Prognostic significance of a polymerase chain reaction-detectable dominant T-lymphocyte clone in cutaneous lesions of patients with mycosis fungoides

Although mycosis fungoides (MF) is considered to be an indolent lymphoma, survival is highly influenced by TNM stage. At diagnosis, most MF patients present with early stage disease and a high probability of long-term survival. Treatment is generally directed towards skin lesions, and achievement and duration of complete responses are variable. A dominant T-cell clone is detectable in the cutaneous lesions of 60% of patients. The aim of this study was to determine whether the presence of a T-cell clonal population influences the clinical course of the disease after topical therapy. Cutaneous biopsies from 68 patients were histologically diagnosed as MF and T-cell clonality was analyzed by in vitro amplification of TCR-gamma chain gene rearrangements (polymerase chain reaction gamma [PCRgamma]). After a median follow-up of 48 months, response to treatment was clinically assessed. Age, sex, duration of symptoms before diagnosis, type of cutaneous lesions (T stage), TNM stage, and PCRgamma were evaluated as predictive factors of response to treatment in univariate and multivariate analyses. Univariate analysis demonstrated that T1 cutaneous lesions (P = .05) and PCRgamma negativity (P = .007) were associated with a higher complete remission rate. Using multivariate analysis, T stage (relative risk, 3.13; P = .06) and PCRgamma (relative risk, 4.4; P = .01) remained independent significant predictive parameters of response. In conclusion, T stage and cutaneous PCRgamma at diagnosis are the two predictive parameters of treatment response for MF. Therefore, the cutaneous PCRgamma findings should be considered in the analysis of future therapeutic trials.     

Laminin and alpha-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathway

Specific isoforms of laminin (LN) are concentrated at neuromuscular junctions (NMJs) where they may participate in synaptic organization or function. In myotubes from C2 cells, LN is concentrated within the majority of spontaneous acetylcholine receptor (AChR) aggregates. Neural agrin substantially increases this colocalization, suggesting that agrin can recruit LN into AChR aggregates. Addition of LN to C2 myotubes induces a more than twofold increase in the number of AChR aggregates. These aggregates have a larger size and are more dense than are those induced by agrin, suggesting that LN is involved in the growth and/or stabilization of AChR aggregates. Consistent with this hypothesis, an antiserum to LN reduces the size of individual AChR aggregates but increases their number. In C2 myotubes, extracellular matrix receptors containing the integrin beta1 subunit are poorly colocalized with AChR aggregates, suggesting that integrins may not be involved in LN-induced aggregation. In contrast, almost all AChR aggregates are associated with dystroglycan immunoreactivity, and monoclonal antibody (mAb) IIH6 against alpha-dystroglycan (alpha-DG), a LN and agrin receptor, causes a concentration-dependent inhibition of LN-induced aggregation. Moreover, S27 cells, which lack a functional alpha-DG, and two C2-derived cell lines expressing antisense DG mRNA fail to aggregate AChRs in response to LN. Finally, LN-induced AChR aggregation does not involve the phosphorylation of the muscle-specific tyrosine kinase receptor (MuSK) or the AChR beta subunit. We hypothesize that the interaction of LN with alpha-DG contributes to the growth and/or stabilization of AChR microaggregates into macroaggregates at the developing NMJ via a MuSK-independent mechanism.     

T1 effects in sequential dynamic susceptibility contrast experiments

Benign osteoblastoma is an uncommon bone tumor accounting for approximately 1% of all bone tumors. There are only 35 cases of skull osteoblastoma reported in the literature. We describe the case of a 23 year old male with a giant osteoblastoma of temporal bone submitted to a total removal of the tumor after an effective embolization of all external carotid branches. The authors discuss diagnostic and management aspects of this uncommon skull tumor.     

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.