Showing papers by "Bethesda Hospital published in 2012"

Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor

Abstract: Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.

Multiple complications and frequent severe hypoglycaemia in 'elderly' and 'old' patients with Type 1 diabetes.

Abstract: Diabet. Med. 29, e176–e179 (2012) Abstract Aim Elderly and old patients with Type 1 diabetes represent a growing population that requires thorough diabetes care. The increasing relevance of this subgroup, however, plays only a minor role in the literature. Here, we describe elderly patients with Type 1 diabetes on the basis of a large multi-centre database in order to point out special features of this population. Method Data of 64 609 patients with Type 1 diabetes treated by 350 qualified diabetes treatment centres were assessed and analysed by age group. Results Compared with the age group ≤ 60 years, patients aged > 60 years (n = 3610 61–80 years and n = 377 > 80 years old) were characterized by a longer diabetes duration (27.7 vs. 7.7 years), an almost double risk for severe hypoglycaemia (40.1 vs. 24.3/100 patient-years), a lower level of HbA1c [60 vs. 67 mmol/mol (7.6 vs. 8.3%)] and higher percentages of microalbuminuria (34.5 vs. 15.6%), diabetic retinopathy (45.2 vs. 8.3%), myocardial infarction (9.0 vs. 0.4%) or stroke (6.8 vs. 0.3%). Elderly patients used insulin pumps less frequently (12.2 vs. 23.8%), but more often used conventional premixed insulin treatment (10.8 vs. 3.8%). Differences between elderly and younger patient groups were significant, respectively. Conclusion Diabetes care of elderly patients with Type 1 diabetes involves individualized treatment concepts. Increased hypoglycaemia risk and functional impairment attributable to diabetes-associated and/or age-related disorders must be taken into account.

Evaluation of 5-Fluorouracil Pharmacokinetics in Cancer Patients with a C.1905+1G>A Mutation in DPYD by Means of a Bayesian Limited Sampling Strategy

Abstract: Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme in the catabolism of 5-fluorouracil (5FU) and DPD deficiency is an important pharmacogenetic syndrome. So far, only very limited information is available regarding the pharmacokinetics of 5FU in patients with a (partial) DPD deficiency and no limited sampling models have been developed taking into account the non-linear pharmacokinetic behaviour of 5FU. The aim of this study was to evaluate the pharmacokinetics of 5FU and to develop a limited sampling strategy to detect decreased 5FU elimination in patients with a c.1905+1G>A-related DPD deficiency. Thirty patients, heterozygous for the C.1905+1G>A mutation in DPYD, and 18 control patients received a dose of 5FU 300 mg/m2 and/or 5FU 450 mg/m2, followed by pharmacokinetic analysis of the 5FU plasma levels. A population pharmacokinetic analysis was performed in order to develop a compartmental pharmacokinetic model suitable for a limited sampling strategy. Clinical aspects of treating DPD-deficient patients with 5FU-based chemotherapy were assessed from the retrospectively collected clinical data. In a two-compartment model with Michaelis-Menten elimination, the mean maximum enzymatic conversion capacity (Vmax) value was 40% lower in DPD-deficient patients compared with controls (p < 0.001). Using a limited sampling strategy, with Vmax values calculated from 5FU concentrations at 30 or 60 minutes, significant differences were observed between DPD-deficient patients and controls at both dose levels (p < 0.001). The positive predictive value and negative predictive value for Vmax, calculated from 5FU levels at 60 minutes, were 96% and 88%, respectively, in patients treated with a single dose of 5FU 300 mg/m2. All seven DPD-deficient patients (two males and five females) who had been genotyped prior to initiation of standard 5FU-containing chemotherapy developed grade 3–4 toxicity, with one case of lethal toxicity in a female patient. No grade 4 toxicity or lethal outcome was observed in 13 DPD-deficient patients treated with reduced doses of 5FU. The average dose of 5FU in DPD-deficient patients with mild toxicity (grade ≤2) was 61 ± 16% of the normal 5FU dose (n= 10). Profound differences in the elimination of 5FU could be detected between DPD-deficient patients and control patients. Pharmacokinetic 5FU profiling, using a single 5FU concentration at 60 minutes, may be useful for identification of DPD-deficient patients in order to reduce severe toxicity. Furthermore, treatment of DPD-deficient patients with standard 5FU-containing chemotherapy was associated with severe (lethal) toxicity.

Osteodensitometry measurements of periprosthetic bone using dual energy X-ray absorptiometry following total knee arthroplasty.

Abstract: Introduction The present study investigates the reaction of bone density as well as the possible factors influencing this reaction following a cement-free total knee arthroplasty (TKA).

Knuckle pads - a rare finding.

Abstract: Knuckle pads are rare harmless subcutaneous nodules that must be differentiated from joint disease of the proximal interphalangeal or rarely of the metacarpophalangeal joints as well as from other masses of the paraarticular tissues. We present a case of an otherwise healthy 36-year-old woman presenting with bilateral knuckle pads located at the dorsal aspect of the proximal interphalangeal joints. No predisposition to a specific musculoskeletal disorder was noted. Ultrasound revealed well-delimited subcutaneous hypoechoic masses without internal flow signals at color Doppler. Histology showed proliferation of myofibroblasts with a decrease of elastic filaments in the deep dermis. The clinical picture, the family history in addition to the histology allowed us to make the diagnosis of knuckle pads. We present the ultrasound findings of knuckle pads and discuss the differential diagnosis of a "swelling" in the dorsal region of proximal interphalangeal joints and metacarpophalangeal joints.

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

Abstract: Background Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance.

Giant cell arteritis followed by idiopathic retroperitoneal fibrosis in the same patient—an unexpected positron emission tomography finding

Abstract: A 78-year-old male patient was diagnosed with GCA, confirmed by positive histology of the temporal artery. Treatment with prednisone 1 mg/kg of body weight was initiated, tapered and stopped after 2 years. Two years later, with unremarkable regular controls, the patient presented with lumbar pain, elevated ESR (41 mm/h) and CRP (27 mg/l). PET CT scan (Fig. 1A) was performed, showing moderately elevated fluoro-deoxy-glucose (FDG) uptake in both femoral arteries and a retroperitoneal metabolically active mass partially obstructing the left urether. MRI scans of the abdomen (Fig. 1B) were consistent with the diagnosis of idiopathic retroperitoneal fibrosis (IRF) with left-sided grade I hydronephrosis. IgG4 was initially elevated to 2.00 g/l (normal range 0.08 1.4 g/l) subsiding to 0.62 g/l under treatment with prednisone (1 mg/kg body weight). With 5 mg of prednisone per day, both diseases have remained inactive for the past 6 months. This case describes a patient suffering from both GCA and IRF, an IgG4-related sclerosing disease often associated with elevation of the IgG4 subclass. IRF has not yet been described in patients with GCA. However, similarities in histopathology with inflammation in the medial and adventitial layers of the aorta suggest common yet unproven pathogenetic mechanisms for IRF and GCA.

Inaugural address of the President-elect and Vice Chair of the Board

Abstract: I am very excited about the wonderful opportunity that you have given me to serve as ASHP’s next president. I would like to begin by acknowledging a few key people in my life. First, my family . . . my mom and dad are my number one cheerleaders. They have been wonderful role models for me because