SSc and the 2013 diagnostic criteria: the case of Paul Klee’s manual pathology and dysgraphia

The German-Swiss modernist painter Paul Klee (1879–1940) suffered in the final years of his life from a severe illness, diagnosed in 1936 as scleroderma, later renamed SSc. New classification criteria for this disease issued in 2013 now allow for a diagnosis to be confirmed. Important for this process, however, is the question of whether or not Klee’s hands were affected by his illness. The morphology of the artist’s hands and evidence of dysgraphic changes in his handwriting are reviewed as indications of his manual pathology. Despite his illness, Klee triumphed over his infirmity, simplifying his painting and drawing styles and substantially increasing his artistic output from 1936 until his death in 1940.     

Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt-induced hypertension

BACKGROUND: The renin-angiotensin-aldosterone system and oxidative stress play a major role in the pathogenesis of hypertension. METHODS: We examined the effects of simvastatin, an HMG-CoA inhibitor, and losartan, an angiotensin type 1 receptor antagonist, in Dahl rats fed a high salt diet (8% NaCl), and treated with either simvastatin (3 mg/kg/d), losartan (10 mg/kg/d), or their combination using the drinking water as vehicle, for 3 weeks. Mean blood pressure (MAP) was measured by tail-cuff plethysmography. Plasma levels of nitric oxide (NO) and prostanoids, as well as plasma and tissue angiotensin II (Ang II) and aldosterone (ALDO) were analyzed by enzyme immunoassay. Renal and aortic superoxide production was determined by fluorescence spectrometry. Vascular reactivity of second-order mesenteric arteries was assessed in vitro. RESULTS: Simvastatin, losartan, and the drug combination attenuated the salt-induced increase in MAP. Plasma NO was elevated by simvastatin, losartan, and the combination, whereas plasma thromboxane was reduced by losartan. Simvastatin, losartan, and the combination reduced renal Ang II, but only the combination reduced cardiac Ang II. Heart and renal ALDO were reduced by simvastatin, losartan, and the combination. Aortic and renal NADPH-dependent superoxide production was reduced by simvastatin, losartan, and the combination. The response to acetylcholine, in mesenteric arteries preconstricted with norepinephrine, was greater in the losartan group. CONCLUSIONS: Thus, treatment with simvastatin and losartan lowered oxidative stress and improved endothelial function. Simvastatin significantly reduced the effect of losartan on vascular reactivity in mesenteric arteries, suggesting that their combination may be contraindicated.     

Prostacyclin Reversal of Lethal Endotoxemia in Dogs

Severe endotoxemia, a condition where microembolization and intravascular coagulation are thought to play important roles, was treated experimentally with prostacyclin (PGI₂). In a study of 24 dogs, 8 control animals injected with 1.75 mg·kg⁻¹ of endotoxin died within 24 h. Six animals given intravenous aspirin 100 mg/kg, 30 min after endotoxin died. 9 of 10 dogs infused with 100 ng PGI₂·kg⁻¹·min⁻¹ for 3 h, given 30 min after the injection of endotoxin survived 24 h (P < 0.025). Injection of endotoxin resulted in a: (a) maximal 62% fall in mean arterial pressure (P < 0.001); (b) transient doubling of mean pulmonary arterial pressure (P < 0.001); (c) initial 70% drop in cardiac index (P < 0.001); (d) decline in blood platelets from 213,700 to 13,700/mm³ (P < 0.001), and leukocytes from 7,719 to < 750/mm³ (P < 0.001); (e) depressed urine output (P < 0.001); (f) 34% decrease in blood fibrinogen (P < 0.01) and an increase in fibrin degradation products > 50 μg/ml (P < 0.001); (g) fivefold increase in circulating cathepsin D titer (P < 0.005) and (h) increase in blood norepinephrine (P < 0.005), dopamine (P < 0.005), and epinephrine (P < 0.001). Aspirin treatment led to an increase in mean arterial pressure (P < 0.001) and mean pulmonary arterial pressure (P < 0.005), but cardiac index, urine flow, platelets, leukocytes, fibrin degradation products, and cathepsin D levels remained similar to untreated controls. After infusion of PGI₂ there was a: (a) prompt increase of cardiac index to base-line levels; (b) late increase in mean arterial pressure (P < 0.005) after the discontinuation of PGI₂ treatment (c) restoration of urine output; (d) increase in circulating platelets to levels still below base line but above untreated control animals (P < 0.05); (e) no effect on circulating leukocyte levels; (f) fall in fibrin degradation products to 11.2 μg/ml (P < 0.05); (g) decline in cathepsin D levels to values 60% lower than the untreated controls (P < 0.025); and (h) reduction in plasma norepinephrine levels to base line at 4 h (P < 0.005). Although the mode of PGI₂ action is not clear, it is effective in the treatment of experimental endotoxemia.     

Occupational hazards of interventional cardiology

Complex catheter-based interventions and rising case volumes confer occupational risks to interventional cardiologists. Despite advances in technology, modern interventional procedures are performed in a manner remarkably similar to the techniques pioneered decades ago. Percutaneous interventions are associated with operator orthopedic injuries, exposures to blood borne pathogens, and the effects of chronic radiation exposure from fluoroscopy. This review highlights the occupational hazards of interventional procedures and provides a glimpse at the technologies and techniques that may reduce risks to operators in the catheterization laboratory.     

Amelioration of Child Depression Through Behavioral Parent Training: A Preliminary Study

Child depression is an impairing condition for which tested treatments have shown relatively modest mean effects. One possible explanation is that the treatments have generally adopted an individual child focus, without addressing the dysfunctional parent–child interactions that often accompany child depression. The present study provides preliminary evidence bearing on this hypothesis, using data from a treatment outcome study in which clinically referred children with a depression diagnosis could receive individual cognitive behavioral therapy (CBT) focusing on the depression or behavioral parent training (BPT) focusing on comorbid conduct problems. Among children in the study who met criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed.) depressive disorders, we identified two groups, matched on gender and age: 15 who received only CBT focused on child depression and 15 who received only BPT focused on child conduct problems. Children were 7 to 13, 20 of whom were male, and race included Caucasian (17), Latino (5), African American (2), and multirace (6). Measures assessed depressive diagnoses and symptoms, as well as parenting stress. Analyses focused on whether BPT alone might lead to reduced depression, and if so how that reduction would compare to the depression reduction achieved through CBT that focused on depression. Both groups showed significant reductions from pre- to post-treatment in depressive diagnoses and depression symptoms, and there were no BPT versus CBT group differences at post-treatment. BPT that focuses on child conduct problems, with no emphasis on depression treatment, may produce significant depression reduction in comorbid children who meet criteria for depressive disorders.