Aortic valvuloplasties: treatment of calcified aortic stenosis in elderly subjects

Since September 1985, transluminal balloon catheter aortic valvuloplasty has been developed in France (Cribier and al.) and all around the world. Indications are still limited, in almost all catheterization laboratories, to elderly patients, with Monckeberg's disease, and with a very high operative risk. Immediately after aortic valvuloplasty, there is a moderate but a significant increase in valve area, without serious complications. Subjective improvement is often spectacular during few months after the valvuloplasty. In long-term evolution, there is sometimes a symptomatic restenosis which require a new valvuloplasty. So, if percutaneous valvuloplasty is efficacy in aortic stenosis in the elderly, long-term evaluation of this new technique is necessary.     

Diagnosis of supravalvular stenosis of the aorta

The authors analyzed the potentialities of combined radiodiagnosis of supravalvular stenosis (SS) and concomitant diseases of the heart and major vessels (Williams-Beuren syndrome) in 7 patients aged 7 mos. to 24 yrs. Polypositional chest and heart x-ray procedure, catheterization of the cardiac cavities, pulmonary artery and aorta, left ventriculography (6), right ventriculography (4) and angiopulmonography were used. The diagnostic potentialities of each method were defined. It was proved that SS practically in all patients was accompanied by major vascular changes in the pulmonary, vertebral, coronary, carotid, subclavicular, renal and other arteries, heart failure (atrial septal defect, and mitral incompetence).     

Deficient coacervation of two forms of human tropoelastin associated with supravalvular aortic stenosis.

Human tropoelastin associates by coacervation and is subsequently cross-linked to make elastin. In Williams syndrome, defective elastin deposition is associated with hemizygous deletion of the tropoelastin gene in supravalvular aortic stenosis (SVAS). Remarkably, point-mutation forms of SVAS correspond to incomplete forms of tropoelastin which include in-frame termination by nonsense mutations, yet the resulting phenotype of these disorders is not explained because expression variably occurs from both normal and mutant alleles. Proteins corresponding to two truncated tropoelastin mutants were expressed and purified to homogeneity. Coacervation of these proteins occurred as expected with increasing temperature, but substantially contrasted with that of the performance of a normal tropoelastin. Significantly, association by coacervation of the truncated SVAS tropoelastin molecules was negligible at 37 degrees C, which contrasted with the substantial coacervation seen for normal tropoelastin. Furthermore their midpoints of coacervation increased and correlated with the extent of deletion, in accord with the loss of hydrophobic regions required for tropoelastin association. Their secondary structures are similar, as evidenced by CD studies. We propose a model for point-mutation SVAS in which aberrant tropoelastin molecules are incompetent and are mainly excluded from participation in coacervation and consequently in elastogenesis. These forms of SVAS may consequently be considered functionally similar to a hemizygous deletion, and mark point-mutation SVAS as a disorder of defective coacervation.     

Palatal schwannoma in an elderly woman

Schwannoma also known as neurilemmoma is a benign tumour derived from schwann cells and is relatively rare in occurrence. Only 1% of the schwannomas in the head and neck region occur at intra-oral sites. Schwannomas usually occur during the third or fourth decades of life and the tongue is the most common intra-oral site. A case of intra-oral schwannoma in a 70-year-old female in the region of hard palate is described which is extremely rare.     

Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.     

Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome

To elucidate the pathomechanism leading to obstructive vascular disease in patients with elastin deficiency, we compared both elastogenesis and proliferation rate of cultured aortic smooth-muscle cells (SMCs) and skin fibroblasts from five healthy control subjects, four patients with isolated supravalvular aortic stenosis (SVAS), and five patients with Williams-Beuren syndrome (WBS). Mutations were determined in each patient with SVAS and in each patient with WBS. Three mutations found in patients with SVAS were shown to result in null alleles. RNA blot hybridization, immunostaining, and metabolic labeling experiments demonstrated that SVAS cells and WBS cells have reduced elastin mRNA levels and that they consequently deposit low amounts of insoluble elastin. Although SVAS cells laid down approximately 50% of the elastin made by normal cells, WBS cells deposited only 15% of the elastin made by normal cells. The observed difference in elastin-gene expression was not caused by a difference in the stability of elastin mRNA in SVAS cells compared with WBS cells, but it did indicate that gene-interaction effects may contribute to the complex phenotype observed in patients with WBS. Abnormally low levels of elastin deposition in SVAS cells and in WBS cells were found to coincide with an increase in proliferation rate, which could be reversed by addition of exogenous insoluble elastin. We conclude that insoluble elastin is an important regulator of cellular proliferation. Thus, the reduced net deposition of insoluble elastin in arterial walls of patients with either SVAS or WBS leads to the increased proliferation of arterial SMCs. This results in the formation of multilayer thickening of the tunica media of large arteries and, consequently, in the development of hyperplastic intimal lesions leading to segmental arterial occlusion.     

Late diagnosis of a neglected cervical carcinoma in an elderly woman: a case report

We report the case of an 88-year-old, Greek patient who was referred to our department with a bleeding mass that occupied her entire vagina. This exophytic tumor had extensive ulcerated areas and originated from the cervix. The biopsies taken from the mass confirmed it to be squamous cell carcinoma. Despite the giant size of the tumor, the parametria and middle and lower vagina were not infiltrated. Rather, the neglected mass created a severe septic condition that was progressing to disseminated intravascular coagulation DIC status. Because of the patient's advanced age and critical condition, we performed a "toilet" operation to remove the tumor mass. We subsequently administered radical radiation therapy with satisfactory results.     

Interleukin-32 plays an essential role in human calcified aortic valve cells

Interleukin-32 (IL-32) is an inflammatory cytokine produced mainly by T, natural killer, and epithelial cells. Previous studies on IL-32 have primarily investigated its proinflammatory properties. The IL-32 also has been described as an activator of the p38 mitogen-activated protein kinase (MAPK) and NF-κB, and induces several cytokines. In this study, we hypothesized that the inflammatory regulators NF-κB, MAP kinase, STAT1, and STAT3 are associated with the expression of the IL-32 protein in human calcified aortic valve cells. This study comprised aortic valve sclerotic patients and control group patients without calcified aortic valve. Increased IL-32 expression in calcified aortic valvular tissue was shown by immunohistochemical staining and western blotting. There was an increase in NF-κB p65 level, p-ERK, p-JNK, and p-p38 MAPK activation underlying IL-32 expression in the study. The level of p-STAT3 but not p-STAT1 was found to be increased in calcified aortic valve tissue. In cultured primary human aortic valve interstitial cells, inhibition of NF-κB or MAPK kinase pathways results in a decrease of IL-32 expression. Treatment of recombinant IL-32 induced the levels of TNF-α, IL-6, IL-1β, and IL-8. Our findings demonstrate that IL-32 may be an important pro-inflammatory molecule involved in calcific aortic valve disease.     

Systemic dissemination of chronic necrotizing pulmonary aspergillosis in an elderly woman without comorbidity: a case report

ABSTRACT: INTRODUCTION: Chronic necrotizing pulmonary aspergillosis usually occurs in mildly immune-compromised hosts or those with underlying pulmonary disease. The radiographic pattern of chronic necrotizing pulmonary aspergillosis is typically a progressive upper lobe cavitary infiltrate with pleural thickening. We report here an atypical case of chronic necrotizing pulmonary aspergillosis mimicking lung cancer, which developed into a disseminated fatal disease in an older woman with no comorbidity. CASE PRESENTATION: An 80-year-old Japanese woman was referred to our hospital for a chest roentgenogram abnormality. Repeated fiber-optic bronchoscopy could not confirm any definite diagnosis, and she refused further examinations. Considering the roentgenogram findings and her age, she was followed-up as a suspected case of lung cancer without any treatment. Then, 10 months later, she complained of visual disturbance and was admitted to our department of ophthalmology. She was diagnosed as having endophthalmitis. After treatment with corticosteroids for 20 days, she developed acute encephalitis and died four weeks later. Autopsy revealed dissemination of Aspergillus hyphae throughout her body, including her brain. CONCLUSIONS: In older patients, even if they do not have any comorbidity, chronic necrotizing pulmonary aspergillosis should be added to the differential diagnosis of solitary pulmonary lesions in a chest roentgenogram.