Microsurgical Decompression for Peroneal Nerve Entrapment Neuropathy

Peroneal nerve entrapment neuropathy (PNEN) is one cause of numbness and pain in the lateral lower thigh and instep, and of motor weakness of the extensors of the toes and ankle. We report a less invasive surgical procedure performed under local anesthesia to treat PNEN and our preliminary outcomes. We treated 22 patients (33 legs), 7 men and 15 women, whose average age was 66 years. The mean postoperative follow-up period was 40 months. All patients complained of pain or paresthesia of the lateral aspect of affected lower thigh and instep; all manifested a Tinel-like sign at the entrapment point. As all had undergone unsuccessful conservative treatment, we performed microsurgical decompression under local anesthesia. Of 19 patients who had undergone lumbar spinal surgery (LSS), 9 suffered residual symptoms attributable to PNEN. While complete symptom abatement was obtained in the other 10 they later developed PNEN-induced new symptoms. Motor weakness of the extensors of the toes and ankle [manual muscle testing (MMT) 4/5] was observed preoperatively in 8 patients; it was relieved by microsurgical decompression. Based on self-assessments, all 22 patients were satisfied with the results of surgery. PNEN should be considered as a possible differential diagnosis in patients with L5 neuropathy due to lumbar degenerative disease, and as a causative factor of residual symptoms after LSS. PNEN can be successfully addressed by less-invasive surgery performed under local anesthesia.     

Successful uses of magnesium sulfate for torsades de pointes in children with long QT syndrome

BACKGROUND: Administration of magnesium sulfate (MgSO4) is an effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. As for children, there are few reports focusing on it. The authors discuss the efficacy of MgSO4 for TdP in children with congenital and acquired LQTS. The authors also discuss the optimal administration dosage and serum magnesium (SMg) concentration during MgSO4 therapy. METHODS: The authors studied seven consecutive LQTS children undergoing MgSO4 therapy for TdP. Of the seven children, five were congenital LQTS and two were acquired LQTS. A bolus injection of MgSO4 was given intravenously over 1-2 min followed by continuous infusion for the next 2-7 days. RESULTS: Of the seven patients, six responded completely to the initial bolus. The bolus dosage was 5.9 +/- 3.8 mg/kg (range, 2.3-12 mg/kg) in these six, and the other remaining one (neonate with congenital LQTS) required a total of 30 mg/kg until complete abolishment. The continuous infusion was given at rates of 0.3-1.0 mg/kg per h and patients did not show recurrence of TdP. The SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. The mean corrected QT (QTc) interval before and after bolus injection did not show significant difference. CONCLUSION: Intravenous infusion of MgSO4 was effective for TdP in children with LQTS, and MgSO4 abolished TdP without shortening the QTc interval. The optimal bolus dosage, infusion rates and SMg concentration were 3-12 mg/kg, 0.5-1.0 mg/kg per h and 3-5 mg/dL, respectively.     

DECREASED BLOOD PRESSURE IN RESPONSE TO AN ANGIOTENSIN II ANTAGONIST IN ADDISON''S DISEASE

The synthetic angiotensin II antagonist, 1-sarcosine, 8-isoleucine angiotensin II was infused in two patients with untreated Addison's disease. Blood pressure decreased following infusion of this angiotensin II antagonist. Re-infusion of the antagonist after cortisol replacement therapy for one month caused a slight increase in blood pressure. Addison's disease is one of the conditions in which the renin-angiotensin system is involved in the maintenance of blood pressure.     

Effect of calcium antagonist,nicardipine, on cerebral blood flow in postasphyxial newborn piglets

An experiment was carried out in nine piglets within 24 h after birth (control group: four, nicardipine group: five) for the purpose of evaluating the effects of a calcium antagonist, nicardipine, on cerebral blood flow changes induced by asphyxia neonatorum. Under respiratory control with a mechanical ventilator, the animals were exposed to hypoxia. The inspiratory oxygen level was lowered at 15 min intervals from 0.08 to 0.06 and then to 0.05. When bradycardia (heart rate: 60/min or less) was observed, 100% oxygen, adrenaline, and sodium bicarbonate were administered for resuscitation. Nicardipine was administered at a dosage of 10μg/kg via bolus injection 30 min after the resuscitation. It was administered thereafter at a rate of 10μg/kg per h. The cerebral blood flow was measured using a laser Doppler velocimeter. The cerebral blood flow, electroencephalograph (EEG), blood pressure, and heart rate were continuously measured for 120min after the resuscitation. In the control group, the mean arterial pressure 35 min after the resuscitation was 60 mmHg or more. However, the cerebral blood flow was lower than the prehypoxia value in the animals with a mean arterial pressure of 75mmHg or less. In the nicardipine group, the mean arterial pressure was lower, but the cerebral blood flow was higher than the prehypoxia value and cerebral ischemia was not induced. The mean arterial pressure 120 min after the resuscitation was 72.0 ± 8.2 mmHg in the control group, while it was 56.7 ± 7.5 mmHg in the nicardipine group. It was significantly lower in the latter. The cerebral blood flow as compared to that before the initiation of exposure to hypoxia (this being considered 100) was 83.1 ± 22.0% in the control group, while it was 125.1 ± 26.2% in the nicardipine group. It was significantly higher in the latter. A suppression burst-like abnormal EEG finding occurred in two of four animals from the control group and was noted in one of five animals from the nicardipine group. In the nicardipine group, the mean arterial pressure was lowered, but a decrease in the cerebral blood flow after asphyxia was totally prevented and the incidence of EEG abnormality was low. It seems possible that this drug protects the brain from asphyxia-induced changes.     

Frequent STAT3 activation is associated with Mcl-1 expression in nasal NK-cell lymphoma

Nasal natural killer (NK)-cell lymphoma was resistant to various antitumor agents. Although high expression of p-glycoprotein has been reported, other molecular mechanism of the chemo-resistance is largely unknown. Activation of STAT3 and expression of major apoptosis-related proteins Bcl-2, Bcl-x, and Mcl-1 were analyzed by immunohistochemistry. Effects of STAT3 inhibitor AG490 on NK-YS cell line were analyzed by Western blotting and flow cytometric apoptosis assay. STAT3 was activated in six of the nine nasal NK-cell lymphomas (67%). In contrast, STAT3 activation was detected in 35% of diffuse large B-cell lymphoma (DLBCL) and in 10% of follicular lymphoma (FL). Frequent activation of STAT3 was significantly correlated with Mcl-1 expression in nasal NK-cell lymphoma, i.e., Mcl-1 was positive in five of six STAT3-active cases and negative in all three STAT3-inactive ones. In DLBCL, not only six out of seven STAT3-active cases (86%) but also eight out of thirteen STAT3-inactive cases (62%) were positive for Mcl-1 expression. Latent membrane protein-1 was positive in four nasal NK-cell lymphomas, among which three cases showed intermediate STAT3 activation. Inhibition of STAT3 activation by JAK inhibitor AG490 decreased Mcl-1 expression and induced apoptosis in STAT3-active NK-YS cells. Serum starvation rather increased the Mcl-1 level in NK-YS cells, and this effect was also canceled by AG490. These results suggest that activation of STAT3-Mcl-1 axis may play a role in the chemotherapy resistance of nasal NK-cell lymphoma. The pathway may be one of the future therapeutic targets of this intractable disease.     

Conformation of sequential peptides containing proline residues

The conformational properties of Boc-Leu₃-(Pro₂GlyLeu₃)_n-Pro₂Gly-OH(n = 0, 1, 3, and 5) and Boc-Leu₃-(Pro₂GlyLeu₃)_n-Pro₂Gly-OBzl (n = 7, 9, and 11) were investigated in various organic solvents of high polarity using molar rotation and CD measurements. The peptides examined are assembled by the N-terminal, internal, and C-terminal segments having the sequences of Boc-Leu₃, Pro₂Gly-Leu₃, and Pro₂Gly-OX (X = H or Bzl), respectively. The conformational studies using the molar rotation of the oligopeptides and polypeptides in MeOH, DMSO, DMF, DMA, and NMP have made it clear that all the peptides have a randomly coiled structure. CD spectral patterns of the peptides in MeOH were essentially the same as each other and indicative of the randomly coiled structure. The additive nature of the total molar rotation and total molar ellipticity in Boc-Leu₃-(Pro₂GlyLeu₃)_n-Pro₂Gly-OX (X = H or Bzl) indicates that the “peptide segment separation” is indeed in operation in organic solvents of high polarity and that the peptide molecule can be considered to be assembled with the small peptide segments having a randomly coiled structure.