Polyneuropathy and myopathy in beta-thalassemia major patients.

The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study. We performed nerve conduction studies and electromyography of upper and lower extremities on 36 beta-thalassemia major (ß-thal) patients. The electrophysiological findings were correlated with demographic data and laboratory parameters of the disease. Patients with ß-thal present polyneuropathy or myopathy at (50%). Polyneuropathy was detected in (38.9%) and myopathy in (27.8%), while polyneuropathy and myopathy were present at (16.7%) with an overlap of the diseases in 1/3 of the patients. There was not a statistically significant correlation of polyneuropathy and myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin, and ferritin. However, there was a statistically significant correlation of polyneuropathy and myopathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver. Our findings suggest that iron overload plays a key role in the pathogenesis of polyneuropathy and myopathy in ß-thal patients, and performing heart and liver MRI for the prediction of such lesions in an annual basis is warranted.

Differences in cardiac structure assessed by echocardiography between renal transplant recipients and chronic kidney disease patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in predialysis chronic kidney disease (CKD) and dialysis patients as well as in renal transplant recipients (RTRs). Left ventricular hypertrophy (LVH) starts early during the course of CKD and is a strong predictor of CVD in this population. Regression of LVH after a successful renal transplantation remains a debatable issue among investigators, whereas there is little data comparing echocardiographic measurements between patients with predialysis CKD and RTRs. AIM: The aim of this study was to compare echocardiographic measurements of LV structure and function between predialysis CKD patients and RTRs of similar renal function level. PATIENTS AND METHODS: We conducted a case control study with individual (1:2) matching from the Renal Transplant and the predialysis CKD Outpatient Clinic. For each of the 36 RTRs, two matched for gender, age and estimated glomerular filtration rate (eGFR) predialysis CKD outpatients (72 patients) were included. All patients underwent transthoracic echocardiography and LV mass, LV mass index [LVM and LVMI = LVM/BSA g/m(2)] and indices of systolic function were measured. In a subgroup of 12 RTRs we retrospectively assessed and compared the LVMI measurements at three different time points, during predialysis, dialysis and post transplant period. RESULTS: The prevalence of LVH was 33% in RTRs and 52% in CKD patients (ns). RTRs had significantly lower LVM and LVMI levels compared with predialysis CKD patients (P = .006 and P = .008) while the other echocardiographic indices did not differ. In the subgroup of 12 RTRs, post-transplant LVMI levels (105 ± 25 g/m(2)) were significantly lower in comparison with predialysis (147 ± 57 g/m(2)) and dialysis LVMI levels (169 ± 72 g/m(2)) (P = .01, P = .01, respectively). CONCLUSION: RTRs had significantly lower LVMI compared with predialysis CKD patients of similar age, renal function, hemoglobin and blood pressure level.

The application of Mechanical Diagnosis and Therapy and changes on MRI findings in a patient with cervical radiculopathy.

Cervical radiculopathy is an unusual presentation for patients with neck pain. Its diagnosis and management is uncertain. This case report presents an example of a patient with cervical radiculopathy who responded to Mechanical Diagnosis and Therapy, and whose MRI findings changed over time.

Assessment of nonimmunologic factors in kidney transplant recipients according to Kidney Disease Improving Global Outcomes.

INTRODUCTION: Cardiovascular disease is the primary cause of death among kidney transplant recipients (KTRs), whereas chronic allograft nephropathy (CAN) is the main reason leading to end-stage chronic kidney disease. The etiologies of both entities include immunologic and nonimmunologic factors. The management of modifiable nonimmunologic parameters has recently been identified by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The aim of our study was to assess the implementation of these guidelines in the outpatient kidney transplantation clinic of our hospital. PATIENT AND METHODS: We retrospectively monitored the records of 48 transplanted KTRs including 32 males of overall mean age 45.1 ± 10.7 years regarding control of anemia, dyslipidemia, mineral bone disorder (MBD), and blood pressure (BP) levels. Data were recorded every 6 months for 2 years, starting 1 year after renal transplantation. RESULTS: The estimated glomerular filtration rate of patients at baseline was 60.3 ± 18.8 mL/min/1.73 m(2) with no significant change during 2 years of follow-up. The control of anemia was satisfactory in 42 patients (88%) with hemoglobin values ≥ 11 g/dL during the follow-up. Regarding dyslipidemia management, the aggregate of patients showed fasting triglycerides ≤500 mg/dL in all measurements. The percentage of KTRs with LDL ≤100 mg/dL tended to improve from baseline versus the end of the study period (20.8% vs 41.7%). Serum calcium was satisfactorily controlled in 77% of patients, serum phosphorus in all patients, whereas parathyroid hormone (PTH) was abnormal in 60% of KTRs with chronic kidney disease stages 3-5. Finally, the BP goal of <130/80 mm Hg was achieved in approximately half of the patients. CONCLUSION: Control of nonimmunologic factors was satisfactory in terms of renal anemia and MBD, whereas dyslipidemia and BP levels were inadequately controlled. There is a clear need for better integration into clinical practice of KDIGO guidelines with regard to modifiable nonimmunologic factors.

Disclosing the truth to terminal cancer patients: a discussion of ethical and cultural issues.

One of the most difficult ethical dilemmas facing health care professionals working in oncology is whether, when, how and how much to tell terminal cancer patients about their diagnosis and prognosis. The aim of this article is to review the trends in this issue worldwide. While a majority of physicians in both developed and developing countries tell the truth more often today than in the past, the assumption that truth-telling is always beneficial to patients can be questioned. The issue of truth-telling is still approached differently in different countries and cultures and there is a need for an increased awareness of cultural differences to truth-telling among patients from ethnic minorities.

Disclosing the truth to terminal cancer patients: a discussion of ethical and cultural issues

One of the most difficult ethical dilemmas facing health care professionals working in oncology is whether, when, how and how much to tell terminal cancer patients about their diagnosis and prognosis. The aim of this article is to review the trends in this issue worldwide. While a majority of physicians in both developed and developing countries tell the truth more often today than in the past, the assumption that truth-telling is always beneficial to patients can be questioned. The issue of truth-telling is still approached differently in different countries and cultures and there is a need for an increased awareness of cultural differences to truth-telling among patients from ethnic minorities

cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury.

BACKGROUND AND PURPOSE: Although the cerebellum has not attracted the same degree of attention as cortical areas and the hippocampus in traumatic brain injury (TBI) literature, there is limited structural and functional imaging evidence that the cerebellum is also vulnerable to insult. The cerebellum is emerging as part of a frontocerebellar system that, when disrupted, results in significant cognitive and behavioral consequences. We hypothesized that cerebellar volume would be reduced in children following TBI and wished to examine the relation between the cerebellum and known sites of projection, including the prefrontal cortex, thalamus, and pons. MATERIALS AND METHODS: Quantitative MR imaging was used to measure cerebellar white and gray matter and lesion volumes 1-10 years following TBI in 16 children 9-16 years of age and 16 demographically matched typically developing children 9-16 years of age. Cerebellar volumes were also compared with volumetric data from other brain regions to which the cerebellum projects. RESULTS: A significant group difference was found in cerebellar white and gray matter volume, with children in the TBI group consistently exhibiting smaller volumes. Repeating the analysis after excluding children with focal cerebellar lesions revealed that significant group differences still remained for cerebellar white matter (WM). We also found a relation between the cerebellum and projection areas, including the dorsolateral prefrontal cortex, thalamus, and pons in 1 or both groups. CONCLUSION: Our finding of reduced cerebellar WM volume in children with TBI is consistent with evidence from experimental studies suggesting that the cerebellum and its related projection areas are highly vulnerable to fiber degeneration following traumatic insult.

A group-IV ferromagnetic semiconductor: MnxGe1-x.

We report on the epitaxial growth of a group-IV ferromagnetic semiconductor, Mn(x)Ge(1-x), in which the Curie temperature is found to increase linearly with manganese (Mn) concentration from 25 to 116 kelvin. The p-type semiconducting character and hole-mediated exchange permit control of ferromagnetic order through application of a +/-0.5-volt gate voltage, a value compatible with present microelectronic technology. Total-energy calculations within density-functional theory show that the magnetically ordered phase arises from a long-range ferromagnetic interaction that dominates a short-range antiferromagnetic interaction. Calculated spin interactions and percolation theory predict transition temperatures larger than measured, consistent with the observed suppression of magnetically active Mn atoms and hole concentration.

Development and validation of an HPLC assay for fentanyl, alfentanil, and sufentanil in swab samples.

A high performance liquid chromatography (HPLC) method for the assay of fentanyl citrate, alfentanil hydrochloride, and sufentanil citrate swab samples was developed and validated in order to control a cleaning procedure. The swabbing procedure involved Super POLX 1200 wipers moistened with water. The assay employed extraction of swabs with water and analysis by isocratic, reversed-phase, HPLC with varying ultraviolet (UV) detection for desired sensitivity, depending on the analyte. The method was shown to be selective and linear from the limits of quantitation (0.10, 0.20, and 0.15 microg/swab for fentanyl citrate, alfentanil, and sufentanil, respectively) to over three times these concentrations. The assay limits (detection levels) per swab area were set at least at 0.2% of the concentrations of the actives in the drug products (0.02, 0.10, and 0.10 microg/swab or approximately 0.03, 0.02, and 0.2% for fentanyl citrate, alfentanil, and sufentanil, respectively). It should be noted that all active concentrations listed in this work were calculated based on the salt form concentration for fentanyl (citrate salt) and the free base forms for alfentanil and sufentanil. No reference standard was available for alfentanil hydrochloride and sufentanil citrate. Drug product was used instead throughout this study.

Development and validation of an HPLC assay for fentanyl and related substances in fentanyl citrate injection, USP.

The stability indicating properties of the USP method for the assay of fentanyl in fentanyl citrate injection were evaluated [1] by analyzing fentanyl drug substance and product after acid, hydrogen peroxide, heat, and light treatment. N-phenyl-N-(4-piperidinyl)propionamide (PPA), which is a known degradation product/process impurity of fentanyl, was not adequately resolved from the fentanyl peak, and mobile phase adjustments did not improve the resolution (Fig. 1). Therefore, the USP method did not meet the requirements for a stability-indicating assay. In addition, the wavelength in the USP method was too high (230 nm) to provide adequate levels for the quantitation of the related substances of fentanyl and, in addition, the acetate ions in the mobile phase could interfere with a lower wavelength detection. An isocratic, reversed phase, stability indicating, high performance liquid chromatographic (HPLC) method for the assay of fentanyl and related substances in fentanyl citrate injection, USP has been developed and validated. The chromatographic conditions employed an Inertsil C8, 5 column (25 cm x 4.6 mm), a mobile phase of aqueous perchloric acid [0.23%, w/v]-acetonitrile [65:35, v/v], and ultraviolet (UV) detection at 206 nm. Under the chromatographic conditions of the method, PPA and seven other known process impurities were separated from the active. Degradation studies showed that the active eluted as a spectrally pure peak resolved from its degradation products.

Method development and validation for the HPLC assay (potency and related substances) for 20 mg paroxetine tablets.

A reversed phase high performance liquid chromatographic (HPLC) method was developed and validated for use as a stability indicating assay (potency and related substances) of paroxetine in paroxetine hydrochloride 20 mg tablets. Assay samples were extracted at a paroxetine concentration of 0.4 mg ml(-1) utilizing mobile phase as the extraction solvent. The chromatographic conditions employed a C18 column (Inertsil, 5 microm, 15 cm x 4.6 mm), isocratic elution with 10 mM 1-decane sulfonic acid sodium salt containing 10 mM sodium phosphate monobasic (pH 3.0)-ACN (60:40, v/v) and ultraviolet (UV) detection at 235 nm.

High-performance liquid chromatography with light-scattering detection and desorption chemical-ionization tandem mass spectrometry of milk fat triacylglycerols.

The utility of reverse-phase high-performance liquid chromatography (HPLC), desorption chemical-ionization mass spectrometry (DCI-MS) and tandem mass spectrometry (MS/MS) for the characterization of triacylglycerols in complex mixtures has been further explored. Triacylglycerols of anhydrous bovine milk fat were separated by using two reverse-phase C18 HPLC columns, and eluents were monitored with an evaporative light-scattering detector. Fifty-eight fractions were resolved and analyzed by positive ion isobutane DCI-MS. The formation of protonated molecules and of major fragments corresponding to the random loss of any one of the constituent fatty acids readily identified acyl carbon numbers and the number of double bonds within each fatty acid. MS/MS was only required when the original mass spectra indicated the presence of more than one triacylglycerol or of impurities in a fraction. Protonated molecules produced by DCI were fragmented using high energy collisional activation, and the resulting ions were detected by MS/MS. Odd-chain triacylglycerols were also readily distinguished using this methodology. The positive ion DCI and MS/MS techniques described here demonstrate the usefulness of this approach for the characterization of triacylglycerols in complex mixtures.

High-voltage irradiation and combination chemotherapy for malignant pheochromocytoma.

A 29-year-old man with metastatic extraadrenal pheochromocytoma developed paraplegia which reversed completely after megavoltage irradiation of the dorsolumbar spine. Later, treated with cyclophosphamide, vincristine, and dacarbazine, he had a temporary decrease in plasma norepinephrine concentration, a partial recalcification of bone lesions, and a decrease in the need for antihypertensive treatment for 12 months. Irradiation and combination chemotherapy should be evaluated further in the management of malignant pheochromocytoma.

High-voltage irradiation and hydroxyurea for pulmonary leukostasis in acute myelomonocytic leukemia.

A 29-year-old man with acute myelomonocytic leukemia had an initial leukocyte count of 192 X 10(9) cells/l and 84% blasts. During the initial treatment with hydroxyurea, 1 g/m2 orally tid, he developed pulmonary leukostasis which responded rapidly to whole-lung radiation with 1.5 Gy in one fraction. Pulmonary leukostasis in hyperleukocytotic AML is an oncologic emergency demanding rapid intervention. The combined treatment with chemotherapy and radiation appears useful.

Determination of left ventricular residual function by analysis of post-extrasystolic beat in mitral stenosis.

Residual function of the left ventricle was assessed in 25 patients with mitral stenosis and a normal left ventriculogram. The post-extrasystolic beat (R2) in sinus rhythm (nine patients) and the first beat after an early beat (R2) in atrial fibrillation (16 patients) were analysed angiocardiographically. Five subjects with a normal heart (controls) were also studied. The results are expressed as percentage changes in left ventricular contractility from the beat preceding the extra beat (R1) to the beat R2. In the control group the mean changes from R1 to R2 were: end diastolic volume +68.3% (increase), end systolic volume -21.7% (decrease), ejection fraction +36.2%, mean systolic ejection rate +22.1%, and mean velocity of circumferential fibre shortening +31%. A significant increase in proportional systolic shortening of all left ventricular axes was found in R2 compared with R1. In five patients with sinus rhythm and nine with atrial fibrillation the results fell within the normal range. In the remaining patients the beat R2 indicated signs of poor left ventricular function. The mean changes from R1 to R2 in the patients with sinus rhythm and those with atrial fibrillation were respectively: end diastolic volume +47.8% and +36.6%, end systolic volume +20% and +27%, ejection fraction +12.5% and +6.2%, mean systolic ejection rate -23.3% and -30.2%, and mean velocity of circumferential fibre shortening -25.5% and -39.2%. The increase in the left ventricular axial systolic shortening was not significant. Thus analysing a post-extrasystolic beat in sinus rhythm of the beat following an early beat with a long diastole in atrial fibrillation is a valuable method of determining the residual function in patients with mitral stenosis who have a normal left ventriculogram in basic rhythm.

Sinus node coronary arteries studied with angiography.

Coronary angiograms of 309 consecutive patients undergoing coronary angiography were reviewed to investigate the blood supply to the sinus node area. Blood was supplied from the right coronary artery in 59% of cases, from the left coronary artery in 38%, and from both coronary arteries in 3%. The posterior sinus node artery was demonstrated in 32 patients (27% of the 119 patients with the sinus node artery originating from the left circumflex and 10.5% of all patients).

Preoperative chemotherapy for giant cell carcinoma of the thyroid.

Reported is the case of a 24-year-old white man with inoperable giant cell carcinoma of the thyroid who achieved tumor regression following therapy with bleomycin, Adriamycin and cisplatinum. After 2 courses of chemotherapy, the tumor was deemed operable, and the patient underwent total thyroidectomy followed by radiation to the neck and upper mediastinum without maintenance chemotherapy. Two-and-one-half years after the initial diagnosis, he developed pulmonary metastases which again responded to Adriamycin and cisplatinum therapy. The above approach suggests that inoperable thyroid carcinoma can be made operable by preoperative combination chemotherapy. This treatment program deserves further exploration for a greater number of patients.