The Effectiveness of Sirolimus Treatment in Two Rare Disorders with Nonketotic Hypoinsulinemic Hypoglycemia: The Role of mTOR Pathway

Nonketotic-hypoinsulinemic hypoglycemia (NkHH) is a very rare problem charcterized by increase in glucose consumption without hyperinsulinism. This disorder has mainly been reported in cases with AKT2 mutation and rarely in cases with PTEN mutation. In cases with PTEN or AKT2 mutation, there is no effective therapy other than frequent feeding to counter hypoglycemia. The mammalian target of rapamicin (mTOR) inhibitor, sirolimus, has been used in hyperinsulinemic hypoglycemia that was unresponsive to other medical treatment. In the insulin signaling pathway, both AKT2 and PTEN function upstream of mTOR. However, the role of Sirolimus on hypoglycemia in AKT2 and PTEN mutations is unknown. Case 1: Six month-old female with AKT2 mutation [c.49G>A (p.E17K)] and evidence of NkHH. Frequent feeding was unsuccesful in correcting hypoglycemia and her proptosis continued to worsen. Sirolimus treatment was started at three years of age. Subsequently, blood glucose (BG) levels increased to normal levels. Case 2: In a male with PTEN mutation (p.G132V (c.395G>T), persistent NkHH started at 16 years of age (fasting BG: 27 mg/dL, fasting insulin 1.5 mmol/L, while ketone negative). Sirolimus treatment was started and hypoglycemia was succesfully controlled. NkHH is a very rare and serious disorder which is challenging, both for diagnosis and treatment. Additionally, AKT2 and PTEN mutations may result in NkHH. Sirolimus treatment, through mTOR inhibition, appeared to be effectively controlling the peristent hypoglycemia and may be a life-saving therapy in this NkHH due to AKT2 and PTEN mutations.     

Short- and long-term results of clinical effectiveness of sodium hyaluronate injection in supraspinatus tendinitis

The objective of the study is to evaluate the short- and long-term effect of intraarticular sodium hyaluronate (SH) application in patients diagnosed with supraspinatus tendinitis (ST) that have shoulder pain on the clinical symptoms of the patients through comparison with conventional physiotherapy methods. A total of 24 patients were included in the study and were randomized into two groups.SH injection and physical therapy modalities (PTM) were administered to Group I and Group II, respectively. Home exercise programs were recommended to all of the patients in both groups. The patients were evaluated using the pain severity [Visual Analog Scale (VAS)], range of motion and functional evaluation (FE) parameters pertaining to pre-treatment, 3rd week, 3rd month and 4th year post-treatment. Patient’s global effectiveness (PGE) evaluation was performed in the 3rd month and 4th year of the treatment. There were no statistically significant differences for Group I’s resting VAS value between pre-treatment controls and controls in the 3rd week and 3rd month, no statistically significant differences were detected for Group II in passive flexion between pre-treatment and the 4th year, also in passive external rotation between pre-treatment and 3rd week (P > 0.05). A statistically significant recovery was detected in both groups in all the other evaluation parameters (P < 0.05). When evaluation was performed among groups, active abduction in the control in the 3rd month, VAS by movement and a statistically significant difference in favor of Group I in FE were determined (P < 0.05). No statistically significant differences were found among groups in PGE (P > 0.05). It was concluded that physical therapy modalities and SH application supplemented by home exercise programs were similar effects in short- and long term for ST which causes pain in shoulder and SH application may be a better alternative with regard to effectiveness and side effects for other treatment methods applied intraarticulary.     

Thrombosis and priapism in a patient with Henoch-Schonlein purpura

Henoch-Schönlein purpura (HSP) belongs to the category of systemic small-vessel vasculitis. Although long-term outcome is generally good, serious complications may occur. Thrombosis and priapism have been reported only as extremely rare complications of HSP. We describe a 37-year-old man who developed recurrent thrombotic events shortly after he had been diagnosed as having HSP. Although he had additional risk factors for thrombosis, such as prothrombin G20210A mutation and use of celecoxib before the last episode, temporal relation of the thrombotic attacks to the onset of HSP suggest that the disease itself may lead to a prothrombotic state. This case is the first adult HSP patient with priapism, which probably developed secondary to thrombosis of the dorsal penile vein.     

Plasma fibronectin level and its association with coronary artery disease and carotid intima-media thickness

BACKGROUND: The exact relation of fibronectin with coronary atherosclerosis is unknown. The aim of the present study was to examine the association of fibronectin level with presence and extent of coronary artery disease (CAD) and intima-media thickness (IMT) of common carotid artery (CCA). DESIGN: The IMTs of CCA of 86 patients who underwent coronary angiography were measured; traditional vascular risk factors were also evaluated in these patients. Fibronectin, lipids, C-reactive protein (CRP) and fibrinogen levels were determined. RESULTS: Plasma fibronectin levels of the patients with CAD were found to be significantly elevated compared to patients with normal vessels (0.46+/-0.11 and 0.36+/-0.12 mg/dl respectively, P = 0.001). Fibronectin levels were not associated with extent of CAD. No significant association was observed between fibronectin level and traditional risk factors. IMTs of right and left CCA in patients with CAD were found to be elevated compared to patients with normal vessels (0.89+/-0.1 mm compared with 0.76+/-0.1 mm, P = 0.001 and 0.93+/-0.2 mm compared with 0.71+/-0.1 mm, respectively P < 0.001). Fibronectin levels were positively correlated with CRP (r = 0.45, P < 0.001), low-density lipoprotein-cholesterol (r = 0.23, P = 0.03) and total cholesterol (r = 0.21, P = 0.04) levels and negatively correlated with high-density lipoprotein-cholesterol (HDL-C) levels (r = -0.24, P = 0.02). IMT of left CCA was positively correlated with CRP levels (r = 0.23, P = 0.04) and negatively correlated with HDL-C levels (r = 0.2, P = 0.04). Logistic regression analysis showed that age (P < 0.01) and fibronectin levels (P = 0.01) were independent predictors for the existence of CAD. CONCLUSIONS: The results suggest that fibronectin levels may be a significant predictor of CAD. However, it was shown that fibronectin levels were not associated with extent of CAD and IMT of CCA.     

Pulsed wave tissue Doppler-derived myocardial performance index for the assessment of left ventricular thrombus formation risk after acute myocardial infarction

Background

Assessment of left ventricular (LV) thrombosis risk after acute myocardial infarction (AMI) is important because of potential embolic sequelae that are reduced by oral anticoagulant agents. The goal of this study was to investigate whether early assessment of LV systolic and diastolic performance with pulsed wave tissue Doppler ultrasound scanning (PWTD) predicts LV thrombosis after AMI.

Methods

Two-dimensional and Doppler ultrasound scanning echocardiographic examinations were performed in 92 consecutive patients (age, 58 ± 10 years; 11 women) with first anterior AMI within 24 hours after arrival to the coronary care unit. From the apical 4-chamber view, the mitral annular velocities were recorded at the lateral corner of the mitral annulus with PWTD. The myocardial performance index (MPI), which combines parameters of both systolic and diastolic ventricular function, was calculated from the PWTD recordings. To analyze LV thrombus formation, the 2-dimensional echocardiographic examination was repeated on days 3, 7, 15, and 30. The patients were divided in 2 groups according to LV thrombus formation.

Results

LV thrombus was found in 32 of 92 patients (35%; group 1) and was not found in 60 patients (65%; group 2). The MPI was significantly higher in group 1 than in group 2 (0.73 ± 0.20 vs 0.53 ± 0.14; P <.001). When an MPI >0.6 was used as the cutoff, LV thrombus formation could be predicted with a sensitivity rate of 81%, a specificity rate of 73%, a positive predictive value of 62%, and a negative predictive value of 88%. In multivariate analyses, only MPI and LV wall motion score index were independent predictors of LV thrombus formation (P = .038 and P = .047, respectively).

Conclusions

The MPI derived with PWTD soon after admission appears to be a useful parameter for assessing the risk of LV thrombosis after AMI. Patients with an MPI >0.6 after AMI seem to be at a higher risk for thrombus formation.     

Cannulation of a LIMA graft via the right brachial arterial route using a MANI catheter: an alternative approach

Some different revascularization methods including coronary artery bypass surgery can be performed in the treatment of coronary artery disease. Saphenous vein grafts and/or arterial grafts including left internal mammary artery (LIMA) can be implanted during coronary bypass surgery. It is necessary to perform cannulation of the LIMA, in order to diagnose and treat these patients. In addition to conventional internal mammary artery catheters, several types of catheters can be used for this purpose. In general, LIMA catheterization via the femoral artery has been preferred over other methods. However, the right brachial arterial approach can be mandatory in some rare conditions. In this report, we describe an alternative method to the conventional techniques of the LIMA graft angiography via the right brachial arterial approach using a MANI catheter. According to our knowledge, no data are available using the MANI catheter for this purpose in the current literature.     

Investigation of the effect of GaAs laser therapy on cervical myofascial pain syndrome

Low-energy laser therapy has been applied in several rheumatoid and soft tissue disorders with varying rates of success. The objective of our study was to investigate the effect of laser therapy on cervical myofascial pain syndrome with a placebo-controlled double-blind prospective study model. It was performed with a total of 53 patients (35 females and 18 males) with cervical myofascial pain syndrome. In group 1 (n=23), GaAs laser treatment was applied over three trigger points bilaterally and also one point in the taut bands in trapezius muscle bilaterally with a frequency of 1000 Hz for 2 min over each point once a day for 10 days during a period of 2 weeks. In group 2 (n=25), the same treatment protocol was given, but the laser instrument was switched off during applications. All patients in both groups were instructed to perform daily isometric exercises and stretching just short of pain for 2 weeks at home. Evaluations were performed just before treatment (week 0), immediately after (week 2), and 12 weeks later (week 14). Evaluation parameters included pain, algometric measurements, and cervical lateral flexion. Statistical analysis was done on data collected from three evaluation stages. The results were evaluated in 48 patients (32 females, 16 males). Week 2 and week 14 results showed significant improvement in all parameters for both groups. However, comparison of the percentage changes both immediately and 12 weeks after treatment did not show a significant difference relative to pretreatment values. In conclusion, the results of our study have not shown the superiority of GaAs laser therapy over placebo in the treatment of cervical myofascial pain syndrome, but we suggest that further studies on this topic be done using different laser types and dosages in larger patient populations.     

Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind,placebo-controlled trial

Hypothyroidism is associated with premature atherosclerosis and cardiovascular disease. Recently, total homocysteine (tHcy) and C-reactive protein (CRP) emerged as additional cardiovascular risk factors. We first investigated CRP and tHcy in different severities of primary hypothyroidism and in a second study we evaluated the effect of L-thyroxine treatment in patients with subclinical hypothyroidism (SCH) in a double-blind, placebo-controlled trial. One hundred and twenty-four hypothyroid patients (63 with subclinical, 61 with overt hypothyroidism, OH) and 40 euthyroid controls were evaluated. CRP was measured using a latex-based high sensitivity immunoassay; tHcy was determined by a fluorescence polarization immunoassay. tHcy values were significantly elevated in OH (P=0.01). In SCH tHcy levels were not augmented as compared to controls. CRP values were significantly increased in OH (P=0.016) and SCH (P=0.022) as compared to controls. In a univariate analysis tHcy correlated significantly with fT4, vitamin B12, folic acid and creatinine levels. In multiple regression analysis only fT4 (beta=0.33) had a significant effect on tHcy. CRP did not correlate with thyroid hormones. In SCH, L-T4 replacement had no significant effect on either tHcy or CRP levels. This is the first paper to show that CRP values increase with progressive thyroid failure and may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. In contrast to overt disease, only CRP, but not tHcy values, are affected in SCH, yet without significant improvement after L-thyroxine therapy.     

Evaluation of left ventricular function using Tei index in patients with preinfarction angina.

OBJECTIVE: The study investigated whether preinfarction angina influences left ventricular functions assessed using Tei index, which is an independent predictor for left ventricular dysfunction in acute myocardial infarction. METHODS: We studied 96 patients with acute myocardial infarction with ST segment elevation (80 men, 16 women; mean age 57.5+/-9.9 years) who were assigned into 2 groups: with and without preinfarction angina. All patients were serially evaluated by 2-dimensional and Doppler echocardiography on the days 1, 6, and 30, and were followed up for 30 days for incidence of complications. RESULTS: We observed that Tei index was lower on the days 1, 6 and 30 (0.49+/-0.20 vs. 0.59+/-0.20, p=0.003, 0.46+/-0.20 vs. 0.56+/-0.20, p=0.001, 0.44+/-0.20 vs. 0.53+/-0.10, p=0.01) in patients with preinfarction angina as compared with those without angina. Tei index significantly decreased during follow-up (0.49+/-0.20, 0.46+/-0.20, 0.44+/-0.20; p=0.02) in patients with preinfarction angina, while it did not change significantly in patients without preinfarction angina (p=0.2). Echocardiographically significant improvements were observed in E deceleration time, isovolumic relaxation time and ejection time in all patients, whereas significant improvements in ejection fraction, wall motion score index and isovolumic contraction time were observed only in patients with preinfarction angina during follow-up. Mortality, Killip class >or=2, pericarditis, atrial fibrillation, and left ventricular thrombus were lower in patients with preinfarction angina. CONCLUSION: These data indicated that the patients with preinfarction angina had better preserved systolic left ventricular function and Tei index values. Also, it was observed that preinfarction angina may cause earlier and more prominent myocardial functional recovery and confer protection against complications on short-term after first acute myocardial infarction.     

The effect of atorvastatin on hemorheological parameters in rabbits fed on a normal diet

The effects of statins have been investigated mostly in hyperlipidemic states so far. We analysed blood cholesterol, triglyceride, albumin, fibrinogen and gammaglobulin levels, haematocrite, hemoglobin, erythrocyte, leukocyte and platelet counts, blood and plasma viscosity and erythrocyte rigidity in 12 rabbits fed on a normal diet (chow) which were given 1 mg/kg/day atorvastatin for 4 weeks. Compared to the baseline levels, erythrocyte rigidity (k=0.12+/-0.05 vs. k=0.7+/-0.02) and gammaglobulin levels (1.03+/-0.23 g/dl vs. 0.78+/-0.27 g/dl) decreased significantly (p=0.008 and p=0.025, respectively). Blood lipids, hematological variables, blood and plasma viscosity did not change statistically. Our findings imply that in a normolipemic state, statins given in low doses may improve erythrocyte rigidity without altering blood lipids in short term. Decreased plasma gammaglobulin levels may be reflecting their immunomodulatory effects.