Clinical experience in temporomandibular joint arthroscopy

Clinical experience of arthroscopy in 12 temporomandibular joints with a clinical diagnosis of closed lock was described. There were 10 patients and all were females with a mean age of 31.2 years (range 20 to 59 years). The antero-lateral approach was used for entry into 11 joints. The clinical findings were adhesions (64%), fibrillation (64%), anterior displacement of disc (36%) and scuffing of the articular surface of the glenoid fossa (9%). Two of the joints that had arthrocentesis prior to arthroscopy did not show any different findings from the rest. Of the 8 patients who had pre-arthroscopy pain, 7 patients (88%) had reduction of the symptom. Three patients (38%) had complete resolution of pain. The range of mouth opening (measured as maximal incisor opening) increased in all patients two weeks following arthroscopy. The average change in maximal incisor opening was 40.3% with a range of 22% to 85%. The mean follow-up was 34 months (range 4 to 68 months).     

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: transgenic rescue and interactions with gene background

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an approximately 50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKCepsilon expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKCepsilon expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes.     

Differential induction of cytochrome P450 gene expression by 4n-alkyl-methylenedioxybenzenes in primary rat hepatocyte cultures

A well-characterized primary rat hepatocyte culture system was used to examine induction patterns of cytochrome 450 gene expression by a series of 4-n-alkyl-methylenedioxybenzene (MDBs) derivatives. Hepatocytes were treated for 24, 48, or 72 hours with 0-500 microM of the MDB compounds, and total cellular RNA and protein from each treatment was evaluated by hybridization and immunochemical techniques. Exposure to MDB congeners possessing increasing 4-n-alkyl side-chain length (C0-C8) resulted in dose- and structure-dependent activation of CYP2B1, 2B2, 3A1, 1A1, and 1A2 gene expression. At equivalent 100 microM concentrations, the C6 and C8 MDB congeners were more effective than the prototypical inducer phenobarbital (PB) with respect to induction potency of CYP2B1, CYP2B2, and CYP3A1 gene expression. In contrast to PB, longer side-chain-substituted MDBs effectively induced CYP1A1 and CYP1A2 gene expression, in addition to the CYP2B and CYP3A genes. At equivalent molar concentrations, the catechol derivative of C6-MDB was ineffective in its ability to induce CYP gene expression, indicating the importance of the intact methylenedioxy bridge in the induction mechanism. Levels of MDB-inducible CYP2B1 and CYP2B2 mRNA were highly correlated with CYP2B1/2 apoprotein levels, ascertained by immunoblot analysis of cultured hepatocyte S9 fractions. Compared with results from previous in vivo analysis (12), the current data indicate that pharmacodynamic factors may influence MDB induction profiles and that differences in MDB effects on CYP gene expression result depending on distinct structure-activity relationships.     

Cyclooxygenase inhibition reveals synergistic action of vasoconstrictors on mesangial cell growth

Since endogenous vasoconstrictors promote mesangial cell growth and increase the biosynthesis of antiproliferative prostaglandins, the effects of cyclooxygenase inhibition on mesangial cell proliferation should be strongly dependent on the prevailing levels of neuroendocrine vasoconstrictors. We compared the effects of indomethacin (10(-6) M), a cyclooxygenase inhibitor, on [3H]thymidine incorporation by cultured rat mesangial cells in the presence of various combinations of angiotensin II (10(-10) M), [Arg8]vasopressin (10(-11) M), (-)-norepinephrine (10(-8) M) and endothelin-1 (10(-11) M). Indomethacin did not enhance [3H]thymidine incorporation in cells treated with each individual vasoconstrictor, or in cells treated with two-way combinations with the exception of modestly increased [3H]thymidine incorporation in cells treated with angiotensin II + (-)-norepinephrine or [Arg8]vasopressin + (-)-norepinephrine. In contrast, in cells treated with any three-way or the four-way combination, indomethacin markedly increased [3H]thymidine incorporation. Importantly, a highly significant interaction (P<0.0001) was observed for thymidine incorporation between the number of vasoconstrictors present and indomethacin treatment, thus demonstrating that cyclooxygenase inhibition reveals a synergistic action of vasoconstrictors on the DNA synthesis in mesangial cells.     

The etiology of pneumonia in malnourished and well-nourished Gambian children

During a 2-year period 159 malnourished children ages 3 months to 5 years with radiologic evidence of pneumonia were investigated to determine the cause of their pneumonia. In addition 119 malnourished children without pneumonia, 119 well-nourished children with pneumonia and 52 well-nourished children without pneumonia were studied as controls. Percutaneous lung aspiration was performed on 35 malnourished and 59 well-nourished children with pneumonia. Bacteria were isolated from the blood, lung or pleural fluid of 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia and from the blood of 5 (4%) malnourished children without pneumonia. Streptococcus pneumoniae and Haemophilus influenzae, which were the two organisms isolated most frequently in both groups of children with pneumonia, were found in 17 (11%) malnourished and 39 (33%) well-nourished children with pneumonia. Mycobacterium tuberculosis was detected in 5 malnourished children with pneumonia. A potentially pathogenic virus was identified in 35% of malnourished children with pneumonia and 40% of well-nourished children with pneumonia, and from 25% of children without pneumonia. The viruses identified most frequently were adenovirus and respiratory syncytial virus.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo osteogenesis assay: a rapid method for quantitative analysis

A quantitative in vivo osteogenesis assay is a useful tool for the analysis of cells and bioactive factors that affect the amount or rate of bone formation. There are currently two assays in general use for the in vivo assessment of osteogenesis by isolated cells: diffusion chambers and porous calcium phosphate ceramics. Due to the relative ease of specimen preparation and reproducibility of results, the porous ceramic assay was chosen for the development of a rapid method for quantitating in vivo bone formation. The ceramic cube implantation technique consists of combining osteogenic cells with 27-mm3 porous calcium phosphate ceramics, implanting the cell-ceramic composites subcutaneously into an immuno-tolerant host, and, after 2-6 weeks, harvesting and preparing the ceramic implants for histologic analysis. A drawback to the analysis of bone formation within these porous ceramics is that the entire cube must be examined to find small foci of bone present in some samples; a single cross-sectional area is not representative. For this reason, image analysis of serial sections from ceramics is often prohibitively time-consuming. Two alternative scoring methodologies were tested and compared to bone volume measurements obtained by image analysis. The two subjective scoring methods were: (1) Bone Scale: the amount of bone within pores of the ceramic implant is estimated on a scale of 0-4 based on the degree of bone fill (0=no bone, 1=up to 25%, 2=25 to 75%, 4=75 to 100% fill); and (2) Percentage Bone: the amount of bone is estimated by determining the percentage of ceramic pores which contain bone. Every tenth section of serially sectioned cubes was scored by each of these methods under double-blind conditions, and the Bone Scale and Percentage Bone results were directly compared to image analysis measurements from identical samples. Correlation coefficients indicate that the Percentage Bone method was more accurate than the Bone Scale scoring method. The Bone Scale scoring method gave an r2=0.767 while the Percentage Bone method gave a value of 0.902. These results indicate that scoring ceramic cubes by the percentage of pores containing bone gives a result that corresponds to image analysis measurements at nearly a 90% confidence level. Thus, the Percentage Bone method of scoring is an accurate and relatively quick scoring method for in vivo bone formation.     

Organism-dependent fungicidal activities of azoles

We investigated the antifungal activities of itraconazole and voriconazole on Aspergillus species by time kill studies, and the results were compared with those obtained for Candida species. Exposure of Aspergillus fumigatus conidia to varying concentrations (1.25 to 10 microg/ml) of itraconazole and voriconazole resulted in cellular death; the cytocidal effect was time and concentration dependent. In contrast, no killing of Candida albicans occurred in the presence of itraconazole and voriconazole at concentrations as high as 10 microg/ml, although candidal growth was inhibited compared to the drug-free control. Amphotericin B (1.25 to 10 microg/ml), on the other hand, killed both A. fumigatus and C. albicans. Similar results were obtained for non-A. fumigatus aspergilli and non-C. albicans Candida species. These observations indicate that both itraconazole and voriconazole are cytocidal agents for Aspergillus species but not for Candida species, suggesting that azoles possess organism-dependent fungicidal activities.