Demonstration of thyrotropin-releasing hormone immunoreactivity in neurons of the mouse spinal dorsal horn

Thyrotropin-releasing hormone-like immunoreactivity was demonstrated in neurons within the superficial laminae (I, II, III) of the mouse spinal dorsal horn by light-microscopic peroxidase immunocytochemistry. The immunoreactivity was distributed in a narrow dorsoventral band that enclosed the substantia gelatinosa (lamina II), with a higher concentration along the lamina II/III border. At present, the functional significance of these neurons is unknown. Their existence within the substantia gelatinosa suggests a role in sensory information processing.     

Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1

The inhibitory activity of gamma-aminobutyric acid (GABA) is considered critical in setting the conditions for synaptic plasticity, and many studies support an important role of GABA in the suppression of nociceptive transmission in the dorsal horn. Consequently, any injury-induced modification of the GABA action has the potential to critically modify spinal synaptic plasticity. We have previously reported that chronic constriction injury of the sciatic nerve was accompanied by long-lasting potentiation of superficial spinal dorsal horn field potentials following high-frequency tetanus. In this study we examined whether the GABA-A receptor agonist muscimol would modify post-tetanic responses in rats with chronic constriction injury. In animals exhibiting maximal thermal hyperalgesia as one sign of neuropathic pain 7 days after loose ligation of the sciatic nerve, spinal application of muscimol (5, 10 or 20 microg) before the high-frequency (50 Hz) tetanus produced a long-lasting depression (rather than potentiation) of spinal dorsal horn field potentials. In separate but related Western immunoblot experiments, we also established that the chronic constriction injury was accompanied by significant decreases in the content of the GABA transporter GAT-1. These data demonstrated that GABA-A receptor agonists may effectively influence the expression of long-lasting synaptic plasticity in the spinal dorsal horn, and that an injury-induced loss in GABA transporter content may have contributed to a depletion of GABA from its terminals within the spinal dorsal horn. These data lent further support to the notion that the loss of GABA inhibition may have important consequences for the development of neuropathic pain.     

Headache in lacunar stroke

The presence of headache within a 72-h interval of stroke onset was investigated in a cohort of 145 lacunar infarcts. Fourteen (10%) experienced diffuse or bilateral headache. Hypertension was less frequent (43 vs 76%; 95% CI: 6 to 60%) and of shorter duration (2.4 vs 7.8 years; t = 2.29; p = 0.02) among patients with headache. Leukoaraiosis was less frequent (40% vs 71%; 95% CI: −57 to −7%) and severe (7 vs 24%; 95% CI: −33 to −2%) in patients with headache. Age, sex, stroke risk factors, type of lacunar stroke, mode of onset, stroke severity, ultrasound and other CT findings were similar in patients with and without headache. No differences in the sixth month neurological or functional outcome were detected between lacunar patients with and without headache. Headache in lacunar stroke cannot be predicted by the clinical characteristics of the stroke and is not due to coexisting cardiembolism, intra or extracranial disease. Hypertensive small-vessel disease is less common and severe in lacunar strokes with associated headache.     

Cyclosporin nephrotoxicity in heart and lung transplant patients

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.      

Selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins

Malignant gliomas are the most frequent primary brain tumors and have a dismal prognosis due to their infiltrative growth. Gene therapy using viral vectors represents an attractive alternative to conventional cancer therapies. In a previous study, we established lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus (LCMV) glycoproteins (GPs) and demonstrated transduction of human malignant glioma cells in culture. In the current approach, we compared the transduction efficacy of LCMV-GP- and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral vectors for malignant glioma cells and normal brain cells in vitro and in vivo. LCMV-GP pseudotypes transduced almost exclusively astrocytes, whereas VSV-G pseudotypes infected neurons as well as astrocytes. LCMV-GP pseudotypes showed an efficient transduction of solid glioma parts and specific transduction of infiltrating tumor cells. In contrast, VSV-G-pseudotyped lentiviral vectors transduced only a few tumor cells in solid tumor parts and infected mostly normal brain cells in infiltrating tumor areas. In conclusion, lentiviral vectors pseudotyped with LCMV glycoproteins represent an attractive option for gene therapy of malignant glioma.     

Blood transfusion practices in military medicine

Background: This observational study was conducted in a small, 45 bed border static hospital, located in a field area, where no blood bank facilities were available. The present study was conducted to elucidate the blood transfusion practices of this hospital.     

Vibrations produced during erbium:yttrium–aluminum–garnet laser irradiation

The purpose of this study was to evaluate vibrations induced by an erbium:yttrium–aluminum–garnet (Er:YAG) laser in the non-contact mode and compare the vibrations with different pulse durations and energy parameters. The experiment was conducted on an extracted tooth built up in silicone impression material. The vibrations were measured by piezoelectric accelerometer for a super-short pulse (SSP), a very short pulse (VSP), and a short pulse (SP) at a frequency of 5 Hz for 1 s. For VSP and SP, the energy parameters tested were 200 mJ, 300 mJ, and 400 mJ. Measurements were performed 15 times for each individual irradiation energy level. The highest values of vibrations were measured for SP (0.160 ± 0.04 m/s²), and the lowest were measured for VSP mode at the energy parameter 200 mJ (0.05 ± 0.02 m/s²). There was a statistically significant (P < 0.01) difference between the various laser pulse modes (SSP, VSP, SP) at different energy parameters. At energy levels of 300 mJ and 400 mJ, the least amount of vibration during cavity preparations with the non-contact Er:YAG laser was produced by SSP mode.     

IN.PACT AV access randomized trial: Japan cohort outcomes through 12 months

Purpose

There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months.

Materials and Methods

Participants were treated with DCB (n = 58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n = 54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety.

Results

Through 6 months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p < 0.001). Through 12 months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p = 0.013).

Conclusion

In this post hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared with PTA.