduces lysis by human natural killer cells.

BACKGROUND: Natural killer (NK) cells have been implicated in a process of delayed xenograft rejection occurring in pig-to-primate organ transplants. As tumor necrosis factor-a (TNF-a) induces expression of both adhesion receptors and major histocompatibility complex class I molecules on porcine endothelium, we investigated the effects of TNF-alpha on human NK cell adherence to and cytotoxicity of porcine aortic endothelial cell (PAEC) monolayers. METHODS: Adherence of human NK cells was measured after PAEC treatment with increasing concentrations of TNF-alpha. Monoclonal antibodies (mAbs) against adhesion molecules on NK cells and PAEC were used in inhibition studies. Resting or TNF-alpha-treated PAEC were used as targets for NK lysis. Increasing titers of anti-swine leukocyte antigen (SLA) class I antibodies or pooled human immune globulin (IVIg) were used to reverse the effects of TNF-alpha on NK lysis. RESULTS: NK cell adhesion to TNF-a-treated PAEC increased in a dose-dependent manner by a maximum of 44%, and was inhibited by mAbs against CD49d, CD11a, CD11b, CD18, and CD2, as well as porcine vascular cell adhesion molecules. In contrast, TNF-alpha treatment of PAEC reduced human NK lysis in a dose-dependent manner. Preincubation of TNF-a-treated PAEC with increasing concentrations of anti-SLA class I mAb increased NK lysis in a titer-dependent manner, and reversed the protective effect on human NK lysis by 77%. Treatment with IVIg, containing antibodies against an a-helical region of HLA class I molecules, had a similar effect. CONCLUSIONS: These results imply that SLA class I molecules can bind to inhibitory receptors on human NK cells, and that these interactions can be augmented by increasing the level of SLA class I molecule expression on porcine endothelium. Strategies that can increase porcine endothelial cell expression of either swine or human major histocompatibility complex class I molecules may reduce human NK activity against porcine xenografts.

Animals↗
PubMed1999

Long-term survival after cardiac retransplantation: a twenty-year single-center experience.

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.

Actuarial Analysis↗
PubMed1999

Branchio-oto-renal syndrome with generalized microdontia: case report.

Branchio-oto-renal syndrome, first defined in 1976, is an autosomal dominant disorder characterized by anomalies of the external, middle, and inner ear in association with preauricular sinuses, branchial cleft anomalies, and varying degrees of renal dysplasia, including aplasia. Less frequently expressed phenotypic abnormalities include lacrimal duct aplasia and stigmata of renal dysgenesis known as Potter facies. Although the precise incidence of the disorder is unknown, it may be more common than is generally appreciated, and it appears to be distinct from other autosomal dominant otobranchial syndromes. Moreover, not all features of the syndrome are expressed in all carriers of the gene. An unusual case of branchio-oto-renal syndrome with generalized microdontia of the permanent dentition is reported.

Branchio-Oto-Renal Syndrome↗
PubMed1999

Aberrant root development of the mandibular premolars: a case report.

A rare case of a patient with aberrant root morphology in all the mandibular premolars is reported. A thorough review of the dental literature revealed little significant data concerning such cases, because much of the literature is concerned with variation in root canal morphology rather than variations in root morphology. Failure to obtain preoperative radiographs of diagnostic quality could result in unexpected complications during endodontic treatment or extraction of such variant teeth.

Adolescent↗
PubMed1999

Assessment of goiter in an area of endemic iodine deficiency.

Urinary iodone (UI) excretion and sonographically measured thyroid volume were investigated in 195 subjects living in 6 separate villages in the Casamance region of southeastern Senegal, West Africa. A comparison of goiter prevalence using thyroid palpation and volume measurement and of iodine excretion expressed as micrograms per gram (microg/g) creatinine or micrograms per deciliter (microg/dl) urine was undertaken, and possible pathogenetic factors were investigated. Ultrasound measured thyroid volumes were above the recommended upper limit of the reference range for an area replete in iodine in 83.1% or females, 52.3% of males, and 80.0% of children aged 13 years or younger. Overall sensitivity and specificity for palpation compared to sonographically demonstrated thyroid enlargement was 51.7% and 91.5%, respectively. Thyroid enlargement was not associated with ethnic origin, thiocyanate ingestion, HLA DR/DQ phenotype frequency, or thyroid growth-stimulating immunoglobulin (TGI) positivity. Median UI was 32 microg/g creatinine with 65.0% having values consistent with iodine deficiency (< 50 microg/g). When results were expressed as micrograms per deciliter, the percentage having values consistent with iodine deficiency (< 5.0 microg/dl) increased to 95.7%. The findings suggest a primary role for iodine deficiency in goitrogenesis in the study population. They demonstrate that classification of the severity of the endemia in this or other study populations in areas of iodine deficiency is dependent on the methods used to determine goiter prevalence (palpation or ultrasound measured thyroid enlargement), or dietary iodine status (iodine excretion expressed as micrograms per gram creatinine or micrograms per deciliter urine).

Adolescent↗
PubMed1999

Development of a luminescent bioassay for thyroid stimulating antibodies.

The hyperthyroidism of Graves Disease (GD) is due to thyroid stimulating antibodies (TSAb) which are thyrotropin (TSH) agonists. They are detected routinely by measuring their ability to inhibit TSH binding to the receptor (TBII), which does not reflect their true biological activity. Current bioassays which measure cAMP by RIA, are not suitable for routine use. We have developed a luminescent bioassay for TSAb, by introducing a cAMP responsive luciferase construct into CHO cells stably expressing the human TSH receptor (TSHR). Clone lulul displays dose dependent TSH response detectable from 10 microU/ml and maximal at 10 mU/ml when a >25 fold increase in light output is obtained. 34 euthyroid sera were tested to determine a reference range, with values >1.5 relative light units (R.L.U.) being considered positive. An international TSAb standard responded in a dose dependent manner with 10 mIU/ml giving an R.L.U. of >10. The assay was adapted to a 96 well format for automatic readout and 100 treated GD samples (50 TBII negative and 50 TBII positive) were tested, 73% being positive. In contrast only 4% of 79 control sera from individuals with Hashimoto's, non-thyroid autoimmunity or multinodular goitre produced R.L.U. >1.5. When 44 of the GD sera were compared in a traditional salt-free bioassay, 61% were positive compared with 75% in the new luminescent assay. In conclusion, we have developed a luminescent bioassay for TSAb, using unfractionated serum which is capable of high throughput suitable for routine use.

Animals↗
PubMed1999

Undetectable urinary free cortisol concentrations in a case of Cushing's disease.

Measurement of the 24-h urinary free cortisol is a valuable screening test of endogenous hypercortisolism and, although false positive results may occur in a few situations, for example endogenous depression, false negative results are unusual. We report a case of a 48-year-old lady with pituitary-dependent Cushing's disease, whose 24-h urinary free cortisol excretion was consistently undetectable in association with increased plasma and salivary cortisol concentrations and reduced dexamethasone suppressibility. The patient had chronic renal impairment (creatinine clearance 21 ml/min) as a consequence of hypertension, despite only modestly increased urea and creatinine concentrations. Urinary free cortisol measurements must be interpreted with caution in patients with renal impairment.

Creatinine↗
PubMed1999

Cardiac transplantation in over 1000 patients: a single institution experience from Columbia University.

Since 1977, the cardiac transplantation program at Columbia has performed 1,137 heart transplant operations with a current one-year survival rate of approximately 90% and a 5-year survival rate of approximately 75% representing the largest single institution experience in North America. Over 2 decades of experience in the selection of donors and recipients has permitted us to expand eligibility limits and relax conventional exclusion criteria allowing us to transplant high-risk donors and medically complex recipients with excellent results. Recipient characteristics, rather than those of the donor, substantially impact outcome following OHT and use of extended donors will improve allocation of donor organs particularly with marginal recipients. During the 2-decade long evolution in our transplant experience, substantial improvements have been made in the areas of immunosuppression, treatment of rejection, and handling of sensitized recipients. Frequent causes of late mortality such as graft rejection, infection, malignancy, and TCAD, have been significantly diminished in the modern area of immune manipulation but remain major causes of death and barriers to long-term survival. The single biggest impediment to growth in OHT is the shortage of donor organs. We have attempted to address this issue by identifying patients who may be better served with a bridging surgical procedure such as a mechanical assist device, or alternative procedures such as transmyocardial laser revascularization, high-risk reparative surgery, or myocardial volume reduction operations. Ongoing research interests at Columbia including LVADs, immunologic sensitization, xenotransplantation, and vasculogenesis offer the potential for continued growth for treatment of end-stage heart disease into the next millennium.

Actuarial Analysis↗
PubMed1998

Disease surveillance at district level: a model for developing countries.

For over a decade we have maintained within a district of 5 million people, a system of prompt reporting of cases of childhood vaccine-preventable diseases, encephalitis, meningitis, hepatitis, and rabies; together with a sentinel laboratory surveillance of cholera, typhoid fever, malaria, HIV infection and antimicrobial-resistance patterns of selected pathogens. The system combined government and private sectors, with every hospital enrolled and participating. Reports were scanned daily on a computer for any clustering of cases. Interventions included investigations, immunisation, antimicrobial treatment, health education, and physical rehabilitation of children with paralysis. All vaccine-preventable diseases have declined markedly, whilst malaria and HIV infections have increased steadily. Annual expense was less than one US cent per head. The reasons for the success and sustainability of this model include simplicity or reporting procedure, low budget, private-sector participation, personal rapport with people in the network, regular feedback of information through a monthly bulletin, and the visible interventions consequent upon reporting. This district-level disease surveillance model is replicable in developing countries for evaluating polio eradication efforts, monitoring immunisation programmes, detecting outbreaks of old or new diseases, and for evaluating control measures.

Adult↗