Can yoga help patients with pain?

Bussing A, Ostermann T, Ludtke R, Michalsen A. Effects of yoga interventions on pain and pain‐associated disability: a meta‐analysis. J Pain 2012; 13: 1–9.     

Pulmonary function in patients with exogenous bronchial asthma treated with cyproheptadine

AIM: To study changes in FEV (forced vital capacity), FRC (functional residual capacity), CC (closing capacity) and MEFVC (maximal expiratory flow volume curve) of exogenous bronchial asthma treated with cyproheptadine.     

Leiden mutation in patients with Crohn’s disease

Background. Inherited resistance to activated protein C is a common risk factor of venous thrombosis. In a majority of patients the defect is caused by single-point mutation in the gene for factor V. This mutated form of factor Va is more stable against proteolytic attack by activated protein C. The prevalence of this inherited defect in the European population is at least 5%. The risk of thrombosis is increased in the case of heterozygosity 5- to 10-fold, in homozygous subjects 50- to 100-fold, but even homozygous individuals will not necessarily suffer from thrombosis. The aim of our study was to determine whether the presence of Leiden mutation might play a role in the pathophysiology and clinical manifestation of Crohn’s disease. Materials and methods. Thirty-four patients with Crohn’s disease (mean age 34 years, range 21–72 years) were studied. None of them had a history of thrombotic episodes. We examined the case history for risk factors: use of oral contraceptive, steroids, cigarette smoking. Levels of fibrinogen, APTT, lupus anticoagulant and levels of IgG and IgM class anticardiolipin (ACL) antibodies were determined. The Leiden mutation was detected by PCR method (Denninger et al., 1995). Results. Fibrinogen was elevated in five cases, lupus anticoagulant in one case, but none of the patients had ACL antibodies in the serum. Molecular analyses showed heterozygosity for the Leiden factor V gene mutation in the case of 30 patients (25%). Conclusion. Thromboembolic events frequently complicate the clinical course of patients with Crohn’s disease; however, we do not have enough knowledge about its role in manifestation of the disease. These results suggested the high frequency of Leiden mutation among our patients and suggest a new genetic background of Crohn’s disease.     

N-acetyltransferase polymorphism in patients with Behçet's disease

OBJECTIVES: The objective of our study was to investigate the possible role of human arylamine N-acetyltransferase 2 (NAT2) polymorphism in susceptibility to Beh?et's disease. METHODS: Eighty-five patients with Beh?et's disease gave their written informed consent to participate in the study. Seven point mutations (G191A, C282T, T341C, C481T, A803G, G590A, G857A) in the NAT2 gene were analysed using polymerase chain reaction/restriction fragment length polymorphism techniques. In addition, each patient received 100 mg dapsone orally to determine their NAT2 phenotype. Dapsone and its metabolite monoacetyl-dapsone were measured in 3-h plasma samples using high-performance liquid chromatography. Subjects with an acetylation ratio (monoacetyl-dapsone/dapsone) less than 0.4 were defined as slow acetylators. RESULTS: Of 85 patients with Beh?et's disease, 54 (63.5%) were identified as genotypically slow acetylators. However, 60% (51 of 85) of patients were diagnosed as slow acetylators according to monoacetyl-dapsone/dapsone ratio. Thus, a low incidence of genotype/phenotype discrepancy (3.5%) was observed in Turkish patients with Behcet's disease. When we compared our results with previous phenotyping and genotyping studies in the Turkish population, frequencies of slow and rapid acetylators were not statistically different in patients with Beh?et's disease. The frequency of the *5B allele was found to be slightly higher in patients with Beh?et's disease than historic controls (44.7 vs 35.6%, P = 0.039). However, there was no significant difference in the frequency of the overall genotypes and alleles of NAT2 between patients and controls. CONCLUSION: Although the frequency of the NAT2*5B allele, responsible for slow acetylation, was slightly higher in patients than historic controls, our results failed to show an association between NAT2-acetylator status and risk for developing Beh?et's disease.     

Should pediatric patients with hyperlipidemia receive drug therapy?

Hyperlipidemia is now established as a major risk factor for causation of coronary heart disease (CHD) in adults; however, there is much debate on the level of coronary risk at which lipid-lowering drugs should be used. These issues of possible harm or lack of benefit from long-term use of lipid-lowering therapy, and cost effectiveness, are also pertinent in the pediatric setting. Evidence from several countries indicates that children have an increasing prevalence of obesity, hyperlipidemia and type 2 diabetes mellitus. Children who have high serum lipids 'track' these increased levels into adulthood. In some countries there is a trend to screen children for hypercholesterolemia. Family history itself is a poor discriminator in determining which children need to be screened and treated. Estimation of apolipoprotein B and/or apolipoprotein E genotype can improve prediction. Measuring high density lipoprotein cholesterol also helps, but obesity appears to be the best marker for screening children at high risk. These considerations should not cloud the need for case finding and treatment of children with genetic disorders. Low fat diets have been shown to be well tolerated and effective in children; however, there are no major long-term studies demonstrating harm or benefit in those on lipid-lowering drugs. Nevertheless, concerns regarding the psychological effect and the theoretical metabolic effects of long-term lipid lowering remain. Lipid-lowering drugs should be generally restricted to children with genetic disorders of lipid metabolism. Children with diabetes mellitus, hypertension or nonlipid-related inherited disorders leading to premature CHD in adults should be treated with diet, and with lipid-lowering drugs when they reach adulthood. Children with secondary hyperlipidemia should be assessed individually. A number of drugs and nutriceuticals are available for use in children, but only a few drugs are licensed for use in children.     

Romiplostim dose–response in patients with myelodysplastic syndromes

Aim

To characterize the romiplostim dose–response in subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim.

Methods

Data from 44 MDS subjects receiving subcutaneous romiplostim (dose range 300–1500 μg week⁻¹) were used to develop a pharmacodynamic model consisting of a romiplostim-sensitive progenitor cell compartment linked to the peripheral blood compartment through four transit compartments representing the maturation in the bone marrow from megakaryocytes to platelets. A kinetics of drug effect model was used to quantify the stimulatory effect of romiplostim on the proliferation of sensitive progenitor cells and pharmacodynamics-mediated disposition was modelled by assuming the kinetics of drug effect constant (k_DE) to be proportional to the change in platelet count relative to baseline.

Results

The estimated values (between subject variability) for baseline platelet count, mean transit time, and k_DE were 24 × 10⁹ l⁻¹ (47%), 9.6 days (44%) and 0.28 days⁻¹, respectively. MDS subjects had a shorter platelet lifespan (42 h) than healthy subjects (257 h). Romiplostim effect was described for responders (78%) and non-responders (22%). The average weekly stimulatory effect of romiplostim on the production rate of sensitive progenitor cells at baseline was 269% per 100 μg week⁻¹ for responders. Body weight, age, gender and race were not statistically related to romiplostim pharmacodynamic parameters. Visual predictive checks confirmed the model adequacy.

Conclusion

The time course of platelet counts in MDS subjects receiving subcutaneous administration of escalating doses of romiplostim was characterized and showed a linear dose–response for romiplostim responders to increase the platelet counts.     

Allen’s test in patients with peripheral artery disease

Introduction

Transradial (TR) approach for coronary and peripheral angiography has become a popular technique. The Allen’s test (AT) could be used to determine the presence of collateral flow in the hand. Recently, angiographic background of modified AT was evaluated, but patients with peripherial arterial disease (PAD) were excluded in these studies. Therefore, the present study was designed to assess reliability of AT in patients with symptomatic PAD.

Methods

The present study comprised 92 symptomatic patients with PAD (Rutherford class 2–6). Perfusion of the hand was assessed with AT before outpatient peripheral angiography.

Results

Significant RA stenosis (n=6, 12.5%) and UA stenosis (n=26, 54.2%) were found in 30 patients with positive AT (62.5%). In patients with negative AT, only UA showed significant stenoses (n=6, 13.6%). Thirty-eight patients with positive AT had anatomic abnormality in the forearm arteries or in the palmar arch (79.2%). Anatomic abnormality in the forearm arteries or in the palmar arch could be detected in 15 cases with negative AT (34.1%, p<0.0001). Conclusions. In the presence of an abnormal AT and concommitant PAD, the use of RA for peripheral or coronary catheterization and angioplasty is not recommended.     

No cardiovascular effects of single-dose pseudoephedrine in patients with essential hypertension treated with β-blockers

OBJECTIVE: The use of the decongestant pseudoephedrine has been cautioned in patients with arterial hypertension, due to the possible rise in blood pressure induced by the sympathostimulatory properties of the drug. This effect could be enhanced in hypertensives treated with beta-blockers, in whom the vasoconstrictor effect of alpha-adrenergic stimulation is unbalanced. The purpose of this study was to investigate the cardiovascular response to pseudoephedrine in hypertensive patients treated with different types of beta-blockers. METHODS: We recruited 29 (18 males) mild-to-moderate essential hypertensive patients [mean age 49(2) years] in a randomized, placebo-controlled, crossover trial. All participants received either placebo, or a nonselective (propranolol 160 mg once daily) or a selective (atenolol 100 mg once daily) beta-blocker for 1 week. At the end of each period, all patients received a single oral dose of pseudoephedrine (60 mg) and their blood pressure and heart rate were monitored at repeated intervals for 2 h. RESULTS: After 1 week of propranolol or atenolol, patients had significantly lower systolic blood pressure and heart rate than after placebo, whereas diastolic blood pressure was not significantly modified. The acute administration of pseudoephedrine did not change systolic and diastolic blood pressure and heart rate from baseline at the end of any of the treatment periods. CONCLUSIONS: A standard oral dose of pseudoephedrine does not significantly affect blood pressure values in hypertensive patients treated with beta-blockers, and therefore may be safely used in this subset of patients.     

Does tramadol affect coagulation status of patients with malignancy?

Aim:

The study investigated the direct effects of tramadol on the coagulation status of women with gynecologic malignancies in vitro.

Materials and Methods:

Citrated whole-blood samples from 21 patients with gynecologic tumors were spiked ex vivo with 2 or 6 μl/ml tramadol. Thrombelastography (TEG) analysis was performed using ROTEM^® to assess clotting time (CT), clot formation time (CFT) and maximum clot formation (MCF).

Results:

In the INTEM assay, CT (P < 0.05) and CFT (P < 0.01) were significantly prolonged with tramadol at a 6 μl/ml concentration compared with baseline. There were no significant differences in MCF values between the baseline and the tramadol-treated samples (P > 0.05). Blood medicated with tramadol (6 μl/ml) clotted slowly (increased CT and CFT).

Conclusion:

The changes observed by TEG demonstrated that tramadol impairs hemostasis in a concentration-dependent manner in the whole blood of women with gynecologic malignancies in vitro.KEY WORDS: Coagulation, malignancy, thromboelastography, tramadol     

Is weight loss possible in patients treated with thiazolidinediones? Experience with a low-calorie diet

BACKGROUND: Weight gain is a frequent side-effect of thiazolidinediones, possibly related to fluid retention and stimulation of pre-adipocyte differentiation. METHODS: We report our experience with a low-calorie diet (800 cal, sodium content 1500 mmol/day) combined with behavior modification on eight patients treated with thiazolidinediones (six pioglitazone and two rosiglitazone). RESULTS: All patients had reported previous weight gain following treatment with thiazolidinediones. All patients lost weight over 12 weeks in the program with their mean +/- SD body weight falling from 270 +/- 54 lbs (123 +/- 25 kg) to 244 +/- 61 lbs (111 +/- 28 kg) (p < 0.01). The weight loss observed was no different from that observed in 16 age- and gender-matched patients with type 2 diabetes not treated with thiazolidinediones (from 263 +/- 54 lbs (120 +/- 25 kg) to 239 +/- 52 lbs (109 +/- 24 kg); p < 0.01). Glycemic control improved while reducing insulin treatment. Blood pressure control also improved and antihypertensive medications were decreased. The degree and time course of weight loss is no different from that in patients treated with other diabetic therapies and is associated with improved glycemic and blood pressure control. CONCLUSIONS: We conclude that a program of caloric restriction and behavior modification is effective in leading to weight loss in patients treated with thiazolidinediones. This effect is reassuring, since thiazolidinediones stimulate adipogenesis.     

Is weight loss possible in patients treated with thiazolidinediones? Experience with a low-calorie diet

SUMMARY

Background: Weight gain is a frequent side-effect of thiazolidinediones, possibly related to fluid retention and stimulation of pre-adipocyte differentiation.

Methods: We report our experience with a low-calorie diet (800cal, sodium content 1500?mmol?day^?1) combined with behavior modification on eight patients treated with thiazolidinediones (six pioglitazone and two rosiglitazone).

Results: All patients had reported previous weight gain following treatment with thiazolidinediones. All patients lost weight over 12 weeks in the program with their mean?±?SD body weight falling from 270?±?54?lbs (123?±?25?kg) to 244?±?61 lbs (111?±?28?kg) (p?<?0.01). The weight loss observed was no different from that observed

in 16 age- and gender-matched patients with type 2 diabetes not treated with thiazolidinediones (from 263?±?54?lbs (120?±?25?kg) to 239?±?52?lbs (109?±?24?kg); p?<?0.01). Glycemic control improved while reducing insulin treatment. Blood pressure control also improved and antihypertensive medications were decreased. The degree and time course of weight loss is no different from that in patients treated with other diabetic therapies and is associated with improved glycemic and blood pressure control.

Conclusions: We conclude that a program of caloric restriction and behavior modification is effective in leading to weight loss in patients treated with thiazolidinediones. This effect is reassuring, since thiazolidinediones stimulate adipogenesis.     

Does body mass index differ between patients with Barrett’s oesophagus and patients with chronic gastro‐oesophageal reflux disease?

BACKGROUND: Obesity has been demonstrated to be a risk factor for the development of gastro-oesophageal reflux disease (GERD). AIM: To perform a prospective cohort study to determine whether there was a difference in body mass index (BMI) between patients with GERD and patients with Barrett's oesophagus (BE). METHODS: We prospectively enrolled patients undergoing endoscopic evaluation for GERD and collected information regarding BMI, tobacco and/or alcohol use, and family history of GERD. Patients with non-erosive reflux disease underwent confirmatory 24-h pH testing. RESULTS: Seven hundred and fifty one patients with GERD (mean +/- s.d. age of 55.4 +/- 14.2 years, 74% male) entered the study, and BE was present in 165 (22%, 90% male, 79% Caucasian) patients. The mean GERD symptom duration was 10.3 +/- 0.4 years (range 1-62 years) with a mean body mass index of 27.8 +/- 0.2 kg/m(2) (range 15-55) Compared with patients having GERD alone, patients with BE were more likely to be older (P = 0.001), male (P < 0.001), current or prior tobacco users (P = 0.002), and with greater duration of GERD symptoms (P < 0.001). There was no significant difference in the BMI for patients with and without BE. CONCLUSIONS: While obesity is a risk factor for both GERD and BMI, patients with BE did not demonstrate increased BMI compared with patients having chronic GERD.     

Population pharmacokinetics–pharmacodynamics of oral everolimus in patients with seizures associated with tuberous sclerosis complex

Everolimus is approved in Europe and in the USA for the adjunctive treatment of patients aged 2 years and older whose refractory partial-onset seizures, with or without secondary generalization, are associated with tuberous sclerosis complex. The objective of this analysis was to establish a population pharmacokinetic (PK)/pharmacodynamic model describing the relationship between seizure frequency and everolimus exposure to confirm the recommended target concentration range of 5–15 ng/mL. The PK model was a two-compartment model with first order absorption and clearance. CYP3A and P-gp inducers and body-surface area were shown to impact everolimus exposure, justifying dose adjustments. A Poisson distribution was found to adequately describe the random nature of daily seizure counts during the screening phase. A placebo effect on the Poisson seizure mean was implemented as an asymptotic exponential function of time leading to a new steady-state seizure mean. The everolimus effect was implemented as an inhibitory E_max function of C_min on the seizure mean, where E_max exhibited an asymptotic exponential increase over time to a higher steady-state value. Increasing age was found to decrease the baseline seizure mean and to prolong the half-life of the increase in E_max. The dependence of seizure frequencies on C_min was explored by simulation. The responder rate increased with increasing C_min. As C_min decreased below 5 ng/mL, variability in response became larger and responder rates decreased more rapidly. The results supported the recommended target concentration range for everolimus of 5–15 ng/mL to ensure treatment efficacy.