Methadone detoxification of tramadol dependence

Tramadol hydrochloride is a centrally acting analgesic with a partial affinity for the opiate receptor (mu), having an analgesic potency estimated to be one tenth that of morphine. While preclinical investigations suggested that abuse liability associated with tramadol use is low, there are increasing numbers of cases reported to the U.S. Food and Drug Administration of abuse, dependence, and withdrawal associated with tramadol use. A case of a patient with tramadol dependence requiring detoxification with methadone is presented. Acute management of significant tramadol dependence has not yet been reported in the literature. Long-term treatment issues are also discussed.     

The new PET imaging agent [11C]AFE is a selective serotonin transporter ligand with fast brain uptake kinetics

A new positron emission tomography (PET) radioligand for the serotonin transporter (SERT), [¹¹C]2-[2-[[(dimethylamino)methyl]phenyl]thio]-5-(2-fluoroethyl)phenylamine ([¹¹C]AFE, 12), was synthesized and evaluated in vivo in rats and baboons. [¹¹C]AFE (12) was prepared from its monomethylamino precursor 11 by reaction with high specific activity [¹¹C]methyl triflate. Radiochemical yield was 32±17% based on [¹¹C]methyl triflate (n=6) and specific activity was 1670±864 Ci/mmol at end of synthesis (EOS, n=6). Binding assays indicated that AFE displays high affinity for SERT (K_i=1.80 nM for hSERT) and lower affinity for norepinephrine transporter (K_i=946 nM for hNET) or dopamine transporter (K_i>10,000 nM for hDAT). In addition, AFE displays negligible binding affinities for other serotonin and dopamine receptors, indicating an excellent binding selectivity in vitro. Biodistribution studies in rats indicated that [¹¹C]AFE enters the brain readily and localizes in regions known to contain high concentrations of SERT, such as the thalamus, hypothalamus, frontal cortex and striatum. Moreover, such binding in SERT-rich brain regions is reduced significantly by pretreatment with either citalopram or the cold compound itself, but not by nisoxetine or GBR 12935, thus demonstrating that [¹¹C]AFE binding in the rat brain is saturable, specific and selective for the SERT. Imaging experiments in baboons indicated that the uptake pattern of [¹¹C]AFE is consistent with the known distribution of SERT in the baboon brain, with high levels of radioactivity detected in the midbrain and thalamus, moderate levels in the hippocampus and striatum and low levels in the cortical regions. The uptake kinetics of [¹¹C]AFE in the baboon brain is rapid, with activity in the midbrain and thalamus peaking at 15–40 min postinjection. Pretreatment of the baboon with citalopram (4 mg/kg) 20 min before radioactivity injection reduced the binding of [¹¹C]AFE in all SERT-containing brain regions to the level in the cerebellum. Kinetic analysis revealed that in all brain regions examined, [¹¹C]AFE specific-to-nonspecific partition coefficients (V₃″) are similar to those of [¹¹C]McN5652 and [¹¹C]2-[2-[[(dimethylamino)methyl]phenyl]thio]-5-fluorophenylamine ([¹¹C]AFA), but lower than those of [¹¹C]2-[2-[[(dimethylamino)methyl]phenyl]thio]-5-fluoromethylphenylamine ([¹¹C]AFM) or [¹¹C]DASB. In summary, [¹¹C]AFE appears to be a PET radioligand with fast brain uptake kinetics and can be used for the visualization and quantification of SERT in vivo.     

Increased Left Ventricular Torsion in Uncomplicated Type 1 Diabetic Patients: The role of coronary microvascular function

OBJECTIVE

We used speckle tracking echocardiography to study the early changes in left ventricular (LV) torsion in young patients with uncomplicated type 1 diabetes and stress magnetic resonance imaging (MRI) to assess its interrelationships with coronary microangiopathy.

RESEARCH DESIGN AND METHODS

We recruited 33 asymptomatic subjects with type 1 diabetes and 32 age-matched healthy control subjects. All subjects underwent echocardiograms. Stress MRIs were performed in 30 subjects (8 healthy control subjects) to compute myocardial perfusion reserve index (MPRI).

RESULTS

A significant increase in LV torsion (2 ± 0.7 vs. 1.4 ± 0.7°/cm, P < 0.05) was identified in longer-term and retinopathy-positive type 1 diabetic subjects (1.9 ± 0.7 vs. 1.4 ± 0.7°/cm, P < 0.05) as compared with the healthy control subjects. The MPRI was independently associated with increased LV torsion.

CONCLUSIONS

We demonstrate that LV torsion is increased in young patients with uncomplicated type 1 diabetes and that coronary microvascular disease may play a key pathophysiological role in the development of increased LV torsion.There is increasing evidence for the presence of diabetic cardiomyopathy as a separate entity. However, detection of early changes in the myocardium is challenging in patients with diabetes. Speckle tracking echocardiography is a novel method of measuring left ventricular (LV) strain and rotation (1,2). Previous studies with tagged magnetic resonance imaging (MRI) have shown increased torsion in both patients with type 1 and type 2 diabetes (3,4). The main aim of this study was to confirm and extend these findings by exploring the potential pathophysiological mechanisms involved. We utilized speckle tracking to measure LV torsion and stress MRI to compute myocardial perfusion reserve index (MPRI), which is a measure of coronary microvascular function.     

Differentiation of rhabdomyosarcoma cell lines using retinoic acid

BACKGROUND: Rhabdomyosarcoma (RMS) is the most frequent sporadic soft tissue sarcoma of childhood and adolescence. The overall 5-year survival rate for patients with RMS is 70% with the use of surgery, radiation, and chemotherapy. Novel therapeutic approaches are necessary to improve on these outcomes particularly among the more aggressive alveolar RMS (ARMS) and late stages of disease, where 5-year survival is less than 20%. Retinoids have been successfully used in the treatment of acute promyelocytic leukemia (APML) and neuroblastoma. PURPOSE: However, analysis of retinoids as a differentiating agent for RMS has been incomplete. This work examined the ability of retinoic acid (RA) to promote differentiation of RMS cell lines by examining the expression of myogenic proteins in five RMS cell lines in response to All-trans Retinoic Acid (ATRA) or 9-cis retinoic acid (CRA). RESULTS: Analysis of growth curves indicates that both retinoids suppress cell growth of Rh4 and Rh28. RD cells only responded to-CRA whereas Rh30 and Rh18 did not respond. Following treatment with ATRA FACS analysis showed an altered cell cycle with the same pattern as the growth curves. ATRA altered cellular morphology of two cell lines, Rh4 and Rh28, and induced Troponin T expression in these cells suggesting a differentiating effect. CONCLUSIONS: These studies suggest that retinoids are effective inducers of growth arrest and differentiation in some RMS cell lines, and offer a basis for further in vivo testing in mice of ATRA as a potential approach to ARMS treatment.     

Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity

Aggressive posterior retinopathy of prematurity (formerly known as fulminate/type II/rush disease) occurs in zone 1 or posterior zone 2. Treatment involves extensive near confluent laser ablation of a large area of avascular retina. Anterior segment ischemia is a rare complication that can occur due to injury to the long posterior ciliary arteries in the horizontal meridians during aggressive posterior laser treatment. The outcome of this rare complication is very poor. This case describes a favorable outcome of intravitreal injection of bevacizumab (Avastin) in a case of anterior segment ischemia.     

Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm that usually affects infants and young children. In this report, we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid (CSF) of an infant with AT/RT. These cells retained the morphological and biomarker characteristics of the original tumor. A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4, Insulin-R, PDGFR and IGF-IR, which appear to depend on Hsp90 to maintain their active form. IGF-IR activity is consistent with data from other established AT/RT cell lines. Inhibition of IGF-IR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells. In addition, neutralizing antibodies to IGF-II also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine. We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells. In addition to previously described cell lines and xenograft models, continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumor.     

Periodontal health status of school children in St. Vincent and the Grenadines.

A national oral health survey of school children was conducted in October through November 1991. The objective was to determine the periodontal status of school children in St. Vincent and The Grenadines (SVG), the pattern and severity of periodontal disease, estimate treatment needs and provide information for health planners. The study had a cross-sectional design, and 1646 schoolchildren representing all school districts were selected via multistage, systematic sampling. Examinations were conducted by three examiners using CPITN probe. Periodontal indicators and treatment needs were determined using the CPITN index. Calculus was the most prevalent condition with values ranging from 26 to 83 percent, bleeding was the least prevalent condition, while children with healthy indicator were intermediate in prevalence. Subjects with healthy indicators ranged from a low of 12 percent among 15-19 year olds, to a high of 51 percent among seven-year-olds. The mean number of healthy sextants varied from three to five, and mean number of sextants with bleeding or calculus varied from one to three. Oral hygiene instruction (OHI) was the most common treatment need, ranging from 49 to 88 percent. The need for prophylaxis was associated with increase in age, with the highest prophylaxis treatment needs of 83 percent, among 15-19 year olds. No significant differences were observed in periodontal status between gender, and also between urban and rural children. A high prevalence of calculus and bleeding was observed among SVG school children. Study recommends initiation of primary prevention programs in form of health promotion and health education.     

Diabetic retinopathy among self reported diabetics in southern India: a population based assessment

AIMS: To estimate the prevalence of diabetic retinopathy among self reported diabetics in a population of southern India. METHODS: A cross sectional sample of subjects aged 50 years and older was selected using a cluster sampling technique from Palakkad district of Kerala state. Eligible subjects were identified through a door to door survey. Ocular examinations including visual acuity and anterior and posterior segment examinations were performed at preselected sites within clusters. History of diabetes was elicited, and height, weight, and blood pressure were measured for all subjects. RESULTS: Among the 5212 examined people (92% response rate), 68 (26.2%) of 260 people with self reported history of diabetes had diabetic retinopathy. The age-sex adjusted prevalence of diabetes among people aged 50 years and older was 5.1% (95% CI 3.9, 6.3, deff 4.33) and of diabetic retinopathy among the diabetics was 26.8% (95% CI: 19.2, 34.4, deff 1.99). Non-proliferative diabetic retinopathy (94.1%) was the most common form of retinopathy seen. Two eyes were blind (presenting vision <6/60) as a result of retinopathy. CONCLUSION: Preventive strategies have to be evolved to ensure that blindness due to diabetic retinopathy does not become a public health problem in India. Further studies are required to understand the risk factors for retinopathy and vision loss in this population.