Prevalence of eosinophilic esophagitis in a United States military health-care population.

Eosinophilic esophagitis (EoE) is a rapidly emerging chronic immune-mediated condition affecting children and adults, both genders, and all races. A large variation in the prevalence of EoE exists in the literature. The aim of this study is to establish the prevalence of EoE in a military health-care population in the United States using a comprehensive electronic medical record search. Using the International Classification for Diseases-9 code for EoE (530.13), the total number of EoE patients enrolled in the military health-care system from October 1, 2008 to September 30, 2009 including active-duty military, dependents of military personnel, and retirees were identified. For each case of EoE identified, demographic data (age, gender, and race) and geographic location was obtained. The overall prevalence of EoE was calculated as well as the prevalence within subgroups. The geographic regional locations were reported per the U.S. Census Bureau regions (Northeast, South, Midwest, and West). A total of 987 EoE patients were identified from 10,180,515 military health-care beneficiaries, establishing an overall prevalence of 9.7 per 100,000 (95% confidence interval [CI] 9.1-10.3). Seven hundred twenty-eight out of 7,707,372 adult patients were identified, establishing a prevalence of 9.5 per 100,000 (95% CI 8.8-10.1). Two hundred fifty-nine out of 2,473,143 pediatric patients were identified, establishing a prevalence of 10.5/100,000 (95% CI 9.2-11.8). EoE was more prevalent in males (odds ratio [OR] 2.03 [95% CI 1.78-2.32]) and higher in Caucasian versus African Americans (18.1 vs. 5.2/100,000, OR 3.47 [95% CI 2.40-5.03]). EoE was more prevalent in the Western region of the United States compared with the Northeast, South, and Midwest regions, with a prevalence of 11.9 versuss 5.2, 9.6, and 9.2 per 100,000, respectively. When comparing Northern with Southern states, there was an increased prevalence in the North (10.9 vs. 7.2/100,000, P < 0.05). In this large nationwide study, increase in prevalence of EoE was seen in younger adults, with a higher prevalence in Caucasians. Geographically, the western United States had a significantly higher prevalence with a slightly higher prevalence in the Northern latitude.

Which is the eligible patient to be treated with pioglitazone? The expert view.

Pioglitazone has an important role in the treatment of patients with Type 2 diabetes. The drug can help patients to achieve sustained glycemic control and may delay the requirement for insulin. Pioglitazone may provide benefits beyond its effects on glycemia, with data suggesting it may confer anti-atherosclerotic and cardioprotective properties. Attention should be given to possible side effects relating to class effects of TZD, and selection of appropriate patients to be prescribed pioglitazone will enable optimum benefits to be derived from pioglitazone treatment.

Mental stress induces transient endothelial dysfunction in humans.

BACKGROUND: Mental stress has been linked to increased morbidity and mortality in coronary artery disease and to atherosclerosis progression. Experimental studies have suggested that damage to the endothelium may be an important mechanism. METHODS AND RESULTS: Endothelial function was studied in 10 healthy men (aged 50. 4+/-9.6 years) and in 8 non-insulin-dependent diabetic men (aged 52. 0+/-7.2 years). Brachial artery flow-mediated dilation (FMD, endothelium dependent) and response to 50 microg of sublingual glyceryl trinitrate (GTN, endothelium independent) were measured noninvasively by use of high-resolution ultrasound before and after (30, 90, and 240 minutes) a standardized mental stress test. The same protocol without mental stress was repeated on a separate occasion in the healthy men. In healthy subjects, FMD (5.0+/-2.1%) was significantly (P:<0.01) reduced at 30 and 90 minutes after mental stress (2.8+/-2.3% and 2.3+/-2.4%, respectively) and returned toward normal after 4 hours (4.1+/-2.0%). Mental stress had no effect on the response to GTN. In the repeated studies without mental stress, FMD did not change. The diabetic subjects had lower FMD than did the control subjects (3.0+/-1.5% versus 5.0+/-2.1%, respectively; P:=0.02) but showed no changes in FMD (2.7+/-1.1% after 30 minutes, 2.8+/-1.9% after 90 minutes, and 3.1+/-2.3% after 240 minutes) or GTN responses after mental stress. CONCLUSIONS: These findings suggest that brief episodes of mental stress, similar to those encountered in everyday life, may cause transient (up to 4 hours) endothelial dysfunction in healthy young individuals. This might represent a mechanistic link between mental stress and atherogenesis.

Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness.

We compared serum TSH results determined in second and third generation assays in patients with thyroid disease and nonthyroidal illnesses (NTIs) to evaluate the usefulness of the more sensitive assay. We studied 19 subjects with untreated hyperthyroidism, 12 hyperthyroid subjects sampled at 4-week intervals after beginning carbimazole, 153 subjects receiving T4 replacement, and 300 hospital in-patients with a variety of NTIs. Serum TSH was measured, using a second generation immunometric method, together with free T4 and free T3. Samples with subnormal TSH (< 0.5 mU/L) were reassayed, using a more sensitive chemiluminescent immunometric method. Both assays revealed undetectable serum TSH levels in 18 of 19 overtly hyperthyroid patients. Undetectable TSH values (in both assays) were found in 30 of 33 patients with low serum TSH levels who were receiving treatment for hyperthyroidism, in association with normal thyroid hormone levels in 11. Undetectable TSH was evident in both patients receiving T4 and those with NTI, but use of the more sensitive assay led to a reduction in the number of subjects with undetectable TSH compared with the second generation results (T4-treated, 55 vs. 77 cases; NTI, 13 vs. 19 cases). There was a significant correlation between serum TSH and free T4 in the whole group on T4 (P < 0.001) and in those receiving T4 with low TSH (r = -0.33; P < 0.05); no significant correlation was evident in subjects with low serum TSH levels associated with NTI. An improvement in assay sensitivity led to a reduction in the number of patients being treated with T4 or with NTI in whom serum TSH was undetectable and, hence, an increase in those in whom overt hyperthyroidism could be excluded. Undetectable TSH results, even in a third generation assay, are not diagnostic of overt hyperthyroidism, but are also found in subjects with treated thyroid disease and NTI.

Enhanced in vivo platelet release reaction and malondialdehyde formation in patients with hyperlipidemia.

Plasma level of beta-thromboglobulin (beta TG), a useful marker of in vivo platelet "release reaction,"was determined by radioimmunoassay in 69 patients, with three types of primary hyperlipidemia (IIa, IIb, IV) and compared with the findings in age- and sex-matched healthy controls and 57 patients with established atherosclerosis and peripheral vascular disease. Malondialdehyde (MDA) formation, used for assessment of prostaglandin synthesis, was determined in 51 and plasma platelet factor 4 (PF4), measured by radioimmunoassay, in 48 of the patients with hyperlipidemia. Results were correlated to five serum lipids and lipoprotein levels in the patients with hyperlipidemia. beta TG was significantly increased in the patients with hyperlipidemia and peripheral vascular disease, compared to those in the controls (p < 0.001); it was significantly higher in the patients with hyperlipidemia than in those with peripheral vascular disease. PF4 and MDA formation were also increased in the patients with hyperlipidemia, and significantly higher levels of MDA were obtained in patients with type IIb and type IV hyperlipidemia than in those with type IIa hyperlipidemia (p < 0.02). beta TG and MDA correlated weakly with total serum cholesterol triglycerides and very low density lipoprotein-triglyceride. There was also a significant correlation between beta TG and PF4, and MDA production. These results indicate that in vivo platelet "release reaction" and MDA formation are increased in hyperlipidemic patients. The release reaction is more enhanced in those with hyperlipidemia than in the patients with peripheral vascular disease. They suggest that the abnormal platelet function is related to the elevated levels of serum lipids and lipoproteins in the hyperlipidemic patients and not only to the atherosclerotic changes associated with hyperlipidemia.

Effect of estrogen replacement therapy upon bone mineral density in thyroxine-treated postmenopausal women with a past history of thyrotoxicosis.

We have shown that previous thyrotoxicosis and subsequent levothyroxine (L-T4) therapy are together associated with reduction in femoral and lumbar vertebral bone mineral density (BMD) in postmenopausal women. To determine whether estrogen replacement therapy exerts a beneficial effect upon bone loss in this situation, we performed a cross-sectional study comparing BMD measurements of the femur and lumbar spine in four groups of women (n = 15 in each group) matched for age and duration of menopause: (i) those with a previous history of thyrotoxicosis who were subsequently receiving both L-T4 and estrogen replacement therapy for at least 3 years (L-T4 + HRT group), (ii) previously thyrotoxic women matched to group (i) for L- dose and duration who had never used estrogen replacement (L-T4 alone group), (iii) those with no history of thyroid disease who had received estrogen replacement therapy for at least 3 years (HRT alone group), and (iv) those with no history of thyroid disease who had never received estrogen replacement therapy (control group). BMD measurements were higher at each site in the HRT alone group than in controls (6.0-13.6% increases in BMD, p < 0.05 for measurements at femoral neck, Ward's triangle, and trochanter) while measurements of BMD were lower at each site in the L-T4 alone group than in controls (3.3-6.1% reductions in BMD), although values did not reach statistical significance. Measurements at each site in the L-T4 + HRT group were higher than those from the L-T4 alone group (2.2-16.1% increases in BMD, p < 0.05 for measurements at lumbar spine), although lower than in the group receiving HRT alone (p < 0.05 for femoral neck and Ward's triangle) and similar to those in untreated controls. Our results indicate that estrogen replacement therapy abolishes reduction in femoral and vertebral BMD in postmenopausal women with previous thyrotoxicosis and subsequent L-T4 therapy. This potentially beneficial influence of estrogen replacement upon both BMD and fracture risk in postmenopausal women with a history of thyroid disease suggests that estrogen administration should be encouraged in this group.

Combination treatment with cholestyramine and bezafibrate for heterozygous familial hypercholesterolaemia.

Cholestyramine and bezafibrate were compared individually and in combination in the treatment of 18 patients with heterozygous familial hypercholesterolaemia. The study used a double blind, placebo controlled block design with a placebo run in period of two months followed by three phases of active treatment, each of two months' duration. Patients were randomly allocated to one of the six possible sequences of medication so that three patients would be treated with each sequence. Two patients withdrew from the study before completion. The median concentration of total cholesterol decreased from 9.65 mmol/l (interquartile range 8.62 to 8.72) to 7.24 mmol/l (6.70 to 7.52) with cholestyramine, to 8.09 mmol/l (7.18 to 8.68) with bezafibrate, and to 6.31 mmol/l (5.84 to 7.27) with the combination. This fall was due almost entirely to a decrease in the low density lipoprotein cholesterol concentration, and the combination was significantly more effective than either drug alone. The 98% confidence intervals for the median differences between the combination and cholestyramine and the combination and bezafibrate were 0.04 to 1.49 mmol/l and 0.51 to 2.18 mmol/l respectively. These results suggest that this combination is an effective and useful treatment in heterozygous familial hypercholesterolaemia.

Medical management of hyperlipidaemia.

There is increasing evidence that plasma cholesterol, and particularly low-density lipoprotein cholesterol, has a causal role in atherogenesis. The benefits of cholesterol lowering in terms of reduction of coronary heart disease is well established. This should encourage the identification and treatment of patients with hyperlipidaemia.

Reflux episodes detected by impedance in patients on and off esomeprazole: a randomised double-blinded placebo-controlled crossover study.

BACKGROUND: Combined with 24-h pH monitoring, the use of impedance is the most sensitive method available for detecting oesophageal reflux. Normal values for impedance have been previously established in healthy controls studied on and off proton pump inhibitors (PPI). AIMS: To determine the effects of PPIs on the total number of reflux episodes in the distal oesophagus measured by impedance in patients with and without gastro-oesophageal reflux disease (GERD). METHODS: In this prospective randomised double-blinded placebo controlled crossover study, all patients underwent two 24-h pH with impedance studies at least 2 weeks apart. Based on a randomisation scheme, patients received either 40 mg of esomeprazole twice daily for 1 week or identical capsule placebo for 1 week, then all patients were crossed over to the other treatment arm. GERD was defined by the validated Johnson-DeMeester score. Reflux by impedance was defined as a 50% decrease from baseline in retrograde movement of liquid between two impedance sites. RESULTS: Sixty-three patients were enrolled and 41 patients completed the study [mean age 52 ± 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African American]. Overall, there was no significant decrease in the total number of distal impedance episodes with esomeprazole compared with placebo (mean change 6.1 ± 22, P = 0.100). When analysed separately by GERD status, among GERD-positive patients, there was a significant decrease in distal impedance episodes while on esomeprazole compared with placebo (mean change -16 ± 22, P = 0.023), but not in GERD-negative patients (mean change -0.35 ± 20, P = 0.872). CONCLUSION: Esomeprazole decreases significantly the number of reflux episodes detected by impedance, but only in patients with GERD.

Inquest into the death of a prisoner co-infected with HIV and hepatitis C: how many more will there be?

Michael Joseph LeBlanc probably became infected with HIV and Hepatitis C while incarcerated in a federal penitentiary. On 18 November 1999, he died at the Regional Hospital in Kingston Penitentiary of complications relating to hepatitis C. Mr LeBlanc died inhumanely, in extreme physical, psychological and emotional distress. His death raises the issues of transmission and prevention of HIV and hepatitis C, compassionate release, and health care and palliative care in federal prisons. An Inquest under the Coroners Act was held in Kingston, Ontario from 30 January to 1 February 2001. These same issues had been raised previously at the October 1997 coroners inquest into the death of William Bell, a person living with AIDS who died while incarcerated in another federal penitentiary.

Catecholamine content of human erythrocytes.

We used high-performance liquid chromatography with electrochemical detection to measure the catecholamine content of human erythrocytes. The ratio of free norepinephrine to epinephrine was three to four times lower than that in plasma and four to seven times lower than that in platelets. This suggests differences in uptake, degradation, or conjugation of norepinephrine and epinephrine by erythrocytes, as compared with plasma and platelets. Erythrocyte free norepinephrine was significantly greater (P less than 0.01) in women than in men.

Is erectile dysfunction a marker for cardiovascular disease?

There is now significant evidence that erectile dysfunction (ED) can be a symptom of cardiovascular disease, and can act as a marker for disease progression. National Health Service (NHS) prescribing restrictions on treatments for ED have recently been reviewed by the Department of Health, and current arrangements will not change. Unrestricted availability of licensed treatments for ED on the NHS, irrespective of the cause of the ED, may encourage men to present for investigation, enabling early detection of cardiovascular disease. Sildenafil citrate (Viagra), an effective treatment for ED, can also have a direct beneficial effect on cardiovascular disease. Unrestricted NHS availability of ED treatments such as sildenafil could facilitate greater achievement of National Service Framework targets for coronary heart disease.

Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis.

OBJECTIVE: The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD. DESIGN: Case-control studies of patients on long-term T4 therapy who have or have not previously received radioiodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement. PATIENTS: Twenty-seven premenopausal and 60 postmenopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group 1), 39 post-menopausal females with a past history of radioiodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post-menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status. MEASUREMENTS: BMD measured by dual-energy X-ray absorptiometry. Serum biochemistry and tests of thyroid function. RESULTS: No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post-menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences in BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3.9%, P < 0.05) and lumbar spine (5.6-8.5%, P < 0.01) BMD results were found in post-menopausal females in group 1 and reductions in femoral trochanter (3.9%, P < 0.01), Ward's triangle (5.6%, P < 0.05) and lumbar spine (8.5%, P < 0.01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group. CONCLUSIONS: Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post-menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.

Use of the single-strand conformational polymorphism method to detect recurrent and novel mutations in the low-density lipoprotein receptor gene in patients with familial hypercholesterolaemia: detection of a novel mutation Asp200-->Gly.

The single-strand conformational polymorphism (SSCP) method was used to look for mutations in the 3' half of exon 4 of the low-density lipoprotein receptor gene in patients with familial hypercholesterolaemia (FH). One set of conditions were found which allowed the detection of four of the mutations that have previously been reported in this part of the gene and detected in patients in the United Kingdom: the 3-bp deletion (del Gly197) the 2-bp deletion (STOP 216), the Asp206-->Glu mutation and the Cys210-->STOP. The method was used to screen 50 patients with definite or probable FH from London. Two were identified who were carriers of the 3-bp deletion of Gly197, one who was a carrier of the Asp206-->Glu mutation and one who was a carrier of a novel mutation that alters Asp200-->Gly. This mutation creates a cutting site for the restriction enzyme MspI. In a further sample of 200 patients from London with FH one additional apparently unrelated individual was detected who was a carrier of this defect. Thus in the sample of 50 patients, four (8%) had a mutation in this part of exon 4 that could be readily detected using the SSCP method, suggesting that this approach will be useful for rapid screening for mutations in patients with FH.

Mortality after the treatment of hyperthyroidism with radioactive iodine.

BACKGROUND: Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. METHODS: We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had died. The data on the causes of death were compared with data on age-specific mortality in England and Wales. The standardized mortality ratio was used as a measure of relative risk, and the effect of covariates on mortality was assessed by regression analysis. RESULTS: During 105,028 person-years of follow-up, 3611 subjects died; the expected number of deaths was 3186 (standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to 1.2; P<0.001). The risk was increased for deaths due to thyroid disease (106 excess deaths; standardized mortality ratio, 24.8; 95 percent confidence interval, 20.4 to 29.9), cardiovascular disease (240 excess deaths; standardized mortality ratio, 1.2; 95 percent confidence interval, 1.2 to 1.3), and cerebrovascular disease (159 excess deaths; standardized mortality ratio, 1.4; 95 percent confidence interval, 1.2 to 1.5), as well as fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9; 95 percent confidence interval, 2.0 to 3.9). The excess mortality was most evident in the first year after radioiodine therapy and declined thereafter. CONCLUSIONS: Among patients with hyperthyroidism treated with radioiodine, mortality from all causes and mortality due to cardiovascular and cerebrovascular disease and fracture are increased.

Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study.

BACKGROUND: Radioiodine is used increasingly as first-line treatment for hyperthyroidism, but concerns remain about subsequent risk of cancer, especially in those treated at a young age. We investigated cancer incidence and mortality in patients treated with radioiodine for hyperthyroidism. METHODS: We did a population-based study in 7417 patients treated in Birmingham, UK, between 1950 and 1991. We compared details of all cancer diagnoses and deaths in 1971-91 from the UK Office for National Statistics with data on cancer incidence and mortality for England and Wales specific for age, sex, and period. FINDINGS: During 72,073 person-years of follow-up, 634 cancer diagnoses were made, compared with an expected number of 761 (standardised incidence ratio [SIR] 0.83 [95% CI 0.77-0.90]). The relative risk of cancer mortality was also decreased (observed cancer deaths 448, expected 499; standardised mortality ratio [SMR] 0.90 [0.82-0.98]). Incidence of cancers of the pancreas, bronchus, trachea, bladder, and lymphatic and haemopoietic systems was lowered. Mortality from cancers at all these sites was also reduced but findings were significant only for bronchus and trachea. There were significant increases in incidence and mortality for cancers of the small bowel (SIR 4.81 [2.16-10.72], SMR 7.03 [3.16-15.66]) and thyroid (SIR 3.25 [1.69-6.25], SMR 2.78 [1.16-6.67]), although absolute risk of these cancers was small. INTERPRETATION: The decrease in overall cancer incidence and mortality in those treated for hyperthyroidism with radioiodine is reassuring. The absolute risk of cancers of the small bowel and thyroid remain low, but the increased relative risk shows the need for long-term vigilance in those receiving radioiodine.