Adrenomedullary function in patients with nonclassic congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is classified into three types based on disease severity: classic salt-wasting, classic simple virilizing, and nonclassic. Adrenomedullary dysplasia and epinephrine deficiency have been described in classic CAH, resulting in glucose dysregulation. Our objective was to investigate adrenomedullary function in nonclassic CAH and to evaluate adrenomedullary function according to disease severity. Adrenomedullary function was evaluated in response to a standardized cycle ergonometer test in 23 CAH patients (14 females, age 9-38 years; 6 salt-wasting, 7 simple virilizing, 5 nonclassic receiving glucocorticoid treatment, 5 nonclassic not receiving glucocorticoid), and 14 controls (7 females, age 12-38 years). Epinephrine, glucose, and cortisol were measured at baseline and peak exercise. CAH patients and controls were similar in age and anthropometric measures. Patients with nonclassic CAH who were not receiving glucocorticoid and controls experienced the expected stress-induced rise in epinephrine, glucose, and cortisol. Compared to controls, patients with all types of CAH receiving glucocorticoid had impaired exercise-induced changes in epinephrine (salt-wasting: p=0.01;simple virilizing: p=0.01; nonclassic: p=0.03), and cortisol (salt-wasting: p=0.004; simple virilizing: p=0.006; nonclassic: p=0.03). Salt-wasting patients displayed the most significant impairment, including impairment in glucose response relative to controls (p=0.03). Hydrocortisone dose was negatively correlated with epinephrine response (r=-0.58; p=0.007) and glucose response (r=-0.60; p=0.002). The present study demonstrates that untreated patients with nonclassic CAH have normal adrenomedullary function. The degree of epinephrine deficiency in patients with CAH is associated with the severity of adrenocortical dysfunction, as well as glucocorticoid therapy.

Fabry disease - Vascular manifestations.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by the deficient activity of alpha-galactosidase A which results in the accumulation of neutral glycosphingolipids in various tissues leading particularly to vasculopathy, cardiomyopathy, neuropathy, and chronic kidney disease. It results in substantial morbidity and premature death in affected patients. Although there are some signs and symptoms suggestive of FD including painful crisis, angiokeratomas, and corneal changes, the majority of FD complications are non-specific (left ventricular hypertrophy, conduction abnormalities, vascular spasms, proteinuria, renal insufficiency), which is why FD still remains largely underdiagnosed. The mechanism by which accumulating glycosphingolipids cause multiorgan disorder is not yet completely understood as it cannot be explained by pure substrate storage. Besides standard therapy of different medical problems in FD patients, specific enzyme replacement therapy has been introduced in the last few years.

Design and characteristics of holographic neural photo-stimulation systems.

Computer-generated holography is an emerging technology for stimulation of neuronal populations with light patterns. A holographic photo-stimulation system may be designed as a powerful research tool or a compact neural interface medical device, such as an optical retinal prosthesis. We present here an overview of the main design issues including the choice of holographic device, field-of-view, resolution, physical size, generation of two- and three-dimensional patterns and their diffraction efficiency, choice of algorithms and computational effort. The performance and characteristics of a holographic pattern stimulation system with kHz frame rates are demonstrated using experimental recordings from isolated retinas.

The development of persistent thrombotic masses in patients with deep venous thrombosis randomized to long-term anticoagulation treatment.

BACKGROUND: The aim of the study was to assess the regression rate of persistent echogenic masses in patients with idiopathic deep venous thrombosis (DVT) who were after initial 6 months randomized to long-term anticoagulation treatment or to discontinuation of anticoagulation. PATIENTS AND METHODS: We followed 168 patients with idiopathic DVT for two years since diagnosis. After 6 months of standard therapy (heparin/LMWH, warfarin with target INR 2-3) we randomized patients with persistent echogenic masses of over 20% of venous diameter to either discontinuation of warfarin or to continuation of warfarin for another 6 months. We evaluated the size of thrombotic masses with duplex ultrasound. RESULTS: After 6 months of standard therapy complete regression was observed in 69 patients while in 99 patients echogenic masses persisted, with 71 patients maintaining an obstruction of at least 20% of venous cross-sectional area. 52 patients were randomized. 27 patients continued warfarin therapy and in 25 patients warfarin was discontinued. After discontinuation of warfarin a further trend to regression was seen in both groups. A significant difference in regression of thrombotic masses between the 6th and 12th month of follow up was seen in patients continuing to receive warfarin, both within the popliteal vein (2.81 +/- 1.56 vs. 2.10 +/- 1.67 mm, p < 0.05) and the femoral vein (3.95 +/- 2.74 vs. 2.30 +/- 1.34 mm, p < 0.05). CONCLUSIONS: After 6 months of DVT treatment persistent echogenic masses can be found in almost two thirds of patients. Even after discontinuation of anticoagulation treatment echogenic masses further regress. However, the rate of regression in patients with deep venous thrombosis between the 6th and 12th month was greater in patients randomized to continue warfarin during this period than in patients without anticoagulation.

Mycobacterium avium paratuberculosis invades human small-intestinal goblet cells and elicits inflammation.

Crohn disease is a chronic inflammatory bowel disease of unknown etiology. Mycobacterium avium paratuberculosis (MAP) was found in the gut of patients with Crohn disease, but causality was not established. Fully developed, germ-free human small intestine and colon were established by subcutaneous transplantation of fetal gut into SCID (severe combined immunodeficiency) mice thereafter infected by direct intraluminal inoculation of MAP. We have found that MAP actively invades the human gut epithelial goblet cells of the small intestine, inducing severe tissue damage and inflammation. These observations indicate that MAP can specifically colonize the normal human small intestine and can elicit inflammation and severe mucosal damage.

[Liver abscesses with portal and mesenteric vein thrombosis in combination with late onset of appendicitis]. / Jaterní abscesy s portální a mezenteriální flebotrombózou v kombinaci s pozdní manifestací apendicitidy.

Pyogenic liver abscesses are caused by appendicitis in less than 10%. Also the ascending septic inflammation of portal vein (pylephlebitis) could be a serious complication of intra-abdominal infection. Although pylephlebitis is not frequent today, its' mortality and morbidity rates remain high. We describe a case of young man with fever, abdominal pain, and multiple hepatic abscesses. After the symptomatic relief due to antibiotic therapy the pain returned as a result of the development of portal and mesenteric vein thrombosis. The cause of either hepatic abscesses or thrombosis was not clear at the time of dismissal. 2 months later the patient underwent acute abdominal revision with appendectomy for acute phlegmonous and gangrenous appendicitis. Since that time he has been without any clinical symptoms.

How does delaying treatment affect the long-term prognosis for patients with acute myocardial infarction treated with primary coronary angioplasty?

BACKGROUND: The benefit of thrombolysis in patients with acute myocardial infarction (AMI) strongly depends on the time from the onset of symptoms to the initiation of treatment. For AMI patients treated with percutaneous coronary interventions (PCI) this delay of treatment seems to be important only up to a certain time level. AIM: To assess the effects of time to treatment of AMI with PCI on the short- and long-term prognosis. METHODS: We followed 339 consecutive AMI patients treated with PCI from 1995 to 1999 in our centre. Patients were divided into five groups according to the time to treatment and ischaemic time (time from symptom onset to reperfusion). RESULTS: Time to treatment <90 min was achieved in 35 (10.5%) patients; 91-210 min in 105 (31%); 211-330 min in 72 (21%); 331-690 min in 74 (22%); and >691 min in 53 (15.5%) patients. According to ischaemic time, the patients were divided into groups: <2 h, 2-4 h, 4-6 h, 6-12 h, and >12 h. The ejection fraction of the left ventricle 3-5 days after AMI was 50%, 51%, 45%, 40%, and 46%, and the 30 day mortality - 5.7%, 2.9%, 11.1%, 10.8%, and 11.3%, respectively. Compared with patients treated later, patients with time to treatment <3.5 h had a significantly higher rate of TIMI 3 flow (93.6% vs 83.9%, p=0.007), lower 30-day mortality (3.6% vs 11.1%, p=0.012), lower 3-year mortality (8.6% vs 19.1%, p=0.003), lower frequency of heart failure during hospitalisation (11.4% vs 28.1%, p<0.001) as well as lower maximal level of creatine kinase (32+/-29 vs 44+/-39 micro kat/l, p=0.005). CONCLUSIONS: The success rate of primary PCI to achieve normal flow in an infarct-related artery is high, but it decreases when treatment is started later than 3,5 h from AMI onset. The short-term and long-term mortality as well as the incidence of heart failure during the acute phase of MI are the lowest when PCI is started within 3,5 h from the onset of symptoms.

[Main clinical and surgical determinants of in-hospital mortality after surgical revascularization of left main coronary artery stenosis: 2 year retrospective study (1998-1999)]. / Les facteurs cliniques et opératoires associés à la mortalité hospitalière après chirurgie d'une sténose du tronc commun de l'artère coronaire gauche. Analyse rétrospective de janvier 1998 à décembre 1999.

UNLABELLED: Stenosis of left main coronary artery (LMCA) is a common finding on coronary angiographies (7 to 10%). Mortality is very high for conservative therapy in comparison with surgery, which provides very good long-term outcome and is accepted as the standard therapy of this condition. Over the last few years, percutaneous coronary intervention (PCI) has become a new alternative in selected patients. AIM OF THE STUDY: To assess in hospital mortality in subjects referred to our surgical unit for coronary artery bypass grafting (CABG) and to identify the main clinical and surgical determinants of in-hospital mortality. METHODS: Two year retrospective analysis (1998-1999) of in-hospital mortality and morbidity of patients having left main stenosis referred for CABG. RESULTS: Among a group of 1443 patients operated for coronary heart disease, LMCA stenosis was found in 330 patients (22.9%). The mean age was 63 +/- 8.6 years. Elective surgery was done in 173 patients (52.4%), and acute operation (i.e. urgent, emergent or desperate) in 157 patients (47.6%). The total in-hospital mortality was 4.2% (14/330). Elective surgery in-hospital mortality was 1.7% (3/173) and urgent surgery in-hospital mortality was 7% (11/157). The main risk factors of in-hospital mortality were age > 68 years, low ejection fraction (LVEF<0.4), history of myocardial infarction, gender (female) and urgency of the operation. CONCLUSION: The proportion of patients undergoing CABG for left main stenosis is relatively high in our center and their mortality is quite low especially for elective operations. As the mortality of patients treated by PCI for LMCA stenosis is similar to surgery in high-risk patients, we postulate that this approach can be a real alternative treatment for such patients. Because of its potential benefit, combined revascularisation is also an alternative that should be considered in some cases. Furthermore, as a new generation of coated stents has emerged in the treatment of restenosis after PCI, we hypothesize that this method can in the near future be accepted as equivalent to surgery. However several randomized clinical trials must first be conduced prove this point.

Tobacco use amongst high school students in the Czech Republic.

OBJECTIVE: We were interested in the prevalence of smoking amongst teen-age students, its possible causes, and their understanding of its associated health risks. METHODS: We constructed a questionnaire that was responded to by a total of 419 students from 5 high schools in Prague, Czech Republic. Students were classified as non-smokers, mild (1-10 cigarettes daily), moderate (11-20 cigarettes daily), and severe smokers (>20 cigarettes daily). The survey also contained questions about passive smoking, motivation for smoking, the understanding of its associated health risks, alcohol consumption, and drugs. RESULTS: We found that amongst 16-20 years old high school students there are 37.5% smokers (38.0% men, and 37.0% women). The majority are mild smokers (82.3%), 15.8% moderate smokers and 1.9% heavy smokers. 29.0% of non-smokers reported passive smoking; i.e. that 65.7% of students are exposed to harmful effect of tobacco smoke. The average onset of smoking is at 14 years of age. The youngest smoker started smoking at the age of 5 years. Parents of 52.0% of students smoke (69.4% of smokers and 41.6% of non-smokers). Most of students know about the risk of lung cancer and cardiovascular diseases (86-99%). CONCLUSIONS: The prevalence of active and passive smoking among high school students is high. Parents smoking is significantly more frequent in teen-age smokers than in non-smokers. We consider the "teen-age" population together with their parents to be the key target for a successful antismoking campaign.

[Long-term prognosis in patients with acute myocardial infarct and treatment with direct coronary angioplasty]. / Dlouhodobá prognóza nemocných s akutním infarktem myokardu pri lécbe prímou koronární angioplastikou.

BACKGROUND: Primary coronary angioplasty (PTCA) has a beneficial effect on the immediate prognosis for patients with acute myocardial infarction. Number of information about effects of direct PTCA on the long-term prognosis are less numerous. The aim of the work was to establish the long-term prognosis for not-selected patients treated by direct PTCA. METHODS AND RESULTS: The studied group consisted of 279 patients with acute myocardial infarction treated by direct PTCA in years 1995 to 1999 for the period of 38 +/- 12 months. Part of them were out-door patients of our clinic. The necessary data of the other patients were obtained by a questionnaire and by a telephone contact. 45 (16%) patients were lost from the follow up. The mortality rate of the study group was compared with data in the central register of Czech Republic. Positive angiographic effect of the direct PTCA (residual stenosis < 50% + flow TIMI 3) was achieved in 90% of patients. 30-day mortality was 6.8%, after excluding patients with cardiogenic shock it decreased to 3.2%. 6 patients (2.2%) had non-fatal infarction within 30 days after the first attack. From 259 patients who survived the acute infarction phase 24 died during the next period of follow up, 18 (7%) patients had a relapse of non-fatal infarction. PTCA of the infarcted artery was done in 15% of patients, PTCA of another artery in 9% of patients. The aorthocoronary bypass was indicated in 6% of patients. Almost half of relapses occurred during the first year after the hospitalisation. The risk factors of the death during the follow up were the age > 70 years, ejection fraction < 35%, impairment of 3 or more coronary artery branches, i.m. in the history, duration of ischemia > 4 hours, and diabetes mellitus. The total mortality was 11.4% in the first year, 1.4% in the second and 3.3% in the third year of the follow up. CONCLUSIONS: The beneficial prognostic effect of the direct PTCA on patients with acute infarction carries through the whole period of follow up. Prognosis of the risk patients remains critical. Next revascularization of the infarcted artery was in our cohort of patients necessary in 21% of patients.

[Comparison of the cost effectiveness of treatment of acute myocardial infarct with primary angioplasty and thrombolysis ]. / Srovnání cenové efektivity lécby akutního infarktu myokardu primární angioplastikou a trombolýzou.

INTRODUCTION: Primary angioplasty (PTCA) or intravenous thrombolysis are the recommended treatment of acute myocardial infarction. According to results of clinical investigations however primary PTCA provides a more favourable short-term as well as long-term prognosis. As this method is much more expensive we were interested in its cost-effectiveness as compared with cheaper intravenous thrombolysis. METHODS: We constructed an decision analysis model (programme DATA 3.5, TreeAge Software) to compare the strategy of primary PTCA and intravenous thrombolysis in acute myocardial infarction. Probabilities of clinical outcomes were obtained from a long-term randomized clinical trial (Zijlstra et al. NEJM, 1999). The relative risk of death in PTCA was 0.54, rehospitalization 0.52 and reinfarction 0.27. The costs of PTCA (100,000,- crowns), of streptokinase thrombolysis (4000,- crowns) and hospitalization (2820,- crowns) were estimated from costs of the catheterization laboratory and information obtained from health insurance companies. We assumed that the subsequent costs of treatment and quality of life after the first infarction were the same in both strategies. In patients with reinfarction we anticipated a reduced quality of life (coefficient of life quality 0.9). The average effect of treatment and costs of both strategies were evaluated in the course of five years. As an acceptable cost-effectiveness (ratio of difference in costs and effect) we considered costs up to 200,000,- crowns per one gained year of life. RESULTS: In the basic analysis we revealed that after 5 years the strategy of primary PTCA is more expensive (125,000,- crowns vs. 4500,- crowns) but has a greater effect, i.e. a longer life span (4.38 vs. 3.81) adjusted to quality of life). The cost-effectiveness (ratio of difference in costs and effect) expressing the costs of one gained year of life when using primary PTCA as compared with thrombolysis was despite the high cost of PTCA acceptable and amounted to 140,350,- crowns. Analysis of the sensitivity of the model confirmed the stability of favourable cost-effectiveness within a wide range of costs and therapeutic effect. CONCLUSION: Primary PTCA is in acute myocardial infarction a cost-effective strategy) providing effect for an acceptable cost) despite the markedly higher costs of the procedure.

The cost-effectiveness of treating all patients with type 2 diabetes with angiotensin-converting enzyme inhibitors.

BACKGROUND: Although guidelines recommend angiotensin-converting enzyme inhibitors for diabetic patients with microalbuminuria, this strategy requires that providers adhere to screening recommendations. In addition, the benefit of angiotensin-converting enzyme inhibitors in normoalbuminuric patients was recently demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of treating all patients with type 2 diabetes. DESIGN: Markov model simulating the progression of diabetic nephropathy. DATA SOURCES: Randomized trials estimating the progression of diabetic nephropathy with and without angiotensin-converting enzyme inhibitors. TARGET POPULATION: Patients 50 years of age with newly diagnosed type 2 diabetes (fasting plasma glucose level > or = 7.8 mmol/L [140 mg/dL]). TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Patients received angiotensin-converting enzyme inhibitors, screening for microalbuminuria, or screening for gross proteinuria. OUTCOME MEASURES: Lifetime cost, quality-adjusted life expectancy, and marginal cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Screening for gross proteinuria had the highest cost and the lowest benefit. Compared with screening for microalbuminuria, treating all patients was more expensive ($15240 and $14940 per patient) but was associated with increased quality-adjusted life expectancy (11.82 and 11.78 quality-adjusted life-years). The marginal cost-effectiveness ratio was $7500 per quality-adjusted life-year gained. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the cost, effectiveness, and quality of life associated with angiotensin-converting enzyme inhibitor therapy, as well as age at diagnosis. The model was relatively insensitive to adherence with screening and costs of treating end-stage renal disease. CONCLUSIONS: Treating all middle-aged diabetic patients with angiotensin-converting enzyme inhibitors is a simple strategy that provides additional benefit at modest additional cost. The strategy assumes that patients meet the older diagnostic criteria for diabetes and makes sense only for those who are not bothered by treatment.

[Successful completion of pregnancy in a dialyzed patient]. / Uspesne ukoncené tehotenství u dialyzované pacientky.

The authors describe the first case of a successful pregnancy in the Czech Republic in a patient treated by continuous ambulatory peritoneal dialysis. The 22-year-old patient became pregnant ten months after the onset of treatment by peritoneal dialysis. During pregnancy deterioration of arterial hypertension occurred, deterioration of anaemia and from the 29th week onwards cholestasis gravidarum developed. The development of the foetus was within normal limits. Because of suspected preeclampsia the pregnancy was terminated during the 35th week by Caesarean section. The patient was delivered of a healthy eutrophic boy without any congenital abnormalities.

[Treatment of macroscopic hematuria complicating renal biopsy by embolization of a branch of the renal artery]. / Lécba makroskopické hematurie komplikující renální biopsii embolizací vetve arteria renalis.

The authors describe a case of recurrent macroscopic haematuria which developed after renal biopsy in a young patient with IgA dominant focal and segmental mesangioproliferative glomerulonephritis. As conservative treatment was not successful, renal angiography was performed which revealed a false aneurysm of the segmental branch of the renal artery at the site of the assumed puncture. After selective embolization with gelaspon granules macroscopic haematuria receded quickly.

[Atypical chronic mesangioproliferative glomerulonephritis]. / Atypický prubeh chronické mezangioproliferativní glomerulonefritidy.

The case report describes the atypical course of a chronic mesangioproliferative glomerulonephritis, which presented with macroscopic haematuria lasting continuously almost 9 years. Proteinuria and macroscopic haematuria ceased after tonsillectomy and a prolonged corticosteroid therapy.