Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression

OBJECTIVE: To evaluate the effect of early 'aggressive' drug treatment on radiographic progression in patients with recent-onset rheumatoid arthritis (RA), compared to conventional stepwise increasing intensity of treatment. DESIGN: Prospective follow-up study with an experimental group and a historical control group both divided into a high-risk subgroup and a low-risk subgroup, based on prognostic factors. The effect of the 'aggressive' and the conventional treatment strategy was compared between both high-risk groups; the low-risk groups, both treated according to the conventional treatment strategy, were used to ensure internal consistency between the experimental and the historical groups. PATIENTS: A total of 228 consecutive patients with recent-onset RA (complaints < 1 yr at study entry). METHODS: The 'aggressive' drug treatment consisted of institution of relatively fast-acting disease-modifying anti-rheumatic drugs (DMARDs) (sulphasalazine, methotrexate) immediately after diagnosis, and rapid adjustment of dosage and/or drug in the case of insufficient response as measured by a change in C-reactive protein (CRP) level. Radiographic damage was assessed according to a modified version of Sharp's method and cumulative disease activity expressed as CRP-area under the curve (CRP-AUC). The occurrence of side-effects was also evaluated. RESULTS: After 2 yr of follow-up, comparison of the two high-risk subgroups showed the radiographic progression in the 'aggressively' treated subgroup to be significantly lower than that in the control group [Sharp score: median (range) 26 (0-100) vs 35 (1-188); P = 0.03]. Cumulative CRP values were also significantly lower than in the control high-risk subgroup [CRP-AUC: median (range) 1963 (212-8515) vs 3025 (46-15 632) mg.week/1; P = 0.002). This was achieved without an increase in the occurrence of side-effects. There was no difference between the two low-risk subgroups with regard to entry characteristics, CRP-AUC values or radiological progression, indicating comparability between the two groups. CONCLUSION: Early 'aggressive' drug treatment, using sulphasalazine and/or methotrexate, aimed at reduction of the CRP level, significantly reduces the (rate of) radiographic progression in RA.     

Postprandial lipemia: effects of intermittent versus continuous exercise

PURPOSE: The purpose of this study was to assess whether exercise performed in continuous and discontinuous formats reduced postprandial lipemia to a similar degree. METHODS: Fifteen normolipidemic and three borderline hyperlipidemic healthy males (ages 30.6 +/- 9.0 (mean +/- SD) yr, BMI 23.1 +/- 1.4 kg.m-2) participated in three trials, each conducted over 2 d. Subjects refrained from exercise for the 2 d preceding each trial. On day one, subjects rested (control trial), or ran at 60% of maximal oxygen uptake in either one 90-min session (continuous exercise trial), or three 30-min sessions (intermittent exercise trial). On day two, subjects ingested a high-fat test breakfast (1.2 g fat, 1.2 g carbohydrate, 70 kJ energy per kilogram body mass). Blood samples were obtained in the fasted state and at intervals for 6 h postprandially. RESULTS: Fasting plasma triacylglycerol (TAG) concentrations did not differ between trials. Areas under the TAG versus time curves were 18.1 +/- 6.7% (mean +/- SEM) and 17.7 +/- 7.6% (both P < 0.05) lower than control in the continuous exercise and intermittent exercise trials, respectively. Plasma glucose responses to the test meal did not differ between trials, but the serum insulin response was lower in the intermittent exercise trial compared with that in the control. CONCLUSION: The results suggest that both intermittent and continuous exercise can reduce postprandial lipemia.     

A mathematical approximation for the solution of a static indentation test

The aim of this study was to compare the incidence of acute adverse events and long-term outcome of two different surfactant dosing procedures in respiratory distress syndrome (RDS). The effects of two surfactant dosing procedures on the incidence of transient hypoxia and bradycardia, gas exchange, ventilatory requirements and 28 d outcome were compared. The patients, comprising 102 infants (birthweight 600-2000 g) with RDS on mechanical ventilation with FiO2 > or = 0.4, were randomized at 2-24 h to receive 200 mg kg(-1) of Curosurf; in 56 it was given by bolus delivery, and in 55 by a simplified technique (dose given in 1 min via a catheter introduced through a side-hole in the tracheal tube adaptor. The baby's position was not changed and ventilation was not interrupted). Two additional surfactant doses (100 mg kg(-1)) were also given, by the same method, if ventilation with FiO2 > or = 0.3 was needed 12 and 24 h after the initial dose. The number of episodes of hypoxia and/or bradycardia was similar in both groups. A slight and transient increase in PaCO2 was observed in the side-hole group. The efficacy of the surfactant, based on oxygenation improvement, ventilator requirements, number of doses required and incidence of air leaks, was similar. No differences were observed in the incidence of intraventricular haemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia or survival. In conclusion, a simplified surfactant dosing procedure not requiring fractional doses, ventilator disconnection, changes in the baby's position or manual bagging was found to be as effective as bolus delivery. The number of dosing-related transient episodes of hypoxia and bradycardia was not decreased by the slow, 1 min, side-hole instillation procedure.     

Treatment of condylar hyperplasia of the mandible using unilateral ramus osteotomies

PURPOSE: The long-term outcome of bilateral and unilateral ramus osteotomies used for the treatment of unilateral condylar hyperplasia of the mandible are evaluated and compared. MATERIALS AND METHODS: Thirteen cases of unilateral condylar hyperplasia of the mandible were surgically treated during a 10-year period from 1985 to 1995. Seven of the patients were treated by bilateral ramus osteotomies alone; six were treated by unilateral ramus osteotomies of the affected side. Unilateral ramus osteotomy was combined with a maxillary Le Fort I procedure in two of the six cases. Preoperative analysis of patients, indications for case selection, and postoperative results relating to facial symmetry, temporomandibular joint (TMJ) pain, occlusion, and stability were compared in the two groups. RESULTS: The postoperative findings and long-term results in both groups of patients were favorable. Symmetry, arch coordination, and occlusion remained stable. TMJ pain and dysfunction were invariably cured postoperatively. Unilateral ramus osteotomies alone, or in combination with maxillary surgery when deemed feasible and applicable by preoperative clinical analysis, was sufficient to restore symmetry and occlusion in dentally compensated cases. CONCLUSIONS: This study shows that patients with unilateral condylar hyperplasia of the mandible and deviation can be treated favorably by unilateral ramus osteotomy of the affected side; bilateral ramus osteotomy did not have any advantage in such cases. In addition, this procedure, combined with a Le Fort I osteotomy of the maxilla, was also effective in restoring occlusal canting and facial symmetry in dentally compensated cases. However, bilateral ramus osteotomy was required in prognathic cases and in cases in which a unilateral procedure would cause excessive rotation of the contralateral condyle.     

Variations of the flexor digitorum superficialis tendon of the little finger

The use of 131I doses of several mCi for scans can stun the thyrocytes and thyroid cancer cells, whereas the usual dose (300 microCi) of 123I does not. We compared the diagnostic accuracy of the 123I (300 microCi) scans and that of 131I (3-10 mCi) scans in 155 patients. The diagnostic accuracy of a 123I scan in detecting functioning thyroid remnant/metastasis was 89.5% (77/86 scans) and that of a 131I scan was 92.9% (39/42) in 6 week-postoperative patients (p = 0.750). For radioablation therapy follow-up patients, the diagnostic accuracy of 123I in determining presence or absence of functioning remnant or metastasis was 69.4% (25/36) and that of 131I was 92.5% (49/53) with a p value of 0.079. The success rates for complete ablation of functioning tissue after radioiodine therapy administered after diagnostic 123I and after 131I were 72% (34/47) and 56% (24/43), respectively, with a p value of 0.125. Our study indicates the following: 1) for the first postoperative evaluation, the diagnostic accuracy of the 123I scan was essentially equal to that of the 131I scan, and the success rate of radioablation therapy appears to be better than 123I scan; and 2) for postablation follow-up surveys, the 131I scan appears to be better but carries the risk of stunning the functioning cells.     

Characterization of the oriC region of Mycobacterium smegmatis

A 3.5-kb DNA fragment containing the dnaA region of Mycobacterium smegmatis has been hypothesized to be the chromosomal origin of replication or oriC (M. Rajagopalan et al., J. Bacteriol. 177:6527-6535, 1995). This region included the rpmH gene, the dnaA gene, and a major portion of the dnaN gene as well as the rpmH-dnaA and dnaA-dnaN intergenic regions. Deletion analyses of this region revealed that a 531-bp DNA fragment from the dnaA-dnaN intergenic region was sufficient to exhibit oriC activity, while a 495-bp fragment from the same region failed to exhibit oriC activity. The oriC activities of plasmids containing the 531-bp sequence was less than the activities of those containing the entire dnaA region, suggesting that the regions flanking the 531-bp sequence stimulated oriC activity. The 531-bp region contained several putative nine-nucleotide DnaA-protein recognition sequences [TT(G/C)TCCACA] and a single 11-nucleotide AT-rich cluster. Replacement of adenine with guanine at position 9 in five of the putative DnaA boxes decreased oriC activity. Mutations at other positions in two of the DnaA boxes also decreased oriC activity. Deletion of the 11-nucleotide AT-rich cluster completely abolished oriC activity. These data indicate that the designated DnaA boxes and the AT-rich cluster of the M. smegmatis dnaA-dnaN intergenic region are essential for oriC activity. We suggest that M. smegmatis oriC replication could involve interactions of the DnaA protein with the putative DnaA boxes as well as with the AT-rich cluster.     

Mortality determinants in massive pediatric burns. An analysis of 103 children with > or = 80% TBSA burns (> or = 70% full-thickness)

OBJECTIVE: Survivors and nonsurvivors among 103 consecutive pediatric patients with massive burns were compared in an effort to define the predictors of mortality in massively burned children. SUMMARY BACKGROUND DATA: Predictors of mortality in burns that are used commonly are age, burn size, and inhalation injury. In the past, burns over 80% of the body surface area that are mostly full-thickness often were considered fatal, especially in children and in the elderly. In the past 15 years, advances in burn treatment have increased rates of survival in those patients treated at specialized burn centers. The purpose of this study was to document the extent of improvement and to define the current predictors of mortality to further focus burn care. METHODS: Beginning in 1982, 103 children ages 6 months to 17 years with burns covering at least 80% of the body surface (70% full-thickness), were treated in the authors' institution by early excision and grafting and have been observed to determine outcome. The authors divided collected independent variables from the time of injury into temporally related groups and analyzed the data sequentially and cumulatively through univariate statistics and through pooled, cross-sectional multivariate logistic regression to determine which variables predict the probability of mortality. RESULTS: The mortality rate for this series of massively burned children was 33%. Lower age, larger burn size, presence of inhalation injury, delayed intravenous access, lower admission hematocrit, lower base deficit on admission, higher serum osmolarity at arrival to the authors' hospital, sepsis, inotropic support requirement, platelet count < 20,000, and ventilator dependency during the hospital course significantly predict increased mortality. CONCLUSIONS: The authors conclude that mortality has decreased in massively burned children to the extent that nearly all patients should be considered as candidates for survival, regardless of age, burn size, presence of inhalation injury, delay in resuscitation, or laboratory values on initial presentation. During the course of hospitalization, the development of sepsis and multiorgan failure is a harbinger of poor outcome, but the authors have encountered futile cases only rarely. The authors found that those patients who are most apt to die are the very young, those with limited donor sites, those who have inhalation injury, those with delays in resuscitation, and those with burn-associated sepsis or multiorgan failure.     

Analysis of nickel refinery dusts

After characterization of bulk samples by inductively coupled plasma emission spectroscopic (ICP-ES) quantitative analysis and X-ray powder diffraction studies, single particle techniques using quantitative image analysis, scanning electron microscopy--energy dispersive analysis by X-ray, and finally laser beam ionization mass spectrometry analysis (LIMA) for surface analysis have been applied to historical nickel refinery dust samples from the nickel refining plant at Clydach in Wales. There were two historical samples of processed material from 1920 and 1929. These samples had a remarkably small particle size range, mean 3 microns and range, 0.75-24 microns. The most significant difference in elemental composition was the presence of 10% arsenic in the 1920 sample compared with 1% in the 1929 sample. The X-ray spectra revealed the presence of NiO in both. However, surprisingly, CuO was identified only in the 1929 sample. Of particular interest was the presence of a component, in the 1920 sample only, identified as the mineral orcelite, a copper-iron-nickel-arsenide-sulphide mineral, predominantly, Ni5-XAs2. Using the LIMA technique, it was found that in both samples, arsenic and arsenic derivative peaks are prominent, indicating the surface availability of arsenic compounds.