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Biomedical subjects

R John

Publications and source records attributed to R John.

At least 91 records · Page 5Linked to original sources

The concurrent prevalence of chloramphenicol-sensitive and multi-drug resistant Salmonella typhi in Vellore, S. India.

A multidrug resistant (MDR) variety of Salmonella typhi emerged as the cause of epidemic typhoid fever in some Asian countries including India, during the late 1980s. We faced the epidemic from April 1990 to the first quarter of 1993. However, during this period we continued to isolate chloramphenicol sensitive (CS) S. typhi also. The relative prevalences showed that the frequency of CS variety was unaffected by the epidemic of MDR variety. This is an unusual epidemiological pattern, which indicates that there may have been factors which favoured the epidemic of the MDR variety but not the CS one.

Chloramphenicol↗

The role of complement in the pathogenesis of postpartum thyroiditis: ultrasound echogenicity and the degree of complement-induced thyroid damage.

Postpartum thyroiditis (PPT) is a transient autoimmune thyroiditis occurring during the postpartum year that is characterized by circulating antithyroid antibodies, abnormal thyroid ultrasound echotexture, and episodes of hyperthyroidism, hypothyroidism, or both. In this study we examined the relationship between lymphocytic thyroiditis, as indicated by echotexture changes, and complement-activating thyroid autoantibodies. Thyroid ultrasound echotexture, thyroid function, and bioactive (complement-activating) thyroid peroxidase (TPO) antibodies have been measured in a group of 63 TPO antibody-positive women during the postpartum year. When the maximum bioactive TPO antibody activity recorded was compared with echogenicity and thyroid status, there was a correlation between hypoechogenicity, elevated antibody activity, and abnormal thyroid status (r = 0.72, p < 0.001). However, 7 cases showed severe ultrasound changes in the absence of any thyroid dysfunction (3 of these cases showed normal bioactive antibody activity), while 4 (all hyperthyroid PPT) showed thyroid dysfunction in the absence of any ultrasound changes. Within the euthyroid ultrasound normal group, bioactive TPO antibody activity remained low throughout the postpartum year. Antibody activity in the hypoechogenic euthyroid women was significantly elevated (p < 0.001) compared with the echo normal group, but was indistinguishable from the activity curve obtained in women whose PPT included a hypothyroid phase. The determination of echotexture by thyroid ultrasonography gives a useful, noninvasive measure of the degree of thyroiditis in these women. However, as a significant number of cases with severe changes in echotexture remained euthyroid, we conclude that the development of thyroid dysfunction is not an inevitable consequence of lymphocytic thyroiditis during the postpartum and suggests that other factors must also be involved in progression to overt thyroid dysfunction.

Autoantibodies↗

Increase in defibrillation threshold in non-thoracotomy implantable defibrillators using a biphasic waveform.

We have previously reported a chronic increase in defibrillation threshold in a non-thoracotomy implantable cardioverter-defibrillator (ICD) system using monophasic waveforms. To determine if this phenomenon is related to the lead system or the waveform used, we studied the chronic defibrillation threshold in consecutive patients receiving an ICD capable of delivering biphasic waveforms with the same lead system previously evaluated. Twenty-five patients received an ICD with biphasic shock waveform and have been followed for 4 to 15 months. All have undergone defibrillation threshold measurements using the identical testing protocol with biphasic waveforms at implant and at 2 months. Coronary artery disease was present in 15, idiopathic dilated cardiomyopathy in 9, and valvular heart disease in 1. The presenting arrhythmia was ventricular fibrillation in 11, ventricular tachycardia in 10, and syncope with inducible ventricular tachycardia in 4. The configuration of the shocking electrodes was randomized; the lead-only configuration was used in 14 patients (56%), and a subcutaneous patch was used in the remaining patients. Mean defibrillation threshold using a step-down technique was 9.8 +/- 1.0 J at implant, 13.2 +/- 1.6 J at 2 months, and 12.4 +/- 1.5 J at 6 months (p = 0.01 by analysis of variance). There was no change in clinical status, cardiac size, radiographic lead position, or impedance between implant and 2 months. These findings suggest the increase in defibrillation threshold in this ICD system is not related to the type of waveform used, but rather is a feature of non-thoracotomy as opposed to epicardial electrodes.

Adult↗

Removal of baboon and human antiporcine IgG and IgM natural antibodies by immunoadsorption. Results of in vitro and in vivo studies.

The safe and effective removal of xenoreactive antibodies in the peritransplant period is likely to be critical for the clinical application of xenotransplantation involving disparate donor species, such as the pig. In an effort to develop an improved method for antibody removal in xenotransplantation, we have studied reusable antihuman antibody (Ig) columns in vitro and in vivo. Two types of columns were tested: (1) an antihuman Ig column containing polyclonal sheep antihuman IgG (heavy- and light-chain-specific) conjugated to sepharose CL-4B (Ig-Therasorb), and (2) an antihuman Ig column using polyclonal antihuman IgM (mu-chain-specific) conjugated to sepharose. Passage of human or baboon plasma through the Ig-Therasorb column resulted in 97.5% and 78.4% mean reductions in total IgG and IgM, respectively. Reductions in total IgG and IgM correlated with lowering of antipig IgG (54-486 fold) and IgM (9-54 fold) antibody titers as assessed by pig endothelial cell ELISA. The ability of the Ig-Therasorb to significantly reduce IgM may be attributed to the light chain specificity of this column. With the anti-IgM column, marked reductions in total (82.6-83.9%) and antipig (27-54 fold) IgM in human and baboon plasma occurred, while levels of total and xenoreactive IgG were slightly affected. Other than a dilutional effect, neither column resulted in significant reduction in albumin, fibrinogen, factor 5, and factor 8. Repeated in vivo use of either column in baboons achieved reductions in IgG and IgM that closely followed the results of our in vitro studies. No subject morbidity or mortality occurred. Use of the Ig-Therasorb column with immunosuppression in two baboons receiving pig renal xenografts achieved sustained reductions in antipig antibodies and prevented hyperacute rejection. Subjects were sacrificed at 11 and 13 days posttransplant with functioning xenografts and were found to have no evidence of vascular xenograft rejection. We conclude that anti-Ig columns represent a safe and effective method for antibody removal, without several of the limitations of other antibody removal techniques. Also, columns appear to be safe for repeated antibody removal in the posttransplant period.

Acute Disease↗

Antibody removal by column immunoabsorption prevents tissue injury in an ex vivo model of pig-to-human xenograft hyperacute rejection.

Hyperacute rejection of a pig-to-primate organ xenograft is triggered by binding of anti-pig endothelial cell antibodies to the vascular endothelium of the xenograft and complement activation. Xenograft survival can be prolonged by pretransplant depletion of antibody with plasmapheresis or organ perfusion. However, these techniques have disadvantages for use immediately pretransplant or in the post-transplant period, including a marked reduction in coagulation proteins. To remove IgM and IgG from human plasma we employed a reusable Ig-binding column containing polyclonal anti-human IgG (heavy chain- and light chain-specific) conjugated to Sepharose beads (Therasorb, Baxter Corp.). Human blood was separated into plasma and cell fractions. Column absorption of plasma followed by recombination of plasma and cell fractions in the perfusion system resulted in 90.5 and 86.0% reduction in total IgG and IgM, respectively, and in a 47.0 and 69.4% reduction in IgG and IgM anti-pig endothelial cell antibodies, respectively. When the cellular fraction was recombined with untreated plasma and used to perfuse pig hearts in an ex vivo perfusion system, there was rapid cessation of normal cardiac rhythm (25.2 +/- 5.6 min) and intense deposition of Igs, complement proteins, and fibrin in the tissues. In contrast, perfusion with blood containing column-absorbed plasma was able to sustain cardiac function, with normal sinus rhythm maintained for 258 +/- 48.1 min, without tissue deposition of IgM or complement proteins and minimal deposition of IgG. We conclude that column absorption can be used effectively to deplete plasma of anti-pig endothelial cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Risk-taking and abusive behaviors among ethnic minorities.

The health status and health outcomes of many ethnic minorities have remained poor, or have deteriorated, despite massive health promotion campaigns. Multiple factors that encourage ethnic minorities to engage in high-risk behaviors and those that discourage health promotive behaviors must be closely examined before any health interventions are likely to be successful in decreasing substance abuse, high-risk sex, accidental deaths and injuries, and violence. Cultural and contextual factors may put some ethnic minorities in jeopardy and at higher risk for poorer health than their White counterparts (B. W. K. Yee, 1995, in press). This review article identifies contributing factors in high-risk behaviors and highlights research gaps for Americans of African, Indian, Asian and Pacific Islander, and Hispanic descent.

Adolescent↗

Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression.

The aim of this study was to assess whether the presentation and progression of autoimmune postpartum thyroiditis (PPT) was related to the degree of thyroid peroxidase autoantibody (TPO-ab)-mediated activation of the complement cascade. One hundred and forty-eight thyroid autoantibody-positive women have been followed during their postpartum year. Seventy-five women remained euthyroid during this time whilst the remaining 73 showed one or more episodes of thyroid dysfunction. Fourteen women showed hyperthyroid PPT, 23 showed a biphasic PPT and the remaining 36 showed hypothyroid PPT. Hyperthyroid PPT was always transient but 29 of the 59 women with hypothyroidism remained hypothyroid or still required thyroxine replacement therapy at the conclusion of the study. Thyroid autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), free triiodothyronine and free thyroxine by the Amerlex M methods and thyrotrophin by the Amerlite TSH (monoclonal) assay. Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA. Bioactive TPO-ab were calculated as the product of the C3 index and TPO-ab level. Basal levels of complement C3 activation were seen in the euthyroid TPO-ab-positive women (C3 index 0.06 at delivery rising to 0.36 at 12 months postpartum; bioactive TPO-ab activity 0.4 kIU/l at delivery rising to 10.4 kIU/l at 12 months' postpartum (N = 75). These parameters were elevated progressively as the severity of the clinical syndrome increased. In 14 hyperthyroid PPT women the C3 index was 0.47 at 8 months' postpartum (bioactive TPO-ab activity = 20 kIU/I; p vs euthyroid group, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Perceptions of acute care nurses in the use of restraints.

1. Staff nurses continue to use physical restraints in well-intended efforts to protect patients from potential harm despite the overwhelming evidence of negative consequences from this practice. The use of physical restraints remains an unresolved clinical practice issue. 2. This stratified, random sample demonstrated that LPNs consistently attached greater importance to the use of restraints than either RNs or Managers, suggesting that the educational level of nurses may have an impact on the continued use of physical restraints. 3. The survey further demonstrates that nurses are aware of many alternatives to restraint use. The authors suggest that alternatives may not be widely used because the measures are often not considered practical.

Acute Disease↗

Pituitary stone: two cases of densely calcified thyrotrophin-secreting pituitary adenomas.

Calcification is a well recognized but relatively uncommon feature of prolactin-secreting, growth hormone-secreting and non-functional pituitary tumours. It varies in extent, but rarely exceeds a tiny amount histologically or radiologically. Thyrotroph adenomas are the rarest of the secretory pituitary tumours, accounting for less than 1% of cases, and partial calcification of such lesions has been reported in only three cases. We describe two patients in whom the clinical and biochemical features indicated the presence of a TSH-secreting adenoma and radiology demonstrated a large 'pituitary stone'. One patient, a 59-year-old female, initially presented with hyperthyroidism, aged 18, and was rendered euthyroid by two subtotal thyroidectomies before a pituitary lesion was suspected, over 20 years later. Autonomous secretion of thyrotrophin was demonstrated by dynamic tests, and the failure of exogenous T3 to reduce the serum TSH. In the absence of tumour expansion and compressive symptoms, pituitary surgery was not undertaken. At the age of 56, she developed symptoms of intermittent ataxia and diplopia, culminating in a focal seizure, and was found on CT scan to have, in addition to the pituitary lesion, a parasagittal meningioma. This was successfully removed at craniotomy. In the second patient, a 42-year-old male, the finding of hyperthyroidism in association with an elevated TSH concentration led to the discovery of a pituitary stone which was removed transethmoidally, together with surrounding adenomatous tissue which stained positively for TSH on immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Serum thyroglobulin: an early indicator of autoimmune post-partum thyroiditis.

OBJECTIVE: The aim of this study was to assess whether autoimmune thyroid damage in post-partum thyroiditis was accompanied by a significant rise in the concentration of thyroglobulin in the serum and whether its measurement could be useful in the prediction of the risk and severity of an episode of post-partum thyroid dysfunction. PATIENTS: Fifty-one women, who had taken part in a larger survey of post-partum thyroiditis, were selected at random for this study. Fourteen women without elevated circulating thyroid autoantibodies and 21 with raised thyroid autoantibodies remained euthyroid throughout the post-partum year. A third group of 14 women had raised thyroid autoantibody levels and showed one or more episodes of thyroid dysfunction during the course of the first year post partum. MEASUREMENTS: Thyroid autoantibodies were measured by ELISA, free T3 and free T4 by the Amerlex M method and TSH by an immunoradiometric method. Serum thyroglobulin was measured by a method free from interference by circulating endogenous thyroglobulin autoantibodies. Thyroid ultrasonography was performed using a General Electric RT3600 scanner operating at 7.5 MHz. RESULTS: Fourteen control women had a mean serum thyroglobulin concentration of 3.3 micrograms/l (SD 4.4; range < 1-12 micrograms/l; 95% confidence interval up to 6.0 micrograms/l). Twenty-one thyroid autoantibody positive euthyroid women had a mean serum thyroglobulin level of 5.8 micrograms/l (SD 6.2; range < 1-36 micrograms/l) which was not significantly different from that seen in the control group. Sixteen thyroid autoantibody positive women who showed one or more episodes of thyroid dysfunction during the post-partum period had a mean serum thyroglobulin of 31 micrograms/l (SD 24.8; range up to 88 micrograms/l) and this was significantly elevated compared with both the control and antibody positive groups (P < 0.001). Serum thyroglobulin concentrations at 3 months post partum correlated with the degree of post-partum hypothyroidism (as indicated by the maximum TSH and the minimum free thyroxine concentrations post partum) and, in those cases where thyroid ultrasound examinations were performed, with the degree of lymphocytic infiltration of the thyroid gland. CONCLUSIONS: The data presented in this paper confirm the destructive nature of post-partum thyroiditis and indicate that the measurement of serum thyroglobulin concentration could assist in the identification of those women at risk of post-partum thyroiditis.

Autoantibodies↗

The role of complement in the pathogenesis of postpartum thyroiditis.

Postpartum thyroiditis (PPT) affects half of the 10% of women who have elevated circulating thyroid autoantibodies during the postpartum year. Because of the similarities between PPT and Hashimoto's thyroiditis, the pathogenic role of complement in PPT has been investigated. Complement fixation by thyroid peroxidase antibodies (TPO Abs) (expressed as log reciprocal titer) in serum from euthyroid TPO Ab-positive women (n = 29) was 0.91 at 1 month postpartum and increased to 1.45 by 12 months postpartum; complement C3 activation, measured by enzyme-linked immunosorbent assay, in a similar group of women (n = 75) was 0.05 at delivery and increased to 0.33 by 6 months postpartum. In women with PPT, there was greater TPO Ab-related complement activation during the postpartum year; complement fixation increased from 1.00 at 1 month postpartum to 1.48 at 4 months postpartum (P < 0.005) (n = 25), and C3 activation increased from 0.11 at delivery to 0.63 at 6 months postpartum (P < 0.005) (n = 73). Bioactive TPO Ab (TPO Ab x C3 index) was significantly higher in PPT women (55 kilo international units of activity (kIU)/L at 6 months postpartum) (Hashimoto range, 30-108 kIU/L) compared with euthyroid TPO Ab-positive women (< 9 kIU/L at all time points; P < 0.005). Serum samples from TPO Ab-negative control women showed no interaction with complement in either assay at any time during the postpartum year (complement fixation < 0.7; complement C3 activation index < 0.01). This detailed examination of the role of complement in the pathogenesis of PPT shows that TPO Ab-driven complement fixation is a marker for thyroid dysfunction in TPO Ab-positive women. The levels of bioactive TPO Ab in PPT fall within the range seen in Hashimoto's thyroiditis, suggesting similarities in their pathology.

Autoantibodies↗

An insoluble aggregate of commercially available bovine serum albumin shows antiproteolytic activity.

Chemical aggregation of bovine serum albumin by extensive chemical crosslinking with glutaraldehyde yielded an insoluble protein preparation with significant antiproteolytic activity. This was presumably due to the presence of alpha 2-macroglobulin in bovine serum albumin preparations. Chemical crosslinking of bovine serum albumin under optimum conditions was found to increase its antitryptic activity by about four times. The results indicate that enhanced rigidity of alpha 2-macroglobulin structure increases its antitryptic activity.

Animals↗

Unusual manifestations of salmonellosis--a surgical problem.

From January 1981 to December 1992, of 6250 cases of salmonellosis treated at the Christian Medical College and Hospital, Vellore, India, 100 patients with focal pyogenic infection caused by salmonellae required surgical intervention in addition to medical therapy. Thirty-one had involvement of the hepatobiliary system, and 10 more had other intra-abdominal infections. Involvement of bone and joint as well as soft tissue constituted 15% each. The site of infection in patients with soft tissue abscesses included skin (7), parotid (2), thyroid (2), breast (1) inguinal node (1), branchial sinus (1) and injection site (1). Three patients had arterial infections. Noteworthy among the cases of genital infections was one case of salmonella infection in a pre-existing hydrocele, and one case of epididymo-orchitis with a loculated salmonella infection. Salmonella infection in a pre-existing ovarian cyst was seen in a patient with endometriosis. The salmonella serotypes most frequently encountered were S. typhi (36) and S. typhimurium (36), followed by S. paratyphi A (15). The importance of recognition of these protean manifestations of salmonellosis in an endemic setting is discussed. The microbiological evaluation of properly obtained specimens is mandatory in such unusual pyogenic infections.

Abscess↗

Salmonellosis complicating aortic aneurysms.

We present our experience with two cases of salmonella infected aortic aneurysms. The treatment of salmonella infected aortic aneurysms has been associated with a high mortality, primarily due to the rapidity with which the post-infective complications of salmonellosis develop. Early diagnosis, adequate anti-microbial therapy and improved vascular surgical methods have resulted in a better prognosis for salmonella infected aortic aneurysms.

Aneurysm, Infected↗