The use of monoamine oxidase inhibitors as adjuncts in the treatment of hypertension and angina pectoris

The newer monoamine oxidase inhibitors have clinical actions in hypertension and angina pectoris similar to those of iproniazid but appear to produce less frequent side effects. Some of the side effects suggest that in addition to amine oxidase inhibition, they may also have a ganglionic blocking action.

The amine oxidase inhibitors are effective and useful in the clinical management of refractory cases of angina pectoris even though they may not alter the electrocardiogram significantly. Since the relief of chest pain also is accompanied frequently by a sense of well-being, cautioning the patient against over-exertion is advisable. Some of the amine oxidase inhibitors are also worthy of a trial in resistant cases of hypertension. However, they should be employed cautiously in these selected cases since their long term effects, even in moderate dosage, on liver and cardiac function are not known.     

A lysolecithin/fatty acid mixture promotes and then blocks neurotransmitter release at the Drosophila melanogaster larval neuromuscular junction

The study of the effect of snake presynaptic neurotoxins with phospholipase A2 activity on nerve terminals has recently unveiled the inhibitory action of a lysophosphatidylcholine (LysoPC)/fatty acid mixture. We report here that these neurotoxins have no activity on Drosophila melanogaster nerve terminals. However, a 1:1 mixture of LysoPC and oleic acid induces an early increase, followed by an inhibition of both evoked and spontaneous neurotransmitter release. This effect is also induced by LysoPC alone. The present findings provide an indirect evidence that the lipid hemifusion-to-pore transition is a key event in neuroexocytosis in Drosophila. Moreover, these findings substantiate the use of LysoPC as a general agonist of membrane fusion at nerve terminals. This novel tool could contribute to the unraveling of the molecular steps involved in neuroexocytosis, particularly in Drosophila, where it is straightforward to combine it with electrophysiology and genetics.     

The physiopathological, clinical and therapeutic aspects of vertigo in peripheral vestibular lesions

The characteristics of vertigo in the pathology of vestibular peripheral lesions are differentiated and described. Symptomatological and clinical aspects are also discussed in the light of the physiopathological mechanisms of vestibular compensation. The therapeutic problem of vertigo is treated on the basis of experimental research on the inhibitory effect of some drugs on the vestibulo-ocular reflex.     

Th1-like Cytokine Production Profile and Individual Specific Alterations in TCRBV-gene Usage of T Cells from Newly Diagnosed Type 1 Diabetes Patients after Stimulation with β-cell Antigens

In order to study cytokine production profile (IFN-γ, IL-4 and TNF-α) and TCRBV-gene usage of peripheral autoreactive T cells from IDDM patients, we have generated antigen-specific T cell lines with either tetanus toxoid, insulinoma membranes or a single β-cell protein, recombinant ICA69, which has been shown to be a target of both autoantibodies and T cells in IDDM. By semi-quantitative polymerase chain reaction (PCR) analysis, we have determined the composition of the T cell receptor repertoire of these T cell lines and compared this with the general peripheral repertoire.T cell responses against β-cell antigens and tetanus toxoid (TT) were shown to be associated with IFN-γ and TNF-α production, suggestive of a Th1-like phenotype of the T-cell lines. The production of IFN-γ was significantly higher in T-cell lines generated with ISG compared to those generated with TT. The cytokine production profiles of the T-cell lines generated with ICA69 did not provide an obvious explanation for the inverse relation between cellular and humoral responses to this protein observed earlier. Upon stimulation with β-cell antigens, outgrowth of T cells using a restricted set of TCRBV elements was observed in newly diagnosed IDDM patients. However, this skewing in TCRBV-gene expression was patient-specific rather than antigen-associated, since the T-cell repertoire that is used for the recognition of these antigens was, overall, heterogeneous.     

Alterations in the Occipital Cortex of Drug-Naïve Adults With Major Depressive Disorder: A Surface-Based Analysis of Surface Area and Cortical Thickness

Objective Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD. Methods A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups. Results We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased. Conclusion Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.     

Gadoxetic acid-enhanced 3.0 T MRI for the evaluation of hepatic metastasis from colorectal cancer: Metastasis is not always seen as a “defect” on the hepatobiliary phase

Purpose

To determine specific imaging features of hepatic metastasis from colorectal cancer, focusing on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI.

Materials and methods

Over a 2-year period, 79 hepatic metastatic lesions were identified from 32 patients (22 men and 10 women) who proven colorectal cancer and underwent gadoxetic acid-enhanced 3.0 T MRI. Hepatic metastases were proven pathologically in 16 patients: by surgical liver resection (n = 14) and by US-guided biopsy (n = 2). The remaining 16 patients were considered to have hepatic metastasis based on imaging studies and clinical information. Two radiologists evaluated the imaging features of each MRI sequence, including high resolution T2WI, dynamic contrast enhancement study with hepatobiliary phase, and diffusion weighted image. We also compared SI of the lesions on T2WI and HBP.

Results

T2WI showed homogeneous high SI (n = 25; 31.7%), target appearance (n = 3; 3.8%), reversed target appearance (n = 2; 2.6%), and heterogeneously high SI (n = 49; 62%). On HBP, homogeneous defect were seen in 22 lesions (27.9%), target appearance in five lesions (6.4%), reversed target appearance in two lesions (2.5%), and heterogeneous defect in 50 lesions (63.3%); including reticular (70%), partially globular (26%), and diffuse GGO-like (4%) patterns. According to the imaging features on HBP, the homogeneous defect and heterogeneous defect groups had a mean ADC value of 0.99 × 10⁻³ and 1.07 × 10⁻³ mm²/s, respectively, without statistically significant difference.

Conclusion

Hepatic metastasis from colorectal cancer usually showed as a heterogeneous defect on HBP and a heterogeneous high SI on T2WI. The generally accepted “true defect” was not a common finding in hepatic metastasis from colorectal cancer.     

Advance care planning documents in nursing facilities: results from a nationally representative survey

This study assessed clinical, demographic, facility, and regional factors associated with documented do-not-resuscitate (DNR) orders, feeding/medication/other treatment (FMT) restrictions, and living wills among nursing facility residents. Using the Nursing Home Component of the 1996 Medical Expenditure Panel Survey, a nationally representative sample of 815 facilities and 5899 residents, three separate multivariate logistic regression models were developed. DNR orders were more prevalent among residents aged 75+ and those with severe cognitive impairment, dementia, emphysema, and cancer, but less common among African Americans and Latinos than whites. Residents with living children were more likely to have DNR orders. Latinos were less likely to have FMT restrictions. Living wills were more common among residents aged 75+ and those with psychiatric/mood disorders and heart disease, but less prevalent among African Americans. Residents with less social engagement and household incomes below 400% of the Federal Poverty Level were less likely to have a living will. Residents with Medicaid as their largest payer were less likely to have an advance care plan than those with Medicare or other payment mechanisms. To increase the use of advance care plans, interventions should focus on groups with less social engagement and lower household income.     

Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping

Cancers of origin in the gallbladder and bile ducts are rarely curable with current modalities of cancer treatment. Our clinical application of broad-based mutational profiling for patients diagnosed with a gastrointestinal malignancy has led to the novel discovery of mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) in tumors from a subset of patients with cholangiocarcinoma. A total of 287 tumors from gastrointestinal cancer patients (biliary tract, colorectal, gastroesophageal, liver, pancreatic, and small intestine carcinoma) were tested during routine clinical evaluation for 130 site-specific mutations within 15 cancer genes. Mutations were identified within a number of genes, including KRAS (35%), TP53 (22%), PIK3CA (10%), BRAF (7%), APC (6%), NRAS (3%), AKT1 (1%), CTNNB1 (1%), and PTEN (1%). Although mutations in the metabolic enzyme IDH1 were rare in the other common gastrointestinal malignancies in this series (2%), they were found in three tumors (25%) of an initial series of 12 biliary tract carcinomas. To better define IDH1 and IDH2 mutational status, an additional 75 gallbladder and bile duct cancers were examined. Combining these cohorts of biliary cancers, mutations in IDH1 and IDH2 were found only in cholangiocarcinomas of intrahepatic origin (nine of 40, 23%) and in none of the 22 extrahepatic cholangiocarcinomas and none of the 25 gallbladder carcinomas. In an analysis of frozen tissue specimens, IDH1 mutation was associated with highly elevated tissue levels of the enzymatic product 2-hydroxyglutarate. Thus, IDH1 mutation is a molecular feature of cholangiocarcinomas of intrahepatic origin. These findings define a specific metabolic abnormality in this largely incurable type of gastrointestinal cancer and present a potentially new target for therapy.