Chronic thromboembolic pulmonary hypertension

Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-014-0592-2) contains supplementary material, which is available to authorized users.     

Chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rapidly progressive and deadly disease, resulting from incomplete resolution of acute pulmonary embolism. Historically, the incidence of CTEPH was significantly underestimated but it may be as high as 3.8% following acute pulmonary embolism. Although the medical management of CTEPH may be supportive, the only curative treatment is pulmonary endarterectomy (PEA). However, a careful screening programme is mandatory to select CTEPH patients who are likely to benefit from PEA. In this review we discuss the pathophysiology, clinical and diagnostic pitfalls, surgical treatment, outcome after surgery, and the potential benefit of medical treatment in inoperable CTEPH patients.     

Laboratory-acquired sporotrichosis.

A case of laboratory-acquired sporotrichosis was diagnosed by immunofluorescence and by culture. The patient was then cured by treatment with oral potassium iodide. The need to handle cultures of Sporothrix schenckii with due caution is stressed.     

Chronic obstructive pulmonary disease.

Outpatient management of chronic obstructive pulmonary disease (COPD) is reviewed in this paper. Smoking cessation is probably important, although its benefit in established COPD is unproven. Bronchodilator therapy may be of more than symptomatic benefit and is indicated in virtually all patients. Specific beta 2-agonists are the most widely used agents and can be given in substantially larger doses than are usually recommended. Ipratropium bromide, an anticholinergic drug, is about as effective as a beta 2-agonist, but in large doses the two drugs do not seem to have additive effects, unlike theophylline and beta 2-agonists. Systemic corticosteroids decrease airway obstruction substantially in a small number of patients with COPD; these agents should be reserved for these patients and used sparingly. Inhaled steroids are of little benefit, as are respiratory stimulants and depressants. Broad-spectrum antibiotic therapy helps to relieve symptomatic exacerbations of COPD, particularly those characterized by increased dyspnea, sputum volume and sputum purulence. Cor pulmonale is best managed by diuretics and oxygen, with digoxin reserved for left ventricular failure and supraventricular arrhythmias. Continuous oxygen therapy at home is indicated for the patients who have chronic arterial hypoxemia.     

Unknown fixed cutaneous sporotrichosis

Sporotrichosis is the most frequent subcutaneous mycosis in Mexico. The clinical forms are commonly described as lympho-cutaneous and cutaneous-fixed. The case of a male patient who developed an eritematous plaque with radial growth is reported. The patient received empirical therapy and topic steroids which modified the clinical picture with vesicles to vesicles, ulcers and blood and honey crusts. Diagnosis of fixed cutaneous sporotrichosis incognito was established by clinical, mycological and histopathological studies. Delayed cellular immunity in vitro and in vivo were normal. The patient received oral itraconazole showing clinical and mycological cure after four months.     

Importance of the sporotrichosis asteroid body for the rapid diagnosis of sporotrichosis

Eighty patients with cutaneous sporotrichosis were studied between 1985 and 1996. The investigation of asteroid bodies (AB) was done by direct microscopic slides examination of pus obtained from the lesions. Patients were divided into two groups: 32 consulting before 1989, and 48 consulting after 1990. In the first group, material was obtained as usual by simple digital pressure of the most productive lesion, and then wet preparation microscopic examination was performed. Fourteen patients with AB were found in this group (43.75%). In the second group the initial pus was discarded and new samples were taken more deeply, and examined up to five slides for each patient. The slides were carefully examined at light microscope. Fourty five patients with AB were detected in this group (93.75%). All eighty samples were cultured and all of them were positive for Sporothrix schenckii. The change of methodology to obtain the samples and the exhaustive observations, increased the possibility of AB detection. ABs are of great diagnostic value and might be of importance to initiate treatment before reporting culture.     

Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation

Chronic hypoxia (CH) augments endothelium-derived nitric oxide (NO)-dependent pulmonary vasodilation; however, responses to exogenous NO are reduced following CH in female rats. We hypothesized that CH-induced attenuation of NO-dependent pulmonary vasodilation is mediated by downregulation of vascular smooth muscle (VSM) soluble guanylyl cyclase (sGC) expression and/or activity, increased cGMP degradation by phosphodiesterase type 5 (PDE5), or decreased VSM sensitivity to cGMP. Experiments demonstrated attenuated vasodilatory responsiveness to the NO donors S-nitroso-N-acetylpenicillamine and spermine NONOate and to arterial boluses of dissolved NO solutions in isolated, saline-perfused lungs from CH vs. normoxic female rats. In additional experiments, the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, blocked vasodilation to NO donors in lungs from each group. However, CH was not associated with decreased pulmonary sGC expression or activity as assessed by Western blotting and cGMP radioimmunoassay, respectively. Consistent with our hypothesis, the selective PDE5 inhibitors dipyridamole and T-1032 augmented NO-dependent reactivity in lungs from CH rats, while having little effect in lungs from normoxic rats. However, the attenuated vasodilatory response to NO in CH lungs persisted after PDE5 inhibition. Furthermore, CH similarly inhibited vasodilatory responses to 8-bromoguanosine 3'5'-cyclic monophosphate. We conclude that attenuated NO-dependent pulmonary vasodilation after CH is not likely mediated by decreased sGC expression, but rather by increased cGMP degradation by PDE5 and decreased pulmonary VSM reactivity to cGMP.     

Polymorphonuclear leukocyte chemotaxis in sporotrichosis

A lesion of sporotrichosis shows a characteristic arrangement of the infiltrate in three zones: the central suppurative zone composed of polymorphonuclear leukocytes, the tuberculoid zone and the round cell zone. For investigating the pathomechanism of the suppurative zone formation, polymorphonuclear leukocyte chemotaxis to sporotrichin was assayed with the agarose plate method. Polymorphonuclear leukocytes in the patients with sporotrichosis showed an enhanced chemotactic index in comparison with that in the control subjects. However, there was no difference in non-specific chemotaxis to bacteria-derived substance between the patients and the control subjects.     

难辨认孢子丝菌病临床分析

探讨孢子丝菌病不典型的临床表现.孢子丝菌病是皮肤科常见的一种深部真菌病,典型的皮肤科特征是慢性肉芽肿、溃疡性损害、炎性结节等.而部分孢子丝菌病的患者由于各种各样的原因导致皮损丧失特征性临床表现,给皮肤科医生尤其是临床经验尚不丰富的年轻医师于该病的诊断带来了一定的困难.本文所讨论的8例患者均为就诊于我科门诊并已确诊为孢子丝菌病病例,皮损与典型的孢子丝菌病皮损表现不相符,希望皮肤科医师在以后的临床工作中遇到一些不典型皮损但是综合患者病史、生活环境、诊治过程等情况可考虑到此种疾病,及时给予明确的诊断,使患者能够得到及时、有效的治疗.     

难治性孢子丝菌病1例

报道1例因非医嘱习惯性口服激素导致的难愈性孢子丝菌病。患者右腕木屑刺伤后,出现局限性红斑伴破溃,曾多次外院就诊,诊断为“孢子丝菌病”,给予抗真菌治疗半年后病情仍不断恶化,遂来我院就诊。皮损经真菌镜检、培养及分子生物学测序均鉴定为孢子丝菌病,病理示感染性肉芽肿。询问病史时发现患者有日常口服激素的习惯,嘱患者停用激素并口服伊曲康唑4个月后治愈。     

Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling

Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O(2) fraction (FI(O(2))) = 0.10], chronic hypercapnia (inspiratory CO(2) fraction = 0.10), hypoxia-hypercapnia (FI(O(2)) = 0.10, inspiratory CO(2) fraction = 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone (P < 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk (P < 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 +/- 1.8 mmHg) was significantly (P < 0.01, ANOVA) elevated compared with control conditions (12.1 +/- 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 +/- 0.9 mmHg) or hypercapnia (11.8 +/- 1.3 mmHg). HPV (FI(O(2)) = 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control (P < 0.05, ANOVA). Addition of N(omega)-nitro-L-arginine methyl ester (10(-4) M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function.     

Chronic obstructive pulmonary disease: emerging therapies

Despite the high prevalence of and mortality from chronic obstructive pulmonary disease, extensive research on the underlying pathophysiology and specific therapeutics for this disease is, relatively, in its infancy. Several novel molecular targets are being investigated as potential treatments for the disease. The most exciting new class of compounds is the phosphodiesterase 4 inhibitors; Ariflo (SB 207499)-a member of this class, and the most advanced in development (Phase III)-was reported recently to have significant clinical efficacy in patients with chronic obstructive pulmonary disease. Phosphodiesterase 4 inhibitors, such as Ariflo, possibly represent the most important advance in pulmonary medicine in recent years.     

Treatment of experimental sporotrichosis in mice

Summary Griseofulvin, Amphotericin B, Trichomycin and Potassium Iodide did not influence the course of experimental sporotrichosis with an infective dose of 2.3×10⁵ cells injected intravenously.This research was in part supported by grant E-576 of the U. S. Public Health Service and a grant from McNeill Laboratory, Incorporated, Philadelphia, Pa.     

Feline sporotrichosis: A case report

The isolation of Sporothrix schenckii from a female European cat it is described. The cat showed lengthened alopecic areas, with prominent nodules in the external surface of the thighs and abdomen. A mycological and histopathological studies of the lesions were carried out. The lesions resolved under treatment with 20% potassium iodide in doses of 0'1 ml/kg oral route in a 8 weeks period.     

Epidemiology of sporotrichosis in Latin America

Summary Applying the concept of epidemiological chain, it is successively analyzed: the etiologic agent, Sporothrix schenckii and its natural reservoirs (sources of infection); the different ways that infecting particles may reach man (mechanisms of infection); the susceptible population and the population at risk; the incidence and distribution by sex and age in countries of Latin America; the prevalence of the disease according to clinical cases in dermatological clinics and the variation of incidence rates in some countries with time; the influence of the environment mainly climatic conditions on the geographic distribution of the disease.Finally, according to Mackinnon's hypothesis, the climate could have a determining role on the predominance of a certain clinical form on another in different countries.This paper was presented at the X^th ISHAM Congress, Barcelona, Spain, 1988.