Protection of Meconium-Induced Lung Epithelial Injury by Protease Inhibitors.

Earlier work form this laboratory showed that exposure of alveolar epithelial cells (AECs) to meconium caused significant cell detachment and that meconium-induced detachment of cells was prevented by a protease inhibitor cocktail. Therefore, it was hypothesized that protease inhibitors might protect AEC monolayers against meconium-induced collapse of epithelial barrier function both in vitro and in vivo. To investigate this theory in vitro, albumin flux was measured across cultured, confluent monolayers of human type II derived cell line A549 on microporous filter inserts. Human meconium was collected from seven healthy full-term neonates and the samples were pooled and diluted prior to analysis. Exposure of AECs to 5% human meconium increased albumin flux across the cultured AEC monolayers, but the increase was significantly blocked by protease inhibitors (P<0.001). In C57/BL6 mice, intratracheal instillation of 5% human meconium increased the passage of Evans Blue Dye (EBD) from the vascular compartment into the alveolar spaces, measured in bronchoalveolar lavage (BAL) fluid after intravenous injection of EBD. Moreover, intratrachial coinstillation of protease inhibitors prevented the meconium-induced increase in EBD passage into BAL fluid (P<0.01). The data presented herein clearly demonstrate that protease inhibitors protect AEC barrier function against meconium-induced injury, and suggest the future possibility of using protease inhibitors in the treatment of meconium aspiration syndrome.

Electron microscopic cochlear observations in bilateral Ménière's disease.

Electron microscopic study of the cochleas of an individual with bilateral Ménière's disease revealed the presence of many abnormal sensory cells in the apical regions of the cochleas. The pathological alterations were greater in the left ear with the greater hearing loss. There were some giant cilia, fusion of cilia, and loss of cilia. The outer hair cells contained diffuse cuticular bodies near or basal to the nuclei. Many outer hair cells were retracted away from the reticular membrane. The population of the nerve endings appeared normal. The inner hair cells of the apical turns appeared essentially normal. The spiral ganglia were normal in number and morphology at the apical turns, and a majority of their cell bodies were of the unmyelinated or partly myelinated types. The stria vascularis showed atrophy; however, the magnitude of this change was consistent with that known to occur in the aging ear. In the distended areas Reissner's membrane showed areas devoid of mesothelial cells, as well as atrophic epithelial cells. The blood vessels were no different from other human cochlear vessels. These abnormalities seen in the stereocilia, the outer hair cells, and Reissner's membrane are a matter of fact. We must admit, however, that not enough electron microscopic studies have been performed on ears from aging individuals or ears with other pathologies to state that these changes are unique to Ménière's disease. Furthermore, there is currently insufficient knowledge to predict whether these changes affect auditory function.

Ultrastructural study of the human spiral ganglion.

Electron microscopic study of the human spiral ganglion was conducted on 17 ears from 12 individuals aged 9 months to 92 years. Two types of neurons, large and small, with distinct cytological characteristics were found. Both types of neurons were myelinated and unmyelinated; however, a majority of the population was unmyelinated (94%). The distribution of myelinated neurons varied greatly among individuals, though a slight increase in their population was noted in aged individuals, the highest count being 28% in a specimen from an individual 75 years old. The small neurons constituted 6% of the population, and their cytoplasms were highly filamentous in both myelinated and unmyelinated types. The findings of this study provide no evidence as to the functional significance of the myelination of spiral ganglion cells.

Obliteration of the ductus reuniens.

The ductus reuniens was successfully obliterated in 52 guinea pig ears. Histopathological study showed that a majority of these specimens demonstrated cochlear hydrops, saccular collapse and normal utricle. These results support the theory of longitudinal flow of endolymph from the cochlea toward the endolymphatic sac via the ductus reuniens and saccule. A major source of endolymph in the saccule appears to be the scala media. In another set of 11 animals in which the ductus reuniens was first obstructed and two months later the endolymphatic duct was blocked, endolymphatic hydrops was shown in the cochleae, saccules, and utricles of all but one. The evidence suggests that cochlear hydrops was caused by obliteration of the ductus reuniens, and the saccular and utricular hydrops occurred subsequently as the result of blockage of the endolymphatic duct. Remnants of otolithic membrane which were attached to the distended saccular wall indicate that the membrane which had collapsed onto the macula after obliteration of the ductus reuniens is capable of subsequent distension. This experiment supports the concept of endolymph flow from the utricle and canals toward the endolymphatic sac. A blocked cutus reuniens might also explain the pathophysiological basis for the auditory form of Meniere's disease.

Nerve fiber synapses on spiral ganglion cells in the human cochlea.

Nerve fiber synapses were observed on the small myelinated and unmyelinated spiral ganglion cells of the human cochlea. The nerve fibers penetrated the junctions of the ensheathing satellite cells and myelin lamellae, and partly invaginated into the perikarya to establish axosomatic synapses. One small myelinated neuron with a nerve fiber synapse demonstrated multipolar cell processes. However, most small neurons with identical ultrastructural characteristics did not show these synapses. Axodendritic synapses were also seen on the dendritic processes of the small neurons and between varicose nerves and unmyelinated nerve fibers some distance from the small neurons. While these observations conform in some aspects with the concept of parasympathetic nerve fibers and neurons in the cochlea, they are also compatible with the idea that the small neurons may have an auditory function influenced by the synaptic contacts of efferent fibers from the olivocochlear bundle.

[Clinical investigation of cefotiam in combination with aminoglycoside or (and) penicillin against complicated infections with hematopoietic disorders].

Clinical investigation of combination use of cefotiam (CTM), aminoglycoside, or (and) penicillin against complicated infections with hematopoietic disorders was performed, and the results were as follows. Fifty-one patients were administered CTM in combination with aminoglycoside or (and) penicillin. The clinical response was excellent 19.6%, good 27.4%, fair 21.6%, and poor 31.4% showing efficacy rate of 47.1%. The combined therapy of CTM and aminoglycoside was clinical effective in 70% of 10 patients with complicated sepsis. Therefore, combination use of CTM and aminoglycoside is considered to be the first choice for the treatment of complicated sepsis with hematopoietic disorders. The clinical effectiveness of CTM was not influenced by the number of mature neutrophil at the first phase of CTM treatment, but was influenced at the end phase of CTM treatment. Gram-negative bacilli were dominantly isolated from the patients. Pseudomonas sp. was isolated from 70% of the patients with sepsis. No remarkable side effects were observed in this investigation.

A prospective, double-blind, randomized trial of caudal block using ropivacaine 0.2% with or without fentanyl 1 microg kg-1 in children.

BACKGROUND: It has been reported that ropivacaine produces vasoconstriction in contrast to vasodilation produced by bupivacaine. It is possible that additives to ropivacaine can provide further analgesic advantages compared with bupivacaine. We thus evaluated whether the addition of fentanyl to ropivacaine prolonged the duration of analgesia after a single shot caudal block. METHODS: A total of 36 children undergoing surgical procedures below the umbilicus were randomly allocated to one of two groups: Group F received ropivacaine 0.2%, 1 ml kg(-1) with fentanyl 1 microg kg(-1) and Group S received ropivacaine 0.2%, 1 ml kg(-1) with saline. The analgesic effect of the caudal block was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and sedation was assessed using the Steward score at 30 min after extubation and at 1, 2, 4, 6, 12 and 24 h. The first analgesic requirement time and side-effects in a 24 h period were also recorded. RESULTS: There were no differences in characteristics between the groups. The end-tidal concentration of sevoflurane at extubation in Group F was significantly lower than in Group S. However, there was no significant difference in time from discontinuation of the volatile anaesthetics to tracheal extubation. No statistical differences were found in the CHEOPS and Steward score, and the time to first analgesia. The incidence of postoperative vomiting was not significantly different. CONCLUSION: We found that the addition of fentanyl 1 mug kg(-1) to ropivacaine 0.2% for caudal analgesia provides no further analgesic advantages over ropivacaine 0.2% alone.

Influence of dryness of the vessel on its patency.

A controlled experimental study of microvascular surgery in rabbits showed that arteries can tolerate dryness for at least 5 hours and veins can tolerate dryness for at least 2 hours. In clinical free-tissue transfer, therefore, drying of the vessel during the usual process of anastomosis is not a major concern.

Experimental evaluation of vascular pedicle in island flaps.

This study was undertaken to evaluate the influence of variations in the vascular pedicle on survival of island flaps. Abdominal island flaps were raised in 128 rats based on the left superficial epigastric vessels. Our results show that stenosis of about one-third of the original external diameter of the artery and vein of the pedicle in our model did not have any significant influence on the survival of the flap and ligation of the femoral artery distal to the branch to the flap did not produce any statistical difference in the viability of the flap.

Antifungal activity of propolis on different species of Candida.

Propolis is a resinous material collected by bees from the buds or other parts of plants. It is known for its biological properties, having antibacterial, antifungal and healing properties. The antifungal activity of propolis was studied in sensitivity tests on 80 strains of Candida yeasts: 20 strains of Candida albicans, 20 strains of Candida tropicalis, 20 strains of Candida krusei and 15 strains of Candida guilliermondii. The yeasts showed a clear antifungal activity with the following order of sensitivity: C. albicans > C. tropicalis > C. krusei > C. guilliermondii. Patients with full dentures who used a hydroalcoholic propolis extract showed a decrease in the number of Candida.

Comparison of bone metabolic markers between maternal and cord blood.

We studied 41 normal pregnant women and their neonates in order to compare bone metabolism between them. We examined more specific bone formation markers (intact osteocalcin, bone-specific alkaline phosphatase) and a recently developed and more sensitive bone resorption marker (C-telopeptide of type I collagen; CTX) than previously available in maternal and umbilical cord venous blood taken at delivery. The concentrations of all markers of bone turnover, including CTX, in cord serum were significantly higher than those in maternal serum. There was no significant correlation between maternal and cord serum levels for any marker. These results indicate that fetal bone turnover is markedly enhanced compared with maternal bone turnover and is independent of maternal bone metabolism in late pregnancy.

Experimental study of sacculotomy in endolymphatic hydrops.

Thirty-nine guinea pigs were used for four groups of experiments: 1. sacculotomy only, 2. sacculotomy and simultaneous obliteration of the endolymphatic duct, 3. sacculotomy followed by obliteration of the endolymphatic duct, and 4. obliteration of the endolymphatic duct followed by sacculotomy. Sacculotomy alone caused only minimal cochlear pathology, whereas sacculotomy on hydropic ears produced severe atrophy of the organ of Corti and cochlear neurons as well as connective cells of the limbus. There was histological evidence that Reissner's membrane in hydropic ears was ruptured by the sacculotomy procedure. The primary cause for the severe atrophic changes is thought to be the toxic effect of intermixing perilymph with a large volume of endolymph. The surgically induced saccular tears appeared to be healed in all ears, and the procedure had no significant effect on the course of endolymphatic hydrops. Although two out of eleven specimens in which sacculotomy was performed on hydropic ears showed tears and collapse of Reissner's membrane, since others with similar tears showed extensive hydrops, the possibility of artifact could not be ruled out. In one specimen with simultaneous sacculotomy and obliteration of the duct, persisting fistulae were noted at the sites of accidental fracture of the osseous spiral lamina; this ear is the only one which failed to develop hydrops following obliteration of the duct. The results of this experiment, namely sacculotomy on hydropic guinea pig ears, suggest that sacculotomy is not a rational procedure for the control of endolymphatic hydrops in Ménière's disease for the following reasons: 1. surgically induced tears in the saccular wall are followed by rapid healing and 2. intermixing of perilymph and a large volume of endolymph causes toxic atrophy of the limbus, organ of Corti and cochlear neurons.