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A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were synthesized and tested for their ability to inhibit the mono-(ADP-ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were established for this series and several compounds were identified as sub-micromolar inhibitors of PARP14, the most potent of which was compound 4t, IC 50 =160nM. Furthermore, profiling other members of this series identified compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity over PARP10, a closely related mono-(ADP-ribosyl)transferase., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We examined the effect of physical training on cardiopulmonary function in 21 patients with chronic obstructive pulmonary disease and compared the results with similar observations in eight untrained patients. The training consisted of daily walking on a treadmill at increasing speeds and grades and other graded physical exercises. Evaluation of pulmonary function, including spirometric studies, lung volumes, and arterial blood gas levels, showed no significant change after training. Hemodynamic functions, including heart rate, cardiac index, stroke index, pulmonary vascular resistance, and arteriovenous oxygen content difference, were similarly unchanged at comparable submaximal loads. Pulmonary arterial wedge pressure increased after training in the treated group at rest and during exercise, but this may be related to changes in respiratory mechanics. Consumption of oxygen and minute ventilation decreased in the treated group during treadmill exercise, suggesting improved neuromuscular coordination and efficiency of walking on the treadmill. Total work performed on the treadmill increased significantly in the trained group. This increase was unexplained by physiologic observations but was thought to be due in part to increased efficiency of walking and increased motivation. We conclude that improvement in the capacity for exercise following physical training for four weeks is not associated with improvement in cardiopulmonary function at submaximal exercise.

A case of hepatothoracic echinococcosis with the unusual manifestation of a large, right, chyliform pleural effusion is presented. The possible etiology, the pathogenesis, and the origin of this chyliform fluid are discussed, and the methods used to differentiate chyliform fluid from true chyle and pseudochyle are described.

Doxycycline (D) is often administered during respiratory infections to asthmatic patients, many of them treated by theophylline (T) as well. We therefore investigated a possible interaction between D and T. Steady-state basal T levels were measured on two successive days before and after three and four days of D administration in ten stable asthmatic patients. Mean T levels before D were 9.9 +/- 3.1 micrograms/mL and after D 10.1 +/- 2.9 micrograms/mL, which are not significantly different. But T levels in four patients increased and in two patients, T levels decreased. We conclude that in some patients, T concentrations may be affected by D. This may require determination of T blood levels and T dose adjustment in some patients treated by T and D.

Salmonella empyema in an immunologically compromised patient with malignant pleural effusion is described. Antimicrobial treatment was ineffective when given parenterally. Intrapleural administration of antibiotics resulted in a rapid rise of the antibacterial activity of the pleural fluid, leading to rapid clinical improvement and eradication of the infections.

The possible role of infection with Mycoplasma pneumoniae (MP) in exacerbation of bronchial asthma in adults was studied in 95 patients hospitalized due to acute asthma. Twenty (21%) of these patients had evidence of a recent MP infection as determined by the presence of high levels of MP-specific IgM antibodies. In addition, high levels of both IgM and IgG but not IgA serum immunoglobulins were observed in the MP-infected group as compared to a control group of 20 non-MP-infected asthmatics. Five out of 20 MP-infected asthmatics exhibited rheumatoid factor (RF) in their sera while patients in the control group were all negative for RF. It is concluded that MP infection may be significant in exacerbation of asthma in adults.

Ventilatory studies and arterial blood gas analyses were performed in 29 patients with chronic renal failure undergoing renal dialysis therapy (RDT). Twenty-three of the 29 had nearly normal pulmonary function, and the accumulation of body water between dialyses did not influence pulmonary function significantly. A trend was observed towards overinflation and air trapping in the presence of normal airway resistance, indicating narrowing of the small airways. Repeated studies over a 16-month period suggest that these patients develop neither chronic obstructive airway disease nor restrictive ventilatory impairment. Six patients had a restrictive ventilatory impairment with a trend to overdistension and air trapping as in the "normal" patients. This was observed both early and late in the course of RDT and appeared to be irreversible but not progressive. These patients had suffered from uremic pleuropericarditis and either had serous effusions or residual adhesions.

The clinical effectiveness of beclomethasone dipropionate (BDP) aerosol and adrenal function after withdrawal of oral corticosteroid therapy were evaluated in 32 severely steroid-dependent asthmatic patients. Twenty-four of 28 patients were able to discontinue oral glucocorticosteroid therapy, while four failed to do so. Ventilatory studies showed no substantial changes at the end of six months' BDP treatment. In 24 patients, adrenal insufficiency was present before BDP therapy was started. In 20 of those patients, the response of cosyntropin returned to normal two months after discontinuation of systemic steroid treatment and administration of BDP.

A group of 18 asymptomatic asthmatic patients and a control group of five healthy individuals were examined in order to evaluate the effect of inhalation of 400 microng of salbutamol on the small airways. All patients were free of symptoms for at least three days before the investigation. On the day of investigation, total lung resistance, static lung compliance, and dynamic compliance at a respiratory frequency of 60 breaths per minute (Cdyn60) were measured. While no change in Cdyn60 occurred in the control group, a statistically significant decrease in Cdyn60 was found before inhalation of salbutamol in all 18 asthmatic patients (P less than 0.005), indicating obstruction of small airways. After inhalation of 400microng of salbutamol, a significant increase in Cdyn60 occurred (P less than 0.005), starting five minutes after inhalation and lasting over one hour, indicating an almost complete abolishment of the frequency dependence of lung compliance in these patients. The present findings indicate that sulbutamol aerosol has a potent bronchodilator effect on the large, as well as the small, airways in the early stage of recovery following an acute asthmatic attack.