Biomedical subjects
Publications and source records attributed to M Grasso.
Papillary fibroelastomas are very rare cardiac tumours that can present with embolization of coronary and peripheral arteries and sudden death. The diagnosis can be made by two-dimensional or transoesophageal echocardiography. A 53-year-old man with an aortic valve papillary fibroelastoma who presented with several transient ischaemic attacks is reported.
Aspartic proteinases have recently been shown to be implicated in antigen processing. We explored the expression of two aspartic proteinases, cathepsins E and D, and of human leukocyte antigen-DR (HLA-DR) molecules in a consecutive series of 80 transbronchial biopsies from transplanted lungs. For controls, we studied five normal donor lungs (not suitable for transplantation on account of thoracic trauma) and macroscopically normal areas of three cancer-affected lungs. Two of the five unsuitable donor lungs showed minimal inflammatory changes. Macroscopically normal samples from the three cancerous lungs showed mild and focal inflammatory infiltrates. In histologically normal lungs, HLA-DR expression was limited to professional antigen-presenting cells. Macroscopically normal lung samples with minimal inflammatory changes from both donor and cancer lungs showed variable HLA-DR expression by alveolar and bronchial epithelial cells and by endothelial cells. All transplanted lung biopsies showed HLA-DR expression by epithelial (alveolar and bronchial) and endothelial cells, with a trend for increased positivity in acute rejection. Cathepsin E was restricted to Clara and to rare bronchus-associated lymphoid tissue-related epithelial cells in histologically normal lung samples, whereas minimal de novo cathepsin E expression by rare alveolar pneumocytes was noted in control lung samples exhibiting minimal inflammatory changes. In all transplanted lung biopsies, cathepsin E was diffusely expressed de novo by hyperplastic alveolar epithelial cells, regardless of the presence or degree of rejection. Cathepsin D was expressed only by alveolar macrophages and by ciliated bronchial cells of normal, minimally inflamed, and transplanted lungs. In transplanted lung, Clara cells and several hyperplastic alveolar pneumocytes coexpressed HLA-DR and cathepsin E, whereas all alveolar macrophages and a few ciliated cells coexpressed cathepsin D and HLA-DR. The present investigation suggests that the de novo expression of cathepsin E and HLA-DR by hyperplastic alveolar pneumocytes of transplanted lung may be crucial for antigen processing and presentation to recipient competent T cells, and thus for the triggering of the immune-inflammatory cascade that leads to rejection.
Proliferating cell nuclear antigen (PCNA) myocyte expression and histopathologic features related to its occurrence were investigated in normal and diseased hearts of adult humans using both immunohistochemical and Western blotting techniques. Ki67 Western blotting was also performed in the same samples used for PCNA blotting. Two hundred seventy-one endomyocardial biopsies, and 15 adult, 1 embryonic and 2 fetal hearts were studied. The biopsies were from normal donor hearts (n = 71), patients with cardiomyopathy and myocarditis (n = 64), and patients with transplantation with (n = 106) and without (n = 30) acute rejection of any grade. The 15 hearts were from 1 heart donor, and from patients with cardiomyopathy (n = 5), valvular heart disease (n = 2), ischemic heart disease (n = 4), amyloidosis (n = 1) and transplantation with acute rejection (n = 2). The PCNA labeling index was plotted against myocyte hypertrophy, inflammatory infiltrates and binucleation index. The PCNA labeling index ranged from 2 to 9% in embryonic and fetal hearts. PCNA was expressed by 1 to 2% of myocyte nuclei in 12% of normal heart biopsies, 1 to 5% of myocyte nuclei in 28% of cardiomyopathy and myocarditis biopsies, and by up to 8% of myocyte nuclei in 53% of biopsies of patients with transplantation, independently of the presence and degree of acute rejection. In the latter biopsies and in myocarditis, some inflammatory cells also showed PCNA expression. PCNA positive myocytes were both mono- and binucleated, and there was no correlation between binucleation and PCNA labeling indexes. Ki67 and PCNA blotting confirmed immunohistochemical results.(ABSTRACT TRUNCATED AT 250 WORDS)
Low doses of acetylcholine induce "endothelium-dependent" dilatation in normal coronary arteries and constriction of diseased vessels. This study investigated morphologic changes induced by perfusion of normal and diseased coronary arteries with low and high doses of acetylcholine. Vessels were excised from a series of beating hearts explanted at transplantation for idiopathic dilated cardiomyopathy and coronary artery disease. Coronary arteries from other explanted hearts, perfused with saline solution under similar conditions were taken as controls. Samples were studied using conventional histopathologic and immunohistochemical methods. Coronary arteries were grouped according to presence or absence of histologically detectable structural modifications of any type and extent. Low doses of acetylcholine induced changes in all but 1 structurally diseased coronary artery, whereas no change was induced in any but 1 histologically normal coronary artery. High doses of acetylcholine induced contraction changes in both normal and diseased vessels. Changes observed in the wall of the contracted vessels were: (1) endothelial cell contraction with protruding nuclei and detachment of their intercellular junctions with exposure of subjacent collagen to flow, (2) contraction of plaque smooth muscle cells, (3) formation of cushions protruding into vessel lumens causing blunt microchannels. Contraction in both intimal and plaque cells occurred even in diseased vessel segments with intimal denudation. These effects seemed to be dose-dependent in structurally normal vessels because low doses of acetylcholine did not produce any morphologically detectable changes in histologically normal coronary arteries, while low doses of acetylcholine induced similar reactions in vessels affected by both atherosclerosis and subintimal fibrocellular thickening.
Distal ureteral stones are usually treated today by extracorporeal shock wave lithotripsy or extraction by retrograde ureteroscopy with or without previous fragmentation. We performed a cost-efficacy study of three methods to treat them: extracorporeal lithotripsy using either a spark gap lithotripter, the unmodified Dornier HM3 (SWL), or the piezoelectric Wolf Piezolith 2300 (EPL) and endoscopic lasertripsy (LISL) using an alexandrite pulsed laser, the HMT Alexantriptor. The records of 520 patients with distal ureteral stones treated by extracorporeal lithotripsy were reviewed to establish the mean cost of the procedure. Concerning LISL, the first 30 stone patients treated in our institution were evaluated. Four measures were examined: (1) number of sessions; (2) success rate; (3) auxiliary maneuvers; and (4) complications. The economics evaluation considered the direct costs related to personnel, consumables, depreciation, and maintenance. The EPL procedure was the cheapest: $873 US, and SWL the most expensive: $3,572 US. The best cost-efficacy rate was seen with LISL because of its 93% success rate and its cost of $1,390 US.
The simultaneous endoscopic approach to upper urinary tract pathology in both an antegrade and retrograde fashion can be cumbersome. The prone split leg and flank roll positions allow such simultaneous access. Of 111 patients in whom the prone split leg position was employed, 41% were treated with simultaneous antegrade and retrograde endoscopy in a two-team approach. Treating large staghorn calculi in this manner, one team debulked the stone burden accessible through the flank nephroscopically, while another team approached the remainder of the stone burden using the pulsed-dye laser ureteroscopically in a retrograde manner. The flank roll position was employed in 15 patients who presented with percutaneous nephrostomies and were deemed treatable preoperatively in a retrograde manner. They were positioned in this manner to allow intraoperative access to the percutaneous nephrostomy tract. Nine of these patients required antegrade treatment. The application of these two positions and the concept of the two-team approach added to the efficiency of treating not only staghorn calculi, but other upper tract pathology. Simultaneous procedures require at least two skilled endoscopists as well as dual light sources, various lithotrites, and several rigid and flexible endoscopes.
The recent evolution of actively deflectable, flexible endoscopes has included the flexible cystoscope. Improvements in optics, deflectability, and the size of the outer sheath and working channel have been accomplished. A superior flexible cystoscope is one with an outer sheath of 16F or less and working channel large enough to admit standard endoscopic instruments (> or = 6F). The 180 degrees two-way thumb-directed deflection and a removable light bundle are significant improvement. We present 55 patients with either urethral, bladder, or upper urinary tract lesions who were treated at the bedside using the flexible cystoscope in many settings. Local anesthesia alone was usually used. Flexible cystoscopy was also used for emergency intraoperative consultation requiring endoscopy. A treatment cart was constructed consisting of a light source, endoscopic instruments, irrigating supplies, and the endoscope. Urethral strictures, perforation, and bladder neck contractures were treated. Ureteral catheters were placed under direct vision. Removal of ureteral stents and foreign bodies, treatment of small bladder tumors with the Nd:YAG laser, and fragmentation of bladder calculi with the pulsed-dye laser were also therapeutic applications. Explanations of each treatment type and the instruments used concurrently with this endoscope are provided.
BACKGROUND: Coronary thrombosis is the major cause of acute myocardial ischaemia but can be, albeit rarely, clinically silent. We investigated a series of autopsy hearts from hospitalized patients who died from non-cardiac causes, to detect and study coronary thrombosis. METHODS: The series consisted of 132 autopsy cases (81 men and 51 women, age range 32-39 years, mean 63 +/- 14), in whom cause of death was confirmed as extracardiac. Major epicardial coronary arteries were isolated from the hearts and routinely processed for histopathological study. We evaluated the presence of coronary atherosclerosis and thrombosis. Plaque size was histologically graded with low magnification lenses. RESULTS: Coronary atherosclerosis, which was found in 110 hearts, caused critical stenosis or occlusion of at least one major vessel in 55 (41.6%) cases. Coronary thrombosis was found in 10 vessels from nine different hearts. One coronary tree presented two thrombi in two different vessels. Thrombi were mural in all but one vessel. We did not observe either deep sub-thrombotic ulceration or atheromatous material mixed with thrombus. Deep thrombus layers often presented organizing features. There was no correlation between thrombosis and degree of vessel stenosis, which was only mildly increased by thrombus. Plaque rupture without thrombus was found in five coronary arteries of five different cases. CONCLUSIONS: Coronary thrombus may overlay the intima of a diseased vessel independently of plaque type and severity. Moreover, thrombosis is more frequent than expected, although it is rare when compared with the spread of coronary atherosclerosis. It may represent a plaque progression mechanism in the natural history of coronary atherosclerosis.
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Impotence following transurethral prostatectomy is one of the main complications that still has a controversial origin. Many authors, reporting their experience, have demonstrated that this complication is due both to psychological problems and to organic causes. We review retrospectively 68 patients submitted to TURP. All patients (53 to 65 years old) were asked about their sexual efficiency before and after TURP, 6-12 months after surgery. Those who complained of erectile failure have been studied using this diagnostic protocol: plasmatic dosage of FSH, LH, Testosterone and Prolactin; penile Doppler ultrasound, polysomnographic recording of nocturnal tumescence test (NPT Test); angiography of the pudenda arteries has been performed in only one patient with pathological penile Doppler ultrasound (IPP < 0.7). The examinations demonstrated an organic impotence not secondary to vascular damage in 10 patients following surgery (incidence 15.6%). Our high incidence of this complication is, according to us, significant even if it should be considered in excess since in our study we used anamnestic criteria alone in the evaluation of sexual efficiency before surgery. In 1984 T. Lue demonstrated, through accurate histological preparations, that cavernous nerves run contiguously to the prostatic capsule at 5 and 7 hours in correspondence of the glandular apex. He suggested that impotence following TURP is due to iatrogenic lesions of these nervous structures during endoscopic resection. Similarly, we have conducted an anatomopathological study on prostate specimens taken from autopsies. We demonstrated the presence of nervous structure contiguously to the prostatic capsule in correspondence with the glandular apex. Thus, impotence following TURP probably occurs after an iatrogenic heat lesion of the periprostatic plexus caused by resection.(ABSTRACT TRUNCATED AT 250 WORDS)
A polymerase chain reaction (PCR) amplification assay was developed to detect Coxsackievirus B3 ribonucleic acid (RNA) in blood and myocardial tissue of explanted hearts from 40 patients who underwent cardiac transplantation and in 1 normal heart. Twenty-one patients were affected by idiopathic dilated cardiomyopathy of different duration and 19 by coronary artery disease. Coxsackievirus B3 in vitro infected Vero cells and cells infected by related human enteroviruses (Coxsackievirus B2, B4, and poliovirus 1) were used as reaction controls. PCR was performed using 4 pairs of primers homologous to Coxsackie-virus B3 sequences. Three sets were located in regions of the genome conserved at nucleotide level between several enterovirus species (replicase gene, 5' noncoding region), while one was located in a Coxsackievirus B3-specific region (VP1 gene). Total RNA was prepared by acid guanidinium isothiocyanate extraction from tissue stored frozen at -80 degrees C. One microgram of total RNA was retrotranscribed with either antisense primer or with random hexanucleotide primers and then subjected to 40 cycles of amplification. PCR products were separated by electrophoresis on a 10% polyacrylamide gel, electrotransferred to a nylon membrane and then hybridized to oligonucleotide probes specific for the coxsackievirus B3 genome radiolabeled with radioactive isotope of phosphorous. All pairs of primers yielded specific amplification products when tested on Coxsackievirus B3-infected Vero cells, with a sensitivity of 1 infected cell out of 10(5) to 10(6) cells starting from 1 microgram total RNA. Primer sets for regions of Coxsackievirus B3 genome highly conserved between related enteroviral species gave positive amplification also when challenged with RNA from cells infected by Coxsackievirus B2, B4 and poliovirus 1.
We have compared the localization of brain and atrial natriuretic peptide-like immunoreactivity in human and porcine hearts, using immunohistochemical techniques at both the light and ultrastructural level and specific antisera to amino-(cardiodilatin) and carboxy-terminal regions of the atrial natriuretic precursor molecule and to brain natriuretic peptide. Atrial myocardial cells in human fetal, normal adult and failing explanted hearts, displayed immunoreactivity for both brain and atrial natriuretic peptide-like sequences. At the subcellular level, brain natriuretic peptide-, cardiodilatin- and alpha-atrial natriuretic peptide-like immunoreactivity were co-localized to secretory granules in atrial myocardial cells. Immunoreactivity was also detected in the left (64%) and right ventricular free walls (23%) of 22 failing explanted hearts, but not in donor cardiac tissues. A gradient of natriuretic peptide immunostaining was observed across ventricular free walls and immunoreactivity for both natriuretic peptide sequences co-localized to secretory granules in a subpopulation of myocardial cells, concentrated in subendocardial regions of the ventricular walls. Brain and atrial natriuretic peptide-like immunoreactivity were also demonstrated in porcine atrial myocardium and cells of the ventricular conduction system. The parallel distribution of cardiac brain and atrial natriuretic peptide-like immunoreactivity suggests a dual regulation and co-storage of the natriuretic peptides in human and porcine hearts.
Urothelial recurrence of renal cell carcinoma after radical surgery is exceedingly rare. We report on a 48-year-old man who underwent upper urinary tract flexible endoscopy to define a filling defect, which was found to be a perforating renal cell carcinoma. After radical nephrectomy the patient had multiple recurrences on the urinary surfaces, ureter and urethra. Urothelial lesions were treated endoscopically. He remains free of tumor 42 months after the last treatment.
The adenylate cyclase system present in particulate fractions prepared from two planarian species was tested for sensitivity to various neurotransmitters. While dopamine and other catecholamines were ineffective, serotonin was capable of stimulating the enzyme. Among the various serotonin agonists tested, only 8-OH-DPAT resulted effective on the adenylate cyclase activity, thus suggesting the presence in planarians of a serotonin receptor of the type 5-HT1A.
A monoclonal anti-idiotype antibody (IgG1k MoAb 3B11D4) raised against the amyloidogenic DEP lambda chain dimer binds a conformational idiotope also present on the monoclonal DEP IgA immunoglobulin. MoAb 3B11D4 does not recognize the reduced and alkylated lambda chain monomers, nor the 15-17-kDa fibrillar light chain fragments which have the same N-terminal sequence of the urinary light chains. The lack of about 70 amino acid residues of the C terminal of the protein prevents the formation of the self-limiting dimer and may facilitate the deposition of the fragments into amyloid fibrils. MoAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning experiments demonstrate that this antibody has the capability to selectively eliminate the idiotype positive cells from peripheral blood. Antibodies with these characteristics could become a useful tool for better understanding the pathogenesis of the disease and for new therapeutic options.
In some patients nocturnal penile tumescence (NPT) is abnormal, while the others diagnostic evaluations and medical history do not indicate any specific organic cause of impotence. Aim of this study was to evaluate heart rate variability during sleep in impotent patients with any demonstrable organic cause of impotence. We studied 50 patients: 26 were psychogenic and 24 organic on the basis of NPT and nocturnal rigidity. A lower orthosympathetic activity has been found in organic patients. Because beta-adrenergic receptors mediate relaxation of corpus cavernosum, it could be hypothesized a penile beta-adrenergic dysfunction in our organic patients.
From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21%) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3%): all were from patients with primary HCMV infection (6 of 13; 46%). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.
We describe our experience of surgical therapy for vasculogenic impotence, using a technique of arterialization of the deep dorsal vein. This technique was chosen because vascular anastomosis can easily be performed, and because of the possibility of inducing haemodynamic mechanisms which favour the maintenance of rigidity, using venous arterialization. The operation was performed on 22 selected subjects with positive results. 12 patients (55%) reported erections which enabled them to have satisfactory sexual relations one year after follow-up. From the data reported we can conclude that penile revascularization, using the technique of arterialization of the deep dorsal vein, in well selected cases of vasculogenic impotence, should be considered a valid alternative to a penile prosthesis implant.