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Biomedical subjects

H Stevens

Publications and source records attributed to H Stevens.

At least 19 recordsLinked to original sources

Bioactive hydroxyphenylpyrrole-dicarboxylic acids from a new marine Halomonas sp.: Production and structure elucidation.

The new marine Halomonas sp. strain GWS-BW-H8hM (DSM 17996) was found to produce 3-(4'-hydroxyphenyl)-4-phenylpyrrole-2,5-dicarboxylic acid (HPPD-1) and 3,4-bis(4'-hydroxy- phenyl)pyrrole-2,5-dicarboxylic acid (HPPD-2). In initial cultivations using marine broth, only low contents of these compounds have been isolated. Improving the conditions and growing the strain on artificial seawater supplemented with tryptone 10 g l(-1), yeast extract 5 g l(-1), L-tyrosine 0.6 g l(-1), glycine 1 g l(-1), and glucose 6 g l(-1), the growth-associated HPPD-1 and HPPD-2 production of a 40-l batch cultivation reached the amounts of 47 mg l(-1) and 116 mg l(-1), respectively, after 65 h. Both compounds showed potent anti-tumor-promoting activities.

Anticarcinogenic Agents↗

The cardiovascular and respiratory health of people with schizophrenia.

OBJECTIVE: To examine the cardiovascular and respiratory health of people with severe mental illness (SMI) and compare findings with the Health Surveys for England. METHOD: A prospective, multi-centre observational prevalence study of 602 patients with schizophrenia-related psychoses carried out in six locations across the UK over 24 months. RESULTS: Compared with general population subjects, people with SMI reported higher rates of angina and respiratory symptoms and had poor lung function. Much of this increased risk could be explained by lifestyle risk factors; there were increased levels of obesity among younger people with SMI. CONCLUSION: Key indicators of the cardiovascular and respiratory health of people with SMI are poor compared with those of the general population. Care plans should prioritize interventions to attenuate lifestyle risk factors. Evidence of increasing obesity in younger patients is of particular concern, predicting even greater health needs in the future.

Adolescent↗

The dental health of people with schizophrenia.

OBJECTIVE: To examine the dental health of community dwelling people with schizophrenia and to compare results with those in the general population. METHOD: Dental health of 428 people with schizophrenia in six different areas of the UK was assessed by a self-report questionnaire. RESULTS: Compared with the general population, significantly more of the younger patients were edentate (3-39% vs. 1-20%) and fewer had more than 20 teeth (70% vs. 83%). None of four dental health targets had been achieved in the patient population. More patients had last visited the dentist because of trouble with their teeth; fewer had visited for a check-up. Fewer patients cleaned their teeth daily; this group had more negative symptoms. CONCLUSION: The dental health of people with schizophrenia is poor. Community mental health teams should encourage them to attend their community dentist regularly.

Adult↗

An autosomal recessive exfoliative ichthyosis with linkage to chromosome 12q13.

A new variant of congenital exfoliative ichthyosis in two related Bedouin families is reported. The ichthyosis appeared shortly after birth as a fine peeling of nonerythematous skin on the palms and soles. The prominent well-demarcated areas of denuded skin in moist and traumatized regions resembled the 'mauserung' phenomenon of ichthyosis bullosa of Siemens (IBS). Unlike in IBS, epidermolysis is absent on histological examination. Electron microscopy revealed a prominent intercellular oedema and numerous aggregates of keratin filaments in basal keratinocytes. Abnormal keratin (K) 1 expression was seen in the affected epidermis; however, all other keratins, including K2e, had a distribution comparable to that seen in normal controls. A maximum two-point LOD score of 2.53 and multipoint LOD score of 3.76 were obtained for marker D12S390, suggesting linkage to the type II keratin cluster on chromosome 12q13. Sequencing of both the K1 gene, the promotor and the 3' calcium regulatory region did not reveal a mutation. K2e and K5 genes, as well as the genes harboured within the minimal region, such as retinoic acid receptor gamma, sterol O-acyltransferase 2, integrin beta7 and insulin-like growth factor binding protein-6, were also excluded. This combination of clinical, histological, ultrastructural and genetic features has not been previously reported in other congenital exfoliative ichthyoses. We therefore suggest that it represents a new form of exfoliative ichthyosis.

Adolescent↗

Quantitative baseline renography 48 hours after renal transplantation predicts long-term graft survival.

Technetium-99m mercaptoacetylglycine (99mTc-MAG3) renography is a successful non-invasive method for the evaluation of renal transplants. In this study we prospectively studied 256 patients after renal transplantation, using the MAG3 uptake capacity in the first 10 min (MUC10), which is an index of renal function representing kidney activity as a fraction of the injected dose. Renal scintigraphy was performed in all patients within 48 h of transplantation. Renograms were obtained over 20 min, after bolus injection of +/-100 MBq 99mTc-MAG3. MUC10 ranged between 0.0 and 94.9. The patients were divided into five groups: group 1, MUC10 <1; group 2, 1< or =MUC10 < 5; group 3, 5 < or = MUC10 <10; group 4, 10 < or = MUC10 < 30; group 5, MUC10 > or =30. In 235 patients, follow-up for 5 years was completed. Considering all the renal transplants, 30% of the grafts ceased functioning within the first 5 years. Six grafts showed a MUC10 of < 1, and none survived the first year. After 5 years, 43% of the grafts with a MUC10 of 1-5 still functioned, as compared with 63% of those with a MUC10 of 5-10, 72% of those with a MUC10 of 10-30 and 83% of those with a MUC10 of > or =30. Kaplan-Meier survival analysis showed significant differences between the five different patient groups based on MUC10 in terms of the percentage of kidneys that ceased to function within 5 years. The period of cold ischaemia and the donor age were known in 178 patients. In contrast to cold ischaemia time, the MUC10 and the donor age showed a significant effect (P<0.05) on graft survival. This study indicates that the MUC10 early after renal transplantation is useful as a prognostic factor in the evaluation of kidney transplants and that a MUC10 of <1 indicates a dismal prognosis for the renal transplant.

Adult↗

Haplotype tagging for the identification of common disease genes.

Genome-wide linkage disequilibrium (LD) mapping of common disease genes could be more powerful than linkage analysis if the appropriate density of polymorphic markers were known and if the genotyping effort and cost of producing such an LD map could be reduced. Although different metrics that measure the extent of LD have been evaluated, even the most recent studies have not placed significant emphasis on the most informative and cost-effective method of LD mapping-that based on haplotypes. We have scanned 135 kb of DNA from nine genes, genotyped 122 single-nucleotide polymorphisms (SNPs; approximately 184,000 genotypes) and determined the common haplotypes in a minimum of 384 European individuals for each gene. Here we show how knowledge of the common haplotypes and the SNPs that tag them can be used to (i) explain the often complex patterns of LD between adjacent markers, (ii) reduce genotyping significantly (in this case from 122 to 34 SNPs), (iii) scan the common variation of a gene sensitively and comprehensively and (iv) provide key fine-mapping data within regions of strong LD. Our results also indicate that, at least for the genes studied here, the current version of dbSNP would have been of limited utility for LD mapping because many common haplotypes could not be defined. A directed re-sequencing effort of the approximately 10% of the genome in or near genes in the major ethnic groups would aid the systematic evaluation of the common variant model of common disease.

Base Sequence↗

Methotrexate osteopathy demonstrated by Technetium-99m HDP bone scintigraphy.

The authors report a case of methotrexate osteopathy as revealed by Tc-99m HDP bone scintigraphy in a patient with rheumatoid arthritis. Methotrexate is used widely in high doses as a chemotherapeutic agent. Lower doses are given in rheumatoid and psoriatric arthritis. Methotrexate affects bone metabolism, resulting in methotrexate osteopathy, characterized by osteoporosis, osseus pain, and even spontaneous (micro)fractures. Radiographic visualization of microfractures is difficult. Tc-99m HDP bone scans have been shown to be very sensitive in the visualization of changes in bone metabolism as a result of methotrexate osteopathy.

Antirheumatic Agents↗

Captopril renography and the relevance of abnormal but bilateral identical curves in the diagnosis of renal artery stenosis.

BACKGROUND: Captopril renography (CR) has been shown to improve the effectiveness of renal scintigraphy in renovascular hypertension, by inhibiting angiotensin-converting enzyme. CR is particularly sensitive and specific in unilateral renal artery stenosis (RAS), but results in patients with bilateral RAS are less favourable. The aim of this study was to investigate the meaning of abnormal but identical renographic curves in the diagnosis of RAS. PATIENTS AND METHODS: One hundred and fifty-eight patients clinically suspected for renovascular hypertension underwent CR, using 50 MBq (99)Tc(m)-mercaptoacetyltriglycine ((99)Tc(m)-MAG(3)), prior to performing renal angiography. CR was performed 1 h after captopril administration. Renograms were analysed according to the consensus criteria. All patients underwent angiography, considered as the "gold standard" in the detection of the presence of RAS (stenosis >50% was defined as significant). All kidneys were categorized into three groups, scintigraphically as well as angiographically: no stenosis, unilateral stenosis and bilateral stenosis. RESULTS: Out of 158 patients 100 (63%) showed a RAS on angiography (58 (37%) unilateral, 42 (26%) bilateral). The sensitivity and specificity of CR evaluated by patient was 83% and 75%, respectively. Thirty patients with completely identical curves were identified, 21 patients with normal curves and nine patients with abnormal identical curves. All but one patient showed no RAS on the angiogram. In this single patient a unilateral stenosis was found. CONCLUSION: Identical curves on the renogram generally suggest no RAS and are probably due to intrinsic parenchymal disease.

Adult↗

[Q fever: not just in sheep].

Four patients, a woman aged 41 years and 3 men aged 12, 47 and 44 years, developed high fever after returning from a farm vacation in the Ardèche (France). They also suffered from severe headache, a painful tightness of the chest, abdominal pain or myalgia. Other symptoms were shivers, tiredness and a cough. While physical examination revealed few abnormalities, the chest X-ray in 3 patients showed an atypical pneumonia. One of these patients developed dural venous sinus thrombosis with increased intraspinal pressure. This patient also showed signs of a slight hepatitis. Serological investigation revealed that all 4 patients were suffering from acute Q fever, a zoonosis caused by the Coxiella burnetii bacterium. All 4 had been present at lambing and sheep-shearing. The patients with pneumonia were treated with antibiotics. All 4 patients recovered well. It is known that animal birth products in particular can contain large numbers of bacteria and therefore be highly infectious.

Acute Disease↗

[Acute and chronic Q fever; epidemiology, symptoms, diagnosis and therapy of infection caused by Coxiella burnetii].

Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium. Domestic ungulates and parturient cats are the primary reservoirs of infection. The animals excrete the bacterium in urine, faeces, milk and amniotic fluid. After desiccation the micro-organism spreads via aerosols. After inhalation or ingestion and an incubation period of 2-6 weeks acute Q fever may develop with atypical pneumonia and hepatitis as major clinical symptoms. The infection also may present as a flu-like illness or remain asymptomatic. Generally, the prognosis is favourable. However, endocarditis or another chronic form of Q fever occasionally develops with possibly fatal outcome. Diagnosis relies upon serologic testing with an indirect immunofluorescence method. Doxycycline is the antibiotic of choice in the treatment of Q fever. Endocarditis needs therapy for years with the addition of rifampin or hydroxychloroquine. Q fever is poorly recognised due to the variety of clinical presentations.

Acute Disease↗

TB PCR in the early diagnosis of tuberculous meningitis: evaluation of the Roche semi-automated COBAS Amplicor MTB test with reference to the manual Amplicor MTB PCR test. .

SETTING: Cecilia Makiwane Hospital, Mdantsane, Eastern Cape, Republic of South Africa. OBJECTIVE: To assess the role of the semi-automated Roche COBAS AMPLICOR(TM)Mycobacterium tuberculosis PCR test in the diagnosis of tuberculous meningitis (TBM). DESIGN: Eighty-three specimens of cerebrospinal fluid (CSF) were collected prospectively from 69 patients with suspected TBM. The COBAS AMPLICOR TB PCR test was compared with the manual AMPLICOR(TM)TB PCR test, clinical and cerebrospinal fluid (CSF) findings, direct ZN smear and radiometric TB culture. RESULTS: CSF from 7/40 (17.5%) patients treated for TBM were positive by TB COBAS AMPLICOR(TM). The sensitivity of the test was not significantly different (p=0.375) from the manual TB AMPLICOR(TM)PCR test. The comparative sensitivities of the TB COBAS AMPLICOR(TM)PCR and the manual AMPLICOR PCR for detecting cases of definite and probable TBM from CSF collected within 9 days of commencing antituberculosis treatment were 40% and 60% respectively. All 29 patients not treated for TBM were negative by COBAS AMPLICOR(TM), giving a specificity of 100%. CONCLUSION: The COBAS AMPLICOR(TM)TB PCR test is a rapid and highly specific diagnostic test for TBM. However, there was a non-significant trend favouring slightly greater sensitivity using the manual AMPLICOR(TM)TB PCR test.

Adolescent↗

Empiric treatment based on Helicobacter pylori serology cannot substitute for early endoscopy in the management of dyspeptic rural black Africans.

BACKGROUND: Evidence that chronic gastric Helicobacter pylori (HP) infection is an aetiological factor in dyspepsia, peptic ulcer disease, gastric carcinoma and lymphoma has led to the suggestion that all serologically positive dyspeptic patients should be treated empirically with antibiotics to eradicate the infection, without endoscopic diagnosis. The following study was performed to determine whether such a policy would prove to be of benefit in rural Africa, where endoscopic facilities are lacking and infection rates high. METHODS: Four district clinics were visited and 97 consecutive patients with persistent upper gastro-intestinal symptoms studied. After history-taking and physical examination, a blood sample was taken for HP serology (IgG anti-HP EIA) and endoscopy was performed. RESULTS: In comparison with similar studies in westernised countries HP was considerably more common (80%), and similar to that reported for the background population (83-86%), but peptic ulceration (17%) and gastric cancer (1%) were not. HP status and antibody levels failed to predict the presence of serious disease; patients with 'alarm' signs (78%), cancer (78%) and peptic ulcers (81%) had similar seropositivity rates to patients with non-ulcer dyspepsia (81%). Interestingly, many patients with distal oesophagitis were seronegative (40%). Haemoglobin concentrations and nutritional status were similar in HP-positive and negative patients. On the basis of published decision analysis strategies, empiric treatment of HP-positive patients with uncomplicated dyspepsia could be expected to produce symptomatic relief in 50% of cases, but would have delayed the diagnosis of 3 cases of cancer if patients over the age of 45 were included. CONCLUSION: The lack of association between HP serology and upper gastro-intestinal disease indicates that serological investigation cannot substitute for endoscopy in the management of black Africans with dyspepsia, and that empiric anti-HP therapy cannot be justified.

Adolescent↗

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI.

Several studies have shown the feasibility of divalent cobalt (Co)-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and traumatic brain injury. Little is known how regional Co uptake relates to other pathophysiological changes after stroke. Therefore, we compared 55Co-PET with functional parameters such as regional cerebral blood flow (rCBF) using C(15)O(2), regional oxygen metabolism (rCMRO(2)) using 15O(2), regional cerebral blood volume (rCBV) and post-gadolinium (Gd) T(1)w-MRI to assess the permeability of the blood-brain-barrier (BBB). Sixteen patients (10 female; six male) aged 43 to 84 (mean 69) years with first ever stroke, as shown by CT or MRI, were examined with 55Co-PET and C(15)O(2)-, 15O(2)- and C(15)O-PET in one single session, in a period varying from 0 to 30 days after stroke-onset. Regions of infarction on C(15)O(2)- and 15O(2)-PET (defined by rCMRO(2)<65% or rCBF<45% of the contralateral value) were subsequently superimposed on the 55Co-PET scan. Clinical status was established using the Orgogozo stroke scale, which was assessed both at day 1 and at discharge (at least 6 weeks after day 1). Accumulation of 55Co was seen in eight out of 16 patients, occurring in areas showing a diminished oxygen metabolism, was only partially related to blood flow, and was located mainly outside the extent of the infarction or luxury perfusion as seen on post-Gd T(1)w-MRI. Statistical analysis showed a negative correlation between the Orgogozo score at discharge and the uptake of radioactive cobalt.

Adult↗

Comparison of COBE Spectra software version 4.7 PBSC and version 6.0 auto PBSC program.

Until recently, the collection of peripheral blood progenitor cells (PBPC) has been semi-automated by using the COBE Spectra, with the operator manually maintaining the position of the white cells being collected. The COBE Spectra Version 6.0 apheresis device offers the user an automated program for the collection of PBPC. In this study, we compared the new software Version 6.0 to that of Version 4.7. Patients (n = 46) undergoing PBPC collection were allocated to cell processing with either Version 4.7 (n = 24) or Version 6.0 (n = 22). The CD34+ cell count, mononuclear cell (MNC) count, white cell count (WCC), hemoglobin (Hb), and platelet content in the autograft product by using the two versions were compared. We divided the analysis into three subsets according to peripheral blood (PB) CD34 content: <10x10(6)/L, 10-50x10(6)/L and >50x10(6)/L. Analysis of the three subsets showed no statistical difference between results obtained when the starting PB CD34+ cell count was 10-50x10(6)/L (P=0.08) or >50x10(6)/L (P=0.4065). At lower starting PB CD34+ cell counts of <10x10(6)/L, Version 4.7 was superior (P=0.0167). However, autograft platelet contamination of the autograft was significantly higher using Version 4.7 (P=<0.0001).

Antigens, CD34↗

Neurone-specific enolase and N-acetyl-aspartate as potential peripheral markers of ischaemic stroke.

BACKGROUND: After stroke, brain-specific proteins (including neurone-specific enolase) leak into the blood. The question addressed in the present study was whether N-acetyl-aspartate (amino acid derivative localized in cerebral neurones) could also serve as a peripheral marker of ischaemic damage. N-acetyl-aspartate levels were determined in the blood of stroke patients and related to clinical outcome, volume of infarction and to serum neurone-specific enolase. METHODS: Blood samples from 19 patients (seven women, 12 men, mean age of 73 years, range 56-88 years) were collected during the first 4 days after stroke and analysed for neurone-specific enolase (radioimmunoassay) and/or N-acetyl-aspartate (mass spectrometry). Clinical outcome was assessed using the Glasgow Outcome Score, and volume of infarction was calculated using computerized tomography (CT). Control values of N-acetyl-aspartate, determined in six female and nine male volunteers (mean age 47.4 years; range 28-73 years) were 0.26 +/- 0.02 mumol L-1. RESULTS: The increase in serum N-acetyl-aspartate was highly significant (P < 0.0001) within the first 24 h and at 72 h after stroke and correlated (P < 0.05) with volume of infarction only in patients with a bad prognosis (Glasgow Outcome Score < 5). Serum N-acetyl-aspartate at 24 h and neurone-specific enolase at 72 h were negatively correlated, suggesting that more N-acetyl-aspartate reaches the blood when brain tissue is less irreversibly affected. CONCLUSION: Serum N-acetyl-aspartate appears to be an early peripheral marker of ischaemically affected brain neurones, and the ratio of N-acetyl-aspartate to a protein marker, such as NSE, may serve as an index of irreversibility.

Aged↗

Androgen receptors in bone-forming tissue.

Androgen receptors (AR) were stained in sections of normal human growth plate of the costo sternal junction obtained at postmortem from one 4-day-old and two 5-day-old male infants, and in osteoblasts, grown in culture obtained from the femora of 3 male patients undergoing orthopaedic surgery for osteoarthritis. In the growth plate AR were found mostly in a narrow band of chondrocytes occupying an area about midway between the proximal and distal end of the epiphysis. Nearly all AR were in the cytoplasm and appeared in a granular form; there was no diffuse staining and the nuclei were either completely devoid of AR or only contained a few. Less-differentiated chondroblasts, perichondrial cells and hypertrophic chondrocytes contained few or no AR. Osteoblasts (and osteocytes) contained numerous AR and almost all were in the cytoplasm. Normal human osteoblasts, in their second or third passage, were grown on coverslips either in a medium with no added androgen or in the presence of 5alpha-dihydrotestosterone or methyltrienolone for a period of 24 h or longer. In control cultures, with vehicle and no added androgen, nearly all AR were found in the cytoplasm, with hardly any in the nucleus. In the presence of added androgen some osteoblasts from two of the specimens demonstrated a clear translocation of AR into the nucleus, whilst osteoblasts from a third specimen failed to translocate. These preliminary results indicate that AR translocation to the nucleus occurs in osteoblastic cells derived from osteoarthritic subjects. However, the ability to translocate may depend on the state of differentiation of the osteoblast and on culture conditions.

Aged↗

Differentiation between recurrent brain tumour and post-radiation necrosis: the value of 201Tl SPET versus 18F-FDG PET using a dual-headed coincidence camera--a pilot study.

The aim of this study was to determine whether it is possible to differentiate between recurrent disease and post-treatment necrosis in patients treated for a primary brain tumour. This prospective study was designed to compare the sensitivity and specificity of 201Tl single photon emission tomography (SPET) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) using a dual-headed coincidence camera. Sixteen patients suspected of having recurrent brain tumour (10 men, 6 women) (mean age 39.5 years, range 21-57 years) were studied. 201Tl SPET and 18F-FDG PET studies were performed on the same day. An increase in activity was considered indicative of tumour recurrence. The images were also quantified using a thallium index and an FDG index. The 18F-FDG PET images were also assessed visually using a 5-point scale. The diagnosis of tumour recurrence was based on clinical course and/or follow-up computed tomography or magnetic resonance imaging. The sensitivity of 201Tl SPET and 18F-FDG PET was 92% (11/12) and 62% (7/12) respectively. One patient initially assessed as having necrosis showed a recurrence 9 months after both studies. McNemar's analysis of these results showed a statistically significant difference (P = 0.023) in the ability of the two methods to separate with accuracy tumour from radiation necrosis. No correlation was found between the thallium index and the FDG index (r = 0.36). We conclude that 201Tl SPET is a sensitive modality for the detection of brain tumour recurrence. 18F-FDG imaging using a dual-headed coincidence camera gave significantly poorer results compared to 201Tl SPET. Our results do not justify continuation of this prospective comparative study.

Adult↗