Design and Characterization of a Soft Robotic Therapeutic Glove for Rheumatoid Arthritis

The modeling and experimentation of a pneumatic actuation system for the development of a soft robotic therapeutic glove is proposed in this article for the prevention of finger deformities in rheumatoid arthritis (RA) patients. The Rehabilitative Arthritis Glove (RA-Glove) is a soft robotic glove fitted with two internal inflatable actuators for lateral compression and massage of the fingers and their joints. Two mechanical models to predict the indentation and bending characteristics of the inflatable actuators based on their geometrical parameters will be presented and validated with experimental results. Experimental validation shows that the model was within a standard deviation of the experimental mean for input pressure range of 0 to 2 bars. Evaluation of the RA-Glove was also performed on six healthy human subjects. The stress distribution along the fingers of the subjects using the RA-Glove was also shown to be even and specific to the finger sizes. This article demonstrates the modeling of soft pneumatic actuators and highlights the potential of the RA-Glove as a therapeutic device for the prevention of arthritic deformities of the fingers.     

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.     

Dissolution of cholesterol gall stones using methyltertbutyl ether: a safe effective treatment.

Methyltertbutyl ether (MTBE) administered by percutaneous transhepatic catheter rapidly dissolves radiolucent cholesterol gall bladder stones. However, complete dissolution and clearance of non-cholesterol debris is essential to prevent recurrence. In this study we analysed 25 consecutive patients with reference to efficacy and recurrence based on the presence or absence of non-cholesterol stone fragments after dissolution. Placement of the catheter was successful in 24 patients, one patient requiring cholecystectomy for bile peritonitis. MTBE was infused and aspirated continuously, four to six cycles per minute, resulting in rapid stone dissolution (median six hours; range 4-23 hours for solitary stones and median seven hours, range 4-30 hours for multiple stones). In 18 patients who had complete dissolution, four (22%) had recurrent stones within six to 18 months. Five patients had residual debris which failed to clear completely despite bile acid treatment. One patient with an incomplete rim of calcium in a large stone did not respond to MTBE treatment. A further patient required cholecystectomy for symptomatic recurrence. There were no serious side effects observed. MTBE treatment is a rapid, safe, and effective treatment for patients who refuse surgery or who for medical reasons cannot undergo cholecystectomy. The results of this study confirm that complete dissolution of all fragments is essential and may prevent recurrence.     

Cloned cDNA to cholecystokinin mRNA predicts an identical preprocholecystokinin in pig brain and gut.

Molecular cloning has established the structure of preprocholecystokinin in porcine cerebral cortex and duodenal mucosa. This precursor is 114 amino acids long, is identical in brain and gut, contains all the cholecystokinin (CCK) peptides previously isolated, and has the characteristics of a prohormone. It contains a putative amino-terminal signal peptide, basic processing sites, and a carboxyl-terminal amidation signal. The CCK mRNAs from brain and gut are approximately 850 nucleotides long and differ by only a few single base changes. This analysis establishes by a strict criterion that CCK is synthesized in both brain and gut and that the different distributions of molecular forms of CCK in the two tissues are most probably a consequence of tissue-specific posttranslational events.     

The pulmonary neuroendocrine system and drainage of the fetal lung: effects of serotonin

The neuroendocrine system of the lungs is maximally developed and activated at birth, but has no clear function. Here, one of its products, serotonin, was tested for an ability to stop lung fluid production or activate reabsorption. Lungs from fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Initial studies on 36 young fetuses (61 +/- 1 days of gestation) showed that untreated controls produced fluid at 1.17 +/- 0.23 ml.kg-1.h-1, with no significant change over 3 h (ANOVA; regression analysis); those given 10(-8) M serotonin during the middle hour showed no significant changes, but those given 5 x 10(-8), 10(-7), 10(-6), or 10(-5) M serotonin reduced production significantly (P < 0.01 to P < 0.0005). Responses were linear up to 10(-7) M (threshold, 10(-9) M) and then become maximal at 50% reduction. However, responses increased with age. Comparison of 40 fetuses divided into groups of 60-61 or 65-67 days of gestation showed a large and significant increase in responses in the older fetuses (P < 0.01), where half the preparations reabsorbed fluid. Serotonin receptors were involved, since 10(-6) M cyproheptadine abolished responses (based on 24 preparations). Amiloride-sensitive Na+ channels were involved, since 10(-6) M amiloride abolished responses (based on 24 preparations). These results, in combination with earlier results from somatostatin and dopamine, together with histochemical and clinical observations, strongly suggest that the neuroendocrine system of the lungs may find a function in clearing fluid from the lungs at time of birth.     

Loss of the normal coupling between the anaerobic threshold and insulin sensitivity in chronic heart failure

OBJECTIVE—To explore whether the anaerobic threshold, a measure of the balance between aerobic and anaerobic cellular metabolism, is related to whole body insulin sensitivity in healthy individuals and in patients with chronic heart failure, which involves is an imbalance of aerobic and anaerobic metabolism.DESIGN—Case-control study.SETTING—A teaching hospital department specialising in heart failure.PATIENTS—20 healthy individuals (mean (SEM) age 55.2 (2.7) years) and 36 patients with chronic heart failure (59.1 (2.0) years, New York Heart Association class I-IV, anaerobic threshold 11.8 (0.7) ml/kg/min, left ventricular ejection fraction 26 (2)%).INTERVENTIONS—An intravenous glucose tolerance test for assessment of insulin sensitivity (minimal model analysis) and a maximum treadmill exercise test for assessment of the anaerobic threshold, derived from measurement of oxygen consumption and carbon dioxide output.MAIN OUTCOME MEASURES—Relation between insulin sensitivity and the anaerobic threshold in patients with chronic heart failure.RESULTS—While anaerobic threshold was positively correlated with insulin sensitivity in healthy controls (r = 0.72, p < 0.001), no such relation was observed in patients with chronic heart failure. In stepwise multiple linear regression analyses of variables in healthy individuals, insulin sensitivity emerged as the only predictor of anaerobic threshold (standardised coefficient = 0.72, p < 0.001), while fasting insulin, incremental insulin area, and total body fat (dual photon x ray absorptiometry) failed to enter into final models (joint R = 0.52, p < 0.001).CONCLUSIONS—In healthy individuals, whole body insulin sensitivity is related, or "coupled," to the anaerobic threshold. The absence of such metabolic coupling in patients with chronic heart failure provides further evidence of disturbed cellular metabolism in patients with this condition.     

Phenotypic consequences of lung-specific inducible expression of FGF-3

Members of the fibroblast growth factor (FGF) family play a critical role in embryonic lung development and adult lung physiology. The in vivo investigation of the role FGFs play in the adult lung has been hampered because the constitutive pulmonary expression of these factors often has deleterious effects and frequently results in neonatal lethality. To circumvent these shortcomings, we expressed FGF-3 in the lungs under the control of the progesterone antagonist-responsive binary transgenic system. Four binary transgenic lines were obtained that showed ligand-dependent induction of FGF-3 with induced levels of FGF-3 expression dependent on the levels of expression of the GLp65 regulator as well as the dose of the progesterone antagonist, RU486, administered. FGF-3 expression in the adult mouse lung resulted in two phenotypes depending on the levels of induction of FGF-3. Low levels of FGF-3 expression resulted in massive free alveolar macrophage infiltration. High levels of FGF-3 expression resulted in diffuse alveolar type II cell hyperplasia. Both phenotypes were reversible after the withdrawal of RU486. This system will be a valuable means of investigating the diverse roles of FGFs in the adult lung.     

Comparison of primary angioplasty and conservative treatment on short- and long-term outcome in octogenarian or older patients with acute myocardial infarction

It has long been established that advanced age is not only associated with greater myocardial infarction frequency but also greater mortality and morbidity. The treatment of acute myocardial infarction (AMI) in 80 year old patients remains problematic with conflicting results; in these patients, the risks of conservative treatment are high and the risks and benefits of thrombolytic therapy are still controversial. The purpose of this study was to evaluate whether primary angioplasty can offer an important alternative method to improve short- and long-term outcomes in octogenarian or older patients who experience AMI. Between May 1986 and March 2000, 171 consecutive 80 year old patients hospitalized for AMI were not randomized to be registered and divided into a medical therapy group (group 1: an historical control group, n=11) and a primary angioplasty group (group 2, n=60). In-hospital mortality was markedly increased with advanced Killip scores (Killip 3 or 4) in both groups. Twenty-four hours after admission, group 1 patients had a significantly higher incidence of progression to higher Killip scores than did group 2 patients (P=0.006). The 30-day overall mortality of group 2 patients was significantly lower than in group 1 patients (30.0% vs 54.1%, P=0.003). Patients without cardiogenic shock treated by primary angioplasty had a significantly lower incidence of overall mortality at 30 days than patients without cardiogenic shock treated conservatively [3.1% vs 24.3%, P=0.016 (Killip 1 and 2); 18.2% vs 52.6%, P=0.044 (Killip 3)]. However, the mortality rate of cardiogenic shock was extremely high and did not differ significantly between groups I and 2 (86.1% vs 88.2%, P=0.99). The 3-year cumulative survival rate was significantly higher in group 2 than in group 1 patients (P=0.0009). In conclusion, primary angioplasty is feasible and effective, and can improve short-and long-term mortalities in octogenarian or older patients with AMI but without cardiogenic shock.     

Thylakoid membrane polypeptides of Chlamydomonas reinhardtii: wild-type and mutant strains deficient in photosystem II reaction center.

Unstacked thylakoid membrane vesicles were obtained from a homogenate of Chlamydomonas reinhardtii by flotation in a 1.8 M sucrose layer containing 5 mM HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid)-10 mM EDTA (pH 7.5). Sodium dodecyl sulfate-gradient gel electrophoresis showed that the wildtype membranes have a total of at least 33 polypeptides ranging in molecular weights from 68,000 to less than 10,000. The wild-type and three non-photosynthetic mutant strains were studied with respect to their photosynthetic electron transport properties, their fluorescence rise kinetics, and their membrane polypeptide compositions. The results showed a strong correlation between the presence of a membrane polypeptide (molecular weight = 47,000) and the activity of the photosystem II reaction center. This polypeptide is missing from F34 (a mendelian mutant lacking Q, the primary electron acceptor of photosystem II), but is partially restored in a suppressed strain of F34 in which there is an incomplete recovery of photosystem II activity. In a thermosensitive mutant, T4, the same polypeptide is present in reduced amount only in cells grown at 35 degrees but not in those grown at 25 degrees. Evidence from fluorescence rise kinetics and partial photochemical reactions show that the cells grown at 25 degree are similar to wild-type cells but the cells grown at 35 degrees are greatly deficient in Q.