Surgical treatment of a primary cardiac lymphoma presenting with tamponade physiology

Primary cardiac lymphomas (PCL) are rare cardiac neoplasms that carry an ominous prognosis. They occur more frequently in immunocompromised patients. We report on an immunocompetent 67-year-old who presented with dyspnea and dysphagia. Echocardiographic evidence of impending cardiac tamponade and obstruction of the inferior vena cava (IVC) with the tumor was seen. The deteriorating hemodynamics of our patient prompted an urgent surgical intervention. Pathohistological diagnosis showed diffuse large B-cell lymphoma of centroblastic subtype. Chemotherapy remains the standard treatment of PCL, with surgery reserved for relieving life-threatening complications of the neoplasm.     

Effectiveness of resistance training in combination with botulinum toxin-A on hand and arm use in children with cerebral palsy: A pre-post intervention study

ABSTRACT: BACKGROUND: The aim of this study was to investigate effects of additional strength training after use of Botulinum Toxin-A (BoNT-A) in the upper limbs of children with cerebral palsy (CP). METHODS: Ten children with CP (range 9 - 17 years, Manual Ability Classification System II) with unilaterally affected upper limbs were assigned to two intervention groups. One group received BoNT-A treatment (group B), the other BoNT-A plus 8 weeks strength training (group BT). Hand activity was measured with Melbourne assessment of unilateral upper limb function (Melbourne) and Assisting Hand Assessment (AHA). Measures of muscle strength, muscle tone, and active range of motion were used to assess neuromuscular body function. Measurements were performed before and two and five months after intervention start. Change scores and differences between the groups in change scores were statistically tested in SPSS version 18, using Mann-Whitney U test and Wilcoxon Signed Rank test, respectively. RESULTS: Both groups had very small improvements in AHA and Melbourne two months after BoNT-A injections, without differences between groups. There were significant, or close to significant, short-term treatment effects in favour of group BT for muscle strength in injected (elbow flexion strength, p=0.08) and non-injected muscles (elbow extension and supination strength, both p=0.05), without concomitant increases in muscle tone. Active supination range improved in both groups but more so in group BT (p= 0.09). There were no differences between the groups three months after training ended. CONCLUSIONS: Strength training strengthens non-injected muscles temporarily and may reduce short term strength loss that results from BoNT-A injections without increasing muscle tone. Moreover, additional strength training may increase active range of motion to a larger extent than BoNT-A alone. None of the improvements in neuromuscular body functions further improved hand activity. Larger clinical trials are needed to further investigate whether strength training can counteract strength loss caused by BoNT-A, whether the combination of BoNT-A and strength training is superior to BoNT-A or strength training alone in improving active range of motion, and whether more task-related strength training is a more effective approach to improve hand activity.     

The cost-effectiveness of personalized genetic medicine: the case of genetic testing in neonatal diabetes

OBJECTIVE

Neonatal diabetes mellitus is a rare form of diabetes diagnosed in infancy. Nearly half of patients with permanent neonatal diabetes have mutations in the genes for the ATP-sensitive potassium channel (KCNJ11 and ABCC8) that allow switching from insulin to sulfonylurea therapy. Although treatment conversion has dramatic benefits, the cost-effectiveness of routine genetic testing is unknown.

RESEARCH DESIGN AND METHODS

We conducted a societal cost-utility analysis comparing a policy of routine genetic testing to no testing among children with permanent neonatal diabetes. We used a simulation model of type 1 diabetic complications, with the outcome of interest being the incremental cost-effectiveness ratio (ICER, $/quality-adjusted life-year [QALY] gained) over 30 years of follow-up.

RESULTS

In the base case, the testing policy dominated the no-testing policy. The testing policy was projected to bring about quality-of-life benefits that enlarged over time (0.32 QALYs at 10 years, 0.70 at 30 years) and produced savings in total costs that were present as early as 10 years ($12,528 at 10 years, $30,437 at 30 years). Sensitivity analyses indicated that the testing policy would remain cost-saving as long as the prevalence of the genetic defects remained >3% and would retain an ICER <$200,000/QALY at prevalences between 0.7 and 3%.

CONCLUSIONS

Genetic testing in neonatal diabetes improves quality of life and lowers costs. This paradigmatic case study highlights the potential economic impact of applying the concepts of personalized genetic medicine to other disorders in the future.Neonatal diabetes mellitus is a rare form of diabetes that is likely to have a monogenic cause, particularly when diagnosed before 6 months of age (1). Recent estimates from multiple national registries show the incidence is close to 1 in 100,000 live births (2). In 50% of cases, the condition spontaneously remits within a few months of age and is termed transient neonatal diabetes, whereas the remaining infants have permanent neonatal diabetes.Of probands with permanent neonatal diabetes, 42% have activating heterozygous mutations in either of the two protein subunits, KCNJ11 and ABCC8, of the ATP-sensitive potassium (KATP) channel, whereas 12% have mutations in the gene encoding insulin (INS) (3–6). In KATP-related neonatal diabetes, sulfonylurea binding allows KATP channel closure in patients whose channels would otherwise remain open and prevent insulin secretion from occurring. Reports indicate that treatment with oral sulfonylurea therapy in place of insulin has been successful in most of these patients, leading to immediate dramatic improvements in glucose control and quality of life (7,8).These recent discoveries have raised questions regarding the extent to which routine testing for these mutations should be performed in any insulin-treated individual with presumed type 1 diabetes. Age at diagnosis of diabetes is a key determinant of a possible monogenic cause, where those diagnosed when aged younger than 6 months have a high likelihood of having a causal genetic variant. However, 1–2% of those diagnosed between age 6 and 12 months may also be monogenic (6,8,9). Some experts have even suggested that all newborns should perhaps undergo screening (10), given that routine newborn screening in all states includes such disorders as maple syrup urine disease, which has an incidence of 1 in 185,000 births.In any consideration of genetic testing, the prevalence of genetic markers that could inform disease prediction, treatment, or outcomes must be weighed against the cost of testing. The promise of personalized genetic medicine is that highly individualized treatments may not only improve the health of patients but may also lower costs in some cases. There have been no rigorous cost-effectiveness analyses of genetic testing policies that lead to transformative changes in the selection of treatments (compare to studies of warfarin pharmacogenetics [11]). To test the hypothesis that genetic testing in some disorders can lead to dramatic health and cost benefits, we conducted a societal cost-utility analysis of a genetic testing policy for permanent neonatal diabetes.     

Long-acting injectable progestin contraception and risk of type 2 diabetes in Latino women with prior gestational diabetes mellitus

OBJECTIVE: To investigate the impact of a long-acting injectable progestin, depo-medroxyprogesterone acetate (DMPA), compared with combination oral contraceptives (COCs) on the risk of diabetes in Latino women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: An observational cohort study of 526 Hispanic women with prior GDM who were not diabetic in their postpartum visit during January 1987 to October 1997 and who elected DMPA (n = 96) or COCs (n = 430) as initial contraception were followed for a maximum of 9.2 years with a median follow-up of approximately 12 months. Oral glucose tolerance tests were performed and choice of contraception method was recorded at each visit as part of routine clinical care. RESULTS: Annual diabetes incidence rates were 19% in the DMPA group and 12% in the COC group, with an unadjusted hazard ratio (HR) of 1.58 (95% CI 1.00-2.50; P = 0.05) for DMPA compared with COCs. Adjustment for baseline imbalances reduced the HR to 1.18 (0.67-2.28; P = 0.57). Additional adjustment for weight gain during follow-up, which was on average 1.8 kg higher in the DMPA group (P < 0.0001), reduced the HR to 1.07. DMPA interacted with baseline serum triglyceride levels and, separately, with breast-feeding to increase the diabetes risk. CONCLUSIONS: DMPA use was associated with an increased risk of diabetes that appeared to be explained by three factors: 1) use in women with increased baseline diabetes risk, 2) weight gain during use, and 3) use with high baseline triglycerides and/or during breast-feeding.     

Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson's disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus

BACKGROUND: The clinical condition of advanced Parkinson's disease (PD) patients is often complicated by motor fluctuations and dyskinesias which are difficult to control with available oral medications. OBJECTIVE: To compare clinical and neuropsychological 12 month outcome following subcutaneous apomorphine infusion (APO) and chronic deep brain stimulation of the subthalamic nucleus (STN-DBS) in advanced PD patients. METHODS: Patients with advanced PD and medically untreatable fluctuations underwent either APO (13 patients) or STN-DBS (12 patients). All patients were clinically (UPDRS-III, AIMS, 12 h on-off daily) and neuropsychologically (MMSE, Hamilton-17 depression, NPI) evaluated at baseline and at 12 months. APO was discontinued at night. RESULTS: At 12 months APO treatment (74.78+/-24.42 mg/day) resulted in significant reduction in off time (-51%) and no change in AIMS. Levodopa equivalent medication doses were reduced from 665.98+/-215 mg/day at baseline to 470+/-229 mg/day. MMSE, NPI, and Hamilton depression scores were unchanged. At 12 months STN-DBS resulted in significant clinical improvement in terms of reduction in daily off time (-76%) and AIMS (-81%) as well as levodopa equivalent medication doses (980+/-835 to 374+/-284 mg/day). Four out of 12 patients had stopped oral medications. MMSE was unchanged (from 28.6+/-0.3 to 28.4+/-0.6). Hamilton depression was also unchanged, but NPI showed significant worsening (from 6.58+/-9.8 to 18.16+/-10.2; p<0.02). Category fluency also declined. CONCLUSIONS: Both APO and STN-DBS resulted in significant clinical improvement in complicated PD. STN-DBS resulted in greater reduction in dopaminergic medications and provided 24 h motor benefit. However, STN-DBS, unlike APO, appears to be associated with significant worsening on NPI resulting from long term behavioral problems in some patients.     

Determination of anti‐convulsant and life‐preserving capacities of three types of auto‐injector therapies against soman intoxication in rats

More effective countermeasures against nerve‐agent poisoning are needed, because current ones do not protect sufficiently, particularly the central nervous system (CNS). The purpose of the present study was to make a comparison of the antidotal capabilities of atropine/obidoxime/diazepam (termed the obidoxime regimen), atropine/HI‐6 (1‐[([4‐(aminocarbonyl)pyridinio]methoxy)methyl]‐2‐[(hydroxyimino)methyl]pyridinium)/avizafone (termed the HI‐6 regimen), and scopolamine/HI‐6/physostigmine (termed the physostigmine regimen) against various doses of soman (2, 3, 4 x LD₅₀). The results showed that each regimen administered twice (1 min and 5 min after exposure) effectively prevented or terminated epileptiform activity within 10 min. However, the regimens differed markedly in life‐saving properties with the physostigmine regimen ranking highest followed in descending order by the HI‐6 and obidoxime regimens. Pretreatment with pyridostigmine increased the potency of the HI‐6 regimen, but not the obidoxime regimen. The latter regimen administered thrice (1 min, 5 min, and 9 min after exposure) did not compensate for the insufficiency. In half of the rats that lived for 7 days, neuropathology was unexpectedly observed predominantly in the left hemisphere unrelated to whether they seized or not. Local glutamatergic excitotoxic activity may occur even if manifest toxic signs are absent. The physostigmine regimen has excellent antidotal capacity, but the very narrow therapeutic window (< 10 min) makes it unsuitable for use in the field. The HI‐6 regimen appears to constitute an efficacious therapy against lower doses of soman (2 and 3 x LD₅₀). Copyright © 2012 John Wiley & Sons, Ltd.     

Smoking cessation A comparative,randomised study between management in general practice and the behavioural programme SmokEnders

Objective - To evaluate whether measurement of albumin creatinine ratio (ACR) on a spot urine specimen can replace a timed overnight collection of urine albumin excretion rate (UAER) in patients with diabetes in primary care. Design - Patients with diabetes attending Rønvik Health Centre were asked to bring a timed overnight collection of urine for measurement of UAER. They were also asked to void a urine specimen for measurement of albumin creatinine ratio. Setting - Primary health care. Subjects - One-hundred-and-six persons with diabetes (47 women, 59 men) aged 13 to 78 years. Results - The sensitivity and specificity of ACR with cut-off values of 2.5 mg/mmol for men and 3.5 mg/mmol for women compared to UAER with cut-off value of 20 mg/24 h was 90%. Conclusions - Spot urine ACR analysed on a DCA 2000 can replace a timed (overnight) collection of urine and measurement of UAER when diabetic patients are reviewed in general practice. This simplifies procedures for the patient as a timed urine collection is no longer necessary. Another advantage is that the results are available after 7 min.     

TNF-alpha promoter polymorphisms in sudden infant death

Several studies indicate that the immune system is stimulated in sudden infant death syndrome (SIDS). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that strongly affects the cytokine cascade. A genetic variant associated with high production of TNF-alpha may thus be of significance in the pathogenesis of SIDS. The purpose of the current study was to investigate possible relationships among the promoter polymorphisms -1031T/C, -857C/T, -308G/A, -244G/A, and -238G/A in the TNF-alpha gene and SIDS. The subjects investigated consisted of 148 SIDS cases, 56 borderline SIDS cases, 41 cases of infectious death, and 131 adult controls. When investigating each single nuclear polymorphism (SNP) separately, associations between -238GG and SIDS (p=0.022) and between -308GA and borderline SIDS (p=0.005) were found. There were no associations between any of the other SNPs investigated. Furthermore, a SNP profile was constructed by creating a genotype pattern from the investigated SNPs. Fifteen gene combinations were obtained, and 4 profiles had significantly different frequencies in SIDS cases and controls. The two SNP profiles -1031CT, -238GG, -857CC, -308GG and -1031TT, -238GG, -857CC, -308AA were found more often in SIDS and may thus be unfavorable. The findings add evidence to the theory that an unfavorable genetic profile in the TNF-alpha gene may be involved in SIDS by exposing the infant to both a high level of and prolonged exposure to TNF-alpha.