Sensorimotor polyneuropathy with 5-aminosalicylic acid: a case report.

A 69-year-old man with ulcerative colitis (UC) developed sensorimotor polyneuropathy. First, he received salazosulphapyridine (SASP) as treatment for the UC. The symptoms of UC disappeared immediately, but he developed skin eruptions and dysesthesia in his lower limbs. When SASP was changed to 5-aminosalicylic acid (5-ASA), his skin eruptions were resolved, however, he developed weakness and atrophy in his right arm as well as progressive worsening of the dysesthesia in his legs and gait disturbance. Deep tendon reflexes (DTR) were absent in all extremities. After 5-ASA was discontinued, the polyneuropathy symptoms recovered gradually. This clinical course suggests that the sensorimotor polyneuropathy may have been caused by 5-ASA.     

Post‐crossing segment of dI1 commissural axons forms collateral branches to motor neurons in the developing spinal cord

The dI1 commissural axons in the developing spinal cord, upon crossing the midline through the floor plate, make a sharp turn to grow rostrally. These post‐crossing axons initially just extend adjacent to the floor plate without entering nearby motor columns. However, it remains poorly characterized how these post‐crossing dI1 axons behave subsequently to this process. In the present study, to address this issue, we examined in detail the behavior of post‐crossing dI1 axons in mice, using the Atoh1 enhancer‐based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs). We found unexpectedly that the post‐crossing segment of dI1 axons later gave off collateral branches that extended laterally to invade motor columns. Interestingly, these collateral branches emerged at around the time when their primary growth cones initiated invasion into motor columns. In addition, although the length of the laterally growing collateral branches increased with age, the majority of them remained within motor columns. Strikingly, these collateral branches further gave rise to multiple secondary branches in the region of MNs that innervate muscles close to the body axis. Moreover, these axonal branches formed presynaptic terminals on MNs. These observations demonstrate that dI1 commissural neurons develop axonal projection to spinal MNs via collateral branches arising later from the post‐crossing segment of these axons. Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output.     

Excitatory amino acid response in isolated nucleus tractus solitarii neurons of the rat

The excitatory amino-acid-induced currents in nucleus tractus solitarii neurons freshly isolated from rats were investigated in a whole-cell recording mode using a conventional patch-clamp technique. At a holding potential of -70 mV, L-glutamate (Glu), N-methyl-D-aspartate (NMDA) with 10(-9) M glycine, kainate (KA), quisqualate (QA) and L-aspartate (Asp) evoked inward currents. The currents increased in a sigmoidal fashion with increasing agonists concentration. The half-maximum concentration (EC50) values were 5 x 10(-5) M for Glu, 10(-6) M for QA, 10(-4) M for KA, 6 x 10(-5) M for NMDA and 5 x 10(-5) M for Asp. The Hill coefficients of the Glu-, QA-, KA-, NMDA- and Asp-induced responses were 1.0, 1.3, 1.1, 1.3 and 1.1, respectively. The Glu-, QA-, NMDA- and Asp-induced currents consisted of a transient initial peak and a successive steady-state component showing no desensitization. These currents had the same reversal potential near +5 mV. In the current-voltage (I-V) relationships for the Glu-, NMDA- and Asp-induced currents, slight outward rectifications were observed in Mg2(+)-free external solution at membrane potentials negative to 0 mV. In the presence of extracellular Mg2+, the currents induced by Glu, NMDA and Asp were suppressed at negative membrane potentials, but the suppression was less for the Glu response. The I-V relationships for QA- and KA-induced responses were almost linear at a membrane potential between -90 and +50 mV with or without the presence of Mg2+.     

The inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons.

Although the effects of local anesthetics on sodium channels and various other channels and receptors have been intensively investigated, there is little information available about their effects on N-methyl-D-aspartate (NMDA) receptors. We examined the effects of four local anesthetics (procaine, tetracaine, bupivacaine, and lidocaine) on NMDA-induced currents by using a whole-cell patch-clamp technique in dissociated mouse hippocampal pyramidal neurons. Procaine and tetracaine produced a reversible and concentration-dependent inhibition of NMDA-induced currents, but lidocaine showed little inhibition at 1 mM or less. The half-maximal inhibition values (mM; mean +/- SEM) for procaine, tetracaine, bupivacaine, and lidocaine at -60 mV were 0.296 +/- 0.031, 0.637 +/- 0.044, 2.781 +/- 0.940 (extrapolated data), and 7.766 +/- 14.093 (extrapolated data), respectively. Procaine 0.2 mM reduced the maximal NMDA-induced currents without affecting the 50% effective concentration values for NMDA. The inhibition by procaine exhibited voltage dependence and was more effective at negative potentials. These results indicate a noncompetitive antagonism of procaine on NMDA receptors and suggest that the inhibition is the result of a channel-blocking mechanism. IMPLICATIONS: We examined the effects of four local anesthetics (procaine, tetracaine, bupivacaine, and lidocaine) on NMDA-induced currents by using a whole-cell patch-clamp technique in dissociated mouse hippocampal pyramidal neurons. Both procaine and tetracaine produced a reversible and concentration-dependent inhibition of the NMDA-induced currents.     

Predicting postoperative renal insufficiency in patients undergoing nephrectomy for renal malignancy: assessment by renal scintigraphy using 99mtechnetium-mercaptoacetyltriglycine

PURPOSE: We performed Tc-mercaptoacetyltriglycine (MAG3) renal scintigraphy in patients with renal malignancy to evaluate the function of each renal unit before and after nephrectomy to see if postoperative functional deterioration could be predicted based on scintigraphy results and creatinine clearance. MATERIALS AND METHODS: A total of 22 men and 13 women with renal malignancy, including 32 with renal cell carcinoma and 3 with urothelial cancer, were prospectively enrolled in this study. Average patient age was 64.3 years (median 65, range 43 to 88). All patients underwent MAG3 renal scintigraphy before and after unilateral nephrectomy. At the same time serum creatinine and endogenous creatinine clearance were determined. RESULTS: Mean serum creatinine was 0.93 mg/dl before and 1.31 after nephrectomy (p <0.0001). Preoperative endogenous creatinine clearance was 70.8 ml per minute per 1.73 m, which decreased to 49.0 ml per minute per 1.73 m after nephrectomy (p <0.0001). Mean MAG3 clearance of the remaining kidney increased 35.1% above baseline from 156.5 to 211.5 ml per minute per 1.73 m following nephrectomy. Spearman rank core analysis revealed that preoperative MAG3 clearance of the remaining kidney significantly correlated with postoperative creatinine clearance (r = 0.596, p = 0.0005). Preoperative MAG3 clearance of the remaining kidney more than 130 ml per minute per 1.73 m coincided with postoperative creatinine clearance above 40 ml per minute per 1.73 m. CONCLUSIONS: MAG3 renal scintigraphy may be useful for predicting renal insufficiency after nephrectomy. The findings in this study suggest that preoperative MAG3 clearance of the remaining kidney less than 130 ml per minute per 1.73 m is a risk factor for postoperative renal insufficiency.     

Genome profiling of melanocytic tumors using multiplex ligation-dependent probe amplification (MLPA): Its usefulness as an adjunctive diagnostic tool for melanocytic tumors

BACKGROUND: The histopathology of melanocytic tumors sometimes presents diagnostic problems. Applicable parameters other than routine pathology are needed. OBJECTIVE: We assessed the feasibility of multiplex ligation-dependent probe amplification (MLPA), a novel PCR-based genome profiling method, in the classification of melanocytic tumors. METHOD: We extracted DNA from paraffin-embedded tissue sections of 24 primary melanomas, 14 Spitz nevi and 17 common melanocytic nevi. We analyzed the copy number gains or losses of a total of 76 genes spanning almost all chromosome arms using commercially available MLPA kits. RESULTS: Although four melanocytic nevi and three Spitz nevi did not yield sufficient DNA for reliable analysis due to small tumor size, the MLPA analysis was feasible and applicable to the remaining 88% of samples. We found multiple genetic aberrations in primary melanomas. The total number of aberrations in each tumor ranged from 1 to 32 (average, 12.04). All but two melanomas showed aberrations at more than three genetic loci. Seventeen (70.8%) of the 24 melanomas showed a copy number loss of either the CDKN2A or CDKN2B gene on chromosome 9p21. All the Spitz nevi and 7 (50%) of 14 common melanocytic nevi had copy number changes at one or two gene loci (average, 1.04). The receiver operator characteristic curve analysis showed that the threshold value of copy number aberrations corresponding to 98% specificity for melanoma was 2.42 and the sensitivity using this threshold value was 92.5%. CONCLUSIONS: MLPA could be used as an adjunctive diagnostic tool for melanocytic tumors.