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A A Ismail

Publications and source records attributed to A A Ismail.

At least 19 recordsLinked to original sources
PubMed2005

Rib fractures predict incident limb fractures: results from the European prospective osteoporosis study.

Population studies suggest that rib fractures are associated with a reduction in bone mass. While much is known about the predictive risk of hip, spine and distal forearm fracture on the risk of future fracture, little is known about the impact of rib fracture. The aim of this study was to determine whether a recalled history of rib fracture was associated with an increased risk of future limb fracture. Men and women aged 50 years and over were recruited from population registers in 31 European centres for participation in a screening survey of osteoporosis (European Prospective Osteoporosis Study). Subjects were invited to complete an interviewer-administered questionnaire that included questions about previous fractures including rib fracture, the age of their first fracture and also the level of trauma. Lateral spine radiographs were performed and the presence of vertebral deformity was determined morphometrically. Following the baseline survey, subjects were followed prospectively by annual postal questionnaire to determine the occurrence of clinical fractures. The subjects included 6,344 men, with a mean age of 64.2 years, and 6,788 women, with a mean age of 63.6 years, who were followed for a median of 3 years (range 0.4-5.9 years), of whom 135 men (2.3%) and 101 women (1.6%) reported a previous low trauma rib fracture. In total, 138 men and 391 women sustained a limb fracture during follow-up. In women, after age adjustment, those with a recalled history of low trauma rib fracture had an increased risk of sustaining 'any' limb fracture [relative hazard (RH)=2.3; 95% CI 1.3, 4.0]. When stratified by fracture type the predictive risk was more marked for hip (RH=7.7; 95% CI 2.3, 25.9) and humerus fracture (RH=4.5; 95% CI 1.4, 14.6) than other sites (RH=1.6; 95% CI 0.6, 4.3). Additional adjustment for prevalent vertebral deformity and previous (non-rib) low trauma fractures at other sites slightly reduced the strength of the association between rib fracture and subsequent limb fracture. In men, after age adjustment, there was a small though non-significant association between recalled history of rib fracture and future limb fracture. Our data highlight the importance of rib fracture as a marker of bone fragility in women.

Aged↗
PubMed2004

A simple and rapid genotyping method for beta-2 receptor (beta2 AR) gene using allele specific multiplex PCR.

BACKGROUND: Polymorphism of the beta2-adrenergic receptor (beta2 AR) gene is an important determinant of the function of this receptor. It affects receptor down-regulation and beta2-agonist responses. It has also been a focus of interest in attempts to elucidate the genetic basis of asthma, hypertension, obesity and cystic fibrosis. Several different techniques have been established to determine beta2 AR genotypes but none of these methods are simple enough to detect simultaneously all the five alleles of our research interest (Arg16/Gly16, -20T/C, Gln27/Glu27, -47T/C and Thr164/Ile164). OBJECTIVES: To develop a simple and rapid PCR based method for the simultaneous detection of five beta2 AR alleles. METHOD: DNA was extracted from whole blood using standard alkali lysis method. Primers specific at the 3' end for the polymorphic sites were designed. The nested allele specific PCR was optimized for reproducibility and specificity. Parameters investigated included concentrations of MgCl2, Taq polymerase, primers and annealing temperature, to produce specific bands of interest. DNA samples were selected at random and submitted for direct PCR sequencing. RESULT: The first PCR produced a fragment of size 710 bp, which was used as template for the subsequent duplex and triplex PCR to detect the mutation sites of the five alleles. The method was found reproducible and specific when used to genotype patients with bronchial asthma. The sequencing results confirmed the specificity of the PCR method. CONCLUSION: The simple and rapid method for the simultaneous detection of the five beta2 AR alleles is suitable for the study of beta2 polymorphism and its clinical consequences.

Alleles↗
PubMed2003

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Age Distribution↗
PubMed2002

Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Age Distribution↗
PubMed2002

Defining incident vertebral deformities in population studies: a comparison of morphometric criteria.

Various morphometric criteria have been used to define incident vertebral deformity. The aim of this analysis was to compare the relative validity of two established criteria and a novel method in which these criteria were combined. Men and women aged 50 years and over were recruited from population registers across Europe and had lateral spinal radiographs performed using a standard protocol. A subsample of individuals had bone mineral density (BMD) at the spine or femoral neck. Subjects were followed prospectively and a subsample had repeat spinal radiographs a median of 3.8 years after the baseline survey. All radiographs were evaluated morphometrically in the radiology coordinating center in Berlin. Anterior, middle and posterior height were recorded in all vertebrae from T4 to L4. On the basis of these morphometric measurements incident vertebral deformity was defined using one of three methods: (i) the change method - a change in any vertebral height of 20% or more between films, plus the additional requirement that a vertebral body have changed in absolute vertebral height by 4 mm or more; (ii) the point prevalence method, where a vertebra satisfies criteria for a prevalent deformity (McCloskey-Kanis) on the follow-up, though not the baseline film; (iii) a combination of the height reduction and the point prevalence criteria. Paired films were also evaluated qualitatively by an experienced radiologist for the presence of incident vertebral deformity. Logistic regression was used to compare the three morphometric methods using known risk factors for vertebral deformity including age, baseline vertebral deformity and BMD, and the qualitative evaluation. Computer simulation was used to determine the potential degree of bias and loss of statistical efficiency due to misclassification for each of the three methods, using the radiologist's assessment of incident deformity as the reference. Six thousand eight hundred subjects were included in this analysis. Of these 450 had sustained an incident vertebral deformity according to at least one of the three morphometric methods. The distribution of risk factors was similar in the subjects who satisfied only one morphometric criterion and those who satisfied neither. However, the subjects who satisfied both criteria had a very different distribution of risk factors: they were older, more likely to be female, more likely to have had a previous vertebral deformity and more likely to have an incident fracture in the opinion of an experienced radiologist. Using computer simulation, at low incidence levels, combining the criteria led to greater statistical efficiency and less bias in estimating associations with risk factors. Thus in this analysis the combination of the point prevalence and 20% change in height criterion for defining incident vertebral deformity showed a stronger relationship with clinical risk factors than either single criterion. Its application in population-based studies would increase the likelihood of detecting risk factors for incident vertebral deformity for a given sample size.

Age Factors↗
PubMed2002

Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS).

Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

Age Distribution↗
PubMed2001

Two-dimensional infrared correlation spectroscopy as a probe of sequential events in the thermal unfolding of cytochromes c.

The sequential unfolding events of horse, cow, and tuna ferricytochromes c (cyt c) as a function of increasing temperature over the range 25-81 degrees C were investigated by resolution-enhanced two-dimensional infrared (2D IR) correlation spectroscopy. The 2D IR analysis revealed that in the thermal denaturation of the two mammalian cyts, the overall sequence of unfolding is similar, with denaturation of extended-chain and turn structures occurring prior to unfolding of alpha-helices, followed by denaturation of residual stable extended-chain structures. In tuna cyt c, denaturation of all extended-chain structures precedes the unfolding of alpha-helices. Moreover, in cow cyt c, unfolding of all helical components occurs as one cooperative unit, but in horse and tuna cyts c, the helical components behave as subdomains that unfold separately, as proposed recently by Englander and co-workers for horse cyt c [Bai et al. (1995) Science 269, 192-197; Milne et al. (1999) J. Mol. Biol. 290, 811-822]. At higher temperatures, following the loss of secondary structure, protein aggregation occurs in the three cyts c. The data presented here establish that variations in the thermal unfolding of cyts c can be associated with specific sites in the protein that influence local flexibility yet have little affect on global stability. This study demonstrates the power of resolution-enhanced 2D IR correlation spectroscopy in probing unfolding events in homologous proteins.

Animals↗
PubMed2001

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Aged↗
PubMed2001

Enumeration of non-communicable disease in rural South Africa by electronic data linkage and capture-recapture techniques.

Non-communicable diseases (NCDs) are becoming increasingly common and important in developing countries, yet their enumeration is problematic. We have attempted to enumerate NCD patients in a rural district of KwazuluNatal, South Africa, using the techniques of electronic data linkage and capture-recapture (CR). We examined four major NCDs (hypertension, diabetes, asthma and epilepsy). Basic patient details were recorded onto EpiInfo software over a 6-week period, from the main hospital clinic at Hlabisa, as well as the 10 outlying peripheral health clinics. Using electronic data linkage of lists from the main hospital, the peripheral clinics, and repeat prescription cards, a district NCD register was produced of 2455 patients. The mean age was 51 +/- 16 years (1 SD) and 76% were female. Of the total NCD patients, 62% had hypertension (age 57 +/- 12 years, 82% female), 16% epilepsy (age 35 +/- 17 years, 49% female), 13% asthma (age 45 +/- 19 years, 60% female) and 12% diabetes (age 54 +/- 13 years, 61% female). Estimated population crude prevalence rates for known NCD cases on the register were 7.4% for hypertension, epilepsy 0.2%, asthma 0.2% and diabetes 0.2%. We also attempted a CR analysis to assess completeness of data, by comparing overlap between patients attending peripheral clinics, and the central Hlabisa Hospital clinic. Matching by name, age, and diagnosis proved feasible, but there was little overlap, and CR calculations were invalid because of the relative independence of sources. We conclude that NCDs are common in rural Africa, and that a simple NCD district register is a potentially feasible and inexpensive option. Capture-recapture analysis is feasible, but requires suitable lists with acceptable overlap of patients.

Adolescent↗
PubMed2001

Endocrinology of gynaecomastia.

Gynaecomastia is the most common disorder of the male breast. It can occur at any age, and for this reason laboratory investigations may be requested by clinicians from many specialties. Gynaecomastia may occur transiently in neonates. It may also occur transiently during puberty, when it is common and generally benign. It must, however, be regarded as unusual in prepubertal children and all young and middle-aged men. Although iatrogenic and benign gynaecomastia are common in the elderly, further investigations may still be justified since breast cancer or other neoplasm must be ruled out. Biochemical investigations, when warranted, are aimed at establishing an underlying cause. Endocrine investigations might include serum oestradiol (or oestrone if available), testosterone, luteinizing hormone, sex-hormone-binding globulin, human chorionic gonadotrophin, prolactin and thyroid function tests. In this review, the source and role of oestrogens in men, the androgen oestrogen dynamics, the causes and clinical entities of gynaecomastia, and interpretation of laboratory tests are described.

Androgens↗
PubMed2001

Synthesis of 1,2-unsaturated pyranosylphosphonate nucleosides from 3,4,6-tri-O-acetyl-D-glycal.

Ferrier rearrangement of 3,4,6-tri-O-acetyl-D-glucal (1) in the presence of triethylphosphite afforded the 2,3-unsaturated pyranose 2. Deacetylation and simultaneous migration of the double bond to 1,2-position in the sugar moiety was achieved by stirring in sodium ethoxide. Tosylation with one equivalent of tosyl chloride afforded 4. Nucleophile displacement of the tosylate of 4 with nucleobase in the presence of NaH/DMF followed by deprotection gave the desired 1,2-unsaturated pyranosylphosphonates 7a-c.

Carbohydrates↗
PubMed2000

Validity of self-report of fractures: results from a prospective study in men and women across Europe. EPOS Study Group. European Prospective Osteoporosis Study Group.

In population-based studies of osteoporosis, ascertainment of fractures is typically based on self-report, with subsequent verification by medical records. The aim of this analysis was to assess the validity of self-report of incident nonspine fractures using a postal questionnaire. The degree of overreporting of fracture (false positives) was assessed by comparing self-reports of new fracture from respondents in the multicenter European Prospective Osteoporosis Study with data from other sources including radiographs and medical records. In the analysis, 563 subjects reported nonspine fractures. Verification of the presence of fracture was possible in 510 subjects. Of these, fractures were not confirmed in 11% (false positives). The percentage of false positives was greater in men than in women (15% vs 9%, p = 0.04), and less for fractures of the distal forearm and hip than for fractures at other sites. In a separate study, the degree of underreporting (false negatives) was assessed by follow-up of 251 individuals with confirmed fracture ascertained from the records of fracture clinics in three European centers (Lubeck, Oviedo, Warsaw). Questionnaire responses were received from 174 (69%) subjects. Of these, 12 (7%) did not recall sustaining a fracture (false negatives). The percentage of false negatives was lower for hip and distal forearm fractures with only 3 of 90 (3%) such fractures not recalled. Using the combined data from both studies, of those who reported a 'date' of fracture on the questionnaire, 91% of subjects were correct to within 1 month of the actual date of the fracture. A postal questionnaire is a relatively simple and accurate method for obtaining information about the occurrence of hip and distal forearm fractures, including their timing. Accuracy of ascertainment of fractures at other sites is less good and where possible self-reported fractures at such sites should be verified from other sources.

Aged↗
PubMed2000

Comparison of questionnaire, breath carbon monoxide and urine cotinine in assessing the smoking habits of Type 2 diabetic patients.

AIMS: Previous studies have suggested that the self-reporting of smoking amongst diabetic patients is unreliable, and that objective markers such as breath carbon monoxide (CO) or urinary cotinine are needed. As these studies have been mostly in young Type 1 diabetic patients, the reliability of smoking history has been assessed in a large group of older Type 2 diabetic patients. METHODS: Two hundred and ninety-nine Type 2 diabetic patients were investigated for smoking habits by unstructured questionnaire, breath CO, and urinary ratio. RESULTS: Mean age of the group was 63 (range 30-80) years and 41% were female. Direct questioning suggested 77 (26%) to be smokers, and of these 852 had raised (>1 microg/mg) urinary cotinine-creatinine , and 71% raised (>8 p.p.m.) breath CO. Assuming urinary cotinine-creatinine as the 'gold standard', the sensitivity, specificity and positive predictive values for questionnaire were 97%, 95% and 85%, respectively; and for breath CO they were 74%, 98%, and 93%. CONCLUSION: It is concluded that at least in this population of Type 2 diabetic patients, a structured smoking history appeared to identify current smokers with good accuracy.

Adult↗
PubMed2000

Does location of vertebral deformity within the spine influence back pain and disability? European Vertebral Osteoporosis Study (EVOS) Group.

OBJECTIVE: Vertebral deformity is associated with back pain and disability. The aim of this analysis was to determine whether location within the spine influences the strength of association between vertebral deformity, back pain and disability. METHODS: Men and women aged 50 years and over were recruited from population registers in 30 European centres. Subjects were invited for an interviewer administered questionnaire, and for lateral spinal radiographs. The questionnaire included questions about back pain, general health and functional ability. The spinal radiographs were evaluated morphometrically and vertebral deformity defined according to the McCloskey-Kanis method. RESULTS: 756 (11.7%) men and 885 (11. 8%) women had evidence of one or more vertebral deformities. Among women with a single deformity, after adjusting for age and centre, those with a lumbar deformity were more likely than those with a thoracic deformity to report back pain, both currently (OR=1.4; 95% CI 1.0, 2.0) and in the past year (OR=1.5; 95% CI 1.0, 2.3). No association was observed in men. Among women with two deformities, those with adjacent deformities were more likely than those with non-adjacent deformities to report poor general health (OR=2.2; 95%CI 0.9, 5.6), impaired functional ability (OR=1.9; 95%CI 0.8, 4. 7) and current back pain (OR=2.1; 95%CI 0.9, 4.9), though none of these associations were statistically significant. By contrast, among men, non-adjacent deformities were associated with impaired functional ability compared with those with adjacent deformities. CONCLUSION: Location within the spine influences the strength of association between self reported health factors and vertebral deformity.

Aged↗
PubMed2000

Risk factors for vertebral deformities in men: relationship to number of vertebral deformities. European Vertebral Osteoporosis Study Group.

Recent epidemiological studies suggest a similar overall prevalence of vertebral deformity in men to that in women, though the influence of increasing age on the prevalence of vertebral deformity is less marked in men. However, most affected men have only a single or two vertebral deformities, which may be unrelated to osteoporosis. The aim of this study was to examine the role of risk factors, previously demonstrated to be associated with vertebral osteoporosis in females, in men with single/dual deformities compared to those with multiple deformities. Age stratified random samples of men aged 50 years and over were recruited from population registers in 30 European centers as part of the European Vertebral Osteoporosis Study (EVOS). Subjects had a lateral spinal radiograph and the presence of vertebral deformity was determined using the McCloskey algorithm. Lifestyle and other risk factor data were obtained from an interviewer-administered questionnaire. In all 6937 men with a mean age of 64.4 (SD = 8.5) years were studied of whom 738 (10.6%) subjects had one or two deformities, and 109 (1.6%) subjects had three or more deformities. There was a marked increase in the prevalence of multiple vertebral deformities with increasing age, but only a modest effect of age on the prevalence of single deformities. Associations between various risk factors for osteoporosis and vertebral deformity were analyzed separately in men with single/dual vertebral deformity from those with three or more deformities using logistic regression. After adjustment for age, there were statistically significant associations between the following risk factors and multiple deformities: previous hip fracture (odds ratio [OR] 10.5), lack of regular physical activity (OR 2.9), low body mass (OR 2.5), and previous steroid use (OR 2.3). By contrast, there were only weak associations with these same variables in males with single/dual deformities and, apart from poor self-reported general health, all of the 95% confidence intervals spanned unity. There was no difference in the reporting of very heavy levels of physical activity under the age of 50 years between men with single/dual deformities and those with multiple deformities. In conclusion, men with multiple deformities showed a similar pattern of risk factor association to those seen in women with vertebral deformity, in contrast to men with single/dual deformities.

Aged↗