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Characterization of plasma hormone levels and lipogenic enzyme activity in chickens divergently selected for oxygen consumption.

The bases for differences in growth and metabolism of lines previously selected for divergence in O2 consumption in comparison to a randombred control population were studied. Body weights, carcass fat, plasma growth hormone (GH), triiodothyronine (T3), thyroxine (T4), malic enzyme, and citrate cleavage enzyme activities were determined. The early growth of the low O2 birds was greater than the high O2 birds, whereas the growth rate of the control population was intermediate to, but not statistically different from, the two O2 lines. Six-week body weights did not differ between the lines. Percent fat of the high O2 birds was less than the other two lines at 1 and 2 weeks of age but greater than the low O2 birds at 3 weeks of age. Percent fat did not differ between the lines at 6 weeks. Plasma T4 levels differed between the lines only at Day 1, when the control population exhibited greater T4 levels than the O2 lines. Plasma T3 levels were lower in the high O2 chicks in comparison to only the control chicks at 0, 1, and 2 weeks of age. No line differences in T3 levels were detected at 3 or 6 weeks. From 1 to 3 weeks, GH levels were greater in the low O2 birds than the high O2, while the control birds had GH levels intermediate to the O2 lines. By 6 weeks, the O2 lines had similar GH levels, but these levels were lower than those of the controls. No consistent line differences in malic enzyme or citrate cleavage enzyme activities were observed.

ATP Citrate (pro-S)-Lyase↗

Low mortality in HIV-infected patients starting highly active antiretroviral therapy: a comparison with the general population.

OBJECTIVES: To assess the mortality in a cohort of HIV-infected patients starting highly active antiretroviral therapy (HAART) compared to the mortality of the general population, focusing on the influence of the CD4 cell count at the time of starting HAART. METHODS: Patients in the HIV Cohort Study in Western Denmark starting HAART before 1 January 2002 were identified. For each patient, 100 population controls matched on age and gender were extracted from the Danish Civil Registration System. Mortality rates were compared between the two cohorts overall, and in four groups defined by baseline CD4 cell counts. RESULTS: A total of 647 HIV-infected patients and 64 700 population controls were included, accounting for 53 and 815 deaths during follow-up. In the HIV group, mortality rates were 70.0 per 1000 person-years at risk in the lowest CD4 cell group (< 50 x 10 cells/l), and 3.2 in the highest (> or = 200 x 10 cells/l). Compared with population controls, mortality rate ratios declined with increasing CD4 cell counts, being 15.3 [95% confidence interval (CI), 9.8-23.8], 8.6 (95% CI, 4.3-16.8), 5.9 (95% CI, 3.0-11.4), and 3.6 (95% CI, 2.0-6.5) in the groups with CD4 cell count < 50, 50-99, 100-199, and > or = 200 x 10 cells/l. CONCLUSION: In comparison with the general population, HIV-infected patients starting HAART with a CD4 cell count above 200 x 10 cells/l had low mortality rates that were comparable with the rates found in other chronic medical diseases. The mortality rates increased considerably when treatment was started at lower baseline CD4 cell counts.

Adult↗

Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study.

OBJECTIVE: To determine the proportion of adults with fibromyalgia syndrome (FMS) in the general population who also meet the 1988 Centre for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS). METHODS: Seventy-four FMS cases were compared with 32 non-FMS controls with widespread pain and 23 with localized pain, all recruited in a general population survey. RESULTS: Among females, 58.0% of fibromyalgia cases met the full criteria for CFS, compared to 26.1% and 12.5% of controls with widespread and localized pain, respectively (p=0.0006). Male percentages were 80.0, 22.2, and zero, respectively (p=0.003). Compared to those with FMS alone, those meeting the case definitions for both FMS and CFS reported a worse course, worse overall health, more dissatisfaction with health, more non-CFS symptoms, and greater disease impact. The number of total symptoms and non-CFS symptoms were the best predictors of co-morbid CFS. CONCLUSIONS: There is significant clinical overlap between CFS and FMS.

Adult↗

Baseline and treatment-induced chromosomal abnormalities in peripheral blood lymphocytes of Hodgkin's lymphoma patients.

PURPOSE: To study chromosomal abnormalities in 49 patients with Hodgkin's lymphoma (HL), before and after treatment and at several times during a 2-year period. METHODS AND MATERIALS: Simple chromosomal aberrations (CAs) and complex chromosomal rearrangements (CCRs) were counted in peripheral lymphocytes by painting of chromosomes 1, 3, and 4 (fluorescence in situ hybridization). A control population was composed of 20 healthy donors and 69 untreated cancer patients who had undergone various radiologic scans. RESULTS: A greater frequency (p < 10(-4)) of spontaneous cytogenetic abnormalities was observed in untreated HL patients compared with the control populations. CCRs were observed exclusively in the HL population (p < 10(-4)). Chemotherapy was associated with a significant increase in the frequency of CAs (p < 10(-4)), according to the chemotherapy regimen (p = 0.002). Immediately after radiotherapy, a significant increase (p < 10(-4)) was observed in CAs according to the size of the irradiation field. Conversely, the significant increases in the frequency of CCRs observed after treatment did not correlate with the chemotherapy regimens, radiotherapy dose, or size of the irradiation field. The evolution of CAs vs. CCRs over time was also dissociated: during the follow-up of these patients, a significant decrease was observed in the frequency of CAs at 6 months and 1 and 2 years. In contrast, after an initial decrease for up to 6 months after treatment, the frequency of CCRs remained constant for up to 2 years. CONCLUSION: Increased cytogenetic abnormalities were observed in untreated HL patients compared with the control populations. The greater frequency of cytogenetic abnormalities persisted in some patients. The presence of CCRs supports the concept of a unique genetic environment in HL patients that persists in response to potentially noxious treatments.

Adolescent↗

Testicular microlithiasis: an unreported feature of McCune-Albright syndrome in males.

OBJECTIVE: To ascertain the incidence of testicular microlithiasis (TM) in boys with McCune-Albright syndrome (MAS). STUDY DESIGN: Study population consisted of 8 boys with MAS whose medical records were reviewed with emphasis on their past genitourinary histories. All of the boys underwent a clinical and ultrasonographic (US) scanning of the scrotal and inguinal regions. US results in boys with MAS were compared with those obtained in two control populations consisting of 20 healthy subjects and 12 boys with idiopathic and untreated central precocious puberty (CPP). RESULTS: Clinical examination revealed urological abnormalities in no patients, whereas US showed a typical picture of TM in 5 of 8 boys. TM was observed in none of the subjects belonging to control populations (v=15.2 and 11.3, respectively; P <.001). CONCLUSIONS: In a series of 8 boys with MAS we demonstrated a high prevalence (62%) of TM that was associated with neither malignant nor nonmalignant conditions. This finding is unlikely to be only occasional, considering the very low prevalence of TM reported until now in healthy children and young adults and in our results in control populations. TM may be another marker for MAS.

Adolescent↗

The functional HERG variant 897T is associated with Conn's adenoma.

OBJECTIVE: Aldosterone secreting adenomas (aldosteronomas) have an unknown molecular origin. Ion channel currents are involved in signal transduction leading to aldosterone synthesis and secretion. HERG (human-ether-a-go-go-related gene) encodes for a potassium channel responsible for the outward rectifying delayed current and it is mutation prone. When mutated it causes most of the familial forms of both long QT and short QT syndromes. Abnormal repolarization in glomerulosa cells might increase aldosterone secretion or induce a proliferative advantage. The aims of this study were to: (1) evaluate HERG expression in aldosteronomas; (2) search for HERG somatic mutations; and (3) determine whether there is any relationship between the common HERG functional variant (A2690C, leading from lysine 897 to threonine, K897T) and aldosteronoma. DESIGN AND METHODS: Aldosteronoma and blood samples from 17 patients were studied to evaluate HERG expression, full-length HERG complementary DNA sequencing, and genotyping for K897T alleles. The prevalence of HERG 897 alleles was also tested in a control population and a population consisting entirely of hypertensive individuals. RESULTS: HERG was expressed in all aldosteronomas analysed. HERG somatic mutations were not detected. The 897T variant of HERG was significantly more common among patients with aldosteronoma (897T allele 41%) than in patients with moderate-severe essential hypertension (897T allele 20%, P = 0.007) or in the control population (897T allele 12%, P < 0.0001). The 897T/T genotype was present in 24% of the aldosteronoma patients versus 7% (P = 0.040) and 3% (P = 0.001) in essential hypertension and in the control population, respectively. When the chi test was performed considering the three groups together, the significance was similar (for alleles P < 0.0001 and for genotypes P = 0.004). CONCLUSION: The common functional HERG variant 897T may predispose to the development of aldosteronoma.

Adrenocortical Adenoma↗

[Postoperative course of systolic and diastolic indices of left ventricular function in aortic valve stenosis in adults. Exercise test with radionuclide angiography].

Resting and stress radionuclide angiography was performed before and, on average, one year after surgery for adult aortic stenosis in 26 patients. The left ventricular ejection fraction, ventricular volumes, left ventricular stroke volume and peak velocity of ventricular filling were studied under basal conditions and at the peak of exercise. Right and left heart catheterisation and coronary angiography were performed before surgery with determination of the conventional indices of left ventricular function. Investigations were completed by pre and postoperative echocardiography. The same procedures were carried out in a control population of the same age. Before surgery, hemodynamic adaptation to exercise, judged by the change in left ventricular stroke volume, solicits the passive properties of the left ventricle: the left ventricular stroke volume increases by an increase in the end diastolic volume. In the control group, the increase in stroke volume is obtained by a decrease in end systolic volume, that is to say by increasing systolic shortening. The peak velocity of ventricular filling increases on exercise but to a lesser degree than in the control population. After surgery the hemodynamic adaptation to exercise results from an improved systolic shortening of the left ventricle but also from an increase in end diastolic volume. The peak velocity of left ventricular filling increases with respect to the preoperative values but remains less than that observed in the control population. No relationship was observed between the hemodynamic adaptation to exercise, the peak velocity of ventricular filling and myocardial mass whichever method was used for calculating the latter parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Two different genetic markers for high and low myopia.

In myopia patients, Rh and acid phosphatase were typed in two groups: group 1 consisted of 214 patients with low myopia (-6 D or less); group 2 of 124 patients with high myopia (more than -6 D). Statistical analysis of the markers showed a good Hardy-Weinberg equilibrium for both groups. In the Rh system there was a significant difference between group 1 and the control population (p < 0.05), but not between group 2 and control (p > 0.1). In the case of ACP there was a significant difference between group 2 and the control population (p < 0.05), but not between group 1 and control (p > 0.25). We conclude that the observed association between myopia and Rh system (chromosome 1) involves low myopia, while the association between myopia and acid phosphatase (chromosome 2) involves high myopia. Further DNA research will lead to more specific results.

Acid Phosphatase↗

Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including loss of heterozygosity at BRCA1 and BRCA2.

PURPOSE: Hodgkin's disease patients who receive mantle irradiation have an age-dependent increased risk of developing breast cancer. To determine if genetic factors predispose these patients to develop breast cancer, we evaluated breast cancer specimens for loss of heterozygosity (LOH) at regions where BRCA1 and BRCA2, two breast cancer tumor suppressor genes, are located. We also evaluated whether breast cancers in patients who were previously treated with radiation have a more aggressive phenotype, and whether the clinical course differed from a sporadic group of breast cancer patients. METHODS AND MATERIALS: All females with Hodgkin's disease who were subsequently diagnosed with breast cancer and for whom tissue blocks were available were included. Using a case-control design, case patients (previously treated with radiation therapy) were matched with sporadic control breast cancer patients for age, breast cancer stage, and date of breast cancer diagnosis. After microdissection of tumor and normal tissue from paraffin-embedded tissue blocks, DNA was extracted and samples were examined for LOH at chromosomal segments encompassing BRCA1 and BRCA2. Breast cancer specimens were also evaluated in a blinded fashion for tumor grade and immunoreactivity to estrogen and progesterone receptors, p53, her2-neu, and topoisomerase II alpha. Comparisons were made between the case and control populations using chi2 analysis, and a paired Student's t test. Survival differences were evaluated using a log-rank test. RESULTS: From January 1960 to December 1983, 917 patients were diagnosed with Hodgkin's disease. Twelve patients were subsequently diagnosed with breast cancer and tissue blocks were available on 10 cases. No statistical difference was observed between the case and control populations for LOH at BRCA1 or BRCA2. In the Hodgkin's disease group, LOH was observed in 30% of tumors at BRCA1 and 10% of tumors at BRCA2 vs. 10% and 0% of tumors in the control group at BRCA1 and BRCA2, respectively. Breast tumors from patients who received radiation therapy for Hodgkin's disease displayed greater nuclear pleomorphism (p < 0.02), and an increase in topoisomerase II alpha expression (p < 0.05) vs. the control population. Five of 10 patients were pregnant at the time of their Hodgkin's treatment, and those patients had a shorter time interval to the development of breast cancer compared with the patients who were not pregnant (12.4 years compared with 18.6 years). There was no significant difference in disease-free survival; however, overall survival was inferior in the population previously treated with radiation therapy for Hodgkin's disease (p = 0.01). 80% of patients with a previous Hodgkin's diagnosis died of breast cancer or treatment related effects vs. 30% in the control group. CONCLUSION: We were unable to find statistical evidence for LOH at BRCA1 and BRCA2 in breast cancers from patients previously irradiated for Hodgkin's disease. Breast cancer diagnosed after mantle irradiation may be more biologically aggressive based on the greater nuclear pleomorphism and increase in topoisomerase II alpha staining. This did not translate into a statistical difference in breast cancer disease-free survival; however, overall survival was significantly inferior in the Hodgkin's disease patients.

Adolescent↗

Tumour necrosis factor-alpha (-308) gene polymorphism in obstructive sleep apnoea-hypopnoea syndrome.

Patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) have elevated circulating levels of tumour necrosis factor (TNF)-alpha. The hypothesis in this study was that OSAHS might be associated with the TNF-alpha (-308A) gene polymorphism, which results in increased TNF-alpha production. This hypothesis was examined in OSAHS patients, their siblings and population controls. A total of 206 subjects were recruited. All underwent sleep studies and clinical review, and were subsequently classified as having OSAHS or not depending on apnoea-hypopnoea frequency, sex, age and symptoms. All subjects had blood collected and genotyping was performed on DNA extracted from peripheral leukocytes. Some 192 random UK blood donors were used as population controls. The results demonstrated a significant association for TNF-alpha (-308A) allele carriage with OSAHS (OR=1.8; 95% Confidence interval: 1.18-2.75) when compared with population controls. Siblings with OSAHS were significantly more likely to carry the TNF-alpha (-308A) allele. In addition, 21 pairs of male siblings discordant for carriage of the -308A allele showed a significant level of discordance for the OSAHS phenotype. In conclusion, this study demonstrates an association of tumour necrosis factor-alpha (-308A) carriage with obstructive sleep apnoea-hypopnoea syndrome, suggesting that inflammation may be implicated in the pathogenesis of this condition.

Adult↗

International actors and population policies in India, with special reference to contraceptive policies.

The international population policy agenda has traditionally been dominated by demographically driven population control policies. However, in the population policy development that preceded the International Conference on Population and Development in 1994, people's reproductive needs and rights received more emphasis. The aim of this study was to analyze how the new emphasis in population policies has been interpreted at the country level. In analyzing population policy rhetoric and its practical interpretations in India in 1994, the authors found that the rhetoric was broadening to encompass women's empowerment and reproductive health and that the use of direct method-specific monetary incentives and disincentives for accepting family planning methods was disapproved. However, population policy options were still considered mainly in terms of their ability to reduce fertility. Furthermore, the increased emphasis on the general market agenda was more important than that on reproductive needs and rights in molding population policies, as was evident in the greater stress on cost-recovery systems and nongovernmental actors. The findings suggest that the broader agenda for population policies and reproductive rights has been interpreted so that it can serve the aims of population-growth control and be implemented in the context of more market-oriented social policies and trade liberalization.

Contraception↗

Bone metabolism in endurance trained athletes: a comparison to population-based controls based on DXA, SXA, quantitative ultrasound, and biochemical markers.

In general, physical exercise appears to have favorable effects on the skeleton. However, a few recent reports have described negative effects, including reduced bone density (BMD) and high bone turnover in runners. The aim of our study was to compare endurance runners to controls with respect to BMD at different sites and ultrasound transmission through the peripheral skeleton, and to use PTH, total serum calcium, and biochemical markers of bone metabolism as a complement in evaluating the effects of endurance running on bone. Thirty runners (mean age 32 years, range 19-54 years) participated in the study. Their main form of training consisted of endurance running at moderate intensity for about 7 hours (range 2-12 hours) per week, and they had been active in their sport for about 12 years (range 1-21 years). For a comparison, 30 age- and sex-matched population based controls were investigated. BMD values, measured by dual energy X-ray absorptiometry (DXA), were higher in runners than in controls for the total body (3.6%; P = 0.03), legs (9.6%; P = 0. 001), femoral neck (10.0%; P = 0.01), trochanter (9.9%; P = 0.01), and Wards triangle (11.8%; P = 0.02), but not in the lumbar spine or in the forearm measured by single energy X-ray absorptiometry (SXA). The quantitative ultrasound measurement of the calcaneus also revealed higher values in runners than in controls for both broadband ultrasound attenuation (9.2%; P = 0.002) and speed of sound (3.1%; P = 0.0001). At all sites, BMD was related to ultrasound measurements in controls, but no such relationship was evident in runners. Concentrations of parathyroid hormone (PTH) were lower (23.2%; P = 0.02) in runners than in controls, whereas total serum calcium concentrations were slightly higher (3.0%; P = 0.003). The levels of PICP (bone formation) and ICTP (bone resorption) in serum were lower (18.0%; P = 0.03 and 22.2%; P = 0.004, respectively) in runners than in controls, but no differences were seen for osteocalcin or bone specific alkaline phosphatase (b-ALP). In conclusion, BMD at the focus of strain for running, that is, the legs, is higher in endurance runners when compared to matched controls. Low bone turnover in runners, indicated by lower levels of PTH and biochemical markers of bone metabolism, point to an influence of endurance running at the cellular level.

Absorptiometry, Photon↗

Pharmacogenetic polymorphisms of the AR and metabolism and susceptibility to hormone-induced azoospermia.

Clinical trials of hormonal male contraceptive regimens have identified a consistent population polymorphism in susceptibility to hormone-induced azoospermia. Using identical hormonal regimens, fewer men of European origin (approximately two thirds) become azoospermic compared with Asian men who virtually all become azoospermic. This variation within and between populations remains unexplained. To investigate pharmacogenetic differences in androgen metabolism or action that might explain variable susceptibility to hormonal-induced azoospermia, we studied single nucleotide polymorphism in the CYP3A4 gene, which encodes the major hepatic T-inactivating enzyme, and CAG and GGC triplet repeats in the AR gene in 75 Australian volunteers participating in a male hormonal contraceptive study and 106 population controls. These men were classified into groups according to whether 6 months of weekly T enanthate injections produced azoospermia (n = 54), near-azoospermia (n = 7), and nonazoospermia (n = 14). Mutagenically differentiated PCR was designed to identify A/G variants in the promoter region of the CYP3A4 gene. Fluorescent-labeled DNA fragments containing either CAG or GGC repeats were amplified from the genomic DNA, and their sizes were determined based on the capillary electrophoresis. The G allele of CYP3A4 gene was absent from the nonazoospermia and near-azoospermia groups, but overall this single nucleotide polymorphism distribution did not differ significantly between men in the azoospermia group or population controls. There were no significant differences in distribution of CAG and GGC triplet repeats among three groups or between them and the population controls based on the maximum likelihood estimate of the odds ratio and CLUMP II analyses. These results suggested that neither genetic polymorphisms in the AR gene (CAG and GGC repeats) nor that in hepatic androgen metabolism (CYP3A4 A/G variant) were the major contributors to the within-population variations in susceptibility to T-induced azoospermia.

Adult↗

Polymorphic forms of prostate specific antigen and their interaction with androgen receptor trinucleotide repeats in prostate cancer.

BACKGROUND: Recent data has suggested that polymorphisms in the prostate specific antigen (PSA) may increase prostate cancer (PC) risk. The PSA gene contains a G/A substitution in the androgen response element (ARE) 1 region. The androgen receptor (AR) gene has polymorphic regions containing variable length glutamine and glycine repeats and these are believed to be associated with PC risk. The effect on PC risks from PSA polymorphisms alone and synergistically with the AR gene was examined in this report. METHODS: One hundred PC patients and an age matched cohort of 79 benign prostate hyperplasia and 67 population controls were entered in this study. DNA was extracted from blood and PSA/ARE promoter region amplified by PCR. PCR products were cut with Nhe 1 restriction enzyme to distinguish G/A alleles. AR/CAG and GGC repeat length was detected by automated fluorescence from PCR products. RESULTS: We found a significantly higher PSA/GG distribution in PC (30%) than either benign prostatic hyperplasia (BPH) (18%) or population controls (16%) (P = 0.025). Furthermore the GG distribution within cases was even greater in younger men (< 65 years; 42%; P = 0.012). Additionally, when PSA genotype was cross classified with CAG repeat, significantly more cases than both BPH and population controls were observed to have a short (< 22) CAG/GG genotype (P = 0.006). CONCLUSIONS: Our results indicate that the PSA/ARE GG genotype confers an increased risk of PC especially among younger men. Moreover, we confirm previous results that a short glutamine repeat in conjunction with GG genotype significantly increases the risk of malignant disease.

Aged↗

Distressful symptoms after radical radiotherapy for urinary bladder cancer.

BACKGROUND: Radical radiotherapy for muscle-invasive urinary bladder cancer can sterilize the tumour with preserved organ function. Here we studied symptoms, symptom distress and trade-off among long-term survivors and compared figures to those of population controls and patients who had undergone cystectomy. MATERIALS AND METHODS: We identified 71 patients who had had urinary bladder cancer treated with radical radiotherapy before 1995. For comparison, 325 patients treated with radical cystectomy and urostomy, continent or non-continent, during the same period and 460 individuals randomly selected from the general population were included. Information was collected by means of an anonymously answered postal questionnaire to avoid investigator-related bias. RESULTS: Answers were obtained from 58 (82%) radiated patients, 251 (85%) cystectomized patients and 310 (71%) population controls. Of the radiated patients, 74% reported little or no distress from symptoms from the urinary tract, 38% had had intercourse the previous month and 57% (men) reported they had ejaculated. Among the cystectomized patients, 13% had had intercourse and 0% (men) had ejaculated. Moderate or much distress from symptoms from the gastrointestinal tract was reported by 32% of the radiated patients, 24% of the cystectomized patients and 9% of the population controls. After radical radiotherapy, 46% of the patients were willing to accept some risk of decreased survival to become symptom-free. CONCLUSIONS: About 3/4 of these long-term survivors after radical radiotherapy for bladder cancer had a functioning urinary bladder with little or no distress from the urinary tract. The prevalence of sexual dysfunction was lower than after cystectomy and the prevalence of distress from the gastrointestinal tract was comparable.

Aged↗

Anti-Helicobacter pylori antibodies prevalence and gastric adenocarcinoma in Portugal: report of a case-control study.

Evidence from large cohort studies has established an increased risk of gastric cancer for individuals infected with Helicobacter pylori (HP). In low incidence countries, like the United Kingdom and Sweden, case-control studies suggested that the prevalence of anti-HP antibodies in gastric cancer patients (at the time of cancer diagnosis) is greater than in control populations. We present results from a case-control study of the prevalence of IgG anti-HP antibodies in gastric cancer patients and a control population in a country with a high incidence of gastric cancer. Sera were studied from 80 gastric cancer patients (GC group) admitted consecutively to our department in 1990/91, and from 80 controls (CT group) matched by age and sex. IgG anti-HP was determined by ELISA. Patients' files were reviewed for evidence of previous diagnosis of peptic ulcer, gastric surgery, tumor localization and histopathological classification. Controls were submitted to a questionnaire for past history of peptic ulcer and gastric surgery. Positive results for anti-HP were: gastric cancer patients, 70.0%; control group, 81.5% (NS). However, the median optical densities (OD, a measure of antibody concentration) were significantly lower in the gastric cancer group than in controls: gastric cancer patients, 0.720 +/- 0.424 OD; control group, 0.906 +/- 0.443 OD (P = 0.004). There were no differences concerning past history of peptic ulcer or surgery. The proportion of positives for cancer of the cardia (66.7%) was lower than for the other tumour localizations (70.4%) (NS). Anti-HP positivity was lower in patients with gastric cancer associated with intestinal metaplasia than in controls (P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Incidence and predictors of fractures in children after solid organ transplantation: a 5-year prospective, population-based study.

UNLABELLED: In this population-based prospective follow-up study, children undergoing solid organ transplantation had a highly elevated risk for fractures: The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. Thus, screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied. INTRODUCTION: The incidence and predictors of fractures after solid organ transplantation are not well documented in the pediatric age group. MATERIALS AND METHODS: A total of 196 children, which is 93% of patients surviving kidney, liver, and heart transplantation in our country, participated in a retrospective chart review at enrollment followed by a 5-year prospective follow-up study between January 1999 and December 2004. Hospital and medical records were reviewed. All children underwent clinical examinations and answered questionnaires concerning fracture history at the beginning and at the end of the prospective follow-up. Radiographs of the thoracic and lumbar spine were obtained. The fracture incidence was compared with data obtained from public health registries. RESULTS: Seventy-five (38%) of the transplant patients suffered from a total of 166 fractures after organ transplantation. The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. The age- and sex-adjusted hazard ratios (95% CI) were 61.3 (40.7-92.4) for vertebral, 17.9 (8.96-35.8) for symptomatic vertebral, 0.99 (0.65-1.50) for nonvertebral, and 2.90 (2.25-3.73) for all fractures in the patients compared with the control population. In a multivariate analysis, older age (hazard ratio [95% CI]; 2.02 [1.07-3.83]), male sex (2.15 [1.22-3.81]), liver transplantation (1.78 [1.01-3.14]), and fractures before transplantation (2.02 [0.92-4.47]) were the most significant independent risk factors. CONCLUSIONS: Children undergoing solid organ transplantation have a highly elevated risk for fractures. Screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied.

Adolescent↗

The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis.

BACKGROUND AND AIMS: We used a multistate modeling approach to assess the effect of ursodeoxycholic acid (UDCA) therapy on the natural course of primary biliary cirrhosis (PBC), which remains controversial. METHODS: Our population included 262 patients with PBC who had received 13-15 mg/kg UDCA daily for a mean of 8 years (range, 1-22 years). Data were analyzed using a multistate Markov model, with histologic stage progression, death, and orthotopic liver transplantation (OLT) as main end points. Survival without OLT was compared with that predicted by the updated Mayo model and with the expected survival in the control population. RESULTS: Forty-five patients developed cirrhosis, 20 underwent OLT, and 16 died by the censor date. Ten deaths were due to liver disease. The overall survival rates were 92% at 10 years and 82% at 20 years. Survival rates without OLT were 84% and 66% at 10 and 20 years, respectively, which were slightly lower than the survival rate of an age- and sex-matched control population (relative risk [RR], 1.4; P = .1) but better than the spontaneous survival rate as predicted by the updated Mayo model (RR, .5; P < .01). The survival rate of patients in stage 1 and 2 was similar to that in the control population (RR, .8; P = .5), whereas the probability of death or OLT remained significantly increased in treated patients in late histologic stages (RR, 2.2; P < .05). CONCLUSIONS: Treatment with UDCA alone normalizes the survival rate of patients with PBC when given at early stages. However, there is a continued need for new therapeutic options in patients with advanced disease.

Adult↗