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PubMed1986

Disk diffusion susceptibility testing of two macrolide antimicrobial agents: revised interpretive criteria for erythromycin and preliminary guidelines for roxithromycin (RU 965).

The 15-micrograms erythromycin disk was twice evaluated for interpretive accuracy against 417 and then 266 strains of gram-positive cocci, Neisseria meningitidis, and Haemophilus influenzae by using the criteria suggested by the National Committee for Clinical Laboratory Standards. These studies suggest a revision of streptococcal and Staphylococcus sp. interpretive guidelines to criteria (greater than or equal to 23 mm = susceptible, less than or equal to 13 mm = resistant) that are more compatible with in vivo erythromycin concentrations. It is also recommended that zone diameters be modified for H. influenzae (greater than or equal to 23 mm = susceptible, less than 22 mm = resistant) and that meningococci not be tested. A wide moderately susceptible category (1.0 to 4.0 micrograms/ml) would primarily include enterococcus strains and those organisms that would then respond only to parenteral administration of erythromycin. Roxithromycin (RU 965 or RU 28965), a new oxime ether erythromycin derivative, was also evaluated by investigator-prepared 15-micrograms disks and later with 30- and 60-micrograms commercial disks. Although roxithromycin was comparable to erythromycin in activity and regression line statistics, changes in the susceptible disk criteria were necessary because of superior roxithromycin serum concentrations and a longer serum half-life. Preliminary susceptible breakpoint criteria were greater than 21 mm = susceptible, 10 to 20 mm = indeterminate, and less than or equal to 9 mm = resistant. By using the recommended interpretive criteria for both macrolides, less than 98% absolute agreement was obtained, therefore suggesting the application of a spectrum class concept.

Erythromycin↗
PubMed2004

Trends in hip and knee joint replacement: socioeconomic inequalities and projections of need.

OBJECTIVES: To examine trends in primary and revision joint (hip and knee) replacement in England between 1991 and 2000. METHODS: Analysis of hospital episodes statistics between 1 April 1991 and 30 March 2001 for total hip replacement (THR) and total knee replacement (TKR). Descriptive statistics and regression modelling were used to summarise patients' demographic and clinical characteristics and to explore variations in joint surgery rates by age, sex, and deprivation. RESULTS: Between 1991 and 2000, the incidence of primary THR increased by 18%, while the incidence of revision THR more than doubled. The incidence of primary TKR doubled, with revision TKR increasing by 300%. Over the 10 year period, the proportion of THR episodes that involved revision operations rose from 8% to 20%. Substantial variations in operation rates by socioeconomic status were seen, with the most deprived fifth of the population experiencing significantly lower rates. Projections estimate that primary THR numbers could rise by up to 22% by the year 2010, with primary TKR numbers rising by up to 63%. CONCLUSIONS: Provision of joint replacement surgery in English NHS hospitals has increased substantially over the past decade. Revision operations in particular have increased markedly. The growth in primary operations has mostly occurred among those aged 60 years and over; rates among young people have changed very little. There is a significant deprivation based gradient in rates. If current trends continue there would be almost 47 000 primary hip and 54 000 primary knee operations annually by 2010.

Adult↗
PubMed2002

Influence of prior pregnancies on disease course and cause of death in systemic sclerosis.

BACKGROUND: Microchimerism from fetal or maternal cells transferred during pregnancy has been implicated in the pathogenesis of systemic sclerosis (SSc). OBJECTIVE: To determine whether a prior pregnancy influenced disease progression and cause of death in patients with SSc. PATIENTS AND METHODS: The patients comprised a retrospective study cohort of 111 women with SSc: 78 patients with prior pregnancies (PP) and 33 who were never pregnant (NP), followed up at Thomas Jefferson University. Differences in age at onset, disease subset, organ involvement, cause of death, and type of antinuclear autoantibodies were evaluated statistically, including regression analysis. RESULTS: The age at onset of SSc in NP patients was 32.0 years compared with 45.7 years in patients with one or two prior pregnancies (p<0.0001), 46.6 years in patients with three or four pregnancies (p<0.0001), and 51.3 years in patients with five to seven pregnancies (p<0.0005). In the 16 patients who had an elective pregnancy termination, 14/16 (87.5%) had diffuse SSc v 2/16 (12.5%) with limited SSc (p<0.0001; odds ratio (OR)=49.0). Of the NP women, 7/30 (23%) died from SSc related causes v 3/78 (4%) women who had pregnancies (p=0.0058; OR=7.6). A carbon monoxide transfer factor (TLCO) of <60% and disease duration >10 years was found in 10/13 (77%) NP patients v 10/23 (43%) patients who had pregnancies (p=0.05; OR=4.7), and a TLCO <50% and disease duration >10 years was identified in 7/13 (54%) NP patients v 6/23 (26%) of the patients who had pregnancies (p=0.09; OR=3.2). CONCLUSIONS: There are differences in the age at onset, clinical course, severity of lung involvement, and cause of death in women who develop SSc before pregnancy compared with those who develop it after pregnancies. The NP patients with SSc had onset of disease at an earlier age, more severe lung involvement, and higher rate of death due to SSc.

Adult↗
PubMed1995

Organochlorine residues in human breast milk: analysis through a sentinel practice network.

STUDY OBJECTIVE: The study aimed to assess through a sentinel practice network the validity of data on levels of organochlorine residues in human milk along with personal, lifestyle, and exposure variables of breastfeeding women; to compare the results of this new approach with those of the Lower Saxony breast milk surveillance programme; and to test hypotheses on potential determinants of contamination levels. DESIGN: Eligible women were enrolled into this cross sectional study by a network of 51 paediatric practices when bringing their babies for a U3 infant screening examination (4th to 6th week after delivery). Lifestyle and exposure factors were obtained by questionnaire. All milk samples were analysed for hexachlorocyclohexane, hexachlorbenzole, DDT, dieldrin, polychlorinated biphenyls (PCB) and heptachlor; half the samples were also analysed for dioxin. Analytic statistics were computed using polychotomous logistic regression (PLR). SETTING: The study was conducted in Lower Saxony, Germany, from summer 1992 to summer 1993. PARTICIPANTS: Altogether 156 primiparous, breast feeding German women, aged 25-35 years, who had been born and had grown up in West Germany, were studied. MAIN RESULTS: Compared with the regular programme, participants in this study had their milk analysed sooner after delivery and were more likely to have grown up in rural areas, less likely to have been exposed to hazardous substances, less likely to have a diet of health food, and slightly less likely to be a smoker at the time of the study. Breast milk contamination levels were comparable in both studies, and in all but two cases well below the tolerable concentrations established by the Deutsche Forschungsgemeinschaft (German Research Fellowship). After adjustment for potential confounders using polychotomous logistic regression, there were statistically significant positive associations between breast milk contamination and age (PCB, test for trend: p = 0.006), average dietary fat intake per week (dioxin, p = 0.01), and proximity of residence to hazardous sites (dioxin, p < 0.05), and negative associations between residue levels and relative body weight at the time of the study (PCB; p < 0.0001) and difference in body weight (weight minus weight before the pregnancy; PCB, p = 0.0002), respectively. CONCLUSIONS: Sentinel practice networks are a feasible and low-biased approach to population based breast milk studies. The contamination levels and associations found are biologically plausible and comparable with the results of other studies. To reduce organochlorine residue levels in human milk in the short term, breast-feeding women should be advised not to try to reduce their weight until after lactation. Public promotion of a lower dietary fat intake may reduce the lifetime accumulation of organochlorine compounds in the human body fat tissue in the long term, resulting in lower concentrations in breast milk as well.

Adult↗
PubMed2001

Predictors of outcome and pathological considerations in the surgical treatment of intractable epilepsy associated with temporal lobe lesions.

OBJECTIVES: To evaluate the influence of clinical, investigative, and pathological factors on seizure remission after temporal lobectomy for medically intractable epilepsy associated with focal lesions other than hippocampal sclerosis. METHODS: From a series of 234 consecutive "en bloc" temporal resections for medically intractable epilepsy performed between 1976 and 1995, neuropathological examination disclosed a focal lesion in 80. The preoperative clinical, neuropsychological, interictal EEG, and neuroimaging characteristics of these patients were assembled in a computerised database. The original neuropathological material was re-examined for lesion classification and completeness of removal. The presence of additional cortical dysplasia and mesial temporal sclerosis was also noted. Survival analysis was performed using Kaplan-Meier curves and actuarial statistics. Logistic regression analysis was used to establish the independent significance of the clinical variables. RESULTS: The probability of achieving a 1 year seizure remission was 71% by 5 years of follow up. Factors predicting a poor outcome on multivariate analysis included the need for special schooling and a long duration of epilepsy. Generalised tonic-clonic seizures, interictal EEG discharges confined to the resected lobe, demonstration of the lesion preoperatively on CT, and complete histological resection of the lesion were not predictive of outcome. Neuropsychological tests correctly predicted outcome in left sided cases but apparently congruent findings in right sided resections were associated with a poor outcome. Pathological reclassification established the dysembryoplastic neuroepithelial tumour as the commonest neoplasm (87%) in this series, with a significantly better seizure outcome than for developmental lesions, such as focal cortical dysplasia. CONCLUSIONS: The findings highlight the importance of dysembryoplastic neuroepithelial tumour in the pathogenesis of medically refractory lesional temporal lobe epilepsy and the prognostic significance of preoperative duration of epilepsy emphasises the need for early recognition and surgical treatment. Cognitive and behavioural dysfunction, however, is associated with a lower seizure remission rate, independent of duration of epilepsy.

Adolescent↗
PubMed1998

Trends in rates of occupational fatal injuries in the United States (1983-92).

OBJECTIVES: An updated version of a national surveillance system of traumatic occupational fatalities was used to explore adjusted and unadjusted trends in rates of fatal injury. METHODS: Data from the national traumatic occupational fatalities surveillance system were combined with data on employment from the United States Bureau of Labor Statistics. Poisson regression was then used to examine trends in rates of occupational fatality injuries while controlling for demographic and workplace characteristics. RESULTS: Adjusted annual changes in rates of fatal injuries ranged from a decline of 6.2% for workers in technical and administrative support occupations--for example, health, science, and engineering technicians, pilots, computer programmers--to an increase of 1.6% in machine operators, assemblers, and inspectors. For industries, annual changes ranged from a decline of 5.3% for workers in public administration--for example, justice, public order, and safety workers--to an increase of 2.6% for workers in the wholesale trade. By comparison, the annual decline over all industries and occupations was 3.1%. In many industries and occupations, an effect modification of annual trends by the age of the worker was also found with the oldest workers experiencing either no decline or a significant increase in rates of fatal injuries. CONCLUSIONS: This general pattern of decline, adjusted for the effects of demographic characteristics of the worker population, is encouraging; however, increases in rates of fatal injuries found in particular industries and occupations, suggest appropriate targets for increased injury prevention efforts.

Accidents, Occupational↗
PubMed2000

Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems.

BACKGROUND: The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients. METHODS: Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables. RESULTS: Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3. 5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups. CONCLUSIONS: This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.

Adult↗
PubMed2006

Influence of estrogen receptor alpha and progesterone receptor polymorphisms on the effects of hormone therapy on mammographic density.

Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch Prospect-EPIC and the English EPIC-Norfolk cohorts. Information on hormone therapy use was obtained through questionnaires at recruitment and after 5 years. Blood samples were collected and consecutive mammograms were available through breast cancer screening programs. For 795 hormone therapy users, one mammogram before and a second mammogram during hormone therapy use was included. For 781 never hormone therapy users, mammograms with similar time intervals were included. Mammographic density was assessed using a computer-assisted method. Changes in density were analyzed using linear regression. A statistically significant difference in percentage density change between hormone therapy users and never users was seen in women with the ESR1 PvuII Pp or pp genotype (2.24%; P < 0.01), but not in those with the PP genotype (0.90%; P = 0.47). Similarly, effects of hormone therapy on percentage density were observed in women with the ESR1 XbaI Xx or xx genotype (2.20%; P < 0.01), but not in those with the XX genotype (-0.65%; P = 0.70). Also, effects were seen in women with the PGR +331 GG genotype (2.04%; P < 0.01), but not in those with the GA or AA genotype (0.98%; P = 0.53). The PGR PROGINS polymorphism did not seem to make women more susceptible to the effects of hormone therapy use. In conclusion, our results suggest that specific polymorphisms in the ESR1 and PGR genes may make women more susceptible to the effects of hormone therapy use on mammographic density.

Aged↗
PubMedDate not supplied

Age-corrected normal values for perimetry.

PURPOSE: Age-corrected values are indispensable in assessing discrete changes in light difference sensitivity (LDS) when evaluating perimetric results. In order to detect incipient visual field defects, the present study aimed particularly to determine function of normal values depending on age and eccentricity. METHODS: A test group (n = 83) of ophthalmologically and clinically unremarkable subjects 18-74 years of age was examined with the 'Centerfield' perimeter. A brief introductory program was first used to familiarize each test person with the situation. Then values in the central visual field (30 degrees) were determined with a threshold-splitting program. In addition, the peripheral visual field was examined after a short break. RESULTS: Age-related normal values were calculated both as group averages and as lines of regression by statistical analysis of the resulting data. In contrast to other perimetric studies, decreases in LDS at different test points for persons aged 20 years to persons over 60 were not linear. CONCLUSIONS: Age-related normal values should be reviewed for other perimeters.

Adolescent↗
PubMed1995

Diagnostic reliability of dermoscopic criteria for detecting malignant melanoma.

BACKGROUND: Recently a new standardized terminology in dermoscopy has been provided by a Consensus Meeting held by the Committee on Analytical Morphology of the Arbeitsgemeinschaft Dermatologische Forschung in Hamburg in order to be applied to further studies in this field. OBJECTIVE: In this study on 159 pigmented skin tumors including 65 melanomas, the validity of various dermoscopic criteria proposed by the Consensus Meeting for detecting melanoma was evaluated. METHODS: In each lesion, a detailed clinical and dermoscopic examination, photographic documentation of the clinical and dermoscopic appearance, surgical excision and histopathologic evaluation were performed. Statistical analyses including chi 2 statistics, logistic regression analysis and CART (classification and regression tree) analysis were applied. RESULTS: The diagnosis of melanoma using dermoscopy could be obtained easily, if combinations of the following criteria were observed: whitish veil, pigment network alterations (e.g. irregular pigment network, narrow pigment network, broad pigment network), irregular extensions, black dots and gray-blue areas. Interestingly, however, clinical and dermoscopic examination to detect melanomas yielded the same results, namely a sensitivity of 94%. The combined use of both methods led to an increase in the diagnostic sensitivity of 95%, whereas the combination of clinical and dermoscopic examination with logistic regression analysis of dermoscopic criteria enabled us to detect all 65 melanomas in our data set, thus providing a sensitivity of 100%. Furthermore, an algorithm for the classification of melanoma based on the evaluation of dermoscopic criteria has been constructed by CART analysis showing that the presence of a whitish veil in combination with a pigment network inevitably indicates melanoma. CONCLUSION: The validity of the various dermoscopic criteria set forth by the Consensus Meeting could be demonstrated as some criteria (e.g. whitish veil, irregular pigment network, irregular extensions) were observed with a significant higher frequency in melanomas.

Algorithms↗
PubMed2006

Plasma aldosterone is independently associated with the metabolic syndrome.

The aim of this study was to analyze the associations of plasma aldosterone and plasma renin activity with the metabolic syndrome and each of its components. We analyzed data from a family based study in the Seychelles made up of 356 participants (160 men and 196 women) from 69 families of African descent. In multivariable models, plasma aldosterone was associated positively (P < 0.05) with blood pressure in older individuals (interaction with age, P < 0.05) and with waist circumference in men (interaction with sex, P < 0.05) and negatively with high-density lipoprotein cholesterol, in particular in individuals with elevated urinary potassium excretion (interaction with urinary potassium, P < 0.05); plasma renin activity was significantly associated with triglycerides and fasting blood glucose. Plasma aldosterone, but not plasma renin activity, was associated with the metabolic syndrome per se, independently of the association with its separate components. The observation that plasma renin activity was associated with some components of the metabolic syndrome, whereas plasma aldosterone was associated with other components of the metabolic syndrome, suggests different underlying mechanisms. These findings reinforce previous observations suggesting that aldosterone is associated with several cardiovascular risk factors and also suggest that aldosterone might contribute to the increased cardiovascular disease risk in individuals of African descent with the metabolic syndrome.

Africa, Eastern↗