Methylphenidate dose–response behavioral and neurophysiological study of the ventral tegmental area and nucleus accumbens in adolescent rats

The psychostimulant methylphenidate (MPD) is the most common medication used in treating ADHD in children. Studies have shown an increasing prevalence among adolescents without ADHD to take MPD as a cognitive booster and recreational drug, even though it is a Schedule II drug and has a high potential for abuse. The objective of this study is to explore if there is an association between the animals’ behavioral and neurophysiological responses to acute and/or chronic methylphenidate exposure within the ventral tegmental area and the nucleus accumbens, and to compare how these two brain structures fire in response to methylphenidate. Freely moving adolescent rats implanted with semimicroelectrodes within the VTA and NAc were divided into three MPD dosing groups: 0.6, 2.5, and 10 mg/kg i.p., as well as a saline control group. The animals were divided into two groups based on their behavioral responses to chronic MPD, behavioral sensitization and tolerance, and the neuronal responses of the two groups were compared for each MPD dosing. Significant differences in the proportion of neuronal units in the VTA and NAc responding to MPD were observed at the 0.6 and 10.0 mg/kg MPD dosing groups. Moreover, the same doses of 0.6, 2.5, and 10.0 mg/kg MPD elicited behavioral sensitization in some animals and behavioral tolerance in others. This specific study shows that the VTA and NAc neurons respond differently to the same doses of MPD. MPD has different neuronal and behavioral effects depending on the individual, the dosage of MPD, and the brain structure studied.     

Quiescent adult neural stem cells are exceptionally sensitive to cosmic radiation

Generation of new neurons in the adult brain, a process that is likely to be essential for learning, memory, and mood regulation, is impaired by radiation. Therefore, radiation exposure might have not only such previously expected consequences as increased probability of developing cancer, but might also impair cognitive function and emotional stability. Radiation exposure is encountered in settings ranging from cancer therapy to space travel; evaluating the neurogenic risks of radiation requires identifying the at-risk populations of stem and progenitor cells in the adult brain. Here we have used a novel reporter mouse line to find that early neural progenitors are selectively affected by conditions simulating the space radiation environment. This is reflected both in a decrease in the number of these progenitors in the neurogenic regions and in an increase in the number of dying cells in these regions. Unexpectedly, we found that quiescent neural stem cells, rather than their rapidly dividing progeny, are most sensitive to radiation. Since these stem cells are responsible for adult neurogenesis, their death would have a profound impact on the production of new neurons in the irradiated adult brain. Our finding raises an important concern about cognitive and emotional risks associated with radiation exposure.     

Ranolazine-induced lipid storage myopathy presenting with respiratory failure and head drop

Ranolazine is an anti-ischemic drug often used along with statins in patients with ischemic heart disease. Ranolazine-induced proximal myopathy or rhabdomyolysis have been rarely reported, but toxic effects of statins could not be completely ruled out in those cases. We report a 68-year-old man with ranolazine-induced myopathy who presented with respiratory insufficiency and head drop. Creatine kinase level was normal. The Patient continued to worsen despite statin cessation but markedly improved after stopping ranolazine. Muscle biopsy showed excessive lipid accumulation predominantly in type 1 myofibers. The precise mechanism of toxicity is not clear. Treating physicians should be aware of this rare but potentially debilitating adverse effect of ranolazine. Prognosis is good upon discontinuation of the offending drug.     

Successful zidovudine therapy for HIV-related severe thrombocytopenia. Report of a sustained remission

Five patients, two homosexuals and three drug abusers, with HIV-related severe thrombocytopenia, four of whom had also bleeding episodes, experienced a full remission of thrombocytopenia after 1,200 mg/day zidovudine treatment. None of the patients had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Platelet counts began an upward trend at the end of the 3rd week and reached values higher than 140 x 10(9)/l towards the end of the 8th week of treatment. Patient's platelets remained stable after more than 4 months of active treatment. This is the first report of zidovudine-induced long-term remission of HIV-associated severe thrombocytopenia.     

Ulnar Nerve Innervation of the Triceps Muscle: Real or Apparent? An Anatomic Study

Background

Since the 18th century, the existence of ulnar nerve innervation of the medial head of the triceps brachii muscle has been controversial. The evidence for or against such innervation has been based on macroscopic dissection, an unsuitable method for studying intraneural topography or intramuscular branching. The study of smaller specimens (embryos or fetuses) by means of serial histologic sections may resolve the controversy.

Questions/Purposes

Using fetal specimens and histology we determined the contributions of the ulnar and radial nerves to innervation of the triceps brachii muscle.

Methods

We histologically examined 15 embryonic and fetal arms. Radial nerve branches obtained from six adult arms were analyzed immunohistochemically to determine motor fiber content.

Results

The medial head of the triceps brachii muscle was always innervated by the radial nerve (ulnar collateral branch). The branches seeming to leave the ulnar nerve at elbow level were the continuation of the radial nerve that had joined the ulnar nerve sheath via a connection in the axillary region. Immunohistochemistry revealed motor and nonmotor fibers in this radial nerve branch.

Conclusions

A connection between the radial and ulnar nerves sometimes may exist, resulting in an apparent ulnar nerve origin of muscular branches to the medial head of the triceps, even though in all our specimens the fibers could be traced back to the radial nerve.

Clinical Relevance

Before performing or suggesting new muscle and nerve transpositions using this apparent ulnar innervation, the real origin should be confirmed to avoid failure.     

A Cost-Effectiveness Analysis of Organ Preservation Methods for Deceased Donor Kidneys at High Risk for Delayed Graft Function in Brazil

The clinical benefit of machine perfusion (MP) was recently assessed in a 1-year Brazilian multicenter prospective randomized trial, that showed that the use of MP was associated with a reduced incidence of delayed graft function (DGF) compared to static cold storage (SCS) in kidney transplant recipients (45% vs 61%). The objective of the present analysis is to consider the cost-effectiveness of MP relative to SCS based on clinical data from this Brazilian cohort. A decision tree model was constructed to simulate a population of 1000 kidney transplant recipients based on data derived from this Brazilian multicenter clinical trial. The model accounts for different health state utilities to estimate the cost-effectiveness of deceased donor kidney transplantation in Brazil comparing 2 kidney preservation methods: MP and SCS. The model accounts for 3 possible graft outcomes at 1 year post-transplantation: success (an immediate functioning kidney), failure (primary nonfunction requiring a return to dialysis), or DGF 1 year post-transplant. MP provided 612 total quality-adjusted life years (QALYs) (0.61 QALYs per patient) as compared to SCS (553 total QALYs, 0.55 QALYs per patient). MP was cost effective relative to SCS (US$22,117/QALY, R$70,606/QALY). The use of MP also resulted in more functioning grafts than SCS (821 vs 787), leading to a cost per functioning graft of US$38,033 (R$121,417). In conclusion, this analysis indicates that, despite the initial added cost associated with MP, the use of MP results in more functioning grafts (821 vs 787) and higher patient quality of life relative to SCS in Brazil.     

A new technique in complex chest wall reconstruction: Open reduction and internal fixation

Background

Reconstruction of complex chest wall deformities is a surgical challenge. A new technique can improve long-term outcomes and result in high patient satisfaction.

Mycoplasma pneumoniae-associated nephritis in children

 Mycoplasma pneumoniae infection is a rare cause of acute nephritis. Six children (2 girls) aged 5–10 years, admitted for nephritis, had serological tests showing recent Mycoplasma pneumoniae infection. The diagnosis of Mycoplasma pneumoniae infection was based on the presence of serum IgM, detected either by immunofluorescence (IF) (n=1) or enzyme-linked immunosorbent assay (n=5). Four children had a renal biospy, with analysis of parenchymal Mycoplasma pneumoniae components by indirect IF and polymerase chain reaction. Extrarenal symptoms were: respiratory (n=3), ear, nose, and throat (n=2), gastrointestinal (n=3), hepatic (n=1), neurological (n=1), articular (n=1), and hematological (n=3). The patients presented with acute nephritis (1 had a nephrotic syndrome) or with acute renal failure and proteinuria. Pathological findings included type 1 membranoproliferative glomerulonephritis (MPGN, n=1), proliferative endocapillary glomerulonephritis (n=2), and minimal change disease (n=1). The patient with type 1 MPGN progressed rapidly towards end-stage renal failure because of a congenital solitary kidney. Among the patients with endocapillary glomerulonephritis, 1 relapsed 6 months later and remained proteinuric, while the other recovered, as did the child with minimal change disease. The search for Mycoplasma pneumoniae antigens and nucleic acids in renal tissue was negative. However, the absence of the microorganism in the kidney is a common feature of post-streptococcal glomerulonephritis. We conclude that Mycoplasma pneumoniae is a rare yet potential cause of acute glomerulonephritis. Received: 13 September 1996 / Revised: 16 June 1998 / Accepted: 18 June 1998     

Objects are highlighted by spatial attention

Selective attention may be focused upon a region of interest within the visual surroundings, thereby improving the perceptual quality of stimuli at that location. It has been debated whether this spatially selective mechanism plays a role in the attentive selection of whole objects in a visual scene. The relationship between spatial and object-selective attention was investigated here through recordings of event-related brain potentials (ERPs) supplemented with functional magnetic brain imaging (fMRI). Subjects viewed a display consisting of two bar-shaped objects and directed attention to sequences of stimuli (brief corner offsets) at one end of one of the bars. Unattended stimuli belonging to the same object as the attended stimuli elicited spatiotemporal patterns of neural activity in the visual cortex closely resembling those elicited by the attended stimuli themselves, albeit smaller in amplitude. This enhanced neural activity associated with object-selective attention was localized by use of ERP dipole modeling and fMRI to the lateral occipital extrastriate cortex. We conclude that object-selective attention shares a common neural mechanism with spatial attention that entails the facilitation of sensory processing of stimuli within the boundaries of an attended object.