Alpha-Fetoprotein as a Modifier of Anatomic Criteria for Transplantation of HCC Patients

BackgroundThe current listing criteria (Milan, University of California San Francisco [UCSF]) for orthotropic liver transplants (OLT) in hepatocellular carcinoma (HCC) patients emphasize the anatomic features of the tumor such as size, burden, and multiplicity. Recent reports showed that patients with large tumors may have equivalent survival to Milan criteria patients. This suggests that differences in biologic behavior of tumors may contribute to the outcome.AimThe aim of this article is to understand the impact of biologic modifiers such as alpha-fetoprotein (AFP) on survival in both Milan and UCSF HCC patients.MethodsWe reviewed all liver transplants reported to the United Network for Organ Sharing between 2002 and 2013. We analyzed the survival of patients transplanted for HCC who fit the Milan criteria and those transplanted with tumors beyond Milan and within UCSF criteria. We tested various AFP level cutoffs in both groups in relationship to the 1-, 3-, and 5-year survival rates below and above the proposed cutoffs.ResultsSurvival difference was significant between Milan patients with AFP ≤ 2500 ng/mL and those with AFP > 2500 ng/mL (59.1% vs 37.4%; P < .001). The mean 5-year survival was 55% for beyond Milan within UCSF patients with AFP ≤ 150 ng/mL and 35.7% for those with AFP > 150 ng/mL (P = .003).ConclusionAFP level should be incorporated in the selection criteria for HCC patients considered for OLT. Milan patients with an AFP level exceeding 2500 ng/mL have reduced survival. Patients with tumors beyond Milan and within UCSF criteria whose AFP ≤ 150 ng/mL achieve acceptable 5-year survival and are good candidates for OLT.     

Kinetic spectrophotometric determination of ampicillin and amoxicillin in dosage forms

A kinetic spectrophotometric method has been developed for the determination of ampicillin (I) and amoxicillin (II). The method involves hydrolysis of the antibiotics with 1.0 M HCl, neutralization with 1.0 M NaOH followed by addition of palladium(II) chloride in the presence of 2 M KCl. The produced yellow colour is measured at 335 nm. The proposed method is valid over the concentration range 8-40 microg/ml and 10-40 microg/ml for I and II respectively with minimum detectability of 0.73 microg/ml and 0.76 microg/ml for I and II respectively. The determination of the studied compounds adopting the fixed concentration method is feasible with the calibration equations obtained, but the fixed time method has been found to be more applicable. The proposed method was applied to commercial dosage forms and the results obtained were in good agreement with those given by USP method.     

Voltammetric determination of N,N'-dinitrosopiperazine in simulated gastric juice

A voltammetric method has been developed for the determination of N,N'-dinitrosopiperazine (DNPZ) in simulated gastric juice. The method is based on measuring the differential pulse polarographic peak produced in pH 3 Britton Robinson buffer. A well defined, diffusion-controlled cathodic wave was obtained at -0.77 V versus Ag/AgCl over the range 0.4-24 microg/ml with minimum detectability (S/N = 2) of 0.072 microg/ml (5 x 10(-7) M). The proposed method was successfully applied to study the possible in vivo production of the nitroso-derivatives of piperazine under the standard nitrosation reaction conditions recommended by WHO. The method has some distinct advantages over the reported GC methods.     

Sensitive spectrofluorimetric and spectrophotometric methods for the determination of thonzylamine hydrochloride in pharmaceutical preparations based on coupling with dimethylbarbituric acid in presence of dicyclohexylcarbodiimide

Two sensitive and selective spectrophotometric and spectrofluoimetric procedures were developed for the determination of thonzylamine hydrochloride (THAH) in tablets and nasal drops. The methods are based on K?nig reaction which resulted in an orange-yellow fluorescent product. The orange-yellow product of the interaction between the dicyclohexylcarbodiimide (DCC), THAH and dimethylbarbituric acid (DMBA) showed an absorption maximum at 492 nm, a first-derivative signal at 494 nm and a fluorescence emission peak at 518 nm (lambda(ex)=492 nm). The orange-yellow color was found to be stable for at least 2 h. The reaction conditions were studied and optimized. The reaction obeys Beer's law over the ranges 8-20 and 0.2-2.0 microg ml(-1) for the derivative spectrophotometric and fluorimetric measurements, respectively. The detection limits were found to be 0.29 and 0.018 microg ml(-1) for the spectrophotometric and fluorimetric measurements, respectively. The proposed methods were applied to the analysis of pharmaceutical formulations containing THAH, either alone or in combination with naphazoline nitrate.     

Voltammetric determination of isoxsuprine and fenoterol in dosage forms and biological fluids through nitrosation

A simple and highly sensitive voltammetric method was developed for the determination of isoxsuprine HCl (I) and fenoterol HBr (II) in dosage forms and biological fluids. The method is based on treatment of the two compounds with nitrous acid followed by measuring the cathodic current produced by the resulting nitroso derivatives. The voltammetric behavior was studied adopting Direct Current (DC_t), Differential Pulse (DPP) and Alternating Current (AC_t) polarography. Both compounds produced well-defined, diffusion-controlled cathodic waves over the whole pH range in Britton–Robinson buffers (BRb). At pH 11 and pH 9, the values of diffusion-current constants (Id), were 9.4±0.3 and 7.7±0.4 for I and II, respectively. The current–concentration plots for I were rectilinear over the range of 0.6–12 μg/ml and 0.1–12 μg/ml in the DC_t and DPP modes, respectively. As for II, the range was 1–20 μg/ml and 0.1–20 μg/ml in the DC_t and DPP modes, respectively. The minimum detectability (S/N=2) were 0.02 μg/ml (≈6×10⁻⁸ M) and 0.01 μg/ml (≈2.6×10⁻⁸ M) for I and II, respectively, adopting the DPP mode. The proposed method was applied to the determination of both compounds in dosage forms and the results obtained were in good agreement with those obtained using reference methods. The proposed method was further applied to the determination of isoxsuprine in spiked human urine and plasma. The percentage recoveries adopting the DPP mode were 98.84±1.18 and 99.26±0.97, respectively.     

Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7)

Spinocerebellar ataxia 7 (SCA7) is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. We have analyzed the SCA7 mutation in 19 families and one isolated case of various geographical origins, presenting with autosomal dominant cerebellar ataxia with progressive macular dystrophy. The SCA7 CAG repeat was expanded in 77 patients and in 11 at-risk individuals, with alleles containing from 37 to 130 repeats, demonstrating that SCA7 is genetically homogeneous. Repeats on normal alleles contained from 7 to 35 CAGs. There was a strong negative correlation (r = -0.84) between the age at onset and the size of the CAG repeat expansion in SCA7 patients. Larger expansions were associated with earlier onset, a more severe and rapid clinical course, and a higher frequency of decreased vision, ophthalmoplegia, extensor plantar response and scoliosis. The frequency of other clinical signs such as dysphagia and sphincter disturbances increased with disease duration. The mutation was highly unstable during transmission, with a mean increase of 10 +/- 16 CAG repeats, which was significantly greater in paternal (15 +/- 20) than in maternal (5 +/- 5) transmissions. This correlated well with the marked anticipation (19 +/- 13 years) observed in the families. Gonadal mosaicism, observed in the sperm of a patient, was particularly important, with expanded alleles ranging from 42 to >155 CAG repeats. The degree of instability during transmission, resulting mostly in expansions, is greater than in the seven other neurodegenerative disorders caused by polyglutamine expansions.      

Devices in heart failure: potential methods for device-based monitoring of congestive heart failure

Congestive heart failure has long been one of the most serious medical conditions in the United States; in fact, in the United States alone, heart failure accounts for 6.5 million days of hospitalization each year. One important goal of heart-failure therapy is to inhibit the progression of congestive heart failure through pharmacologic and device-based therapies. Therefore, there have been efforts to develop device-based therapies aimed at improving cardiac reserve and optimizing pump function to meet metabolic requirements. The course of congestive heart failure is often worsened by other conditions, including new-onset arrhythmias, ischemia and infarction, valvulopathy, decompensation, end-organ damage, and therapeutic refractoriness, that have an impact on outcomes. The onset of such conditions is sometimes heralded by subtle pathophysiologic changes, and the timely identification of these changes may promote the use of preventive measures. Consequently, device-based methods could in the future have an important role in the timely identification of the subtle pathophysiologic changes associated with congestive heart failure.     

Depression in multiple sclerosis

Introduction

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Prevalence of depression in MS is significant. Existence of mood disorders alters the patients’ life quality.

Objective

To determine the prevalence of depression in MS and establish the relationship between the severity of the disease, the onset of depression and their correlation with neuroimaging.

Methods

Fifty patients with MS aged 20 to 50 years followed at the Neurology Department of Charles-Nicolle Hospital from 2008 to 2012 participated in this study. The evaluation included a neuropsychological assessment, physical examination with EDSS and MRI.

Results

Association between MS and depression is common and known. In our study, prevalence of depression was 65%. Coexistence of other psychiatric disorders was found in around 10% of patients. Mood disorder was inaugural in some cases and delayed in others. This suggests that depression in MS may be linked to the disease or a result of a functional disability process. Occurrence of depression was not directly related to disease severity in all cases studied.

Conclusion

Depression is a possible manifestation of MS. This mood disorder is due to the demyelinating brain damage or to a genetic susceptibility. However, a fortuitous association cannot be excluded.