Changes in Properties of Spinal Dorsal Horn Neurons and Their Sensitivity to Morphine after Spinal Cord Injury in the Rat

Background: To gain a better understanding of spinal cord injury (SCI)-induced central neuropathic pain, the authors investigated changes in properties of spinal dorsal horn neurons located rostrally and caudally to the lesion and their sensitivity to morphine in rats after SCI.

Methods: The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to mechanical stimuli of wide-dynamic-range (WDR) and high-threshold neurons rostral and caudal to the lesion were recorded. Effects of cumulative doses of systemic (0.1-3 mg/kg) and spinal (0.1-5 [mu]g) administration of morphine on spontaneous activity and evoked responses to the stimuli of the neurons were evaluated.

Results: Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were only observed in neurons rostral to the SCI site. Significant increases in responses to the mechanical stimuli were seen both in WDR and high-threshold neurons located both rostrally and caudally to the lesion. The responses to nonnoxious and noxious stimuli were significantly greater in caudal WDR neurons than in rostral WDR neurons. In contrast, the responses to pinch stimuli were significantly higher in rostral high-threshold neurons than those in caudal high-threshold neurons. Systemically administered morphine had a greater effect on responses to nonnoxious and noxious stimuli of rostral WDR neurons than those of caudal WDR neurons. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to nonnoxious stimuli compared with those in sham-operated control animals.     

Lack of modifying effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN)

The modifying effects of atrazine, and/or tamoxifen, on thyroid carcinogenesis were investigated in a rat two-stage carcinogenesis model following N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2800 mg/kg, body weight) or vehicle alone. Starting 1 week later, the animals were fed a diet supplemented with 0, 5, 50 or 500 ppm of atrazine, 500 ppm atrazine plus 5 ppm tamoxifen, or 5 ppm tamoxifen in the DHPN-treated groups, and 0 or 500 ppm of atrazine in the DHPN-untreated groups for 24 weeks. At autopsy major organs, including the thyroid, pituitary, liver, kidney, testis, epididymis, and brain, were collected and histopathologically examined. Body weights were significantly (P<0.05) decreased by the high doses of atrazine or tamoxifen, the effect being enhanced in combination. Relative thyroid weights were significantly increased (P<0.05) only in the tamoxifen-treated group and pituitary weights were elevated with 500 ppm atrazine plus tamoxifen (P<0.05). Relative liver weights were increased by the high dose of atrazine. However, the atrazine and/or tamoxifen treatments did not induce significant histopathological changes in the major organs, including the thyroid, nor cause significant changes in serum TSH levels. These results suggest that neither atrazine nor tamoxifen may promote thyroid carcinogenesis, alone as well as in combination.     

Antinociceptive Interaction of Intrathecal alpha sub 2 -adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats

Background: The intrathecal alpha2 -adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2 -adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine.

Methods: Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2 -adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored.

Results: Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in micro gram) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure.     

A case of chronic persistent cough (CPC) caused by gastroesophageal reflux (GER) (including a study of CPC caused by suspected GER)]

A patient, an 80-year-old female, had complained of a cough for 20 weeks, and was not cured by cough medicine. Gastroesophageal reflux was considered as the cause of the cough because of her symptoms and gastrointestinal fiberscopy (GIF) and barium meal studies. She made favorable progress on a histamine H2 blocker and cysapurid for 4 weeks. Therefore we diagnosed her cough as caused by gastroesophageal reflux. We also studied the incidence of chronic persistent cough in patients suspected of gastroesophageal reflux because of symptoms and GIF results. Among 676 cases examined by GIF at Niigata-kenritsu Myoko Hospital, we detected 7 cases who complained of heartburn and in whom we observed hiatal hernia and reflux esophagitis by GIF. Only one of them, the present case, complained of a cough. CPC caused by gastroesophageal reflux is not seen frequently, but the possibility of GER as the cause of CPC should be considered.     

Mercury-selenium interaction in workers exposed to elemental mercury vapor

Mercury (Hg) and selenium (Se) levels were determined for erythrocytes, plasma and urine of 25 male and 29 female workers exposed to elemental mercury (Hgo) vapor. Interrelationship between the Hg levels and the Se levels was examined by the correlational analysis and the stepwise regression analysis. Indicators of Se status (erythrocyte Se levels, plasma Se levels and urinary Se levels) were closely intercorrelated; similarly, indicators of exposure to Hgo vapor (erythrocyte inorganic Hg levels, plasma Hg levels and urinary Hg levels) were significantly intercorrelated. Since plasma Hg level was one of the significant independent variables in determining the erythrocyte Se and plasma Se levels, Hgo vapor exposure was thought likely to influence the Se metabolism in workers. None of the Se status indicators were significant as determinants of the indicators of Hgo vapor exposure.     

Ultrastructure of lentigo maligna in the oral cavity

A rare case of lentigo maligna in the oral cavity was investigated by light and electron microscopy. Cutaneous lentigo malignas often develop to malignant melanomas. However, the electron microscopic examination revealed that even though there were a large number of melanosomes, most of them were late stage and had membrane structure, and positive staining with HMB-45 was not recognized. From our findings, it is difficult to conclude that oral lentigo malignas develop malignant melanomas, and thus further studies are needed.     

Effects of isoflurane on oxygenation during one-lung ventilation in pulmonary emphysema patients

Background: Hypoxic pulmonary vasoconstriction has an important role in human one-lung ventilation (OLV) in the lateral decubitus position under general anesthesia. During OLV, inhalational anesthesia may inhibit hypoxic pulmonary vasoconstriction and the decrease in arterial oxygenation. We studied the effect of isoflurane administration on arterial oxygen tension in chronic obstructive pulmonary disease patients.
Methods: Ten patients who had thoracoscopic laser ablation of bullous emphysema were studied. Patients received 2% isoflurane in oxygen from induction until the first 20 min of OLV in the lateral decubitus position, then were switched to 1% isoflurane lasting 20 min and next were switched to 0.5% isoflurane lasting 20 min. After each 20-min inhalation, pulmonary and hemodynamic parameters were measured. The given concentrations for isoflurane were merely vapor meter concentrations.
Results: PaO₂/FIO₂, Qs/Qt respiratory rate peak inspiratory pressure and PaCO₂ showed no significant changes at each point of isoflurane. Expiratory tidal volume significantly decreased (P<0.05) with 0.5% isoflurane compared to that with 2% isoflurane. Cardiac output, mean arterial pressure, mean pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance showed no significant changes at each point of isoflurane.
Conclusions: In patients with pulmonary emphysema, arterial oxygenation is not affected by low isoflurane concentration during OLV in the lateral decubitus position.