Biomedical subjects

A Manes

Publications and source records attributed to A Manes.

14 recordsLinked to original sources

PubMed2005

Pulmonary hypertension in primary Sjögren's syndrome: report of a case and review of the literature.

A 61-year-old female with a history of vaginal dryness, Raynaud's phenomenon, xerostomia and xerophthalmia presented with exertional dyspnoea and weakness. Laboratory and instrumental examinations enabled us to make the diagnosis of primary Sjögren's syndrome, while cardiologic and imaging investigations evidenced isolated pulmonary hypertension and ruled out pulmonary fibrosis. Oral anticoagulant and furosemide therapy induced a partial improvement of exertional dyspnoea and weakness.

Anticoagulants↗

PubMed2005

Pulmonary arterial hypertension associated to connective tissue diseases.

Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sjögren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.

Algorithms↗

PubMed2004

Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2.

The efficacy and safety of combining bosentan, an orally active dual endothelin receptor antagonist and epoprostenol, a continuously infused prostaglandin, in the treatment of pulmonary arterial hypertension (PAH) was investigated. In this double-blind, placebo-controlled prospective study, 33 patients with PAH started epoprostenol treatment (2 ng.kg(-1)min(-1) starting dose, up to 14+/-2 ng.kg(-1)min(-1) at week 16) and were randomised for 16 weeks in a 2:1 ratio to bosentan (62.5 mg b.i.d for 4 weeks then 125 mg b.i.d) or placebo. Haemodynamics, exercise capacity and functional class improved in both groups at week 16. In the combination treatment group, there was a trend for a greater (although nonsignificant) improvement in all measured haemodynamic parameters. There were four withdrawals in the bosentan/epoprostenol group (two deaths due to cardiopulmonary failure, one clinical worsening, and one adverse event) and one withdrawal in the placebo/epoprostenol group (adverse event). This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension. Several cases of early and late major complications were reported. Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension.

Antihypertensive Agents↗

PubMed2002

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension.

Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in >1,100 patients. Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance. These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.

Dose-Response Relationship, Drug↗

PubMed2001

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor beta (TGF-beta) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. METHODS: We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-beta-receptor proteins, including endoglin and activin-receptor-like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. RESULTS: We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activin-receptor-like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor-like kinase 1 in normal and diseased pulmonary arteries. CONCLUSIONS: Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension.

Activin Receptors↗

PubMed2001

Medical therapy of pulmonary hypertension. The prostacyclins.

Prostacyclin is a substance produced by endothelial cells that induces vasodilation and inhibition of platelet aggregation and of vascular cell migration and proliferation. A dysregulation of the prostacyclin metabolic pathways has been shown in patients with pulmonary arterial hypertension. The clinical use of prostacyclin has been made possible by the synthesis of stable analogues that possesses different pharmacokinetic properties but share similar pharmacodynamic effects. The greatest experience has been collected with intravenous epoprostenol while other compounds like subcutaneous UT-15, inhaled iloprost and oral beraprost are currently in different stages of clinical development. Although favorable results have been reported for each compound, different benefit-to-side effects profiles characterize the various modalities of the administration.

Epoprostenol↗

PubMed2000

BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a potentially lethal disorder, because the elevation of the pulmonary arterial pressure may result in right-heart failure. Histologically, the disorder is characterized by proliferation of pulmonary-artery smooth muscle and endothelial cells, by intimal hyperplasia, and by in situ thrombus formation. Heterozygous mutations within the bone morphogenetic protein type II receptor (BMPR-II) gene (BMPR2), of the transforming growth factor beta (TGF-beta) cell-signaling superfamily, have been identified in familial and sporadic cases of PPH. We report the molecular spectrum of BMPR2 mutations in 47 additional families with PPH and in three patients with sporadic PPH. Among the cohort of patients, we have identified 22 novel mutations, including 4 partial deletions, distributed throughout the BMPR2 gene. The majority (58%) of mutations are predicted to lead to a premature termination codon. We have also investigated the functional impact and genotype-phenotype relationships, to elucidate the mechanisms contributing to pathogenesis of this important vascular disease. In vitro expression analysis demonstrated loss of BMPR-II function for a number of the identified mutations. These data support the suggestion that haploinsufficiency represents the common molecular mechanism in PPH. Marked variability of the age at onset of disease was observed both within and between families. Taken together, these studies illustrate the considerable heterogeneity of BMPR2 mutations that cause PPH, and they strongly suggest that additional factors, genetic and/or environmental, may be required for the development of the clinical phenotype.

Adolescent↗

PubMed1998

Leiomyoma of the urinary bladder.

Leiomyoma of the urinary bladder is a rarity but should be considered in the differential diagnosis of intramural neoplasm. We report a case illustrating clinical and pathological features in particular the immunohistochemistry. Etiology and differential diagnosis are discussed.

Diagnosis, Differential↗

PubMed1998

Primary pulmonary hypertension: insights into pathogenesis from epidemiology.

Primary pulmonary hypertension (PPH) is a rare disease that affects young people predominantly of female gender. Early epidemiologic studies have shown that the diagnosis is usually made 1 to 2 years after symptoms onset, and the mean survival is reduced to 2 to 3 years thereafter. New insights into the pathogenesis of PPH by epidemiologic studies may be obtained through the utilization of informatic technologies coupled to a clear definition of the disease. Early stages of precapillary pulmonary hypertension could be identified through screening tests like echocardiography in populations with higher incidence, such as familial PPH and the conditions associated with pulmonary hypertension. These latter conditions are hemodynamically and pathologically similar to the primary form, and they can give insight into several possible aspects of the pathogenesis of PPH. Prospective registries are very useful in coordinating the collection of epidemiologic data, and new technologies, such as informatics, may improve the management and the continuous updating of the databases.

Adult↗

PubMed1997

The clinical and histological features of transitional cell carcinoma of the bladder with microcysts: analysis of 12 cases.

OBJECTIVE: To describe the clinical course and histological features of transitional cell carcinoma (TCC) of the bladder with microcysts. PATIENTS AND METHODS: Among 940 patients with bladder TCC diagnosed at our institution during a 5 year period. 12 (1.2%; eight men and four women, mean age 71.1 years, range 52-85) were diagnosed histologically as having microcystic TCC. Sections of the tumours were stained with haematoxylin and eosin, periodic acid-Schiff and Alcian blue and clinical data obtained from the patients' records. RESULTS: Of the 12 patients with bladder TCC with microcysts, three had tumours confined to the epithelium, six had tumour invasion of the lamina propria and three had muscle invasion. One patient had low-grade TCC and 11 had high-grade TCC; six patients had a second primary tumour; three had a colon carcinoma, one a villous adenoma of the caecum, one a locally advanced carcinoma of the prostate and the last a squamous cell carcinoma of the uterine cervix. CONCLUSIONS: Microcystic TCC was associated with high-stage and high-grade bladder tumours and with other primary tumours, especially of the colon. Screening these patients for asymptomatic tumours of the colon is suggested.

Aged↗

PubMed1997

Transvesical prostatectomy in elderly patients.

PURPOSE: We assessed the results of transvesical prostatectomy in patients older than 80 years. MATERIALS AND METHODS: We studied 98 patients 80 to 90 years old who underwent transvesical prostatectomy between 1986 and 1993, including those with a large prostate (preoperative estimated weight more than 80 gm.), numerous or large cystolithiasis and large bladder diverticulum, which are indications for open prostatectomy. Clinical data were obtained by chart review. RESULTS: The indications for surgery were urinary retention in 53 patients (54%), severe obstructive urinary symptoms in 18 (18.4%), cystolithiasis in 17 (17.3%), prostatic bleeding in 10 (10.2%) and bladder diverticulum in 2 (2%). Accompanying diseases were present in 69 patients (70.6%), including ischemic heart disease in 41 (42%), diabetes mellitus in 17 (17.3%) and arterial hypertension in 14 (14.3%). A total of 59 patients (60.2%) underwent surgery while under general anesthesia and 39 (39.8%) received regional anesthesia. Average operative time was 62 minutes. Of the patients 40 (40.8%) received 1, 14 (14.3%) received 2 and 2 (2%) received 4 units of blood. No postoperative deaths or life threatening complications were noted. The immediate postoperative complications included urinary tract infection in 20 patients (20.5%), wound infection in 3 (3.0%) and orchiepididymitis in 3 (3.0%). Postoperative mild to moderate incontinence was noted in 2 patients (2.0%). Bladder neck constriction and urethral strictures occurred in 4 (4.1%) and 3 (3.0%) patients, respectively. CONCLUSIONS: Transvesical prostatectomy can be performed safely in elderly patients with a low morbidity rate.

Age Factors↗

PubMed1995

The value of radionuclide scrotal imaging in the diagnosis of acute testicular torsion.

OBJECTIVE: To assess the accuracy of radionuclide scrotal imaging (RSI) in the diagnosis of testicular torsion and torsion of testicular appendages. PATIENTS AND METHODS: Eighty-seven patients (mean age 30.1 years, range 8-65) who presented with acute scrotal pain were evaluated by RSI and the results correlated with the clinical and surgical findings. RESULTS: Of the 87 patients, 44 underwent scrotal exploration and 42 patients were treated conservatively. One patient with a 'missed torsion' pattern on RSI refused operation and was lost to follow-up. Of the 44 patients who underwent surgery, testicular torsion was found in 30 and torsion of testicular appendages in 14 patients. The specificity of the RSI in diagnosing testicular torsion was 100% and the sensitivity was 98%. An area of increased tracer activity in the presence of a normal radionuclide angiogram was suggestive of torsion of testicular appendages with a specificity of 93%. Of the 42 patients who were treated conservatively, 19 had epididymitis, according to clinical and RSI findings, 10 had torsion of testicular appendages, two had orchiepididymitis, two had hydrocele, two had haematocele and seven patients had normal testes. At a follow-up examination, normal testicles were found in all 42 patients. CONCLUSION: The RSI may assist in the evaluation of nontraumatic acute scrotum, and can clearly distinguish among testicular torsion, torsion of testicular appendages and epididymitis.

Adolescent↗

PubMed1995

Changing trends in the management of iatrogenic ureteral injuries.

PURPOSE: We evaluated changing trends in the management of late diagnosed iatrogenic ureteral injuries before and after the introduction of percutaneous nephrostomy. MATERIALS AND METHODS: The study included 44 patients of whom 24 were treated primarily by immediate reconstructive surgery from 1979 to 1984 and 20 were treated primarily by percutaneous nephrostomy tube insertion beginning in 1985. RESULTS: Six of the 24 patients underwent ureteroneocystostomy and 18 underwent end-to-end uretero-ureteral anastomosis to repair the injury. Postoperatively 18 patients had a urinary tract infection. Hospital stay after reconstructive surgery ranged from 14 to 35 days (average 18). Long-term followup showed a normal upper urinary tract in 22 patients and mild to moderate hydroureteronephrosis in 2. Of the 20 patients who underwent percutaneous nephrostomy 16 (80%) had complete spontaneous recovery of the injured ureter after 14 to 66 days (average 32). Hospital stay after the insertion of the percutaneous nephrostomy tube ranged from 3 to 5 days. Urinary tract infection developed in 4 patients and mild hydronephrosis was noted in 1 on long-term followup. CONCLUSIONS: The primary management of ureteral injury by percutaneous nephrostomy resulted in significantly decreased reoperation and morbidity rates, and enabled spontaneous recovery of the injured ureter in the majority of patients.

Female↗

PubMed1989

[Spermatic cord liposarcoma].

In a 36-year-old man with a left scrotal mass a tumor was found and excised through an inguinal incision, together with the testis and the contents of the inguinal canal, in continuity. Histological examination showed a liposarcoma of the spermatic cord. Only 55 cases of this rare scrotal tumor have been reported. The literature indicates that while there is a tendency to local recurrence, there have been no reports of distant metastases. It appears that radiotherapy and chemotherapy are not necessary in this condition.

Adult↗