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Biomedical subjects

H Adams

Publications and source records attributed to H Adams.

At least 37 records · Page 2Linked to original sources

Benign solitary fibrous tumour of the thigh: morphological, chromosomal and differential diagnostic aspects.

Solitary fibrous tumours (SFTs) are rare and usually benign neoplasms of mesenchymal origin that are often found in the visceral pleura (fibrous pleural tumour, FPT) or other serosal surfaces. They have also been found in soft tissues. We report the case of an SFT localised in the thigh of an 86-year-old woman. The tumour specimen was examined morphologically, immunohistochemically and molecular genetically, using comparative genomic hybridisation (CGH). The latter detects unbalanced chromosomal alterations in human neoplasms by competitive nucleic acid hybridisation and consecutive computer image analysis. The tumour consists of fibroblast-like cells, arranged in a typical "patternless pattern". Immunohistochemically, the tumour stained positively for vimentin, CD34, CD99, and focally for actin and desmin. No reaction occurred with keratin or S100 protein antibodies. CGH detected a single loss on chromosome 13q.

Aged↗

Patterns of chromosomal imbalances in benign solitary fibrous tumours of the pleura.

Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise 12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible genes involved in early tumorigenesis.

Aged↗

New hypointense lesions on MRI in relapsing-remitting multiple sclerosis patients.

BACKGROUND: Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability. OBJECTIVE: We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial. METHODS: Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics. RESULTS: At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS > or = 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction. CONCLUSIONS: Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients' clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.

Cladribine↗

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↗

Quantitative tissue sodium concentration mapping of the growth of focal cerebral tumors with sodium magnetic resonance imaging.

Tissue sodium concentration (TSC), as determined by in vivo 23Na magnetic resonance imaging (MRI) and the ex vivo classical 22Na radionuclide dilution assay (RDA), has been compared in a rat model of a focal glioma. The 23Na MRI method used a three-dimensional, twisted projection acquisition scheme at short echo time to minimize signal losses from relaxation of transverse magnetization. Calibration standards within the field of view allowed quantification of the sodium signal in terms of a TSC after correction for B1 nonuniformity and tissue water concentration. The 23Na MRI method measured focally increased TSC values in tumors that were equivalent statistically to the destructive 22Na RDA method. The noninvasive 23Na MRI method provided a quantitative means with which to monitor focal brain tumor growth.

Animals↗

Immunocytochemical localization of a calmodulinlike protein in Bacillus subtilis cells.

To determine possible functions of the calmodulinlike protein of Bacillus subtilis, the time course of its expression during sporulation and its cellular localization were studied. The protein was expressed in a constitutive manner from the end of logarithmic growth through 8 h of sporulation as determined by antibody cross-reactivity immunoblots and enzyme-linked immunosorbent assays (ELISAs). In partially purified extracts, the immunopositive protein comigrated upon electrophoresis with a protein which selectively bound [(45)Ca]CaCl(2), ruthenium red, and Stains-all. Previous studies showed increased extractability of the calmodulinlike protein from B. subtilis cells when urea and 2-mercaptoethanol were used in breakage buffers, implying that the protein might be partially associated with the membrane fraction. This was confirmed by demonstrating that isolated membrane vesicles of B. subtilis also gave positive immunological tests with Western blotting and ELISAs. To more precisely locate the protein in cells, thin sections of late-log-phase cells, sporulating cells, and free spores were reacted first with bovine brain anticalmodulin specific antibodies and then with gold-conjugated secondary antibodies; the thin sections were examined by transmission electron microscopy. The calmodulinlike protein was found almost exclusively associated with the cell envelope of these fixed, sectioned cells. A possible function of the calmodulinlike protein in sensing calcium ions or regulating calcium ion transport is suggested.

Animals↗

A comparison of barium swallow and erect esophageal transit scintigraphy following balloon dilatation for achalasia.

We evaluated the relationship between radionuclide esophageal transit studies and barium swallow appearances in a group of patients following forceful balloon dilatation for the treatment of achalasia of the cardia. Paired erect radionuclide esophageal transit studies and erect barium swallows of a group of patients who had undergone pneumatic balloon dilatation for the treatment of achalasia were analyzed. Indices derived from the radionuclide transit study were the percentage of maximum activity remaining in the esophagus 30 s after swallowing a dilute volume of tracer (A30 s) and the percentage of retained activity remaining at 100 s after washout with a bolus of water (A100 s). Indices derived from the barium swallow were a subjective grading of the degree of esophageal dilatation on a 4-point scale and a similar grading of the maximum distensibility of the gastroesophageal channel. Twenty five pairs of radionuclide and barium studies in 18 patients were analyzed. There was statistically significant correlation between the amount of retained activity on the radionuclide studies and degree of esophageal dilatation on the barium studies (r = 0.69 for A30 s, r = 0.56 for A100 s, P = < 0.01). There was no correlation between the amount of retained activity on the radionuclide studies and the degree of distension of the gastroesophageal channel on barium studies. The relationship between the radionuclide esophageal transit curve and barium appearances of the esophagus following pneumatic balloon dilatation for the treatment of achalasia is complex. The transit study provides unreliable information about the distensibility of the gastroesophageal channel and should not be relied upon in isolation for assessment of the efficacy of treatment.

Adolescent↗

Management of tuberculosis in Wales: 1986-92.

OBJECTIVES: To describe the epidemiology of childhood tuberculosis in Wales and to assess the standard of management of patients with tuberculosis. DESIGN: Retrospective study of data retrieved from case notes and review of radiographs of all identified patients. SUBJECTS: Forty eight cases of tuberculosis and 10 of tuberculosis chemoprophylaxis in children under 15 years of age, in Wales, between January 1986 and December 1992. MAIN OUTCOME MEASURES: Management of childhood tuberculosis in Wales compared with the published recommendations of the Joint Tuberculosis Committee of the British Thoracic Society. RESULTS: Documentation was poor in most of the 48 cases of tuberculosis and only 31 (65%) were formally notified. One third of patients were asymptomatic and were detected by contact tracing; only eight (17%) were culture positive. Only 20% of patients from ethnic minorities had previously been immunised with BCG. Management and chemotherapy varied widely. Few patients were managed jointly by paediatricians and chest doctors. Only 10% completed treatment with a recommended chemotherapy regimen. In 37% of patients treatment was inadequate, and in the remainder either the choice of drugs or the duration of treatment was inappropriate. No patient died, nor had any relapsed by June 1995. CONCLUSIONS: Very few cases of childhood tuberculosis were managed according to the recommendations of the British Thoracic Society.

Adolescent↗

Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass.

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

Adolescent↗

The lipase from Staphylococcus aureus. Expression in Escherichia coli, large-scale purification and comparison of substrate specificity to Staphylococcus hyicus lipase.

The genes coding for the mature part of the lipases from Staphylococcus aureus NCTC8530 and Staphylococcus hyicus have been cloned and overexpressed in Escherichia coli as fusion proteins with an N-terminal hexa-histidine tag. The enzymes accumulated in the cytoplasm and were purified using sequential precipitation with protamine sulphate and ammonium sulphate, followed by metal-affinity and hydroxyapatite chromatography. The yield of pure lipase was 4.5 mg/g wet cells for S. aureus lipase and 13 mg/g for S. hyicus lipase. The purified enzymes need calcium for activity, albeit with different affinities, and a low residual activity was found in the absence of calcium. In contrast to S. hyicus lipase, not only strontium but also barium can replace calcium with full retention of activity of S. aureus lipase. Whereas S. hyicus lipase is optimally active at pH 8.5, the optimum pH for enzymatic activity for S. aureus lipase was found to be pH 6.5. The S. aureus lipase has a narrow substrate specificity: short-chain triacylglycerols and acyl esters of both p-nitrophenol and umbelliferone are readily degraded, whereas medium- and long-chain lipids, as well as phospholipids, are poor substrates. In contrast, S. hyicus lipase prefers phospholipids as substrate and hydrolyses neutral lipids irrespective of their chain length. The results are discussed in view of the large sequence similarity between both lipases.

Esters↗

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↗

Case report: paediatric intramuscular haemangiomata--don't overlook the phlebolith!

Three children presented with soft tissue masses which were clinically suspected to be soft tissue sarcomas. The identification of phleboliths on initial radiological studies should have suggested the correct diagnosis of benign intramuscular haemangiomata. Subsequent referral to a paediatric oncological unit, and the unnecessary parental anxiety so generated, could have been avoided.

Calculi↗

The iodide perchlorate discharge test in women with previous post-partum thyroiditis: relationship to sonographic appearance and thyroid function.

BACKGROUND: Post-partum thyroid disease occurs in 50% of anti-thyroid peroxidase (TPO) antibody positive women (detected at 16 weeks' gestation) and is characterized by a transient episode of hyper, hypo or hyper-hypothyroidism. In approximately 20% of these women the hypothyroidism is permanent. However, the extent of long-term thyroid dysfunction, possibly mediated by immune attack, in those anti-TPO Ab + ve women who have had only transient or no thyroid dysfunction during the postpartum period is not clear. OBJECTIVE: We have therefore studied the frequency of iodide organification defects by iodide perchlorate discharge testing, and of thyroid morphological abnormalities by ultrasound scanning in euthyroid women following their episode of post-partum thyroiditis (PPT). DESIGN: The study group comprised 17 women with previous PPT (PPT + ve) and 12 women who had positive anti-TPO antibodies during pregnancy but who did not develop PPT (PPT - ve). Women were studied 15-47 months following their episode of PPT. RESULTS: Iodide perchlorate discharge tests were positive (more than 10% discharge) in 7 (41%) PPT + ve and 5 (42%) PPT-ve subjects (P = NS). Morphological abnormalities on thyroid ultrasound were detected in 7 of 14 (50%) PPT + ve and 7 of 9 (77%) PPT - ve subjects (P = NS). There was a strong association between abnormalities of iodide organification and morphology: of 11 subjects with positive iodide perchlorate discharge tests, 10 had abnormal (positive) ultrasound scans; of 12 subjects with negative iodide perchlorate discharge tests 8 had negative ultrasound scans (P = 0.013, Fisher's exact test). CONCLUSIONS: Long-term subtle defects of thyroid function and morphology are common in women with anti-TPO antibodies in pregnancy, whether or not they develop post-partum thyroiditis. The clinical significance of these findings is unclear but a continuing thyroid pathological process is suggested.

Adult↗

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↗

Preoperative staging of carcinoma of the bronchus: can computed tomographic scanning reliably identify stage III tumours?

BACKGROUND: The aim of preoperative computed tomographic (CT) assessment of patients with carcinoma of the bronchus is to stage the tumour accurately, and forewarn the surgeon of any possible local extrapulmonary extension of tumour in patients considered to have potentially resectable disease. The ability of CT scanning to differentiate between conventionally resectable lung cancer (TNM stages I and II), locally advanced but resectable lung cancer (TNM stage IIIa), and locally advanced but unresectable lung cancer (TNM stage IIIb) was determined in a group of patients accepted for surgery. METHODS: Computed tomographic scans of 110 patients who underwent thoracotomy for intended resection of carcinoma of the bronchus, including 52 cases with stage III and 58 cases with stage I or II disease, were reviewed and the CT features and radiological interpretations correlated with the surgical and pathological findings. RESULTS: Thirteen CT scans were judged not to have been of diagnostic quality: of the remaining 97 cases 45 had stage III lung cancer, of whom 30 had successful resections, and 52 had stage I or stage II tumours. There was no difference in the frequencies of CT observations--including contiguity of tumour and mediastinum or chest wall, apparent mediastinal or chest wall invasion, proximity of tumour to the carina, mediastinal nodal enlargement, pulmonary collapse or consolidation and pleural effusion--in patients with stage I/II disease and patients with stage III disease. Similar results were found when the same observations were compared in all patients with resected disease and those with unresectable tumour. Sensitivity and specificity of CT was 27% and 96% respectively for tumour unresectability, 50% and 89% for mediastinal invasion, 14% and 99% for chest wall invasion, and 61% and 76% for mediastinal nodal metastases. Only 19 of 45 stage III tumours were correctly identified as being stage III and resectable or unresectable. CONCLUSIONS: In patients being considered for thoracotomy for resection of lung cancer, CT scanning used as the sole method of staging is of limited value for differentiating between stage I/II and stage III tumours. Patients should not be denied the opportunity for curative surgery on the basis of equivocal CT signs.

Carcinoma, Bronchogenic↗

Client variables associated with selection and outcome in a methadone tapering program.

Based on archival information on 36 methadone maintenance patients, indicators of success in a methadone tapering program were investigated. None of the variables selected for study were found to differentiate successful from unsuccessful taperers. However, patients who were offered the opportunity to participate in the tapering program had significantly fewer years of heroin use prior to their admittance to a methadone maintenance program than patients in the general methadone maintenance population. In addition, the racial composition of patients attempting to taper included significantly fewer Black patients than the racial composition of the general methadone maintenance population. Possible explanations are offered.

Adult↗

The effect on apparent size of simulated pulmonary nodules of using three standard CT window settings.

This study was undertaken to determine whether three commonly used combinations of CT display window settings permit accurate measurement of pulmonary nodule size during thoracic CT examination. Forty-five rounded nodules of synthetic material of approximate soft tissue density (+70 Hounsfield units; HU), varying in size from 5.8 mm to 21.4 mm, were suspended in surgical gauze (-900 HU to -950 HU) to simulate pulmonary nodules. CT images were obtained for each nodule using 10 mm and 2 mm CT collimation and the size of each nodule was measured at three window settings: (a) 'soft tissue setting': window width (WW) 400 HU, window level (WL) +20 HU; (b) 'lung setting'. WW 850 HU, WL -750 HU; (c) 'broad lung setting': WW 1350 HU, WL -550 HU. Measurements obtained using either lung setting were highly accurate irrespective of collimation while measurements obtained using soft tissue settings were inaccurate. The choice of display window settings is an important consideration when CT is used to assess the size of pulmonary nodules.

Humans↗