Serum sickness-like reactions to cefaclor. In this study, we evaluated whether the high number of reports of serum sickness to cefaclor was present in every country and year, and whether these figures from voluntary reporting facilitated an estimation of the relative risk. A nested case-control study was performed with reports of all suspected adverse reactions (ADR) to cefaclor, amoxicillin and cephalexin in the period 1968-1987, as reported to the WHO Collaborating Center for International Drug Monitoring from the U.S.A., the U.K., Sweden, Canada and Germany. The ADR-reporting odds ratio was defined as the ratio of the odds of the number of ADR-reports of serum sickness to cefaclor and amoxicillin or cephalexin and the odds of similar reports of non-serum sickness to cefaclor and amoxicillin or cephalexin. The ADR-reporting odds ratio adjusted for country, age, gender, origin of the report and year of marketing was 12.4 for cefaclor vs amoxicillin and 18.5 for cefaclor vs cephalexin. In children (< 15 years of age) and in adults (> 15 years of age), the relative risk of developing serum sickness of cefaclor vs amoxicillin was estimated at 13.9 (95% confidence interval (95% CI): 6.0-32.2) and 2.9 (95% CI: 0.9-9.4) respectively in the U.S.A., and at 15.1 (95% CI: 7.2-31.5) and 5.5 (95% CI: 2.0-15.0) respectively in the other four countries together. In this study, the ADR-reporting odds ratio facilitated a valid estimation of the relative risk.


Late sequelae of hysterectomy and diverticulosis: colovaginal fistulae. Three cases of colovaginal fistulae were recently diagnosed and treated. Colovaginal fistulae are not commonly reported and their diagnosis may be difficult to make. Our cases presented with a complaint of vaginal discharge, history of hysterectomy, and diagnosis of diverticulosis. The diagnosis and treatment of colovaginal fistulae are discussed.


The role of exercise in reducing coronary heart disease and associated risk factors. Despite public health efforts, heart disease remains a leading cause of death and disease in the United States. There is sufficient evidence to justify the inclusion of regular exercise in efforts to reduce overall coronary heart disease (CHD) morbidity and mortality. This paper reviews the supportive evidence for this stance as well as the role of exercise in managing the major CHD risk factors of atherogenic serum lipids, hypertension, and obesity. Recognition of exercise as a lifestyle behavior is addressed and recommendations for prescribing exercise for adults interested in preventing CHD are presented.


Optical property changes as a result of protein denature in albumen and yolk. Heat-induced changes in the scattering and absorbing properties of tissue begin with the denaturation of protein. Using egg albumen and egg yolk as tissue phantoms, the changes in absorption and scattering coefficients and the average cosine of the scattering angle have been quantified from 350 to 850 nm for heating corresponding to an empirical damage parameter from 3.7 to 1430 (albumen) and from 0.067 to 28 (yolk). In addition to being useful for modelling the response of tissue to laser light, the changes in optical properties yield information on the particle size distribution in the phantoms. For a low damage parameter the albumen has a large percentage of small, so-called Rayleigh scattering, particles owing to the initial denaturation of the protein. As the damage parameter increases, the percentage of these particles decreases. In the yolk, the effect of denaturation of proteins on the scattering characteristics is still present but less pronounced, because of the initial highly scattering nature of the tissue and perhaps to other rate processes that also occur.


Dynamic optical property changes: implications for reflectance feedback control of photocoagulation. During laser treatment, coagulation affects the optical properties of the tissue. In particular, the formation of a white lesion significantly increases the scattering coefficient. This change in the optical properties in turn affects the laser light distribution in the tissue. The white lesion formed during photocoagulation of the retina has a dynamic effect upon reflection and fluence rate. This problem has been simulated on a model medium consisting of a thin absorbing layer covered with a 1 cm thick layer of albumin. The albumin layer is subdivided into coagulated (white) and uncoagulated (clear) layers. The optical properties of each layer have been determined and these values have been used to model light distribution in the medium. One-dimensional adding-doubling and three-dimensional Monte Carlo methods have provided light distributions in the medium for varying thicknesses of the coagulated albumin. Computed fluence reaching the absorbing layer decreased in the presence of a 275 microns or thicker coagulated layer. The coagulated layer attenuates light because it is highly scattering; however, this scattering also leads to a sub-surface peak in fluence rate at a level higher than the incident fluence. The latter effect outweighed the former for coagulated layer thicknesses less than 275 microns. Computed reflectance of argon laser light from a semi-infinite coagulated region initially increased linearly as a function of thickness. As the coagulation thickness increased beyond 4-5 optical depths, the reflectance approached a constant value, R infinity, at 9 optical depths (2 mm). Experimentally measured total reflectance is shown to be an inadequate indicator of the thickness of a lesion (finite coagulated volume); however, central reflectance from a lesion measured with a CCD camera confirmed the computed trends. These results provide a theoretical foundation for control of lesion thickness using reflectance images.


Optical properties of in vitro epidermis and their possible relationship with optical properties of in vivo skin. Using a spectrophotometer with an internal integrating sphere, the absorption (mu a) and reduced scattering (mu s') coefficients of in vitro epidermis were evaluated from reflectance and transmittance measurements. mu a and mu s' varied from 24 to 0.2 cm-1, and from 32 to 21 cm-1 respectively, on passing from 400 to 800 nm. Moreover, using an external integrating sphere, the reflectance spectrum of in vivo skin was compared with the reflectance spectrum calculated with a Monte Carlo model, in which the mean values of mu a and mu s' and different anisotropy parameters were used as input data. In vivo results show that the principle of similarity is entirely valid for wavelengths greater than 600 nm and may be considered a good approximation in the 400-600 nm band, and suggest that optical characteristics of in vivo skin may be inferred from reflectance measurements.


Time-resolved spectroscopy of the human forearm. For spectroscopic purposes, the forearm is a conveniently large object to be investigated because consistent oxygenation and blood volume changes can be obtained. Human forearm spectral properties were investigated using picosecond near-IR laser spectroscopy. The behaviour of the temporal point spread function in resting conditions and during ischaemia, venous occlusion and exercise is reported. The effect of path length inaccuracy on muscle oxygen consumption, obtained by combining spectral data with the path length, is discussed.


Effects of optical constants on time-gated transillumination of tissue and tissue-like media. Light transillumination was used to study structures inside turbid media. Time-gated viewing was performed to suppress multiply-scattered light and thus improve spatial resolution. We demonstrate that, for the case of scattering-dominated attenuation (scattering coefficient much greater than the absorption coefficient), the detection of early transmitted light will be practically insensitive to variations in the absorption coefficient. This is an important observation for the development of time-gated optical mammography, since optical mammography using continuous-wave light is based on increased light absorption in the tumour region caused by the neovascularization surrounding a tumour. In order to detect tumours in time-gated viewing it is the scattering coefficient of the tumour that must be characteristic. The scattering coefficient is measured to be lower in the tumour region than in the surrounding breast tissue for one resected breast specimen.


Frequency domain imaging of absorbers obscured by scattering. Multiple pixel, frequency domain measurements of phase shift, theta, and modulation, m, in a phantom containing an absorber obscured by a relatively non-absorbing scattering solution are presented in combination with a theory of photon migration imaging. Results employing a single point source show that two dimensional theta measurements made in the presence (theta presence) and in the absence (theta absence) of an absorber can be used to create delta theta images. delta theta (theta absence-theta presence) images can be used to detect as well as locate the three dimensional position of the absorber. Images of mpresence measured in the presence of the absorber normalized by mabsence also provided detection and two dimensional location of its position. Images of % mpresence/mabsence at higher modulation frequencies provided greater resolution as predicted by photon migration theory. Neither theta nor m images alone could be used to detect or locate the presence of the absorber.


Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media. Studies of Raman scattering, fluorescence and time-resolved light scattering were conducted on cancer and normal biomedical media. Fourier transform Raman spectroscopic measurements were performed on human normal, benign and cancerous tissues from gynecological (GYN) tracts. A comparison of the intensity differences between various Raman modes as well as the number of Raman lines, enables one to distinguish normal GYN tissues from diseased tissues. Fluorescence spectroscopic measurements on human breast tissues show that the ratio of fluorescence intensity at 340 nm to that at 440 nm can be used to distinguish between cancerous and non-cancerous tissues. Separate studies on normal and cancerous breast cell lines show spectral differences. The measurements of back-scattered ultrafast laser pulses from human breast tissues show differences in the scattered pulse profiles for different tissues. These studies show that various optical techniques have the potential to be used in medical diagnostic applications.


Quantitative histochemical analysis of human artery using Raman spectroscopy. We have developed a method for using near infrared Raman spectroscopy to quantitatively analyze the histochemical composition of human artery. The main contributors to bands observed in the Raman spectra of normal and atherosclerotic aorta are the proteins collagen and elastin, cholesterol lipids, and calcium hydroxyapatite. The Raman scattering cross-sections of different bands for these components have been determined in order to understand their relative contributions to the Raman spectra of biological tissue. The Raman signal is observed to behave linearly with the concentration of the components, even in a highly scattering medium such as a powder. Using these data, we have developed a linear model that can be used to extract the quantitative contribution of an individual component to the spectrum of a mixture. The model has been applied to several mixtures of known composition of tissue constituents in order to evaluate its precision and accuracy. The calculated fit coefficients from the spectra are in agreement with the measured values within experimental uncertainties. The spectra of different types of atherosclerotic aorta have also been modeled, and we have extracted quantitative information regarding the relative concentration of biological constituents in atherosclerotic aorta.


The use of different time/temperature combinations in the optimization of sterilization of Ringers/glucose infusion solution. The effect of sterilization temperature and sterilization efficacy (F0) on the amount of 5-hydroxymethyl-2-furaldehyde (5-HMF) and glucose, number of particles generated and color of Ringers/glucose infusion solution is described. The infusion solution was a 5% glucose solution containing Ringer-type electrolytes. The solutions were autoclaved in a pilot scale autoclave using different temperature/time combinations to produce the target F0 values of 10, 15, 20 and 25 minutes. The amounts of 5-HMF and glucose were determined by HPLC. The use of the shortest possible sterilization cycle to yield the target F0 resulted in the lowest 5-HMF concentrations in the Ringers/glucose infusion solutions studied. The spectrochromatograms of the sterilized solutions showed that glucose is degraded into various degradation products in the presence of Ringer-type electrolytes. It was also demonstrated by SEM/EDX that a significant part of the particles result from the leaching of the silicon oil used in the manufacture of rubber stoppers for LVP solutions. The number of particles generated in different solutions and the particle size distributions were determined with a Coulter-Counter. The particle size distributions show no clear correlation between sterilization process conditions and the number of particles. The results show that it is possible to minimize the amount of 5-HMF generated even when the same F0 is used, by choosing the highest sterilization temperature possible. This also leads in practice to the shorter sterilization processes, saving both process time and energy.


Compendial issues: WHO.

Compendial issues: WHO. It is important to remember that: 1. WHO is an international organization representing 182 member countries. 2. WHO has a constitutional mandate inter alia to "develop, establish and promote international standards with respect to biological, pharmaceutical and similar products." 3. Its present programme covers such activities as WHO Good Manufacturing Practices, the International Pharmacopoeia, International Nonproprietary Names (INN), WHO Certification Scheme, the Model List of Essential Drugs and many other subjects concerning safety, efficacy and quality. 4. Emphasis is now directed to the feasibility of further harmonization of requirements for drug registration and quality control having regard to the number of countries with increasing manufacturing facilities.


Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats. Poloxamer (Pluronic) nonionic surfactant vehicles are a series of chemically-related block copolymers finding widespread use in parenteral formulations as solubilizing and wetting agents for traditional, low-molecular weight organic drug molecules, as well as stabilizing agents for proteins and polypeptide drugs. We report the effects of poloxamer 407 (Pluronic F-127) on plasma cholesterol and triglyceride concentrations in rats. Poloxamer 407 injected into rats by intraperitoneal injection (dose = 1.5 gm/kg) resulted in sustained (greater than 96 hour) hypercholesterolemia and hypertriglyceridemia. A larger dose of poloxamer 407 was required to elevate plasma triglyceride relative to total cholesterol. Ingestion of commercial rat chow had a negligible effect on plasma cholesterol and triglycerides levels in control (no poloxamer injection) animals, but consumption of food by animals that received an intraperitoneal injection of poloxamer 407 (30% w/w) resulted in significantly (p < .05) greater elevations in plasma cholesterol and triglycerides than in fasted animals administered poloxamer 407. The route of poloxamer 407 administration, namely intramuscular vs. intraperitoneal injection, was observed to be a more important factor for poloxamer-induced elevations in plasma cholesterol than poloxamer-mediated elevations in plasma triglycerides. Our results also provide suggestive evidence that the mechanism responsible for the elevation of plasma cholesterol following intraperitoneal injection of a poloxamer 407 solution (30% w/w) to rats may be due to stimulation of 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase activity in the liver by the poloxamer vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)


Investigational trends: clean room environmental monitoring. GMP problems associated with microbiological environmental monitoring are among those most commonly cited as objectionable during FDA inspections of parenteral drug manufacturing facilities. This presentation describes FDA inspection approaches and techniques and audit applications used in evaluating the effectiveness of firms environmental monitoring programs. Environmental monitoring programs involve considerable data, and many variables are interrelated to make difficult detection of patterns and trends during FDA audits. Consequently, systematic computer-aided audit techniques have been developed by the author to permit detection of patterns, trends and GMP documentation problems by the FDA. The strategies and techniques described in this paper may provide management with ideas about ways to review and audit their own environmental data. Presented are some practical details about the use of a portable computer to systematically assess trends and patterns. Several program applications (algorithms) were developed to determine if cleanroom environmental data are under a state of control.


Vaporized hydrogen peroxide sterilization of freeze dryers. The feasibility of using vapor hydrogen peroxide (VHP) as an alternative to steam sterilization has been examined using a pilot plant freeze dryer equipped with a prototype vapor generator. Specific objectives of the study discussed in this presentation were to: 1. Identify critical process variables affecting the lethality of VHP to Bacillus stearothermophilus spores, particularly within dead legs in the system. 2. Measure the efficacy of system degassing after sterilization. 3. Determine the effect of repeated sterilization cycles on the integrity of elastomeric components of the freeze dryer. Penetration of adequate concentrations of hydrogen peroxide vapor into small diameter piping, such as tubing connected to pressure gauges, is the most challenging aspect of VHP sterilization of freeze dryers. Prior to equipment modifications, spore strips placed within such dead legs remained positive irrespective of the number of gas/degas pulses and system pressure. Equipment modifications necessary to effect complete kill of biological indicators placed in system dead legs is discussed. Results of this study support the conclusion that vaporized hydrogen peroxide shows promise as an alternative sterilization method for freeze dryers.


Mapping size distributions of parenteral fluorocarbon emulsions by a novel method of centrifugal sedimentation followed by densitometry. A novel method for characterization of size distributions of parenteral fluorocarbon emulsions is described. Prepared emulsions were centrifuged to sediment droplets above predetermined diameters out of a known supernatant sample volume using the Bostok-Stoke's equation. Centrifugation times may be calculated using centrifuge parameters and physical properties of the fluorocarbon oil phase and the dispersion medium. The fluorocarbon content of the supernatant sample volume at successive centrifugation times was determined both by densitometry and by Gas Chromatography. A close correlation was found between the two methods. The density data was processed and converted into a volume distribution histogram by means of a program written in BASIC. The speed, simplicity of use, non reliance on costly equipment and good correlation to absolute particle counting methods makes the density method suitable for submicron size characterization.


Key issues relating to the genetic stability and preservation of cells and cell banks. The long term maintenance of genetically stable cells is important for ensuring reproducible results and continuity in the advance of microbiology, cell biology and biotechnology. As actively growing cultures, cells are constantly at risk of changing, and the necessity for subculturing living materials increases the chances for genetic change and contamination. Many techniques are available for stabilizing living cells; the method employed must be compatible with the intended use of the culture. The most commonly utilized means of preserving living cells are by freezing to cryogenic temperatures, and freeze-drying. Master stocks are usually maintained at liquid nitrogen or comparable temperatures, while working stocks can be frozen or freeze-dried, and maintained at more economical and easily managed temperatures where possible. However, low temperature techniques may cause damage that can result in genetic change, or potential selection when only a small portion of the population survives. Therefore, a good preservation program must include a comprehensive cell characterization regimen that is applied both before and after preserving the cells to ensure that changes are detected when they do occur. Assurance of long term stability necessitates well designed safekeeping and security measures that include minimizing specimen handling through well designed inventory systems, validation and monitoring of storage temperatures, provisions for backup inventory, and training of personnel. Cell banking also requires good cataloguing and data management practices to avoid duplication and misidentification, and to ensure proper tracking of specimens and ease of access.


Eikenella corrodens in human oral and non-oral infections: a review. There is substantial evidence in support of the existence of distinct clinical forms of human periodontal disease. Moreover, these different forms of periodontal disease may be associated with relatively distinct subgingival microflora, often involving microaerophilic or anaerobic Gram-negative bacterial species. Eikenella corrodens is a facultative Gram-negative bacillus which is a common inhabitant of the oral cavity and the intestinal and genital tracts. Its primary ecologic niche within the oral cavity appears to be dental plaque, both in periodontally healthy individuals and in periodontitis patients. However, E. corrodens is recognized as an infrequent human pathogen capable of causing extraoral infections, either as the sole infectious agent or as part of a mixed infection, its potential role in the etiology of periodontal disease is not well understood. E. corrodens is often present in the supra- and subgingival plaque of periodontally healthy subjects. On the basis of cross-sectional and longitudinal studies, E. corrodens appears to be somewhat more prevalent in subgingival plaque samples of periodontitis subjects than periodontally healthy individuals. However, the percentage of E. corrodens in the total cultivable microflora did not vary between the two groups. Microbiologic studies attempting to define the relationship between E. corrodens and periodontal disease assume that this species is essentially homogeneous and that all strains exhibit comparable pathogenic potential. However, E. corrodens exhibits 1) variable colony morphology, biochemical and serologic reactivity; 2) marked phenotypic diversity with respect to outer membrane protein and lipopolysaccharide structure; and 3) marked diversity in the restriction patterns of total genomic DNA. Thus, it is possible that a limited number of clones of E. corrodens may be associated with periodontal disease and/or extraoral infection, while other strains are relatively harmless commensals. Additional studies, possibly employing strain-specific nucleic acid probes, may be required to define the role of E. corrodens as a human periodontal pathogen.


The effectiveness of scaling and root planing with curets designed for deep pockets. This study evaluates the effectiveness of subgingival scaling and root planing with longer shank, thinner blade, rigid curets compared to the standard rigid Gracey curet. A total of 35 non-molar teeth from 7 patients provided 140 root surfaces for evaluation; 52 root surfaces were instrumented with the rigid longer shank curets; 52 with the standard rigid Gracey curets; and 36 provided untreated controls. A bilateral matched design was utilized where contralateral teeth in the same arch were instrumented. Instrumentation was standardized at 15 minutes per tooth. Both scaled and unscaled teeth were extracted immediately after the experimental procedures. They were viewed under a stereomicroscope with a 0.10 mm grid to assess the percent of surface covered by calculus and unaltered cementum. The curet efficiency was also evaluated. The results indicated a significant treatment effect compared to the controls in relation to the percentage of residual calculus and curet efficiency. However, there was no significant difference between the rigid longer shank and standard rigid Gracey curets. There was a difference noted when tooth surfaces were evaluated. Mesial tooth surfaces had the least remaining calculus and demonstrated the best curet efficiency.


The effect of insulin-like growth factor-I and human growth hormone on periodontal ligament fibroblast morphology, growth pattern, DNA synthesis, and receptor binding. Repopulation of the detached root surface by cells from the periodontal ligament (PDL) is a prerequisite for new attachment formation. Stimulation of PDL-cell growth may therefore serve as an essential method to enhance formation of new attachment. Studies have demonstrated that insulin-like growth factor-I (IGF-I) has a mitogenic effect on fibroblasts originating from various connective tissues and cell-lines. Further, human growth hormone (hGH) is known to regulate the plasma concentration of IGF-I and to mediate cellular biological effects. In the present study we examined the effect of IGF-I and hGH on morphology, growth pattern, and DNA synthesis. The expression of IGF-I and hGH receptors on the surface of cultured PDL fibroblasts is also described. A primary fibroblastic cell line was established from rat PDL tissue, and blind, photographic recordings of morphology and growth pattern, as well as incorporation of [3H]thymidine in cellular DNA, was carried out in the presence and absence of IGF-I and hGH. The presence of specific membrane receptors was investigated by binding of [125I]IGF-I and [125I]hGH. The analysis of photographs showed that IGF-I and hGH had no effect on morphology and growth pattern. Incorporation of 3H-thymidine, however, was increased in a dose-dependent manner by IGF-I, whereas hGH alone or in combination with IGF-I produced no dose-dependent response. Maximum effect (% of control) on DNA synthesis was 176% for IGF-I and 91% for hGH.(ABSTRACT TRUNCATED AT 250 WORDS)


Regenerative surgery of intrabony periodontal defects using ePTFE barrier membranes: scanning electron microscopic evaluation of retrieved membranes versus clinical healing. Sixteen intrabony defects in 12 patients were treated by gingival flap surgery including root surface debridement and placement of an expanded polytetrafluoroethylene (ePTFE) membrane. The membranes were removed after 4 to 6 weeks and examined by scanning electron microscopy (SEM) for bacterial contamination and adherent connective tissue elements. Twelve months postsurgery, the defect sites were reexamined for changes in probing attachment level and probing bone level. Comparison of ultrastructural findings and clinical observations revealed that extent of bacterial contamination of the membrane correlated inversely with clinical assessment of attachment gain. The results indicate that the extent of oral exposure and bacterial contamination of the ePTFE membrane at the time of removal may be an indicator of the long-term success or failure of the regenerative procedure.


Oral conditions in individuals with selective immunoglobulin A deficiency and common variable immunodeficiency. Saliva and serum samples were collected from 36 individuals with selective immunoglobulin A deficiency (IgAd) and 23 patients with common variable immunodeficiency (CVI). The oral examination included registration of the teeth, Russell's periodontal index (PI), pocket formation, and salivary flow rate in both unstimulated and stimulated saliva. No differences were found in salivary flow rate, number of teeth, or pocket depth when donors with IgAd or CVI were compared to age and sex matched controls. However, mucosal manifestations of lichenoid type were more frequent in both types of immunoglobulin deficient individuals. An increased PI was also seen in CVI patients. Increased serum IgG and salivary IgM levels were found in the IgAd population.


The effect of the distance from the contact point to the crest of bone on the presence or absence of the interproximal dental papilla. This study was designed to determine whether the distance from the base of the contact area to the crest of bone could be correlated with the presence or absence of the interproximal papilla in humans. A total of 288 sites in 30 patients were examined. If a space was visible apical to the contact point, then the papilla was deemed missing; if tissue filled the embrasure space, the papilla was considered to be present. The results showed that when the measurement from the contact point to the crest of bone was 5 mm or less, the papilla was present almost 100% of the time. When the distance was 6 mm, the papilla was present 56% of the time, and when the distance was 7 mm or more, the papilla was present 27% of the time or less.


A stereomicroscopic and immunohistochemical study of vasculature in gingiva bleeding after probing. This study investigated the stereomicroscopic appearance of gingival sulcular surfaces and the histologic alterations of subepithelial vasculature of gingiva bleeding after probing. Sixty-four pairs of gingival biopsies from 49 patients were obtained and the results of stereomicroscopically visible vasculature were observed in half of the specimens. The number of biopsies showing that the vasculature of bleeding gingiva was significantly greater than those of non-bleeding gingiva. The immunohistochemical marker UEA-1 was used to identify endothelial cells on the vascular walls of 34 gingival biopsies from 15 patients. Following stereomicroscopic examination, tissue preparation with routine and UEA-1 stainings was performed. Volumetric and numerical analyses of vasculature in 6 divided portions of subepithelial connective tissue were measured. The results showed that significantly greater numbers of UEA-1 staining vessels were found within the apico-superficial portion of bleeding gingiva than those of non-bleeding gingiva. However, there was no specific correlation between the UEA-1 positive vessels within gingival tissue and stereomicroscopic visibility of vasculature on the surface appearance. It is suggested that increased vascularity in gingiva may be responsible for bleeding on clinical probing.


Entrance of Actinobacillus actinomycetemcomitans into HEp-2 cells in vitro. A strain of actinobacillus actinomycetemcomitans, freshly isolated from a juvenile periodontitis patient, and the FDC Y4 laboratory strain of Aa were tested for their capacity to adhere to and enter the epithelial cell line HEp-2 cells in vitro. Immunofluorescence microscopy as well as scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that both strains adhered to the outer surface of the HEp-2 cells. In the TEM studies, the specimens were also treated with Aa specific antibodies and gold labeled protein A. These examinations showed that only the freshly isolated strain of Aa was found within the HEp-2 cells. The intracellular Aa were found to be viable, and in one case one of them was seen to undergo division. It is concluded that freshly isolated Aa has the ability to enter epithelial HEp-2 cells in vitro, and it is tentatively suggested that this may play a role in the pathogenesis of periodontal disease.


The relationship of gingival fluid leukocyte elastase activity to gingival fluid flow rate. Recent studies have suggested that leukocyte elastase activity (EA) in tissue exudates is an indicator of inflammatory disease. We assayed gingival fluid (GF) EA with a selective peptide substrate and compared it to GF flow rate with regard to its ability to detect differences in the clinical status of existing inflammatory periodontal disease in 56 human subjects. Compared to healthy sites (Gingival Index = 0, 1 to 3 mm) and mild gingivitis sites (GI = 1, 2 to 5 mm), mean GF EA was significantly (P < 0.05) higher at periodontitis sites with deep probing depths (GI = 2, 6 to 9 mm depth), but not at periodontitis sites with intermediate probing depths (GI = 2, 4 to 5 mm). When expressed as specific EA (i.e., normalized to GF protein content), mean EA was also significantly higher at deep periodontitis sites compared to healthy sites and mild gingivitis sites. In addition, specific EA was significantly higher at periodontitis sites with intermediate probing depths than at healthy sites. As predicted by previous studies, these significant increases in specific EA were associated with significant increases in mean GF flow rate. In contrast to specific EA, however, mean GF flow rate was significantly higher at gingivitis sites than at healthy sites. A strong correlation was observed between GF flow rate and specific EA (rs = 0.737, P = 0.0006). Thus, GF flow rate and GF EA appear to be related indicators of inflammation, but GF flow rate may be more sensitive to early inflammatory changes leading to mild gingivitis.


Cell populations associated with active probing attachment loss. The purpose of this study was to evaluate the ability of cell populations to differentiate between untreated progressing periodontitis sites (P) and untreated non-progressing sites (NP). Pairs of biopsies were obtained from untreated periodontal patients, one biopsy from a site which had lost probing attachment of 2 mm or more within the previous month, the other biopsy from a non-progressing site. Cell populations were identified on 1 micron sections in a defined connective tissue area at the junctional epithelium. The cell types counted were fibroblasts, mast cells, monocytes/macrophages, polymorphonuclear leukocytes (PMNs), lymphoid cells, plasma cells, endothelial cells, total inflammatory cells, and the total number of cells. The number of fibroblasts, mast cells, monocytes/macrophages, and inflammatory cells, as well as their percentage of the total number of cells, differed significantly between P- and NP-sites. In addition, the actual total counts differed between groups. The difference between groups was more significant for percent fibroblasts than for any other cell type. It appears that cell populations, particularly fibroblast counts, can aid in the histological discrimination between P and NP periodontitis lesions.


Comparative efficacy of the standard flossing procedure and a new floss applicator in reducing interproximal bleeding: a short-term study. This was a parallel stratified study which examined the effect on gingival health of a new floss holder and applicator, designed to deliver a 25 microliters dose of 0.1% chlorhexidine solution to each interdental embrasure during the flossing procedure. Fifty-two patients with simple chronic gingivitis were stratified according to age, sex, and baseline interdental bleeding score and then assigned to one of three treatment groups. One of the following interdental cleaning agents was used once daily during a 2-week period: conventional floss; a flossing device with chlorhexidine; or a flossing device with placebo solution. Gingival health was assessed using the interdental bleeding index (IBI); i.e., the ratio of bleeding sites to the number of sites tested by stimulation with an interdental cleaner. The percentage reduction in bleeding amounted to 38.3% for conventional floss, 51.5% for the flossing device with chlorhexidine, and 51.4% for the flossing device with placebo. The reductions in both flossing device groups were significantly greater than that of the conventional floss group as determined by one-way ANOVA (F = 4.0; P = 0.024) and multiple range tests. There were no statistically significant differences between the two flossing device groups. There was no difference in patients' perception of ease of use of their respective materials; however, 72% of chlorhexidine users and 94% of placebo users, but only 24% of conventional floss users, felt that their interdental cleaning regimens left their mouths feeling fresher. It is therefore postulated that the pleasant tasting spray may have been an important stimulus to extended use of the new device and may explain its greater effectiveness.


Destructive periodontal disease in healthy children. This study determined the prevalence of destructive periodontal disease affecting the deciduous dentition among otherwise healthy subjects, who were diagnosed with juvenile periodontitis (JP) in their permanent dentitions. There were 4,757 subjects in this retrospective, cross-sectional study. Diagnosis of JP was based on age (< or = 15 years), negative medical history, and radiographic evidence of arc-shaped alveolar bone loss. The study population was one-third white and two-thirds black and the male/female ratio was 1:1, reflecting the general patient population. The prevalence among whites was 0.3%, with a female/male ratio 4:1; whereas among blacks the prevalence was 1.5%, with a female/male ratio approximately 1:1. Among the black JP subjects with radiographs of the mixed dentition, 85.7% presented evidence of bone loss, and of those with radiographs of the deciduous dentition, 71.4% had discernible alveolar bone loss. This study suggests that JP is much more prevalent in blacks and that it does indeed occur in the prepubertal years affecting the deciduous as well as the permanent dentitions in otherwise healthy children. These data imply the importance of including a periodontal evaluation in the examination of children, using the periodontal probe and radiographs sufficient to adequately view the alveolar bone.


Salivary and metabolic factors involved in oral malodor formation. Saliva plays a central role in the formation of oral malodor. Such formation has as its basis bacterial putrefaction, the degradation of proteins, and the resulting amino acids by microorganisms. Saliva provides substrates that are readily oxidized and in the process facilitates oxygen depletion. This favors the reduced conditions conducive to production of odoriferous volatiles. At the same time, saliva is a major source of oxygen for the oral bacteria which generally is inhibitory of their formation. The pH is also critical to malodor development; acidity inhibits, whereas neutrality and alkalinity favor malodor production. Since the pH on oral mucosal surfaces where odor formation occurs is largely determined by the fermentative and putrefactive activities of the adhering bacteria, these acid-base processes are necessarily of major regulatory importance. Because oral malodor and periodontitis both involve excessive oral putrefaction, a better understanding of putrefaction could lead to more substantive methods of oral malodor treatment than exists today, as well as identifying new approaches to amelioration of the bacterial attack on the soft tissues leading to the destruction associated with periodontal disease.


Measurement of oral malodor: current methods and future prospects. Measurement of oral malodor is complicated by a variety of parameters including complexity of gaseous molecular species, sampling difficulties, temporal variations, choice of suitable subject populations, and lack of agreement on reference standards. Since oral malodor is a perceived olfactory stimulus, direct sampling and assessment by human judges may be the most logical measurement approach. However, as with other psychophysical assessments, human malodor measurement by the human nose may vary widely among and between judges, and consequently cannot be confidently reproduced in other laboratories. Such shortcomings have led several investigators to propose quantitative approaches based on measurement of volatile sulfide compounds which are associated with oral malodor. Highly sensitive and discriminatory measurements of volatile sulfides can be made using gas chromatography although for rapid sampling of larger subject populations, portable sulfide monitors may be more appropriate. Future research in this field should consider: 1) improved and simplified instrumentation for more rapid through-put and reliability; 2) development and definition of reference standards for oral malodor assessment; 3) formulation of clinical studies with appropriately sized, well-defined patient populations; and 4) further development of within mouth, site-specific measurements.


Biochemical and clinical factors influencing oral malodor in periodontal patients. The amounts of volatile sulfur compounds (VSC) and methyl mercaptan/hydrogen sulfide ratio in mouth air from patients with periodontal involvement were 8 times greater than those of control subjects. Our studies demonstrated that, in patients with periodontal disease: 1) the concentration of disulfide, which is converted to VSC, increased in proportion to the total pocket depth; 2) 60% of the VSC was produced from the tongue surface; 3) the amount of tongue coating was 4 times greater than in control subjects; and 4) VSC production and the methyl mercaptan/hydrogen sulfide ratio of the tongue coating were increased. 2-Ketobutyrate, which is a byproduct of the metabolism of methionine to methyl mercaptan, was higher in the saliva of patients with periodontal disease. This implies that metabolism of methionine to methyl mercaptan increases in the oral cavity of patients with periodontal pockets. Since free L-methionine, rather than protein, is the main source for methyl mercaptan, we estimated the methionine supply from the gingival fluid into the oral cavity of patients with periodontal involvement. The results showed that the ratio of methionine to whole free amino acids was significantly higher than that of cysteine. Our studies suggest that not only microorganisms, but also the tongue coating and gingival fluid are factors which enhance VSC production in patients with periodontal disease.


The long plantar wing distal metaphyseal osteotomy. The authors introduce the long plantar wing distal metaphyseal osteotomy of the first metatarsal through a medial plantar approach. This procedure for mild-to-moderate hallux valgus is capable of correcting an increased proximal articular set angle and first intermetatarsal angle concomitantly. The biomechanical, surgical, and clinical rationale for this procedure are discussed.


Non-oral etiologies of oral malodor and altered chemosensation. A number of non-oral causes for oral malodor have been discussed. Several well documented etiologies for non-oral malodor include renal failure, cirrhosis of the liver, and diabetes mellitus. Each of these conditions has been examined using analytical instrumentation. In addition there appear to be several other metabolic conditions involving enzymatic and transport anomalies (such as trimethylaminuria) which lead to the systemic production of volatile malodors that manifest themselves as halitosis and/or altered chemoreception. Our studies include patients who have been referred to us after being examined by numerous clinical specialists with no identification or relief from their problem. This is due in part to the intermittent nature of many of these problems as well as an apparent lack of knowledge concerning many of these metabolic problems and their relation to oral symptoms.


Dynamic plantar pressure analysis. Comparing common insole materials. A comparison of five commonly used insole materials (Spenco, PPT, Plastazote, Nickelplast, and Pelite) was made to evaluate their effectiveness in reducing plantar vertical pressures on human subjects during walking. With the use of the EMED-SF pedograph force plate system, dynamic measures of vertical force, force-time integral, peak plantar pressure, pressure-time integral, and area of foot-to-ground contact were compared with the force plate covered with each of the insole materials and without any interface material.


Surgical management of chronic tophaceous gout. A case report. Severe chronic tophaceous gout can be a surgical challenge. A classic case of marked first and fifth metatarsophalangeal joint involvement is presented.


Avulsion fracture at the plantar lateral base of the first metatarsal. Two case reports. The anatomy, mechanism, and two treatment approaches of an avulsion fracture at the plantar lateral base of the first metatarsal without any joint dislocation were discussed. The authors presented an injury that has not been reported in the literature but has only been seen as a part of Lisfranc's fracture dislocation types B and C.


Maffucci's syndrome. Review of the literature and case report. Maffucci's syndrome, a rarely occurring congenital disorder, may present early in life as either a pathologic fracture, an incidental radiographic finding, or primarily as multiple hemangiomas. Patients endure years of orthopedic complications, and are faced with a grim prognosis, with the majority developing either skeletal or extra-skeletal malignancies by the end of their fourth decade.


Epidermal inclusion cysts following minimal incision surgery. One of the most frequent causes of epidermal inclusion cysts is trauma involving the epidermis with subsequent implantation of epidermal cells into the dermis or subcutis. Minimal incision surgery is capable of achieving this because it is performed by using small incisions and rapidly rotating power instruments. The technique requires that the surgeon master a high degree of dexterity and knowledge of the anatomy without the aid of direct visualization. Van Enoo and Cane suggest the use of fresh, sharp skin blades to protect against invagination of skin edges which could lead to epidermal inclusion cysts. They also state that an improper position or an incision that is too small will cause tension, which can lead to heat buildup with subsequent sloughing and dehiscence. It may also drive some epidermal cells underneath the dermis and foster an epidermal cyst. Other surgeons using small incisions suggest thorough and copious irrigation to flush away debris and to avoid potential foreign body reactions. The periosteum should be reflected away from the point where the drill bit exits the bone to prevent bone chips from being forced subperiosteally and potentially causing a foreign body reaction. By virtue of the technique, minimal incision surgery lends itself to a greater risk of causing epidermal inclusion cysts. Surgeons who use these techniques must be aware of this potential complication.


Osteomyelitis of the distal phalanx following trauma to the nail. A case report. A case in which inadequate treatment of a nail plate injury resulted in chronic osteomyelitis has been described. Because of its distinct anatomy, trauma to the nail and its associated structures should not be summarily dismissed as an innocuous injury but should be thoroughly examined for phalangeal fracture and laceration of the nail bed.


Uncertainty effects in orientation discrimination of foveally seen lines in human observers. 1. The effect of spatial uncertainty on line orientation thresholds was studied in normal observers. Vertical lines, 5 min of arc long, built up a matrix in which one of the line elements could be tilted to the left or right. The orientation thresholds depended strongly on the number of alternative test positions. There was a linear relation between log (threshold) and log (P), where P is the probability that a particular line element was the one being tested. 2. The uncertainty effect was shown to be time dependent. The effect was more marked for the shortest stimulus duration (1 s). However, even with a 6 s stimulus duration, allowing several re-fixations, the thresholds were significantly higher in the presence of uncertainty, compared to the situation in which the test position was fixed and known to the observer. 3. When the measurements were restricted to the centre line in a matrix, thresholds were more than twice as high when the test line could be in any of the centre 3 x 3 positions, compared to the case in which there was no uncertainty as to the test position. Foreknowledge of location of the test line within the matrix improved the threshold further, even if the whole matrix was displaced to different retinal positions. 4. It is concluded that the physiological mechanism mediating threshold improvement probably operates on a cortical processing apparatus more central than V1.


Electrophysiological responses in the rat tail artery during reinnervation following lesions of the sympathetic supply. 1. Responses to perivascular stimuli have been recorded with intracellular microelectrodes from the smooth muscle of isolated segments of the main caudal artery of rats at various times between 7 and 128 days after all four collector nerve trunks had been lesioned near the base of the tail at 21 days of age. 2. In proximal segments (< 40 mm distal to the lesions), excitatory junction potentials (EJPs) and neurogenic alpha-depolarizations (NADs) evoked by stimuli presented via a proximally located suction electrode were similar to those in the same segments of unoperated control animals of the same age. Supramaximal EJPs in these segments decreased in amplitude with age. 3. Stimuli just supramaximal for EJPs in innervated preparations failed to evoke responses in segments farther than 30-40 mm distal to the lesions at any time after the nerves had been cut and 1 cm excised. Higher voltages evoked slow depolarizing potentials (SDPs) which were of longer time course than EJPs. Similar responses occurred in segments over 60 mm distal to the lesions at 20-50 days after the nerves had been frozen, and in all segments sampled over 100 mm distal to nerve lesions. 4. Spontaneous transient depolarizations (STDs) were recorded at all depths of the media in denervated segments. These occurred at frequencies similar to those of spontaneous events (including attenuated spontaneous EJPs) in innervated segments. 5. The earliest signs of reinnervation (24-42 days after freeze lesions) consisted of very small amplitude EJPs of normal time course which facilitated markedly during a short train of stimuli (5-10 Hz); these were followed by NADs which were large relative to the amplitudes of the EJPs. Less commonly, small focal EJPs of brief time course (resembling spontaneous EJPs in superficial cells of innervated arteries) were evoked in very restricted regions of the vessel wall. 6. At later times (57-128 days postoperative), six of eight segments located 40-70 mm distal to freeze lesions showed EJPs of nearly control amplitude, but NADs that were larger than in equivalent segments from control animals. In the remaining two cases, reinnervation at this level was similar to that seen at the earliest postoperative times. High stimulus voltages prolonged the decay of EJPs in both control and reinnervated arteries. 7. Sensitivity to exogenous noradrenaline, assessed in terms of membrane depolarization, was increased in both denervated and reinnervated segments. 8. Catecholamine fluorescence disappeared from the arteries at a distance greater than 30-40 mm distal to the site of the nerve lesions.(ABSTRACT TRUNCATED AT 400 WORDS)


Thermal and PGE2 sensitivity of the organum vasculosum lamina terminalis region and preoptic area in rat brain slices. 1. The effects of local applications of prostaglandin E2 (PGE2) on the unit activity of fifty-one neurones in the organum vasculosum lamina terminalis (OVLT) region and fifty-eight neurones in the preoptic area (POA) were investigated in small tissue slices from the rat hypothalamus containing the OVLT and POA isolated from each other. 2. Of these, thirty OVLT and twenty-eight POA neurones were warm sensitive and increased their discharge rate in response to a rise in tissue temperature. One OVLT neurone and one POA neurone were cold sensitive and showed the opposite type of responses to changes in temperature. The thermosensitivity of these neurones was still observed in a Ca2+ free-high Mg2+ solution. 3. Perfusion with PGE2 in doses between 1 and 250 nM changed the discharge rate in forty-two of fifty-one OVLT neurones and in thirty-two of fifty-eight POA neurones in a dose-dependent manner. The responses to PGE2 were not lost during synaptic blockade. The threshold dose of PGE2 to alter the discharge rate of the OVLT neurones (4.8 +/- 1.1 (S.E.M.) nM, n = 16) was significantly lower than that of the POA neurones (40.9 +/- 12.2 nM, n = 16). 4. Fifteen of forty-two OVLT neurones exhibited the responses with a slower onset (latency 5-13 min) and a longer duration (20 min to 3 h), but such responses were observed in only one of thirty-two POA neurones. 5. The responses of OVLT and POA neurones to PGE2 (50-250 nM) were reversibly blocked by a concurrent application of AH6809, a prostanoid EP1 and/or a DP receptor antagonist. 6. While there was no clear correlation between the type of thermosensitivity and the type of response to PGE2 among the POA neurones, a significantly higher incidence of inhibitory response to PGE2 was found among the warm-sensitive neurones in the OVLT region. 7. The lower threshold responses to PGE2 and the higher incidence of PGE2 responsiveness among OVLT neurones are consistent with previous findings which showed that the highest density of PGE2 receptor binding and the highest pyrogenic sensitivity to microinjected PGE2 were observed in the OVLT region. The results provide further evidence for the critical involvement of the OVLT region in mediating the febrile responses to blood-borne endogenous pyrogen through the local release of PGE2.


A patch-clamp study on the muscarine-sensitive potassium channel in bullfrog sympathetic ganglion cells. 1. A voltage-independent K+ channel was characterized and effects of muscarine were studied in cultured bullfrog sympathetic ganglion cells using the cell-attached patch-clamp configuration. 2. Three types of single-channel current were recorded from 2- to 10-day-old cultured cells in the presence of tetraethylammonium (2-20 mM), tetrodotoxin (1-2 microM), Cd2+ (0.1 mM) and apamin (20 nM). 3. The most frequently observed channel was a voltage-independent K+ channel which was open at the resting membrane potential and had a conductance of 52.6, 78.9 and 114.9 pS at a [K+]o of 2, 40 and 100 mM, respectively. This channel was designated background K+ channel. 4. Two other channel types were observed less frequently. One had a conductance of 26 pS (external K+, 118 mM) and a long open time of several seconds at the resting membrane potential. The second channel had a smaller conductance (20 pS) and displayed a voltage-dependent activation. 5. The open probability of the background K+ channel varied between patches, ranging from 0.0005 to 0.486. The open time distribution was fitted by a single exponential with a time constant of 0.51 ms. Both of these parameters were independent of the membrane potential. The closed time distribution consisted of at least four exponentials having time constants of 0.17, 3.7, 120 ms and several seconds. 6. Muscarine (10-20 microM) applied to the membrane outside the patch pipette reversibly enhanced the activity of the background K+ channel. This effect was associated with an increase in the open probability, which resulted from an increase in the mean open time concomitant with a decrease in the mean closed time. Muscarine did not change the single-channel conductance of this channel. 7. The effects of muscarine were blocked by atropine (1 microM). 8. It is concluded that there exists a muscarine-sensitive, voltage-independent K+ channel in cultured bullfrog ganglion cells. This K+ channel appears to contribute to the generation of the resting membrane potential and underlie the slow inhibitory postsynaptic potential of these neurones in situ.


Anoxia induces time-independent K+ current through KATP channels in isolated heart cells of the guinea-pig. 1. Isolated ventricular heart cells of the guinea-pig were exposed to anoxia (PO2 < 0.1 Torr) which induced a time-independent K+ current. This current was studied with the patch clamp technique in the whole-cell and cell-attached configuration. 2. The latency until anoxia-induced changes of whole-cell current developed was distributed exponentially (mean 10.5 min; n = 41). The current was abolished within 2-4 s of reoxygenation. 3. The reversal potential of the anoxia-induced change of whole-cell current at 5.4 and 15 mM [K+]o was -82 and -61 mV, respectively. 4. Analysis of current noise in whole-cell current during the phase of the slow development of the anoxia-induced current yielded a slope conductance of unitary currents of 8.1 pS (5.4 mM [K+]o) which is far below the 30 pS of KATP channels in inside-out patches with no Na+ and Mg2+ in the bath. 5. Reduced unitary current induced by anoxia was recorded in single-channel measurements with 10.4 mM-K+ in the pipette. 6. Using 150 mM-K+ in the pipette, anoxia caused unitary inward currents with a slope conductance of 83 pS. The open probability of the channels (P(o)) reached maximum values between 0.6 and 0.95. The channels closed within 1-3 s of reoxygenation. 7. At voltages between -85 and -45 mV and maximum P(o), open time histograms were dominated by a fast exponential (tau 01 = 0.55 +/- 0.21 ms, mean +/- S.D.) and one or two slow exponentials. 8. Voltage ramp experiments showed that single-channel currents were slightly rectifying in the inward direction. 9. Glibenclamide (1 microM) reversibly blocked the anoxia-induced whole-cell and single-channel currents. 10. It is concluded that during anoxia it is only KATP channels which open by a sufficient decrease of submembrane ATP levels.


Sympathetic nervous system activity during skin cooling in humans: relationship to stimulus intensity and pain sensation. 1. Our aim was to determine the relationship between efferent sympathetic nervous system activity to skeletal muscle (MSNA) and both the dynamics of the stimulus and pain sensation during localized skin cooling in humans. MSNA in the lower leg (peroneal microneurography), heart rate, arterial blood pressure, hand skin and muscle temperatures and perceptions of pain were recorded in ten healthy subjects before, during and after immersion (3 min) of a hand in water of different temperatures ranging from non-noxious to extremely noxious (28, 21, 14, 7 and 0 degrees C). 2. Immersion produced an abrupt, water temperature-dependent fall in hand skin temperature (initial 30 s) followed by a more gradual decline. In contrast, the fall in hand muscle temperature was almost linear during immersion. Throughout immersions at the 28, 21, and 14 degrees C water temperatures and during the initial phase of the 7 degrees C level, sensations ranged from not painful to somewhat painful; however, the latter phase of the 7 degrees C immersion and the entire 0 degrees C level were perceived as intensely painful. 3. During the initial 15-30 s of immersion at the 21-7 degrees C water temperatures, MSNA decreased from control levels in all subjects (47-58% on average, P < 0.05), whereas mean arterial blood pressure did not change. MSNA then returned to and remained at control levels throughout the 28-14 degrees C immersions, although arterial pressure, primarily systolic, rose slightly. 4. After some delay, MSNA increased during immersion at both the 7 degrees C (P < 0.05 at 90 s) and 0 degrees C (P < 0.05 at 60 s) levels in a progressive, water temperature-dependent manner, achieving peak values of approximately 200 and 300% of control, respectively, by 2.0-2.5 min. These elevations in MSNA were associated with parallel increases in arterial pressure. 5. Heart rate rose during the onset of immersion at all water temperatures (P < 0.05), but fell rapidly to control levels after 60-90 s. The increases were small (approximately 5 beats/min) and similar at the 28-7 degrees C levels, but were twice as great at the coldest water temperature.(ABSTRACT TRUNCATED AT 400 WORDS)


Sympathetic activity is influenced by task difficulty and stress perception during mental challenge in humans. 1. Our aim was to determine the influence of the type of task, the absolute and relative difficulty of the task, and the perceived stress associated with performance of the task on sympathetic circulatory regulation during cognitive challenge in humans. 2. Sympathetic nerve activity to skeletal muscle (MSNA) determined from peroneal microneurography, heart rate and arterial blood pressure were recorded continuously in twelve subjects during a modified Stroop colour word test (CWT) and mental arithmetic (MA), each performed over six levels of increasing absolute task difficulty. Performance (percentage correct) on each task was assessed and ratings of perceived stress obtained. Responses to CWT and MA were compared at similar levels of performance and perceived stress. 3. MSNA decreased at task onset, remained below baseline levels at low levels of difficulty which were not perceived as stressful, increased above baseline levels at higher levels of difficulty which were perceived as stressful, and increased further during recovery. Thus, the regulation of MSNA was stress dependent. At similar levels of stress perception there were no differences in MSNA between CWT and MA. Although performance declined as task difficulty increased, there was no particular 'threshold' level of performance associated with the stimulation of MSNA. 4. Arterial pressure and heart rate were elevated above baseline levels throughout the mental tasks. Arterial pressure increased over the first 3-4 levels of each task and then plateaued whereas heart rate did not vary across increasing levels of task difficulty. Heart rate and arterial pressure responses to CWT were higher than those to MA. 5. These data demonstrate that during cognitive challenge the stimulation of MSNA is governed primarily by perceived stress which is dependent, in part, on the absolute level of task difficulty. In contrast, neither performance nor the type of cognitive task appear to be important determinants of MSNA. Arterial pressure is influenced by the task and level of difficulty. Heart rate is independent of task difficulty but may be task dependent.


Calcium sensitizing action of carnosine and other endogenous imidazoles in chemically skinned striated muscle. 1. The imidazole-containing compounds carnosine and homocarnosine, endogenous to skeletal and cardiac muscle, have been tested for effect on the contractile behaviour of chemically skinned (saponin or Triton X-100) skeletal and cardiac muscle. 2. Carnosine, at millimolar concentrations which are near physiological for many skeletal fibres, and in a concentration-dependent fashion, shifts the curve relating [Ca2+] to steady-state tension to lower [Ca2+] in both skeletal (frog but not crab) and cardiac (rat) muscle preparations. 3. Of other imidazoles endogenous to heart, homocarnosine is somewhat more effective, while N-acetyl L-histidine is much less so. 4. The maximum level of Ca(2+)-activated force is increased significantly by homocarnosine in cardiac trabeculae. 5. We propose that the cellular imidazoles related to carnosine are natural 'Ca2+ sensitizers' in striated muscle. Alterations in their levels as a result of disease or training, and between different fibre types, may contribute to differences in contractile performance of the intact tissues.


Metabolic changes during ischaemia and their role in contractile failure in isolated ferret hearts. 1. The effects of global ischaemia on phosphorus metabolites, intracellular pH (pHi) and developed pressure were measured in isolated whole ferret hearts using 31P nuclear magnetic resonance (NMR) spectroscopy. 2. Brief (10 min) periods of global ischaemia reduced left ventricular developed pressure (LVDP) to undetectable levels. This fall in LVDP was accompanied by a fall in the intracellular concentration of phosphocreatine (PCr) and increases in the concentrations of inorganic phosphate (Pi) and phosphomonoesters. There was no change in the intracellular ATP concentration ([ATP]i). pHi fell approximately linearly at a rate of 0.04 pH units min-1. 3. When ferret hearts were exposed to cyanide (CN-) in the presence of alpha-cyano-4-hydroxycinnamate (CHC), a blocker of lactate efflux, the changes in pHi and [Pi]i which occurred were similar to those observed during global ischaemia. However, developed pressure only fell to around 15% of the control value. 4. Removing the intracellular acidosis (by reducing the CO2 level of the gas with which the perfusate was equilibrated) during exposure to CN- and CHC caused an increase in developed pressure, consistent with the fall in pHi being responsible for a substantial fraction of the fall in developed pressure. 5. Taken together, these results suggest that most, but not all, of the fall in developed pressure during ischaemia can be explained by the effects of the changes in pHi and [Pi]i on the contractile apparatus. 6. Action potential recordings made with a suction electrode during short periods of global ischaemia showed that there was no decrease in action potential duration over the period when developed pressure was falling, eliminating action potential shortening as a possible cause of the fall in developed pressure. 7. In hearts in which the rate of glycolysis had been reduced by glycogen depletion, global ischaemia led to a marked shortening of the action potential. NMR experiments showed that under these conditions [ATP]i decreased by around 50% over the first 10 jin of ischaemia, while the intracellular acidosis which occurred was smaller than that in a control ischaemic period. 8. The time course of the decline of [ATP]i was examined in several hearts during long (45 min and over) ischaemic periods without prior glycogen depletion. After 45 min of ischaemia [ATP]i fell to around two-thirds of the control value, while pHi declined to approximately 6.1. Resting pressure did not increase. On reperfusion pHi recovered rapidly to control levels. [ATP]i, however, did not recover. 9. If ischaemia was prolonged further, [ATP]i eventually became undetectable after 70-90 min.(ABSTRACT TRUNCATED AT 400 WORDS)


Identification of a new transport system (y+L) in human erythrocytes that recognizes lysine and leucine with high affinity. 1. The effect of neutral amino acids on the transport of L-lysine across the human erythrocyte membrane was studied. 2. All neutral amino acids tested (range 0.3-5 mM) inhibit the influx of L-[14C]lysine (1 microM). The inhibition pattern is biphasic, and tends to reach a maximum at approximately 50% of the original flux. The concentrations that give 25% inhibition are (mM): L-cysteine (2.7), L-alanine (1.3), L-serine (0.9), L-isoleucine (0.6), L-phenylalanine (0.35), L-methionine (< 0.3), L-leucine (< 0.3). L-lysine and L-arginine completely inhibit the rate at the highest concentration. 3. These results can be explained by assuming that L-lysine transport occurs through two independent transporters that differ in their affinity for neutral amino acids. A detailed kinetic analysis of the effect of L-leucine on L-lysine entry is consistent with this hypothesis. 4. Using a new experimental strategy, the substrate and inhibitor transport parameters for the two systems were determined. The half-saturation constants for lysine (+/- S.E.M.) are found to be: KmA, 0.014 +/- 0.002 mM and KmB, 0.112 +/- 0.017 mM. The maximum rates differ by a factor of 8.2 (VmaxB/VmaxA). The leucine inhibition constants are: KiA, 0.022 +/- 0.003 mM and KiB, 30.36 +/- 7.9 mM. If the sodium in the incubation medium is replaced by potassium, the apparent affinity for leucine (1/KiA) is reduced approximately 30-fold. 5. The maximum inhibition caused by leucine decreases as the lysine concentration is raised, showing that leucine acts upon the higher affinity system. 6. When added to the trans side, L-leucine, L-phenylalanine and L-isoleucine do not cause inhibition, but stimulate the flux by approximately 30%. This indicates that these analogues are also transported. 7. In conclusion, in the concentration range 1-100 microM, lysine crosses the red cell membrane through two distinct transport systems, one of which recognizes both neutral and cationic amino acids with high affinity.


Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart. 1. We have measured the time-dependent pacemaker current, I(f), in single cells, or small clusters of two or three cells dissociated from embryonic chick hearts with the whole-cell patch clamp technique, and in multicellular reaggregates of dissociated cells with the two-microelectrode voltage clamp technique. 2. We observed time-dependent current (I(f)) in the -90 to -60 mV range from aggregates of ventricular cells, as in our earlier results from this preparation, which we previously attributed to the potassium ion current mechanism, IK2. We also observed I(f) in single atrial cells and aggregates of atrial cells. 3. The range of activation of I(f) was -120 to -90 mV in atrial preparations (either single cells or aggregates). The activation range of I(f) in ventricular cells was also -120 to -90 mV which is approximately 30 mV negative to the I(f) activation range in ventricular cell aggregates. The reasons for this shift of I(f) in ventricular preparations are unknown. 4. The I(f) component clearly underlies the spontaneous pacemaker depolarization which is observed in ventricular heart cell aggregates during the first week of embryonic development. However, I(f) is not a significant factor underlying spontaneous activity in atrial preparations. The pacemaker current in these cells is a net inward background component, which is significantly reduced in amplitude with development, as is the I(f) component in the ventricle.


Tectal and tegmental excitation in dorsal neck motoneurones of the cat. 1. Intracellular recordings were made from 116 splenius (SPL) and 103 biventer cervicis and complexus (BCC) alpha-motoneurones in nineteen cats anaesthetized with alpha-chloralose. 2. Electrical stimulation in the contralateral tectum evoked disynaptic excitatory postsynaptic potentials (EPSPs) in the motoneurones when a train of stimuli was applied in the ventral layers throughout the superior colliculus. In the rostral half of the superior colliculus, these EPSPs were due to stimulation of ascending collaterals of tectofugal neurones. EPSPs of a presumed trisynaptic linkage could only be evoked from the dorsal and intermediate tectal layers in the caudal half of the superior colliculus. It is concluded that the tectofugal neurones which evoked the disynaptic EPSPs are mainly located in the caudal half of the superior colliculus. 3. Disynaptic EPSPs were evoked in the motoneurones by a train of stimuli in the contralateral fields of Forel and Zona incerta, which were due to stimulation of ascending collaterals from the tectofugal neurones. 4. Spatial facilitation experiments revealed that tectal disynaptic EPSPs in the neck motoneurones were mediated via reticulospinal neurones with convergent input from cortico-reticular neurones. 5. A train of stimuli in the ipsilateral tectum evoked EPSPs with latencies compatible with a trisynaptic linkage, while disynaptic EPSPs at low threshold could be elicited from the underlying tegmentum. Similar disynaptic EPSPs could be evoked from the ipsilateral fields of Forel. It is suggested that some of the disynaptic tegmental EPSPs in SPL and BCC motoneurones can be mediated via a tegmento-reticulospinal pathway which originates in the cuneiform nucleus.


Ankle stiffness of standing humans in response to imperceptible perturbation: reflex and task-dependent components. 1. It has been demonstrated that subjects can alter the reflex stiffness of the elbow and wrist in response to imperceptibly slow perturbations applied through a complaint coupling. We used this technique to measure ankle stiffness in standing subjects as a means of examining reflex activity. 2. During unperturbed stance, a linear relationship between ankle torque and ankle angle is expressed as a load stiffness. The load stiffness predicted from a subject's measured physical dimensions corresponds closely with the value measured by standing the subject on a force platform. 3. Slow perturbations were applied at waist level, through a spring, to standing subjects. The perturbations caused sway similar in magnitude and rate to the sway of normal stance. Ankle stiffness was measured during the period when the perturbations were unperceived. The contribution to ankle stiffness of reflexes that use visual information was assessed by eye closure. The ability of reflexes based on sensory information from the legs to maintain upright posture was assessed when subjects balanced a load equivalent to their own body, in a situation where neither visual nor vestibular information could assist. Ankle stiffness was measured while the load was perturbed. 4. The results show that a simple mechanical model of stance predicts the torque-angle relationship at the ankle. This relationship determines the minimal ankle stiffness required to stand, and reflex muscle stiffness is a necessary component of this ankle stiffness. Visual, vestibular and lower limb sensorimotor reflexes each contribute to ankle stiffness; however, the local sensory reflexes alone are sufficient to stand. For responses to unperceived perturbations, standing subjects can alter their reflex ankle stiffness according to intentional set.


A potential-dependent fast outward current in single smooth muscle cells isolated from the newborn rat ileum. 1. Whole-cell outward currents have been studied in single smooth muscle cells isolated from newborn and adult rat ileum, using fire-polished glass micropipettes. 2. Two major outward currents, delayed (I(do)) and fast inactivating potential-dependent (I(fo)), have been observed in the newborn rat ileal cells. I(fo) is activated between -50 and -40 mV from the holding potential of -80 mV, whereas I(do) usually starts to activate at membrane potentials positive to -20 mV. Activation of I(do) was fast, its time-to-peak decreased from 10.8 +/- 0.9 ms (n = 5) at -30 mV to 4.5 +/- 0.7 ms (n = 4) at 20 mV. 3. I(fo) decay was monoexponential and its time constant did not depend on the membrane potential. Dependence of I(fo) inactivation on membrane voltage in normal physiological salt solutions (PSS) could be described by the Boltzmann equation with the following parameters: a half-inactivation potential, V0.5 = -70.8 mV and slope factor, k = 7.7 mV. 4. Recovery of I(fo) from inactivation was fitted by a single exponential and was potential dependent. The average time constant was 28.4 +/- 2.4 ms (n = 11) at -120 mV, 47.7 +/- 3.0 ms (n = 6) at -100 mV and 89.6 +/- 5.3 ms (n = 13) at -80 mV. 5. Removal of Ca2+ ions from the PSS (in the presence of 5 mM-Mg2+) increased I(fo) amplitude by about two times, and shifted its voltage dependence of inactivation towards negative membrane potentials by about 16 mV (V0.5 = -87.2 mV). Removal of Mg2+ from the PSS (in the presence of 2.5 mM-Ca2+) exerted no effects upon either inactivation dependence (V0.5 = -74.2 mV) or I(fo) amplitude. 6. I(do) and I(fo) had different sensitivities to K+ channel blockers. With 10 mM-external TEA+ I(do), was preferentially suppressed, while 5 mM-4-aminopyridine (4-AP) completely blocked I(fo). I(fo) was also partially blocked by a higher TEA+ concentration (30 mM), which suppressed I(fo) to 0.55 +/- 0.02 (n = 9). The blocking effect of 4-AP on I(fo) was potential, use and time dependent. 7. Ileal cells isolated from the adult rat demonstrated the presence of two populations of smooth muscle cells. One has an outward current which seems to be similar to that described in the newborn rat. However, in other cells spontaneous transient outward currents, well described in other single smooth muscle cells, but not found in newborn rat ileal cells, have been observed.


Mechanism of cardiac Na(+)-Ca2+ exchange current stimulation by MgATP: possible involvement of aminophospholipid translocase. 1. The sensitivity of outward Na(+)-Ca2+ exchange current to charged amphiphiles and phospholipids was tested in giant excised inside-out membrane patches from guinea-pig and rabbit myocytes. 2. Screening of membrane surface potentials with dimethonium (10 mM), spermine (200 microM) and spermidine (100 microM) was without effect, while the positively charged ionic detergents hexadecyltrimethylammonium and dodecyltrimethylammonium strongly inhibited steady-state outward exchange current (0.1-10 microM). 3. Interventions expected to increase negative surface charge included treatment of the cytoplasmic surface with phospholipase D, application of dodecylsulphate (1-10 microM), application of the short-chain phosphatidylserine derivative, dicapryl phosphatidylserine (C10PS), and inclusion of 1-3% phosphatidylserine in the hydrocarbon mixture used to coat electrodes. Each intervention strongly stimulated Na(+)-Ca2+ exchange current in a similar way to MgATP, reducing the fractional decay of outward exchange current (inactivation) during application of high cytoplasmic sodium. 4. The MgATP-stimulated exchange current was inhibited with a Ki of approximately 1 microM by pentalysine, which is known to associate with phosphatidylserine head groups. After 'deregulation' of the exchanger by chymotrypsin, pentalysine was without effect. 5. Inclusion in the pipette of 0.2 mM-pyridyldithioethylamine (an oxidizing inhibitor of aminophospholipid translocase) abolished stimulation of outward exchange current by MgATP without inhibiting basal outward exchange current or sodium pump current. 6. Application to the cytoplasmic side of 1.5 mM-diamide, which reportedly decreases membrane phospholipid asymmetry, apparently reversed the effect of MgATP. After treatment with diamide and subsequently with dithiothreitol, Na(+)-Ca2+ exchange current was again stimulated by MgATP. Diamide was without effect when secondary exchange regulation had been previously removed by chymotrypsin. 7. Potassium current carried by the surface potential-sensitive ionophore, nonactin, was stimulated by MgATP when extracellular surface charge had been neutralized. The effect was largest (40-90%) when low ionic strength cytoplasmic solutions were employed, consistent with an increase of negative membrane charge on the cytoplasmic side during MgATP application. 8. Potassium current carried by nonactin was inhibited by MgATP when cytoplasmic surface charge had been neutralized and extracellular solutions of low ionic strength were employed, consistent with a decrease of negative membrane charge on the extracellular side. 9. These results indicate that the stimulatory effect of MgATP on Na(+)-Ca2+ exchange current could involve changes of charged membrane lipids, that the effect probably involves a transmembrane, oxidation-sensitive protein, that pentalysine-sensitive sites are involved, that phosphatidylserine mimics the effect of MgATP, and that the effect extends to a simple surface potential-sensitive ionophore.(ABSTRACT TRUNCATED AT 400 WORDS)


Calcium release from separate receptor-specific intracellular stores induced by histamine and ATP in a hamster cell line. 1. The specificity of intracellular Ca2+ stores to Ca(2+)-mobilizing agonists was studied in DDT1 MF-2 vas deferens cells of the Syrian hamster. 2. Application of histamine (100 microM) or ATP (100 microM) to the DDT1 MF-2 cells caused an initial increase of intracellular Ca2+ followed by a lower phase as measured by using Indo-1 as fluorescent probe at 22 degrees C. The basal Ca2+ level (146 nM) was enhanced to 309 nM by histamine and to 379 nM by ATP. 3. A transient rise in intracellular Ca2+ lasting for about 2 min was measured in the presence of histamine or ATP in the absence of extracellular Ca2+. The basal Ca2+ level (78 nM) was increased to 128 nM by histamine and to 145 nM by ATP. 4. A transient hyperpolarization was elicited in single cells as measured with microelectrodes by both agonists under Ca(2+)-free conditions with a similar time course as the change in internal Ca2+. The hyperpolarization observed in the presence of histamine amounted to 23 mV and 31 mV with ATP. The histamine-induced responses were abolished by the H1 histaminoceptor antagonist mepyramine (10 microM) and the responses evoked by ATP were blocked by the P2 purinoceptor antagonist suramin (300 microM). 5. A second internal Ca2+ response could only be evoked under Ca(2+)-free conditions by applying a higher agonist concentration or after replenishing the intracellular stores with Ca2+ from the extracellular space. 6. A second addition of an optimal concentration (100 microM) of the agonist to the cells under Ca(2+)-free conditions did not evoke mobilization of internal Ca2+ or hyperpolarization, but resulted in a rise of the cellular inositol (1,4,5)-trisphosphate content (Ins(1,4,5)P3) as determined by a radioligand binding assay. 7. The cells responded to both agonists (100 microM) with a transient Ca2+ response if successively applied at a maximal effective concentration (100 microM) under Ca(2+)-free conditions. 8. Simultaneous stimulation of H1 histaminoceptors and P2 purinoceptors resulted in the absence of external Ca2+ in an additional increase in internal Ca2+ represented by the amplitude and area of the response and in an increased response area of the hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)


An internal viscous element limits unloaded velocity of sarcomere shortening in rat myocardium. 1. Peak twitch force (F0) and sarcomere length (SL) were measured in trabeculae that had been dissected from the right ventricle of rat heart and that were superfused with a modified Krebs-Henseleit solution at 25 degrees C. Sarcomere length was measured by laser diffraction techniques. Force was measured with a silicone strain gauge. Unloaded velocity of sarcomere shortening (V0) was measured by the 'isovelocity release' technique. 2. At [Ca2+]o = 1.5 mM and SL below 1.9 microns, V0 increased in proportion to SL, while V0 was independent of SL above 1.9 microns. At [Ca2+]o = 0.5 mM, V0 was proportional to SL up to 2.2 microns. At [Ca2+]o = 0.2 mM, V0 was proportional to SL up to 2.3 microns which is the longest SL that we were able to study in our trabeculae. 3. A unique relationship was observed between V0 and F0, irrespective of whether F0 was altered by variation of [Ca2+]o or sarcomere length above slack length. 4. Passive viscosity (Fv) was measured during the pause between contractions in the presence of 1.5 mM [Ca2+bdo and in the range SL = 2.0-2.1 microns by applying 0.1 micron stretches at various velocities up to v = 30 microns s-1. The force response to stretch, corrected for the contribution of parallel elastic force, showed viscoelastic characteristics with an exponential increase to a maximum (Fv) during stretch and an exponential decline after the end of the stretch. Fv increased, by 0.3%F0 microns-1 s-1, in proportion to v < 5 microns s-1; the increase of Fv was smaller at higher v, suggesting non-Newtonian viscous properties. 5. The time constant of the increase of force during the stretch decreased (tau rise congruent to 7 ms to tau rise congruent to 4 ms) with increases in v (congruent to 4 microns s-1 to v congruent to 10 microns s-1; P = 0.02). The time constant of decay of force at the end of the stretch also decreased with increases in v (tau decay congruent to 8 ms at v congruent to 4 microns s-1 to tau decay congruent to 3 ms at v congruent to 30 microns s-1; P < 0.001). Calculated stiffness of the elastic term of the viscoelastic element was independent of v, i.e. 45-50 N mm-3.(ABSTRACT TRUNCATED AT 400 WORDS)


[Primary brain lymphoma in AIDS. 17 cases studied by MRI before stereotaxic biopsies]. Determining which semiological criteria might help to suggest lymphoma when an intracerebral mass in observed in a patient with AIDS. The use of these criteria might shorten the duration of the anti-toxoplasmic test treatment and to perform puncture earlier. The fast growth of the lymphomas may account for the rapid death of these patients if untreated, but as a corollary, its increase in size can be objectively measured over a short period, about ten days. MEANS: Retrospective study of 17 lymphomas diagnosed with stereotaxic puncture. The most discriminating criteria are ventricular encasement or an original site in the white matter, as well as the moderate character of the edema and of the mass effect relative to the volume of the tumor. Other arguments also help: simple lesion, large size, sinuous contour, no signs of hemorrhage. The diagnosis of lymphoma can often be proposed at once. A control must then be performed very soon, with stereotaxic puncture if the volume of the lesion has increased in the meantime.


[Thrombosis of the superior vena cava in Behçet's disease. Apropos of 13 cases]. The author reports 13 cases of Behçet's disease with thrombosis of superior vena cava. The thrombosis of superior vena cava achieve to superior cava syndrome. In all cases, the X ray of the chest showed a discreet widening of the superior mediastinum related to collateral circulation confirmed by angiography. The thrombosis interest the brachial veins in 9 cases. The analysis of the results point out to the importance of the chest X ray in orientating the diagnosis. The etiological diagnosis is always clinical.


[Cutaneous-mucosal hyalinosis with cerebral sites. 3 new cases]. The authors report about 3 new cases of cutaneous-mucosal hyalinosis, or Urbach-Wiethe disease, with cerebral sites. The intracranial calcifications were detected without any neurological presenting features, and were discovered incidentally on radiographs of the skull. The CT examination allows specifying the site of these calcifications, in the gyri of the hippocampus.


[Gastric diverticulum mimicking adrenal mass. X-ray computed tomographic aspect]. Gastric diverticulum may simulate a left adrenal metastase as reported in our case. Prior opacification of the gastrointestinal tract and sometimes imaging in prone position are necessary to avoid an useless puncture for staging lung cancer.


[Major dysplasia of the trochlea. Contribution to the measurement of A.T. T.G. Proposal of a x-ray computed tomographic protocol]. The A.T. T.G.'s scanographic measure sets problems in the major dysplasic trochlear groove because point G.T. is quite impossible to determine. We purpose to define it by an original procedure based on bidimensional reconstruction of A.T. T.G. system. Point G.T. is defined by extrapolation: it is situated at the junction of proximal trochlear scan section with the line representing distal trochlear groove.


[X-ray computed tomography of duodenal lipoma]. Duodenal lipoma is a rare, often asymptomatic tumor; the circumstances of its discovery have become more frequent as CT examinations are more commonly performed. The merits of a CT examination for this condition is to allow both a positive diagnosis and the follow-up of these fatty tumors which have very few clinical expressions, thus avoiding complementary examinations or even useless laparotomies. The authors describe three cases of incidental discovery of duodenal lipomas.


[Bone involvement with osteolytic predominance in systemic mastocytosis. A clinical case]. Systemic mast cell disease is a rare condition, in which the frequent involvement of bones is likely to raise diagnostic problems. There are other concomitant visceral involvement as a rule. The skin lesions, if present and recognized, are suggestive. The positive diagnosis of bone lesions can be ensured by biopsy. On the basis of one clinical case, we specify the clinical and radiological appearance of systemic mast cell disease.


[Measurement of femoral bone density using dual photon absorptiometry. Values in osteoporosis]. X-ray absorptiometry allows measuring the density of bone in the upper end of the femur in 3 mains areas: the neck, Ward's triangle and the greater trochanter. Failin prospective data, it is not possible at present to know whether one of these areas has better performances than the others for the assessment of fracture risks. The interpretation of the measurement is based on the idea that bone demineralization is the main risk factor of osteoporotic fracture. It is carried out on the basis of reference normal values, which must be determined in the French population. More sophisticated predictive models of fracture risks are being developed. In young adults, the reproducibility of the measurements is lower than 2% for the neck and the trochanter, and around 2.5 to 3% for Ward's triangle. The density of femoral bone is not well correlated to that of the other bony sites (os calcis, ulna, vertebrae: r = 0.3 to 0.7). On the other hand, the correlation between the right and left femur is good, as well as that of the three femoral measurement areas between them. A fracture of the upper end of the femur is often associated with a decrease in femoral bone density (-12 to -15%, according to the site of measurement), while the measurement in the ulna or the spine is normal or just slightly lowered. Femoral bone rarefaction is also noted in vertebral osteoporosis. Dual photon absorptiometry allows, in most cases, an accurate and reproducible measurement of the femoral bone density. This measurement is indicated to assess the risk of osteoporosis on menopause and in elderly subjects and/or those with lumbar osteoarthritis.


[Pelvic endometriosis of urinary and digestive sites. Apropos of 7 cases]. Seven cases of pelvic endometriosis of the urinary or digestive tracts are reported: 4 cases of vesical endometriosis, 1 case of ureteral involvement, 1 rectal case and 1 sigmoid location. The authors point out the difficulty of the clinical preoperative diagnosis--in despite of cyclic troubles--and underline the interest of complementary explorations performed at the time of periods: ultrasound, cystoscopy, rectosigmoidoscopy and coelioscopy. The MR imaging, showing high intensity a T1-weighted images and prominent high intensity on T2-weighted images, is very suggestive of an endometrial lesions. A joint medical and surgical treatment is required. Endoscopic excision, endoprosthetic tube, excision-suture, resection-anastomosis and a complementary medical treatment using Danazol. Decapeptyl or progestational agents have to be proposed. Per-operative microscopy is advised as routine procedure in order to avoid excessive surgery.


The unique pharmacologic profile of nabumetone. Nabumetone is a novel nonsteroidal antiinflammatory drug (NSAID) with a unique pharmacologic profile. It is nonacidic and demonstrates minimal prostaglandin synthesis inhibition. Because it is nonacidic, nabumetone cannot dissociate in the stomach after oral administration. In contrast, acidic NSAID (active cyclooxygenase inhibitors) can dissociate and concentrate by "ion trapping" in the gastric mucosa, inhibit prostaglandin synthesis and, therefore, cause topically induced erosive mucosal damage. After absorption, nabumetone is converted by first pass metabolism to the active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA), an effective inhibitor of prostaglandin synthesis. 6MNA is hepatically, not renally, cleared and differs from other NSAID because it does not undergo enterohepatic circulation in animals or man. This is thought to contribute to its apparent lack of severe gastrointestinal irritancy. The pharmacologic profile of nabumetone can be summarized in terms of the very large "therapeutic ratio" in comparison with other NSAID.


[Post-traumatic osteolysis of the distal extremity of the clavicle]. Post-traumatic osteolysis of the acromial extremity of the clavicle is a rare condition, usually occurring sometime after an injury to the shoulder. Three cases of PTOAC and one case of athlete's osteolysis are reported. The semiology is summed up, as well as the differential diagnoses and the associated forms. This is a benign disease, which should be suggested by the clinical findings and diagnosed on the radiographs, which demonstrate early signs of osteolysis. The treatment is mainly based on immobilization.


New approaches to the management of rheumatoid arthritis. The approach to the treatment of rheumatoid arthritis is currently undergoing fundamental change. The demonstration of erosions by magnetic resonance imaging early in the disease, when conventional radiographs only show soft tissue swelling, demands rapid intervention with more effective drugs. The increasing use of methotrexate earlier in the course of the disease is justified, in view of the favorable benefit/risk ratio. New experimental therapies, such as photopheresis, the fusion protein, DAB486 interleukin 2, FK 506, and monoclonal CD4+, may also be utilized earlier if their safety profiles permit. Conventional therapeutic regimens are being administered differently in an attempt to improve efficacy and safety.


[Primary breast sites of malignant non-Hodgkin's lymphoma. Apropos of 10 cases]. The authors describe 10 cases of malignant non Hodgkin's lymphoma in a mammary site in women aged 38 to 82 years. The clinical examination and the sometimes suggest an adenocarcinomatous lesion, thus leading to a useless surgical exeresis. An initial histological study provides the diagnosis. A complete assessment of extension allows an accurate staging and the refinement of the therapeutic schedule. Exclusive radiation therapy seems to be justified in low-malignancy forms remaining strictly confined to the breast. For the high- and medium-malignancy forms, the essential weapon is chemotherapy, which seems to improve the duration and rate of remission.


[Cholangiography: a routine procedure in elective cholecystectomy?]. A prospective study to evaluate the selective or routine use of intraoperative cholangiography on elective cholecystectomy was performed. 178 patients were studied, listing criteria to explore the biliary tract with the cholangiography aspects. The criteria showing choledocholithiasis were the alkaline phosphatase and/or bilirubin increase, dilated common bile duct, large cystic duct, small stones and pancreatitis or jaundice on the past history. The patients were divided in 4 groups: 1) no criteria: 61 (34.3%); 2) one criterion: 53 (30%); 3) two criteria: 22 (12.3%); 4) more than two criteria: 42 (23.4%). The false-positive was 1.6% to the first group, 3.8% to the group 2 and 0% to the other groups. We concluded that the intraoperative cholangiography must be achieved on patients that have at least one choledocholithiasis criterion.


An overview of the clinical pharmacokinetics of nabumetone. Nabumetone is a new, nonacidic, nonsteroidal antiinflammatory drug. At least 80% of nabumetone is absorbed, and food, milk, and aluminum antacids increase the rate, but not the extent, of absorption. It is rapidly metabolized in the liver to 6-methoxy-2-naphthylacetic acid (6MNA), the major circulating active metabolite. At steady state, the time to maximum plasma concentration for 6MNA is 1 to 4 h. 6MNA has a very low clearance rate and long half-life (about 24 h). In general, steady state plasma concentrations of 6MNA increase in proportion with increases in the dose of nabumetone administered. Steady state plasma concentrations of 6MNA in the elderly are slightly higher than in healthy volunteers; however, this does not appear to be clinically significant. Preliminary studies in patients with impaired renal function indicate that the pharmacokinetics are not altered in patients with mild to moderate disease.


[Ectopic opening of the ureter in the urethra in adult women. Radiological diagnosis apropos of 17 sites]. To study diagnostic problems encountered by physicians and radiologists in adult females with ureteral ectopia into the urethra. CASE MATERIAL AND METHODS: Retrospective study of 17 localizations in 16 women, 15 to 65 years of age at the time of the definitive diagnosis of duplication of the ipsilateral urinary tract, the ectopia being connected to the upper pelvicalyceal system. Radiological confirmation of the diagnosis had been obtained in 14 cases. The ectopic ureter was thin in 11 cases. In 5 of 6 cases with megaureter, the distension involved only the distal intrapelvic part of the ureter. The ectopic meatus was juxta-cervical in 5 cases, much lower in the other cases. Of the 11 cases investigated by intravenous urography, 8 exhibited severe monocalyceal hydronephrosis of the upper pelvis whereas 6 upper pelvicalyceal systems were dysplastic. The lower pelvicalyceal system was congenitally normal in all cases. Most of the false negative diagnoses of intra-urethral ectopic ureter in adult female result from technically inadequate permicturating urethrocystography. The diagnosis should be evoked, especially in women with recurrent cystitis, on the urographic association of: duplication of the upper urinary tract, dysplastic or chronically distended atrophied upper pelvicalyceal system, pseudo-normal architecture of the lower pelvicalyceal system because of the unusually developed "upper" calyx.


Therapeutic implications associated with renal studies of nabumetone. Nonsteroidal antiinflammatory drugs (NSAID) decrease renal prostaglandins and may cause a decrease in renal blood flow, glomerular filtration, and sodium excretion. In some cases, these effects result in renal failure, edema, or hypertension. Patients with decreased effective circulating fluid volume are at greatest risk for development of these renal side effects. In addition, NSAID can cause interstitial nephritis. However, in double blind and open label controlled clinical trials, nabumetone had an effect on renal function in less than 1% of patients, regardless of sex or advanced age. Furthermore, in patients with normal or impaired renal function, single or multiple doses of nabumetone did not cause significant changes in creatinine clearance or serum creatinine values. However, with any NSAID including nabumetone, renal function should be measured before beginning therapy and periodically thereafter in patients at risk for the development of renal impairment.


[Giant lithiasic diverticulum of the urethra. Apropos of a case]. In the following observation, the authors report one case of lithiasegenic diverticulum. Etiologies (congenital or acquired), complications and principal radiological diagnosis methods are reviewed.