Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

The phenotype of Graves' orbitopathy is associated with thyrotropin receptor antibody levels.

PURPOSE: Graves' orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO. METHODS: Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively. RESULTS: Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis. CONCLUSIONS: TSH-R-Ab were significantly associated with GO's phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.

Health care access of thyroid disease patients in Serbia during the COVID-19 pandemic.

PURPOSE: The aim of this study was to assess the impact of repurposing health care facilities in response to COVID-19 on the access of patients with thyroid disease to health care. METHODS: This study consisted of a web-based survey. The survey was anonymous and consisted of forty questions. RESULTS: This survey included 206 respondents. 91.3% of the respondents had health insurance through the Republic Fund of Health Insurance, 9.7% had private or both health insurances, and 3.4% did not have any health insurance. A significant proportion of respondents (60.4%) had to switch from public to private health care to reach a physician and 73.8% had to switch from public to private laboratories. For the 91.9%, this was perceived as a financial burden. Before the pandemic, 83.1% of respondents reported regular follow-up by physicians, which decreased to 44.9% during the pandemic (p < 0.01). 76.3% of the respondents regarded that their thyroid disease was managed optimally before the pandemic, while this figure declined to only 48% during the pandemic (p < 0.01). CONCLUSIONS: The COVID-19 pandemic disrupted the medical care of thyroid patients in Serbia. For the patients treated in the public health care system, access to general practice was hindered, while access to specialist care was disrupted. It led to a switch from public to private health care, which was perceived as a financial burden for almost all the respondents. However, private health care proved to be an important safety net when the public system was overwhelmed.

Clinical value of functional thyrotropin receptor antibodies in Serbian patients with Graves' orbitopathy.

PURPOSE: Thyrotropin receptor autoantibodies (TSH-R-Ab) are heterogeneous in their biological function and play a significant role in the pathophysiology of both Graves' disease and Graves' orbitopathy (GO). The clinical significance and utility of determining functional TSH-R-Ab in a Serbian collective were evaluated. METHODS: 91 consecutive patients with GO were included in this study. Total TSH-R-Ab concentration, referred to as TSH-R binding inhibitory immunoglobulins (TBII) was detected using a competitive-binding immunoassay. Stimulating and blocking TSH-R-Ab (TSAb and TBAb) were measured with cell-based bioassays. RESULTS: Stimulating TSAb activity and TBII positivity were detected in 85 of 91 (93.4%) and 65 of 91 (71.4%) patients with GO (P < 0.001). Blocking TBAb activity was observed in only one patient who expressed dual stimulating and blocking TSH-R-Ab activity. The sensitivity rates for differentiating between clinically active versus inactive and mild versus moderate-to-severe GO were 100% and 100% for TSAb, respectively. In contrast, these were 82% and 87% only for TBII. Seven of eight (87.5%) and one of eight (12.5%) euthyroid patients with GO were TSAb and TBII positive, respectively (P < 0.031). TSAb serum levels significantly predicted GO activity compared to TBII (odds ratio, OR, 95%CI: 3.908, 95%CI 1.615-9.457, P = 0.003; versus 2.133, 0.904-5.032, P = 0.084, univariate analysis; and OR 4.341, 95%CI 1.609-11.707, P = 0.004; versus 2.337, 0.889-6.145, P = 0.085 multivariate analysis). CONCLUSION: Stimulating TSAb are highly prevalent in patients with GO and show superior clinical characteristics and predictive potential compared to the traditionally used TBII.

Antithyroid drugs in Graves' hyperthyroidism: differences between "block and replace" and "titration" regimes in frequency of euthyroidism and Graves' orbitopathy during treatment.

PURPOSE: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves' hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether 'Block and Replace' (B + R) and 'Titration' (T) regimes are equivalent in terms of frequency of euthyroidism and Graves' Orbitopathy (GO) during ATD therapy. METHODS: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution's policy. RESULTS: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27-0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. CONCLUSION: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Mutations in CRLF1 cause familial achalasia.

We here report a family from Libya with three siblings suffering from early onset achalasia born to healthy parents. We analyzed roughly 5000 disease-associated genes by a next-generation sequencing (NGS) approach. In the analyzed sibling we identified two heterozygous variants in CRLF1 (cytokine receptor-like factor 1). Mutations in CRLF1 have been associated with autosomal recessive Crisponi or cold-induced sweating syndrome type 1 (CS/CISS1), which among other symptoms also manifests with early onset feeding difficulties. Segregation analysis revealed compound heterozygosity for all affected siblings, while the unaffected mother carried the c.713dupC (p.Pro239Alafs*91) and the unaffected father carried the c.178T>A (p.Cys60Ser) variant. The c.713dupC variant has already been reported in affected CS/CISS1 patients, the pathogenicity of the c.178T>A variant was unclear. As reported previously for pathogenic CRLF1 variants, cytokine receptor-like factor 1 protein secretion from cells transfected with the c.178T>A variant was severely impaired. From these results we conclude that one should consider a CRLF1-related disorder in early onset achalasia even if other CS/CISS1 related symptoms are missing.

Further studies on delineating thyroid-stimulating hormone (TSH) reference range.

The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.

Glucocorticoid effect on insulin sensitivity: a time frame.

It is well known that glucocorticoids induce insulin resistance, but the exact time scale in humans is not well known. The aim of the study was to determine the time scale of effects of pharmacologic doses of glucocorticoids on insulin sensitivity. Subjects were treated with repeated methylprednisolone infusions and oral prednisone for Graves' orbitopathy. Insulin sensitivity was determined using euglycemic hyperinsulinemic clamp (EHGC) before, during the first glucocorticoid infusion and after 2 months of treatment. EHGC started 2 h after the start of the glucocorticoid infusion, and lasted for 2 h. In another group of patients, insulin sensitivity was determined by short insulin tolerance test (SITT) before and during the first glucocorticoid infusion. SITT started 15 min after the start of the glucocorticoid infusion and lasted for 15 min. Ten subjects were included in each protocol. All were euthyroid during the study period. Four hours after the start of the glucocorticoid infusion significant reduction of insulin sensitivity was observed, which did not change for a further 2 months of glucocorticoid treatment [before 7.82 (95% confidence interval (CI) 5.35-10.29), first infusion, 4.93 (95% CI 2.99-6.87), after 2 months 5.36 (95%CI 3.91-6.81) mg/kg/min]. No significant change in insulin sensitivity occurred during the first 30 min of glucocorticoid infusion [before 139.7 (95%CI 94.1-185.3), during 146.7 (95%CI 106.3-187.1) mumol/l/min]. In humans, glucocorticoid- induced insulin resistance develops quickly, in about 4 h, and does not change during further glucocorticoid treatment.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

Autoimmunity and thyrotropin level in developing thyroid malignancy.

OBJECTIVE: Malignancies and autoimmune thyroid disease are still controversial, but recent studies prove that a long lasting thyroid disease may be linked with malignancy, e.g. papillary thyroid carcinoma in patients with Hashimoto thyroiditis. Having in mind that thyrotropin is a thyroid growth factor, the relationship between its serum values, as well as the levels of anti-peroxidase and anti-thyroglobulin antibodies and thyroid malignancy in patients with nodular thyroid goiter was examined. PATIENTS AND METHODS: Six-hundred-thirty-seven medical records, which included the thyroid fine-needle aspiration cytology were retrospectively evaluated. Patients were grouped regarding the levels of thyrotropin, anti-peroxidase and anti-thyroglobulin antibodies (in or out of the reference ranges) and compared with cytology findings for establishing their prognostic potential for malignancy. RESULTS: Elevated serum thyrotropin (≥ 4.5 mIU/L) was found in 27.3% of patients with thyroid malignancy compared with 10.8% with benign and 16.1% with unspecified cytology finding (p < 0.01). In the group of patients with malignant cytology findings 7.0% of them had elevated anti-peroxidase antibodies level, and 1.4% had anti-peroxidase antibodies level in reference range. In the group of patients with malignant cytology findings 4.2% of them had elevated anti-thyroglobulin antibodies level, and 1.4% had anti-thyroglobulin antibodies level in reference range. CONCLUSIONS: In patients with elevated serum thyrotropin concentration and/or chronic thyroiditis the occurrence of thyroid malignancy is increased.

Effect of weight loss on the pulsatile insulin secretion.

The aim of the study was to assess whether pulsatile insulin secretion is variable in the same individual and is related to changes in insulin sensitivity. Insulin sensitivity and pulsatility were measured before and after weight reduction in nine obese subjects. A pulsatility analysis was done using the PulsDetekt program. Blood was sampled every 2 min over a period of 90 min. The secretion randomness was quantified using approximate entropy (ApEn), and ApEn normalized by SD of the insulin time series (nApEn). Lower values indicate more regular secretion. Insulin sensitivity was measured using the homeostasis model assessment. Data are presented as median, minimum-maximum. After weight loss insulin sensitivity was increased (12.16, 7.60-76.70 vs. 38.96, 19.88-74.96%), the number of insulin pulses was reduced (11, 8-16 vs. 9,6-12), and they were more regular (ApEn, 0.92, 0.53-133 vs. 0.69,0,40-1.27; nApEn, 1.07, 0.74-1.33 vs. 0.97, 0.54-1.42). Before and after the weight loss there was a correlation between ApEn and nApEn and insulin sensitivity. Therefore, insulin secretion regularity is variable in the same individual and is related to insulin sensitivity.

Optimizing the diagnostic criteria for standard (250-microg) and low dose (1-microg) adrenocorticotropin tests in the assessment of adrenal function.

ACTH stimulation is the standard test for assessment of adrenal function. It was suggested that the low dose (1 microg) would be more sensitive for detecting mild secondary adrenal insufficiency than the usual dose of 250 microg. The aim of this study was to find the optimal diagnostic criteria and to compare standard dose test (SDT) with the low dose test (LDT). A group of patients treated with corticosteroids for the 6 months was considered to have hypothalamo-pituitary-adrenal impairment. Studies were performed in 14 corticosteroid-treated and 28 control subjects in random order on 2 consecutive days. Tests were analyzed using the receiver operating characteristic curve method. The best test was cortisol increment at 15 min of the LDT. It was significantly better than the cortisol concentration at 15 min of the SDT, the best test during the SDT (receiver operating characteristic curve area and 95% confidence interval: LDT, 0.997 and 0.956-0.999; SDT, 0.827 and 0.662-0.929; P = 0.0113). For the cortisol increment at 15 min of the LDT at 100% sensitivity, the diagnostic value was 100 mmol/L, and the specificity was 96%. Therefore, the LDT is superior to the standard dose test in the assessment of secondary adrenal insufficiency.

Effect of insulin sensitivity on pulsatile insulin secretion.

OBJECTIVE: The aim of the study was to determine whether derangements in insulin pulsatility are related to the presence of insulin resistance or whether these changes occur only in non-insulin-dependent diabetes mellitus (NIDDM). DESIGN AND METHODS: The study included 26 obese, 11 NIDDM and 10 control subjects. The obese group was divided into a low insulin (plasma insulin <20 mU/l, OLI, 14 subjects) and a high insulin (OHI, 12 subjects) group. For pulsatility analysis blood was sampled every 2 min for 90 min. Pulsatility analysis was carried out using the PulsDetekt program. The insulin secretion randomness was quantified using interpulse interval deviation (IpID) and approximate entropy (ApEn). ApEn and ApEn normalized by s.d. of the individual insulin time series (nApEn) were calculated. Lower values of ApEn and IpID indicate more regular secretion. Homeostasis model assessment (HOMA) was used to quantify insulin sensitivity. RESULTS: Insulin pulses were significantly less regular in the OHI and the NIDDM groups compared with the control and the OLI groups (control: ApEn 0.54+/-0.16, nApEn 0.69+/-0.19, IpID 2.53+/-0.99; OLI: ApEn 0.64+/-0.12, nApEn 0. 79+/-0.15, IpID 2.92+/-1.09; OHI: ApEn 0.88+/-0.07, nApEn 0.92+/-0. 07, IpID 3.95+/-0.84; NIDDM: ApEn 0.92+/-0.16, nApEn 0.99+/-0.09, IpID 4.41+/-0.53; means +/- s.d.). There was no difference in the pulse regularity between the OHI and the NIDDM groups. CONCLUSIONS: Decrease in insulin sensitivity was correlated with the reduction of insulin secretion regularity. Therefore irregular insulin secretion is related to a reduction in insulin sensitivity, and it is not unique to NIDDM.

Microalbuminuria is associated with salt sensitivity in hypertensive patients.

We have investigated 59 patients with mild-to-moderate uncomplicated essential hypertension in order to estimate whether salt sensitivity is associated with greater urinary albumin excretion. Patients whose average mean blood pressure (BP) value on day 5 of the high-sodium regimen (300 mmol/l NaCl) exceeded 10 mm Hg or more than that on day 5 of the low-sodium regimen (40 mmol/l NaCl) were classified as salt sensitive. We have demonstrated that salt sensitive patients (n = 29) manifest greater urinary albumin excretion than salt resistant patients (51.5 +/- 15 vs 11.5 +/- 12.8 mg/24h). Hypertensive patients selected as salt sensitive had a longer duration of hypertension (87 +/- 62 vs 41.5 +/- 33.6 months); greater body mass index (BMI) (29.0 +/- 4.7 vs 24.7 +/- 3.6 kg/m2); lower urinary excretion of sodium after 3 days of sodium loading (172.1 +/- 23.3 vs 245.8 +/- 21.6 mmol/day); and slightly, but significantly higher mean BP (121.3 +/- 7.4 vs 115.3 +/- 5.3 mmHg) than salt resistant patients (n = 29). Nevertheless, there was no significant correlation between duration of hypertension and the degree of urinary albumin excretion in salt sensitive patients. On the other hand, a significant correlation was demonstrated in a group of salt resistant hypertensive patients, suggesting that salt sensitivity could be linked with an early tendency to abnormal albumin excretion, while in salt resistant patients it may depend on hypertension-related renal disfunction. Therefore, measurement of microalbuminuria in patients with essential hypertension can be a useful marker for salt sensitivity.

Inhibition of skin cancer by IP6 in vivo: initiation-promotion model.

A two-stage mouse skin carcinogenesis model was used to examine the effects of IP6 on initiation and promotion phases of tumorigenesis. Seven week old ICR female mice were divided into 6 groups, each consisting of 20 animals. Initiation was performed by a single application of the carcinogen 7,12-dimethyl benz(a)anthracene (DMBA) (50 micrograms) to the back skin. Three weeks later, local application of the promoter TPA was started (2.5 micrograms, 2 x/week) and continued up to the end of the experiment (22 weeks). Mice were also administered 2% IP6 in drinking water over the entire duration of the experiment, or during the initiation (initial 3 weeks) or promotion (final 19 weeks) periods only. The animals consuming IP6 during the initiation stage showed an approximately 50% reduction in the mean number of papillomas per animal, as well as in the number of tumor bearing mice. However, no such inhibition was observed when IP6 was given during the tumor promotion stage. In a separate experiment the effects of IP6 on epithelial cell growth were assessed by BrdU labeling at several time points. Statistically significant inhibition of cell proliferation was observed during the initiation stage (one week after DMBA treatment) in the group given IP6. No inhibition was evident during the promotion stage.

Functional capacity late after partial left ventriculectomy: relation to ventricular geometry and performance.

OBJECTIVES: While partial left ventriculectomy (PLV) may improve functional status, the duration and determinants of this improvement are poorly known. This study sought to assess the relationship between left ventricular (LV) shape and function and functional status in late survivors after PLV for non-ischemic dilated cardiomyopathy (DCM). METHODS: We assessed the relations between LV shape and function and functional status in 17 consecutive patients who survived >12 months after PLV for non-ischemic DCM. Invasive diagnostic studies were performed before, early after, at mid-term after, and late after PLV. According to their functional status after >12 months of follow-up, patients were divided into responders (n=10) or non-responders (n=7). RESULTS: After PLV, the LV systolic major-to-minor axis ratio was higher in responders at early, mid-, and late follow-up (P=0.003, P=0.008 and P=0.04, respectively). LV circumferential end-diastolic stress decreased early after PLV, but increased afterwards in non-responders only (P=0.049). LV ejection fraction was similar in the two groups at baseline, and at early and mid-follow-up, but was lower in non-responders at late follow-up (P=0.006). However, LV end-diastolic and end-systolic volumes, and LV end-systolic circumferential stress showed no difference between the two groups. CONCLUSIONS: It appears that poor functional capacity in late post-PLV survivors is related to postoperative LV geometry.

Fulminant septicemic syndrome of Bacillus cereus in a leukemic patient.

We report a rapidly fatal Bacillus cereus septicemia in a leukemic patient receiving remission-induction therapy. Symptoms resembling food poisoning and fever preceded coma accompanied by neurologic abnormalities. Autopsy revealed necrotizing leptomeningitis with subarachnoid hemorrhage and coagulation necrosis of the liver with bacterial infiltration. These clinicopathologic findings were closely similar to those of reported cases. Because of a rapidly fatal clinical course, suspicion of this syndrome early in the course is important to determine an appropriate treatment. Therefore, we propose that this type of septicemia should be termed as fulminant septicemic syndrome of Bacillus cereus.

[Enteral nutrition in patients with ileostomies and jejunostomies]. / Enteralna ishrana bolesnika sa ileo-i jejunostomom.

Jejuno- and ileostomy are common surgical procedures. Due to shortening of effective bowel length intestinal failure, or short bowel syndrome develops. Degree of intestinal failure depends upon 1. resection length, 2. resection location, 3. function of the bowel remnant, stomach, pancreas and liver, 4. adaptive capabilities of the bowel remnant and 5. the disease that was cause of the surgery. In majority of these patients adequate nutrition can be achieved using enteral nutrition. Water and mineral absorption differs between jejunum and ileum. Jejunal mucosa is permeable to sodium and water, causing jejunal content to be isoosmolar to plasma. When sodium concentration in jejunal content is less than 90 mmol/l secretion of sodium into the lumen occurs. Ileal sodium absorption takes place against concentration gradient. Potassium concentration of jejuno- and ileostomy effluent is fairly constant at about 15 mmol/l. Main therapeutic problem is water and mineral loss. In jejunostomy patients hyponatremia is a major concern. Urinary sodium concentration of less than 5 mmol/l is a sign of sodium deficiency. This group of patients should have daily urinary output of more than 800 ml, and urinary sodium concentration of more than 20 mmol/l. Another important problem is malnutrition. Weight changes, albumin and trasferin are important follow-up parameters. Often neglected problem is large stomal effluent volume, that can incapacitate patient for the usual life. All these problems can be prevented by the adequate nutritional support. Oral' fluids should have minimal sodium concentration of 90 mmol/l. Intake of sodium poor fluids should be restricted. If plasma or urinary sodium are low intravenous sodium supplementation is warranted. Magnesium and zinc should be monitored and supplemented. Addition of vitamin D can improve their absorption. Vitamins B12 and K must be given parenteral, because their resorption is severely impaired. Patient should eat usual food rich in carbohydrates and proteins, but exact menu must be individualized, and reached by trial and error process. Fat absorption is proportional to fat intake. Fat does not increase stomal effluent, therefore there is no reason to restrict intake. In order to reduce stomal effluent volume and bowel motility H2 blockers, proton pump inhibitors and antidiarrhoeal drugs (codeine or loperamide) should be used.

Daily profiles of aldosterone levels during normal, high and low sodium intake in patients with essential hypertension.

The episodic secretion of aldosterone depends on the dietary sodium intake, alterations in posture and follows ACTH circadian rhythm. Aldosterone daily profiles have been studied in 23 supine essential hypertensive patients on normal sodium intake. Secretory pulses at a frequency of two to five pulses per 12 hr have occurred, independent of PRA levels. Among 13 patients with normal PRA two lost pulsatility when sodium was loaded (10 g/24 hr) and the same happened with two others on sodium restricted diet (2 g/24 hr). These results suggest a profound effect of dietary sodium intake on the pulsatile pattern of aldosterone secretion, particularly in normal PRA essential hypertension.