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Biomedical subjects

M Grasso

Publications and source records attributed to M Grasso.

At least 163 records · Page 9Linked to original sources

Endomyocardial biopsy of normal donor hearts before cardiac transplantation. A morphological and morphometrical study in 97 cases.

Endomyocardial biopsies from 97 normal donor hearts were examined. Morphometric analysis showed: mean myocyte diameter 22.21 +/- 6.93 mu, mean nuclear dimension 7.32 +/- 2.33 mu, mean nuclear/sarcoplasmic ratio 0.33 +/- 0.02. 31 biopsies showed enlarged myocytes (mean diameter 31.65 +/- 3.98 mu) with increased nuclear size (mean 10.45 +/- 1.39 mu), but preserved nuclear/sarcoplasmic ratio (mean 0.33 +/- 0.01). The mean age of these latter subjects was significantly higher. Endocardial thickness mean value was 17.73 +/- 4.58 mu, but in 28 cases the value exceeded the considered upper normal limit of 20 mu. Interstitial mononuclear cells were rare and randomly present. Interstitial fibrosis was observed in 15% and focal fibrosis in 27% of cases. Our results show that histology of biopsies from clinically normal hearts can widely vary, sometime overriding the pathologic boundaries. These apparently "benign" abnormalities should be kept in mind when specific pathologic substrates of cardiac diseases have to be defined.

Adolescent↗

Premutation for the Martin-Bell syndrome analyzed in a large pedigree segregating also for G6PD-deficiency. I: A working hypothesis on the nature of the FRAX-mutations.

A large Sardinian family including 13 Martin-Bell syndrome (MBS) patients, several instances of normal transmitting males or females, and the G6PD-Mediterranean mutant segregating in some of its branches, has been thoroughly investigated with the hope of gaining further insight on the nature of the FRAX-mutation. All the MBS patients and the 15 obligate heterozygous women present in the pedigree could be traced back through their X-chromosome lineage to the same ancestress, who must have been heterozygous for a silent premutation at the FRAX-locus. This premutation appears to have turned into a true FRAX-mutation at least 9 times during the gametogenesis of the ancestress' X-related descendants of whom four are males. This finding alone suggests that the transition from the FRAX premutation to the true mutation can be the result of intra- as well as interchromosomal events. This conclusion is supported by the additional observation that the genetic phase between the FRAX and the G6PD loci remained unaltered when the transition occurred in a repulsion double heterozygote for the premutation and the G6PD-Mediterranean mutant. The data described are compatible with the hypothesis that MBS patients and normal transmitting males are, respectively, hemizygous for deletion or duplication products generated by aberrant recombination events at a highly recombinogenic site of the region Xq27-Xqter. The overall message stemming from this report is that no firm conclusion can be drawn on the genetic linkage between the FRAX-locus and other markers of this region until the nature of the FRAX-mutations and the mechanism of their occurrence are fully understood.

Adult↗

Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study.

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.

Adult↗

Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity.

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.

Adolescent↗

Techniques in endoscopic lithotripsy using pulsed dye laser.

The pulsed dye laser represents a new tool in the treatment of ureteral calculi. Laser energy channeled through a delicate optical fiber is used to disimpact and fragment calculi. Standard ureteroscopic instruments including graspers, baskets and dilatation balloons can be used with the laser system. Interchangeable optical fibers ranging from 200 to 400 micrometers deliver up to 120 mJ of energy to the stone's surface. For two weeks in 1989 an endourology clinic was held in upper Egypt. Eighty patients ranging in age from nine years to sixty-seven years old were evaluated and treated endoscopically. Endoscopes ranging from 6.9F to 12.5F were used to deliver the optical fiber. All stones visualized endoscopically were fragmented. Greater than 60 percent of the stones fragmented were composed of pure calcium oxalate monohydrate. Schistosoma hematobium was endemic among our study group. Bilharzial strictures of the distal ureter were noted in 30 percent of these patients. Treatment of these strictures using both balloon dilatation and graduated Teflon dilators is reviewed. Techniques in treating different types of ureteral calculi were explored. Large calcium oxalate dihydrate stones were treated most efficiently with the 3-point fragmentation technique. The shear off-center technique was used for the calcium oxalate monohydrate calculi. Variations in total energy delivered and frequency of pulsation allowed for prompt stone disimpaction as well as prevention of retrograde fragment migration. Concurrent use of stone baskets and graspers with the pulsed dye laser was explored.

Adolescent↗

Transhepatic laser lithotripsy of choledocholithiasis: initial clinical experience.

Three patients with symptomatic intra- and extrahepatic choledocholithiasis who were not good candidates for retrograde endoscopy, surgery, or extracorporeal shock wave lithotripsy (ESWL) were treated successfully with endoscopically guided tunable dye laser lithotripsy via a 12-F transhepatic sheath. There were no complications secondary to the use of the laser. On the basis of this initial experience, transhepatic laser lithotripsy is a technically feasible and safe alternative when choledocholithiasis cannot be managed with retrograde endoscopy, ESWL, or surgery. Its role in the management of choledocholithiasis relative to other transhepatic techniques remains to be determined.

Adult↗

Pulsed dye laser lithotripsy--currently applied to urologic and biliary calculi.

The flash lamp excitation of coumarin dye to produce light energy of the specific wavelength of 504 nm is the basis for the new wave of pulsed dye lasers. Numerous urological applications have been developed. Treatment of ureteral and renal calculi has proven to be an atraumatic and effective treatment modality. Most recently, this technology has been applied to the endoscopic treatment of biliary calculi. The authors review the most recent treatment techniques in both biliary and urinary stone disease.

Cholelithiasis↗

Postpubertal cryptorchidism: review and evaluation of the fertility.

We assessed the fertility of 91 patients affected by unilateral cryptorchidism who were subjected to postpubertal orchidopexy in the last 15 years. All cases were clinically examined, evaluated by semen analysis and Doppler ultrasound of the spermatic artery. Twenty-two patients underwent testicular biopsy. The results indicate that orchidopexy is not the best treatment for postpubertal cryptorchid patients. After orchidopexy, 83.5% of patients were azoospermic or oligospermic, with or without asthenospermia.

Adolescent↗

[Endomyocardial biopsy in the heart transplant patient: the state of the art].

Data regarding 2176 endomyocardial biopsies (EMB) (Nov. '85-Dec. '89) performed in 164 transplanted hearts (4 etherotopic) from 158 patients (6 retransplants) are herein reported. This study was aimed to evaluate: 1) Incidence and characteristics of early ischemic myocardial damage. 2) The influence of different immunosurveillance protocols on incidence, degree and aggressiveness of acute rejection and the inflammatory infiltrate composition. 3) The immunophenotype of infiltrating cells in moderate acute rejection episodes. 4) HLA-DR antigen expression on myocyte sarcolemma. 5) Characterization of cells expressing immune response mediators. 6) Myocardial localization of opportunistic infections. 7) Useful information on chronic rejection. Our results demonstrate that: a) Mild rejection seldom progresses to moderate degree. b) Different immunosuppressive protocols can influence the incidence of acute rejection: in fact, in OKT3 protocol, the incidence of rejection episodes is higher than in other protocols as well as aggressiveness toward myocytes. c) Infiltrating cells maintain T lymphocyte prevalence with minor amounts of B lymphocytes and macrophages in the 3 different protocols. T cell subset characterization showed a slight prevalence of CD8 bearing cells over CD4 positive cells whereas CD57 cells were few and scattered. d) Class II Major Histocompatibility Complex (HLA-DR) expression never occurs on myocyte sarcolemma. e) TNF alpha is expressed in acute cardiac rejection by immunologically activated T lymphocytes and macrophages and the number of immunoreactive cells increases with progression of the rejection. f) Human cytomegalovirus infections can be primary or recurrent. Myocardial involvement has been observed in primary forms. Virus can affect endothelial cells (with no inflammatory reaction) or myocytes (myocarditis) and its diagnosis requires a combination of immunohistochemical and molecular biology techniques. Diagnosis of Toxoplasma gondii infection can be usually accomplished by routine histopathological study. g) Chronic rejection diagnosis is rarely based on biopsy derived information.

Biopsy↗

Expression of tumor necrosis factor in human acute cardiac rejection. An immunohistochemical and immunoblotting study.

The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNF alpha) in endomyocardial biopsies from human cardiac allografts. TNF alpha immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNF alpha reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNF alpha is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction.

Biopsy↗

Expression of natriuretic peptide in ventricular myocardium of failing human hearts and its correlation with the severity of clinical and hemodynamic impairment.

Atrial natriuretic peptide (ANP) was immunohistochemically investigated in (1) right ventricular endomyocardial biopsy specimens from 87 apparently healthy donor hearts taken from victims of cerebral accidents; (2) 1 normal heart not suitable for transplantation (HBsAg carrier); (3) right ventricular endomyocardial biopsy specimens from 151 patients with dilated cardiomyopathy (DC); and (4) 57 explanted hearts, 26 with DC and 31 with ischemic heart disease. No ANP immunoreactivity was found in normal ventricles. Failing hearts showed ventricular positivity in 31% of the DC biopsy series, in 61% of the left ventricles, and in 30% of the right ventricles of the explanted heart series. An endoepicardial gradient was observed, because ANP positivity was greater and more extensive in the subendocardial layers. Ultrastructural studies were performed on biopsy specimens from 10 normal hearts and 132 DC biopsy samples. No ANP-storing granules were found in biopsy samples of normal ventricles, whereas ANP granules were seen in 15 of 132 (11.4%) DC cases. In parallel immunoblotting, investigation showed the same 13 kDa band protein in 1 normal atrium as well as in 8 failing atria and ventricles. ANP immunoreactivity was positively correlated with higher New York Heart Association functional classes as well as with higher left ventricular end-diastolic pressure (p less than 0.005), end-diastolic volume (p less than 0.005) and end-diastolic volume index (p less than 0.005). In conclusion, apparently healthy ventricles do not show ANP immunoreactivity, whereas failing ventricles do. ANP expression seems to be independent of the underlying disease, but positively related to the clinical status and the degree of left ventricular impairment and dilatation.

Adult↗

Plasma sex hormone binding globulin in patients with prostatic carcinoma.

The concentrations of sex hormone binding globulin (SHBG) were measured in the plasma of 56 men, who were 47 to 85 years of age, by time-resolved immunofluorometric assay with a monoclonal antibody. Twenty-five of the men had untreated carcinoma of the prostate and 17 had untreated prostatic hyperplasia. There were 14 healthy control subjects. SHBG levels were significantly higher in patients with prostatic carcinoma (37.6 +/- 8.4 nmol/l) than in those with prostatic hyperplasia (24.5 +/- 5.2 nmol/l; P less than 0.05) or control subjects (14.9 +/- 2.8 nmol/l; P less than 0.01). It is not known why SHBG levels are higher in patients with carcinoma or hyperplasia of the prostate. The contradictory results obtained in other studies may be due to heterogeneity of the binding globulin causing its values to vary in the different assays used.

Aged↗

[Arterialization of the deep dorsal vein in selected cases of vasculogenic impotence].

We report our study of surgical treatment of vasculogenic impotence using the technique of arterialization of the deep dorsal vein. The results of the operation performed in 13 selected cases are good although the follow-up is still short. The reasons why we consider this technique preferable to the others available for penile revascularization are discussed.

Arteries↗

Origin of extra chromosome 21 in 343 families: cytogenetic and molecular approaches.

As the knowledge of parental origin and meiotic stage of nondisjunction is the prerequisite to evaluation of the possible etiological factors in trisomy 21, we have examined 343 families with at least one Down syndrome child. Of these, 322 were primary trisomies, including 24 mosaics, and 21 were structural rearrangements. This study was carried out by analysing chromosome 21 cytogenetic heteromorphisms and molecular RFLPs. In our study first maternal meiotic nondisjunction (75.3%) is the most common mechanism leading to primary trisomies. In the 24 mosaic cases, the most frequent error occurred at the first meiotic division (83%). The origin of structural rearrangements was maternal in 15 of 21 cases. Trisomy 21q21q was due to an isochromosome, and not to a translocation.

Chromosomes, Human, Pair 21↗

Crossing over and chromosome 21 nondisjunction: a study of 60 families.

To test the hypothesis that meiotic nondisjunction may be caused by reduced chiasma frequency, hence recombination, we investigated 60 families with a trisomic child affected with Down syndrome (DS). We analyzed cytogenetic heteromorphisms (CH) and a number of restriction fragment length polymorphisms spanning regions 11.1 through 22.3 of 21q in both parents, in the DS child and, when available (21 families), in a normal sib. The parental origin and meiotic stage of nondisjunction were determined by combining the results of both CH and RFLP analysis. Crossover events were detected as switches in the parental haplotype expected in both DS and normal sibs. Available recombination frequency data were used to calculate the expected number of crossover events in nondisjoined and in normally segregating chromosomes, given the allele combination present in each family. The observed number of crossover events in normal meioses and in second-division nondisjunctions were consistent with the calculated figures. However, a significant reduction in the observed number of crossover events was found in nondisjoined chromosomes derived from errors in the first meiotic division and, in particular, in the proximal portion of 21q.

Chromosomes, Human, Pair 21↗

Effect of x-rays on chromosome 21 nondisjunction.

In a series of 156 females and 149 males with a Down syndrome (DS) child, a case-control study was performed to evaluate the effect of abdominal-pelvic exposure to diagnostic x-rays prior to conception on nondisjunction (ND). Cytogenetic analysis using QFQ banding allowed unequivocal identification of ND parents as cases. Partners of ND parents were treated as control group. Odds ratio for the association of x-rays exposure and ND occurrence (stratified for sex and age) was 1.85 (borderline to significance: with a 95% confidence interval 1-3.44). Such an association appeared highly significant in older fathers and borderline to significant in younger mothers, when age groups were analyzed separately. By comparing mean parental ages at birth of the propositus, the prevalence of exposure to x-rays appeared moderately associated with aging in control parents of both sexes. Furthermore, the mean age of unexposed ND parents of paternally derived SD cases was the same as the referent population's, suggesting that age is not a risk factor for ND in the male, except for being associated with increasing exposure risk. Conversely, risk attributable to x-rays exposure in the female appears to be progressively diluted with increasing age, by strongly age-dependent high risk, presumably due to biologic factors that are not affected by environmental exposure.

Adult↗