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Biochemical markers of liver fibrosis and lymphocytic piecemeal necrosis in UDCA-treated patients with primary biliary cirrhosis.

BACKGROUND/AIM: We have previously shown that the histological stage and severity of lymphocytic piecemeal necrosis (LPN) are independent predictive factors of cirrhosis development in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cirrhosis (PBC). Our aim during this study was to determine whether biochemical parameters classically used in PBC management and measured under UDCA could be considered as reliable surrogate markers for these histological prognostic indices in clinical practice. METHOD: The study included 153 patients with PBC who had undergone a control liver biopsy after 2 years of UDCA therapy. The relationships between histological and biological features were assessed by variance analysis and logistic regression. The diagnostic value of independent markers was assessed in terms of their sensitivity, specificity, positive predictive value (PPV) and negative value (NPV) and receiver-operating characteristic curves. RESULTS: Two variables were independently associated with extensive fibrosis (i.e. advanced histological stages): serum levels of bilirubin and hyaluronic acid (HA). A fibrosis index ([bilirubin (micromol/l)/14]+[HA (microg/l)/143]) higher than 1.5 exhibited good PPV and specificity (>74%) but rather poor NPV and sensitivity (<64%) regarding a diagnosis of extensive fibrosis. The only independent marker of LPN was aspartate aminotransferase (AST) activity. AST activity of more than twice the upper limit of normal showed acceptable PPV (>70%) but very low sensitivity (<25%) for a diagnosis of LPN. CONCLUSIONS: Serum bilirubin and HA levels measured under UDCA therapy are of acceptable diagnostic value for extensive fibrosis, but none of the biochemical tests commonly employed in the management of PBC can be considered as surrogate markers of LPN. Taken together with our previous results, these findings suggest that liver biopsy may be necessary to screen UDCA-treated patients who might require additional therapies.

Aspartate Aminotransferases↗

Determinants of subsidiary ventricular pacemaker suppression in man.

To investigate the relative contribution of the duration and rate of overdrive to subsidiary ventricular pacemaker suppression, in six patients with complete heart block after His-bundle ablation, ventricular overdrive stimulation studies were performed. The studies, which were spread over a mean follow-up period of 745 days, were carried out invasively with a temporary lead (one patient) as well as noninvasively with the implanted pacemakers and chest wall inhibition (five patients). The overdrive pacing rate was increased in steps of 10 beats/min, and the pacing duration was 15, 30, 60, 90, and 120 seconds at each level. A recovery period of 2 minutes was allowed after each overdrive stimulation. Incremental ventricular overdrive stimulation at increasing pacing durations consistently caused progressive suppression of ventricular impulse formation. Nonparametric variance analysis demonstrated a significant (P less than 0.0001) influence of both the pacing rate and duration on ventricular recovery time. Nonlinear regression showed an exponential increase in recovery time with incremental pacing rate and a biphasic increase in recovery time with incremental pacing duration. Beyond a pacing duration of 60 seconds ventricular impulse suppression was primarily dependent upon the pacing rate. A nonlinear regression model was applied to predict the number of beats required for return of the escape rhythm toward prepacing control values. The predicted maximum mean number of beats was 15.4 +/- 5.9 and independent of the rate and duration of pacing, although, the initial temporary instability of the escape rhythm was directly related to the degree of overdrive.

Adult↗

Continuous quality improvement reduces length of stay for fast-track patients in an emergency department.

OBJECTIVE: To demonstrate how continuous quality improvement (CQI) can identify rational and effective means to reduce length of stay for minor illness/injury in an ED. METHODS: A CQI team documented the process of fast-track (FT) patient flow and prioritized the causes of delay. In Phase I, two solutions were implemented. In this Phase II of the study, three changes were implemented, including expansion of the FT area, realignment to provide a full-time FT nurse, and a detailed, stricter triage classification. The outcome was assessed by examining the interval from presentation to release from the ED (length of stay; LOS). Differences were ascertained by analysis variance for consecutive FT patients not requiring radiography, ECG, or blood testing. Intervals from three pre-Phase II intervention 48-hour periods and one post-Phase II intervention 48-hour period were analyzed. RESULTS: Before the Phase I changes, the mean +/- SD LOS was 92 +/- 46 min. After the Phase I changes, the LOS was 67 +/- 31 min. After the Phase II changes, this was reduced to 57 +/- 34 min (p < 0.05). CONCLUSION: The formal application of CQI techniques in the ED can change patient flow and reduce LOS for FT patients.

British Columbia↗

Clinical comparison of the XPERT non-contact tonometer and the conventional Goldmann applanation tonometer.

Intraocular pressure (IOP) in the right eye of 113 patients was measured with one XPERT NCT air-puff non-contact tonometer (XPERT) and compared with IOP measured with one Goldmann applanation tonometer (GAT). Precision of the methods was judged by variance analysis, indicating that GAT was slightly more precise than XPERT. The slope of the linear relationship between the methods did not differ significantly from 1.0. Mean difference between the methods was 0.92 mmHg, XPERT measuring lower than GAT, p = 0.00017. The intra-individual difference between methods ranged from -8.00 to 8.67 mmHg, and standard deviation (SD) of differences was 2.52 mmHg. The 95% limits of agreement between the two methods were -5.85 to 4.01 mmHg. The SD of differences is of approximately the same size as previous XPERT vs GAT as well as previous GAT vs GAT studies.

Adolescent↗

Social-demographic aspects in the attitudes towards mental illness in a Finnish population.

Attitudes towards mental illness were studied in a random population of 1,000 subjects from southern and northern Finland using a Likert-type attitude scale. Correlations between attitudes and social-demographic variables were studied with one-way variance analysis and with specific multivariable techniques (AID and MCA). The best correlations were established between educational standard and attitudes, and between age and attitudes; higher education and younger age correlated with positive attitudes. Even social group and attitudes seemed to be distinctly correlated: the higher the social status, the more positive the attitudes. No difference could be demonstrated between residents from southern and northern Finland; rural subjects, however, possessed distinctly more negative attitudes than urban residents. According to the authors the most striking result was the observation that females show somewhat (statistically very significantly) more negative attitudes than males. It could also be established that the attitudes of female subjects varied greatly in various groups of variables.

Adolescent↗

Hippocampal EEG in rats after chronic toluene inhalation.

Sixteen rats were chronically implanted with bipolar electrodes in the hippocampal regions containing cells generating electric theta-activity. The animals were divided into 4 groups of which 2 were exposed to 500 p.p.m. of toluene in inhalation chambers, for 8 or 16 hours per day for 5 days per week in 12 weeks respectively, and 2 served as controls. The hippocampal electric activity was recorded 48 hours after each weekly exposure, ensuring a minimal amount of toluene in the tissue during the recordings. EEG-recordings were read blindly by two experienced scientists, and the frequency of theta-waves in the exposed groups were compared to their respective control group at each recording by Student's t-test. Frequencies of theta-activity in the exposed groups were found to differ from their respective control group by variance analysis. Each point on the frequency versus time plot were further analysed by Student's t-test. Compared to the non-exposed group the eight hours daily exposed group showed an initial period of increased frequency of the regular theta-waves together with an increased incidence of theta-activity after 1-2 weeks of exposure. In the sixteen hours daily exposed rats two weeks of toluene inhalation produced a significant reduction in the theta-wave frequency. This change was also reached after eight weeks of exposure in the eight hours daily exposed group. At this moment the theta-activity was frequently disrupted by short amplitude irregular waves, a phenomen which increased gradually throughout the rest of the exposure period. The average blood concentration of toluene was 16.7 micrograms/ml and 17.7 micrograms/ml and not significantly different for the eight and sixteen hours exposed groups respectively.

Administration, Inhalation↗

High repeatability of the amplitude and duration of the nycthemeral rhythm of the plasma melatonin concentration in the Ile-de-France ewe.

In order to determine individual variability in the amplitude and duration of the nycthemeral rhythm of the plasma melatonin concentration, 12 ovariectomized estradiol-treated Ile-de-France ewes were submitted to a sequence of 34 long days (LD1, 16L:8D), 21 short days (SD, 8L:16D), and 21 LD (LD2). Intensive blood sampling (hourly from 1 hr before dusk to 1 hr after dawn) was performed for 4 consecutive nights in each of the photoperiodic situations (LD1, SD, LD2), i.e., a total of 12 nights per ewe. Plasma melatonin was assayed by radioimmunoassay. Instantaneous amplitude (difference between each hourly measurement of the plasma melatonin concentration during the nocturnal elevation and the mean diurnal melatonin concentration), mean individual amplitude (same definition but using the mean melatonin concentration during the nocturnal elevation) and duration of elevation of plasma melatonin concentrations were calculated for each ewe and each night and analyzed by variance analysis. Instantaneous amplitude varied significantly with photoperiod, with night intra-photoperiod, with ewes, and time intra-night. Mean individual amplitude varied significantly with photoperiod and with ewe but not with night intra-photoperiod. Dramatic differences between individuals appeared in the amplitude and duration of melatonin rhythms. The lowest mean individual amplitude (all nights of measurement) found was 95 pg/ml and the highest was 544 pg/ml. Overall repeatability coefficient of the mean amplitude of melatonin elevation was 0.71 (P < 0.001). Duration of melatonin elevation varied significantly with photoperiod, with nights intra-photoperiod and with ewes. During LD periods, mean duration of melatonin elevation was equivalent to duration of the night (from 7 to 8 hr), while during SD it varied with ewes from 9 to 16 hr. Repeatability coefficient of the duration of melatonin elevation in SD was 0.57 (P < 0.05). It is concluded that amplitude and duration (in SD) of the nycthemeral rhythm of the plasma melatonin concentration are highly repeatable individual characteristics in the ewe.

Animals↗

The Sexual Arousal and Desire Inventory (SADI): a multidimensional scale to assess subjective sexual arousal and desire.

INTRODUCTION: Sexual arousal and desire are integral parts of the human sexual response that reflect physiological, emotional, and cognitive processes. Although subjective and physiological aspects of arousal and desire tend to be experienced concurrently, their differences become apparent in certain experimental and clinical populations in which one or more of these aspects are impaired. There are few subjective scales that assess sexual arousal and desire specifically in both men and women. AIMS: (i) To develop a multidimensional, descriptor-based Sexual Arousal and Desire Inventory (SADI) to assess subjective sexual arousal and desire in men and women; (ii) to evaluate convergent and divergent validity of the SADI; and (iii) to assess whether scores on the SADI would be altered when erotic fantasy or exposure to an erotic film was used to increase subjective arousal. METHODS: Adult men (N = 195) and women (N = 195) rated 54 descriptors as they applied to their normative experience of arousal and desire on a 5-point Likert scale. Another sample of men (N = 40) and women (N = 40) completed the SADI and other measures after viewing a 3-minute female-centered erotic film or engaging in a 3-minute period of erotic fantasy. MAIN OUTCOME MEASURES: Principal components analyses derived factors that the scale descriptors loaded onto. These factors were categorized as subscales of the SADI, and gender differences in ratings and internal validity were analyzed statistically. Factors were considered subscales of the SADI, and mean ratings for each subscale were generated and related to the other scales used to assess convergent and divergent validity. These scales included the Feeling Scale, the Multiple Indicators of Subjective Sexual Arousal, the Sexual Desire Inventory, and the Attitudes Toward Erotica Questionnaire, the Beck Depression Inventory (BDI)-II, and the Beck Anxiety Inventory. RESULTS: Descriptors loaded onto four factors that accounted for 41.3% of the variance. Analysis of descriptor loadings > or = 0.30 revealed an Evaluative factor, a Physiological factor, a Motivational factor, and a Negative/Aversive factor based on the meaning of the descriptors. Men's and women's subjective experiences of sexual desire and arousal on the Physiological and Motivational factors were not significantly different, although on the Evaluative and Negative factors, statistically significant differences were found between the genders. Mean scores on the Evaluative factor were higher for men than for women, whereas mean scores on the Negative factor were higher for women than for men. Internal consistency estimates of the SADI and its subscales confirmed strong reliability. Mean scores on the Evaluative, Motivational, and Physiological subscales of the SADI were significantly higher in the fantasy condition than in the erotic clip condition. Women had significantly higher mean scores than men on the Physiological subscale in the fantasy condition. Cronbach's alpha coefficients demonstrated excellent reliability of the SADI subscales. Evidence of convergent validity between the SADI subscales and other scales that measured the same constructs was strong. Divergent validity was also confirmed between the SADI subscales and the other scales that did not measure levels of sexual arousal, desire, or affect, such as the BDI-II. CONCLUSION: The SADI is a valid and reliable research tool to evaluate both state and trait aspects of subjective sexual arousal and desire in men and women.

Adult↗

Subjective global assessment of nutrition a useful diagnostic tool for nurses?

UNLABELLED: Malnutrition in maintenance haemodialysis (HD) patients is closely related with morbidity and mortality in this population. AIM OF THE STUDY: To evaluate feasibility, performance and information given by SGA (subjective global assessment), a semi-quantitative method of nutritional evaluation (based on a medical questionnaire and a simple clinical examination) carried out by a group of 12 nurses. METHOD: In March 1999, a feasibility study was organised to evaluate 9 patients during HD. Since July 1999, a nutritional evaluation of all the patients meeting the required parameters (e.g. duration of HD > 6 months, day sessions) has been set up every 4 months. RESULTS: In March 1999, preliminary results demonstrated an average learning time per SGA of 15'. In July 1999, 32 patients were evaluated, albuminemia (micromol/l) and pre-albuminemia (g/l) were analysed according to the SGA classification (A = good nutrition, B= light to moderate malnutrition, C= severe malnutrition). The albuminemia and the prealbuminemia of patients A (respectively 541+/-45 and 0.37+/-0.10) were higher than those of patients B (482+/-41 and 0.31+/-0.01), and those of patients C (381+/-54 and 0.19+/-0.1), by variance analysis (p < 0.0001). The information drawn from the SGA reveal a severe malnutrition, a light to moderate malnutrition, and good nutrition in respectively 13%, 63% and 25% of the patients, and a noticeable muscular atrophy (moderate to severe) in 43% of cases. Anorexia and major gastro-intestinal symptom (nausea, vomiting, and diarrhoea) are found in 14% of cases. CONCLUSION: Beside traditional methods of screening and evaluation of malnutrition in HD patients, the use of SGA by a nursing team uncovers useful information on nutritional status of patients, especially in areas lacking facilities such as a laboratory, dietetic department or permanent presence of doctors.

Aged↗

A study on the adhesion of restorative materials to irreversible hydrocolloid impression materials.

AIM: The purpose of this study was to evaluate the adhesion of restorative materials to irreversible hydrocolloid impression materials. MATERIALS AND METHODS: Three irreversible hydrocolloid impression materials were tested with four restorative materials: a base metal alloy, an amalgam, an autopolymerising resin composite and a heat polymerising resin. Samples were prepared with and without a collar. Half of the samples were cleaned with methanol by wiping. The other half were not methanol-wiped. All the samples were submerged into the impression materials and were subsequently placed in an impression- holding device in two different positions. A pullout test using a Hounsfield machine was used after the impression materials were set. RESULTS: Variance analysis was used in comparing the results obtained. Statistically, the four restorative materials showed different values regarding the adherence of the impressions materials to them (composite resin 52.47N, metal 26.36N). Samples with adherence to a collar were found to be more retentive than those without a collar. Samples with impression materials with a full collar were more retentive than those without a collar, and the samples cleaned with methanol were again less retentive than those which were not methanol wiped. CONCLUSION: The results of this study show that adhesion may be seen between restorative materials and irreversible hydrocolloid impression materials, and this adhesion may affect the accuracy of the impression.

Alginates↗

Provider profiling: severity-adjusted versus severity-based outcomes.

Providers will continue to experience increasing pressure to demonstrate cost-effective, high-quality care. For relevant comparisons between providers, outcomes must be evaluated with respect to severity of illness and mortality risk. However, most hospitals use patient classification methods, such as Medicare and Health Care Financing Administration diagnosis-related groups (DRGs), which group together different levels of severity and mortality risk. The most common approach for developing severity-adjusted outcomes for groups of cases with dissimilar severity levels is to divide a statistic by a factor such as the Medicare case mix index, which was not designed or intended for that purpose. As an alternative, providers are increasingly using severity-based methods that classify patients as to severity levels within each diagnosis-related group. The key to severity-based profiling is the classification of cases to similar patient groups and comparison to selected benchmarks for variance analysis at each severity level. Effective provider profiling requires that hospital staff and physicians work together toward the common goal of accurate and complete documentation and coding of all medical conditions. Through use of more accurate severity-based profiling, providers are better able to identify opportunities to improve performance and demonstrate cost-effectiveness and quality to buyers, beneficiaries, and third-party reviewers.

Acute Disease↗

Cationic channels sensitive to extracellular ATP in rat lacrimal cells.

1. Responses of isolated rat lacrimal cells to local applications of ATP were studied using tight-seal whole-cell recording and/or Fura-2-derived calcium concentration measurements. 2. In cells where variations in Ca2+ concentration were prevented by use of a strong Ca2+ buffer, ATP was found to induce an inward current response at negative holding potentials. With 10 microM-ATP, the current amplitude ranged between 20 and 200 pA. The reversal potential of this ATP-induced current was close to 0 mV with normal external solution and shifted to -19 +/- 3 mV (mean +/- S.D.) when the concentration of external monovalent cations was halved. These results indicate that the channels have a cationic selectivity. The response amplitude decreased markedly from trial to trial, indicating a desensitization process which was irreversible on the time scale of the recordings. 3. Steady state I-V curves for the ATP-induced current in normal saline showed a marked inward rectification. This rectification appeared to be linked to a time-dependent activation of the channels, as hyperpolarizing voltage jumps elicited a time-dependent current increase. This relaxation could be fitted by a double-exponential function, with time constants (at -120 mV) of 0.9 +/- 0.3 ms and 110 +/- 6.4 ms. 4. Variance analysis of the ATP-induced current gave a single-channel current value of 0.34 pA at -60 mV. The single-channel current amplitude varied linearly with potential, with a slope close to 6 pS. The relation between noise covariance and time could be fitted by a double-exponential function, with time constants (at -60 mV) of 0.8 +/- 0.4 ms and 6.8 +/- 3.4 ms (mean +/- S.D.). 5. In an isotonic Ca2+ solution, 10 microM-ATP induced an inward current at -60 mV with a calculated single-channel current amplitude obtained from noise analysis close to 0.2 pA. In an external solution containing 10 mM-calcium and no sodium, 50 microM-ATP elicited a current with a reversal potential of -19 mV. 6. Fura-2 measurements were performed in intact cells or in cells dialysed with a low concentration of Ca2+ buffer (e.g. 0.5 mM-EGTA). Under such conditions ATP induced increases of the internal Ca2+ concentration with very variable amplitudes. In some cells Ca2+ rises of 50 nM or lower were found. Minimal activation of Ca(2+)-dependent channels was then observed. In other cells large Ca2+ rises (up to 500 nM) were observed and were then correlated with marked activation of Ca(2+)-dependent channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination.

The present study was conducted to examine the effect of a lipophilic analog of muramyl dipeptide, 6-O-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine (6-O-S-Abu-MDP), a macrophage activator, on the prophylactic activity of liposomal amphotericin B (L-AmpB) against disseminated candidiasis in mice. Multilamellar vesicles containing AmpB and (6-O-S-Abu)-MDP were prepared by using dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (7:3 molar ratio). Hale-Stoner mice (6 to 8 weeks old) were injected with 7 X 10(5) CFU of Candida albicans 336 isolated from a patient. Groups of mice were injected intravenously with different doses of L-AmpB and L-(6-O-S-Abu)-MDP, individually or in combination, 2 days before challenge with C. albicans. The mice were injected with a fixed dose of L-AmpB (1.2 mg/kg in 400 mg of lipid per kg) and various doses of L-(6-O-S-Abu)-MDP (0.6, 1.2, 2, and 4 mg/kg in 400 mg of lipid per kg) or vice versa. Other control groups included untreated mice and those receiving empty liposomes (400 mg of lipid per kg), free AmpB (0.6 mg/kg), or free (6-O-S-Abu)-MDP (4 mg/kg). The mice receiving L-AmpB (1.2 mg/kg) plus L-(6-O-S-Abu)-MDP (0.6 to 4.0 mg/kg) survived up to 25 to 30 days as compared with those injected with L-AmpB alone (15 days) or with L-(6-O-S-Abu)-MDP alone (10 to 15 days). All the mice in other control groups died within 7 to 11 days. The kidney cultures of the mice that received L-AmpB (4 mg/kg) plus L-(6-O-S-Abu)-MDP (1.2 mg/kg) were free of C. albicans infection, unlike those injected with L-AmpB. Variance analysis of these findings indicates a synergistic activity between L-AmpB and L-(6-O-S-Abu)-MDP in the prophylaxis of candidiasis.

Acetylmuramyl-Alanyl-Isoglutamine↗

Antifungal activity of HWA-138 and amphotericin B in experimental systemic candidiasis.

HWA-138, a pentoxifylline analog, has been shown to increase yeast urinary clearance and to reduce yeast counts in the kidneys of rats infected with Candida albicans. Furthermore, HWA-138 has also been shown to prevent amphotericin B-induced acute renal failure in rats. We report here on the effects of HWA-138 alone and in combination with amphotericin B in the treatment of systemic candidiasis in mice. When single doses of HWA-138 were administered intravenously (10, 25, or 50 mg/kg of body weight) into infected mice, no significant improvement in survival was observed. In infected mice treated intravenously with multiple doses of HWA-138 (10, 25, or 50 mg/kg once daily for 5 consecutive days), a significant increase in survival time was seen only in animals also receiving 25 mg of HWA-138 per kg (14 +/- 3 days test versus 9 +/- 1 days control; P less than 0.05). The coadministration of subtherapeutic doses of amphotericin B and HWA-138 resulted in increased survival time. Combination therapy with amphotericin B (0.1-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) resulted in a significant increase in survival time over controls (19 +/- 4, 19 +/- 5, and 21 +/- 9 days, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P < 0.05). Variance analysis of these findings indicate synergistic activity between amphotericin B and HWA-138 in the treatment of experimental candidiasis in mice.

Amphotericin B↗

Differential susceptibility of aeromonads and coliforms to cefsulodin.

Cefsulodin was evaluated as a potential selective agent for aeromonads. Resistance of Aeromonas and coliform isolates was determined by using a standard disk diffusion technique. A total of 119 Aeromonas and 78 coliform strains were isolated. For 102 of 130 [corrected] Aeromonas isolates (environmental and reference strains), the MIC of cefsulodin was < 8 micrograms/ml. Results of MIC tests by the agar dilution method showed that a concentration of cefsulodin of 10 micrograms/ml or less inhibited the growth of 96% of isolates. In comparison, for 81 of 94 coliform isolates (environmental and reference strains), the MIC of cefsulodin was > 32 micrograms/ml. Because cefsulodin suppresses growth of Aeromonas and other oxidase-positive organisms, total coliform (TC) and Escherichia coli counts on Chromocult Coliform agar (CC agar) without cefsulodin and on CC agar with 10 mg of cefsulodin per liter (CC-CFS) were compared. Variance analysis of data from 14 sewage-polluted irrigation water specimens did not demonstrate any statistically significant difference in the enumeration of E. coli with CC and CC-CFS media. On average, the CC agar recovered 2.46 times as many TCs as CC-CFS. However, Aeromonas colonies made up an average of 58.6% of the TC counts on CC agar. Because no Aeromonas spp. were recovered on CC-CFS, background interference was eliminated and the counts that were obtained reflected more accurately the number of TCs. Results of this study suggest that cefsulodin may be a useful selective agent against Aeromonas spp. which should be included in coliform chromogenic media when high levels of accompanying flora are expected.

Aeromonas↗

Correlation between genetic regulation of antibody responsiveness and protective immunity induced by Plasmodium berghei vaccination.

High (H) and low (L) antibody responder lines of mice were produced by two independent bidirectional selective breedings for quantitative antibody responsiveness to heterologous erythrocytes (selection I and selection II). In both selections the antibody response to P. berghei antigens was 8- to 10-fold higher in H than in L lines. The character "high response" presents an incomplete dominance o- 18% in selection I and 67% in selection II. In selection II the variance analysis indicates that at least three independent loci intervene in the regulation of responsiveness to P. berghei antigens. The innate resistance and the protective efficacy of vaccination against P. berghei infection induced by parasitized erythrocytes was measured in H and L lines and in the interline hybrids F1, BcH, and BcL of selections I and II. No very significant difference was observed in the innate resistance to P. berghei infection between H and L mice of both selections. Vaccination induced a very efficient protection in the two H lines (94 and 95% survival), whereas only a weak protection was induced in the two L lines (16 and 31% survival); the degree of protection is intermediate in interline hybrids F1, BcH, and BcL. In both selections a good linear correlation was demonstrated between the level of vaccination-induced antibody and the degree of resistance measured as percentage of survival. The present results indicate that the vaccination-induced P. berghei immunity is essentially due to the antibody response, whereas the bactericidal activity of macrophages and the cell-mediated immunity do not play a determinant role.

Animals↗

Optical coherence tomography of the retinal nerve fibre layer in mild papilloedema and pseudopapilloedema.

AIMS: To determine the degree to which optical coherence tomography (OCT) can distinguish differences in retinal nerve fibre layer (RNFL) thickness between eyes with mild papilloedema, pseudopapilloedema, and normal findings. METHODS: 13 patients with mild papilloedema, 11 patients with congenitally crowded optic nerves, and 17 normal subjects underwent neuro-ophthalmic examination, automated visual field testing, and fundus photography. Spinal fluid pressure measurements were obtained in a subgroup of five patients with pseudopapilloedema and 11 patients with mild papilloedema. Circular OCT scans using a diameter of 3.38 mm surrounding the optic disc were performed in each eye of patients and subjects. Fundus photographs were analysed by two observers who diagnosed crowding or papilloedema and graded amounts of swelling. Findings were assessed by descriptive statistics and variance analysis. RESULTS: RNFL thickness was greater in the superior and inferior quadrants and showed a high degree of correlation between each group of patients and subjects. A statistically significant difference was found in mean RNFL thickness between both groups of patients with optic disc swelling and normal subjects. However, there was not a statistical difference in mean nerve fibre layer thickness between patients with papilloedema and those with congenitally crowded optic nerves. CONCLUSIONS: OCT demonstrates measurable differences in nerve fibre layer thickness between normal subjects and patients with either papilloedema or pseudopapilloedema. However, OCT does not appear to differentiate between those individuals with congenitally crowded optic nerves and those with mild papilloedema caused by increased intracranial pressure.

Adolescent↗

Repeatability of measurements and sources of variability in tests of cardiovascular autonomic function.

OBJECTIVE: To determine the repeatability and sources of variability of clinical tests of cardiovascular autonomic function. DESIGN: The commonly used electrocardiographic related tests of autonomic function were studied. Two repeat measurements of all tests were made on all subjects on four separate days over a four week period. SUBJECTS: Ten normal subjects with no known autonomic dysfunction were investigated. MAIN OUTCOME MEASURES: These were deep breathing (subject seated and supine), Valsalva manoeuvre, standing up from lying position, and normal relaxed breathing (subject supine). During the tests the electrocardiogram and respiratory pattern were recorded by computer. Beat to beat RR intervals were measured automatically from the electrocardiogram, and from these the results of the tests were calculated. RESULTS: Variance analysis showed significant between subject variability for all tests (p < 0.005), but some tests showed a much smaller relative within subject variability than others. Average repeatability data (within subject SD) for each test were calculated, and included deep breathing sitting (max-min) RR (46 ms), Valsalva ratio (0.17), and lying to standing RR ratio (0.11). These compare with between subject SDs of 65 ms, 0.38, and 0.13 respectively, at mean values of 305 ms, 1.92, and 1.15 respectively. The data highlighted one subject with the poorest repeatability, whose electrocardiogram turned out on closer inspection to be under atrial rather than sinus control at times. Poor repeatability in the other subjects was related to variability in the respiratory pattern, and in the deep breathing test, repeat variability was significantly correlated (r = 0.79) with variability in the respiratory amplitude (p < 0.05). CONCLUSIONS: Repeatability data should be available to each laboratory carrying out autonomic function tests. The data provided in this study could be used as a baseline. Poor repeatability highlights the need to re-examine the test procedures, or the test data from specific subjects. Variability of respiratory pattern is associated with poor repeatability, and so careful instructions on respiration should be given to each subject before the tests.

Adult↗