Spinal analgesia and auditory functions: a comparison of two sizes of Quincke needle.

AIM: Spinal anaesthesia may produce complications ranging from minor problems such as pain on injection, backache and urinary retention to more serious consequences such as post-dural puncture headache (PDPH), neurological complications like meningitis, cranial and peripheral nerve palsies and even cardiac arrest. Impaired auditory function is a relatively lesser-recognized complication of spinal analgesia. The objective of this study was to investigate the effects of spinal analgesia on vestibular dysfunction, using different sizes of the same type of spinal needle. METHODS: The study included 30 ASA I patients who had received spinal analgesia for lower abdominal surgery. Pure tone audiometry was performed before surgery and on postoperative day 2. In addition, any patient with hearing impairment of >15 dB was scheduled to undergo electrocochleography. Hearing levels were measured from 250 Hz to 8 kHz. In group 1 (n=15), a 26gauge Quincke needle was used. In group 2 (n=15), a 23-gauge Quincke needle was used. RESULTS: Comparison of hearing thresholds showed a significant reduction in the hearing level (P<0.05) in 2 patients in group 2 but none in group 1. CONCLUSION: The use of a 23-gauge Quincke needle is associated with a greater reduction in the mean hearing level compared to a 26-gauge needle of the same type.

The effect of 2-hydroxypropyl-beta-cyclodextrin on in vitro drug release of steroids from suppository bases.

The effects of 2-hydroxypropyl-beta-cyclodextrin (HPCD) on drug solubility and drug release from suppository bases were studied for dexamethasone (DX), dexamethasone acetate (DXA), hydrocortisone (HC), hydrocortisone acetate (HCA), and prednisolone acetate (PNA). It was found that HPCD significantly increased the aqueous solubility of all five steroids, and the increased drug solubility significantly influenced the drug release from the polyethylene glycol (PEG) base but not from the cocoa butter base.

Effects of ascorbic acid on collagen matrix formation and osteoblast differentiation in murine MC3T3-E1 cells.

Treatment of mouse MC3T3-E1 cells with ascorbic acid initiates the formation of a collagenous extracellular matrix and synthesis of several osteoblast-related proteins. We recently showed that ascorbic acid dramatically increases alkaline phosphatase and osteocalcin mRNAs and that this induction is blocked by inhibitors of collagen triple-helix formation (Franceschi and Iyer, J Bone Miner Res 7:235). In the present study, the relationship between collagen matrix formation and osteoblast-specific gene expression is explored in greater detail. Kinetic studies revealed that ascorbic acid increased proline hydroxylation in the intracellular procollagen pool within 1 h and stimulated the cleavage of type I collagen propeptides beginning at 2.5 h. Mature alpha 1(I) and alpha 2(I) collagen components were first detected at 10 h and continued to increase in both cell layer and culture medium for up to 72 h. Ascorbic acid also increased the rate of procollagen secretion from cell layers to culture medium. The secretion of another matrix protein, fibronectin, was only slightly affected. Alkaline phosphatase or its mRNA was first detected 2-3 days after ascorbic acid addition, but osteocalcin mRNA was not seen until day 6. Two inhibitors of collagen triple-helix formation, ethyl-3,4-dihydroxybenzoate and 3,4-dehydroproline, inhibited procollagen hydroxylation and alkaline phosphatase induction. 3,4-Dehydroproline also inhibited the induction of alkaline phosphatase and osteocalcin mRNAs. Surprisingly, induction was not blocked if cells were exposed to ascorbic acid before inhibitor addition. Alkaline phosphatase was also partially inhibited if cells were grown in the presence of purified bacterial collagenase. These results indicate that the induction of osteoblast markers by ascorbic acid does not require the continuous hydroxylation and processing of procollagens and suggest that a stable, possibly matrix-associated signal is generated at early times after ascorbic acid addition that allows subsequent induction of osteoblast-related genes.

Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells.

The MC3T3-E1 mouse calvaria-derived cell line has been used to study the role of collagen synthesis in osteoblast differentiation. MC3T3-E1 cells, like several previously characterized osteoblast culture systems, expressed osteoblast markers and formed a mineralized extracellular matrix only after exposure to ascorbic acid. Mineralization was stimulated further by beta-glycerol phosphate. Ultrastructural observations indicated that the extracellular matrix produced by ascorbic acid-treated cells was highly organized and contained well-banded collagen fibrils. Expression of osteoblast markers followed a clear temporal sequence. The earliest effects of ascorbic acid were to stimulate type I procollagen mRNA and collagen synthesis (24 h after ascorbate addition), followed by induction of alkaline phosphatase (48-72 h) and osteocalcin (96-144 h) mRNAs. Procollagen mRNA, which was expressed constitutively in the absence of ascorbate, increased only twofold after vitamin C addition. In contrast, alkaline phosphatase and osteocalcin mRNAs were undetectable in untreated cultures. Actions of ascorbic acid on osteoblast marker gene expression are mediated by increases in collagen synthesis and/or accumulation because (1) parallel dose-response relationships were obtained for ascorbic acid stimulation of collagen accumulation and alkaline phosphatase activity, and (2) the specific collagen synthesis inhibitors, 3,4-dehydroproline and cis-4-hydroxyproline, reversibly blocked ascorbic acid-dependent collagen synthesis and osteoblast marker gene expression.

The functional deficiency of B lymphocytes in patients with lung cancer is due to inadequate T-cell help and excessive suppression by T and non-T cells.

The proliferative and plaque-forming cell (PFC) responses of unseparated mononuclear cells (MNC) and B- and T-cell-enriched populations of cells were analyzed in 15 patients with lung cancer to determine the mechanisms involved in the functional abnormality of their B cells. The PFC responses of the MNC of the patient group were significantly lower than those of normal controls. In addition, the enriched B cells of several patients showed a further decrease in their PFC responses after coculture with autologous T cells compared with their respective MNC responses. The proliferative response against phytohemagglutinin (PHA) was also lower in many of the patients after similar cocultures. Cocultures of patients' B cells with T cells from normal controls significantly enhanced the PFC responses in 7 patients. In most of the normal controls, B lymphocytes showed a significant decrease in their PFC responses after coculture with the patients' T cells. Although the percentages of total T cells, T-helper, and B cells were within the normal range, the number of suppressor T cells was significantly higher in the patient group. These results indicate that a combination of insufficient T-cell help, excessive suppression by both T and non-T cells, and a possible intrinsic B-cell abnormality are responsible for the B-cell functional deficiency observed in patients with lung cancer.

Methylation of the alpha-fetoprotein gene in productive and nonproductive rat hepatocellular carcinomas.

The extent of methylation of Hpall-Mspl and Hhal sites in DNAs isolated from normal rat livers and from the transplantable hepatocellular carcinomas (THC) THC 7777 and THC 252 was compared. It was found that the overall level of methylation of the internal cytosine in CCGG sequences was lower in the THC DNAs than in the normal liver DNAs. This difference could also be detected in the extent of methylation of CCGG sites flanking a 400-base pair repetitive sequence. Examination of methylation of specific sites within the alpha-fetoprotein gene revealed differences between the DNAs that appear to reflect both the level of activity of the gene and the overall level of methylation of cellular DNA. This gene, which is repressed in normal adult liver and the nonproductive THC 252 and highly active in the productive THC 7777 (S. Sell et al., Cell Biol. Int. Rep., 4: 235-254, 1980), contains several CCGG sites that are methylated in both normal liver and THC 252 DNA but not in THC 7777 DNA. However, Hhal (GCGC) sites in the alpha-fetoprotein gene were less methylated in both hepatoma DNAs than in liver DNA, which the exception of one site in the productive tumor found to be no longer methylated.

In vitro release of salicylic acid from lanolin alcohols-ethylcellulose films.

Lanolin alcohols-ethylcellulose films were investigated as a potential drug delivery system for the controlled release of salicylic acid. The effects of changes in film composition, drug concentration, drug solubility, and stirrer speed on the in vitro release of salicylic acid have been examined. The drug release has been found to obey a diffusion-controlled matrix model and square root of time release profile both in the suspension and solution cases.

Solution activity product (KFAP) and simultaneous demineralization-remineralization in bovine tooth enamel and hydroxyapatite pellets.

The effects of changing the ion activity product of the remineralization solution at pH 4.5 (pKFAP 108-118) on the remineralization behavior of demineralized bovine tooth enamel and hydroxyapatite pellets have been studied. Solutions containing calcium-4.5, phosphate, and fluoride in acetate buffers were used. The 45Ca/F molar ratios indicated the formation of fluoridated hydroxyapatite in the enamel or the pellet when the pKFAP values for remineralizing solutions were less than 112. When the pKFAP values were greater than 112, the 45Ca/F ratios were found to be much less than 5. Also, when the pKFAP values were large (greater than 112), the remineralization patterns based on the fluoride distribution in the tooth (or pellet) were found to be different than when the pKFAP values were small (less than 112). The hypothesis that a pKFAP value of 112 is the demarcation between remineralization only and simultaneous dissolution-remineralization has been proposed based on these results.

Condensation of chromatin into chromosomes preserves an open configuration but alters the DNase I hypersensitive cleavage sites of the transcribed gene.

DNase I was used to probe the molecular organization of the chicken ovalbumin (OV) gene and glyceraldehyde 3-phosphate dehydrogenase (GPD) gene in interphase nuclei and in metaphase chromosomes of cultured chicken lymphoblastoid cells (MSB-1 line). The OV gene was not transcribed in this cell line, whereas the GPD gene was constitutively expressed. The GPD gene was more sensitive to DNase I digestion than the OV gene in both interphase nuclei and metaphase chromosomes, as determined by Southern blotting and liquid hybridization techniques. In addition, we observed DNase I hypersensitive sites around the 5' region of the GPD gene. These hypersensitive sites were not always at the same locations between the interphase nuclei and metaphase chromosomes. Our results suggest that chromatin condensation and decondensation during cell cycle alters nuclease hypersensitive cleavage sites.

Novel topical fluoride delivery system I: remineralization of ground bovine teeth.

Laboratory studies were carried out on a newly conceived fluoride-containing remineralizing system with bovine teeth. The prototype fluoride delivery device involved micronized calcium fluoride maintained at the tooth surface with a cellulose film. Together with salivary calcium and phosphate (or simulated saliva), this system was able to generate and maintain the appropriate thermodynamic activity driving force for significant fluorapatite deposition in a reasonably short time (approximately 48 hr).

Novel topical fluoride delivery system II: remineralization of human teeth.

A recently conceived calcium fluoride-containing remineralization system was tested using human teeth in vitro. The influence of several variables (surface pretreatment, demineralization time, and remineralization time) was studied. Appreciable levels of fluoride taken up by pumiced human teeth were found at depths up to 50 micrometers when remineralization was carried out in either the remineralizing solution or saliva. The successful performance of the delivery device in these laboratory studies is encouraging and indicates that the logical evolution of the crude devices studied thus far could lead to clinically practical fluoride delivery devices.

Evaluation of lanolin alcohol films and kinetics of triamcinolone acetonide release.

The film-forming potential of lanolin alcohol was evaluated. Inclusion of ethylcellulose in lanolin alcohol improved film integrity. The hardness and modulus of elasticity of these lanolin alcohol-ethylcellulose films were improved by incorporating propylene glycol or cetyl alcohol. Triamcinolone acetonide release from selected film compositions was investigated. The data were analyzed from the viewpoint of the first-order kinetic theory and the release from a planar system having a homogeneous or granular matrix. The results suggest that the drug release follows a diffusion-controlled matrix model and a square root of time release profile. The release rate constants were proportional to drug concentration. Drug release was maximal from a system containing the drug in a near-saturated solution.