Biomedical subjects
Publications and source records attributed to A Musca.
A case of CSS is reviewed, along its difficult diagnosis, to check if its late discovery is attributed to inevitability or to erroneous approach.
In the light of recent fresh reports of drug-induced lung lesions, the authors suggest an updated classification of these based on data found in the literature. Special attention has been reserved to the pathogenetic mechanisms underlying specific clinical pictures.
Erythrocytes from a patient with hypokalemic periodic paralysis (HPP) have been studied, in order to investigate the presence of alterations of membrane cation active transport systems. An original 23Na-NMR method has been used, capable of evaluating quantitatively the Na+ efflux due to the Na+/K+/Cl- cotransport. This method uses a loading system to increase internal cellular Na+ concentration: in the patient with HPP both the internal Na+ concentration after loading and the Na+/K+/Cl- cotransport activity were decreased in comparison to the controls. Our data seem to confirm that the fall of K+ serum levels during attacks in HPP must be ascribed to a shift of K+ from extra- to intracellular compartment (with consequent changes in the fibrocellular membrane polarity), due to an alteration of membrane cation transport system: which does not only consist in a hyperactivity of Na+/K+ ATPase (already described by other AA.), but also in a "secondary" decreased K+ efflux driven by the cotransport. The decrease of cotransport activity may be considered as "compensatory" (in fact, the intracellular Na+ content is normal), since this transport system can work as a kind of "emergency" system that can "help" the ATPase-dependent pump in extruding any excess of cell Na+ content, or can be depressed by any decrease of this value, caused by an hyperactivity of the Na+/K+ ATPase. The decreased cotransport activity results in a powerful contribution to the increase of intracellular potassium due to the hyperactivity of the Na+/K+ pump. This method could supply a useful diagnostic marker in all uncertain cases.
This study explored the relationship between clotting activation and tissue plasminogen activator and its inhibitor in cirrhotic patients with different degrees of liver failure. Sixty-seven patients (40 men, 27 women; age = 31-77 yr) with cirrhosis diagnosed by liver biopsy were divided into three subgroups (A, B and C) on the basis of Child-Pugh classification. Tissue plasminogen activator antigen and activity, plasminogen activator inhibitor antigen and activity, fibrin/fibrinogen degradation products, and D-dimer were measured in each patient. Forty-two patients with normal levels of fibrin/fibrinogen degradation products and D-dimer showed significant progressive decreases of plasminogen activator inhibitor antigen levels (p < 0.01) and activity (p < 0.0001) from class A to class C. This decrease was significantly related to prothrombin time (p < 0.003). Tissue plasminogen activator values were not different in the three Child classes. Twenty-five patients (7 class B and 18 class C) with high circulating values of fibrin/fibrinogen degradation products and D-dimer had higher values of tissue plasminogen activator antigen (20.0 +/- 10.1 ng/ml vs. 5.9 +/- 3.0 ng/ml; p < 0.0001) and activity (6.9 +/- 2.2 U/ml vs. 2.1 +/- 1.3 U/ml; p < 0.0001) and lower values of plasminogen activator inhibitor antigen (6.9 +/- 4.1 ng/ml vs. 14.8 +/- 5.6 ng/ml; p < 0.0001) and activity (4.1 +/- 2.8 U/ml vs. 9.8 +/- 3.7 U/ml; p < 0.0001) than did patients with normal values of fibrin/fibrinogen degradation products and D-dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors review the pathophysiologic mechanisms involved in bowel motility and in its alterations. Several symptoms are present in a form of bowel disease usually defined as "irritable bowel", in which a lot of polymorphic aspects appear to coincide. The first part of the paper is concerned with the symptoms and suggested pathophysiology and pathogenesis of the disorder while the latter part deals with the non-pharmacologic and pharmacologic treatment options.
Sodium balance plays a primary role in blood pressure regulation. Atrial natriuretic peptide, a recently discovered natriuretic substance, seems to participate in renal sodium handling, but its behavior in essential hypertension has not been fully defined. In our study, to avoid the "contamination" of factors other than hypertension, we evaluated the plasma levels of atrial natriuretic peptide in young men at military draft age. Our main results showed that plasma atrial natriuretic peptide levels are higher in young hypertensives with low plasma renin activity and low urinary excretion of active kallikrein. The influence of a positive genetic background for essential hypertension on plasma atrial natriuretic peptide levels was also investigated. Our data showed slightly elevated levels of the atrial hormone in young normotensives with a family history of hypertension.
Thirty T cell clones were generated from T cell blasts, infiltrating the liver of autoimmune chronic active hepatitis (CAH) patients, stimulated with autologous hepatocytes expressing class II major histocompatibility complex (MHC) molecules and interleukin 2 (IL2). Sixteen clones were CD4+ and 14 were CD8+; all were CD25+ and WT31+, revealing that all cell lines expressed the alpha/beta chains of T cell receptor. Five CD4+ and 4 CD8+ T clones proliferated in response to hepatocytes expressing both class I and class II antigens. The hepatocyte recognition was MHC restricted because only class II MHC-matched hepatocytes were able to stimulate the CD4+ T clones, while only class I-matched hepatocytes stimulated CD8+ T clones, and because MoAbs to monomorphic determinants of class II antigens or to class I antigens appeared to block the response of the CD4+ and CD8+ T clones, respectively. These findings, together with the observation that autologous irradiated peripheral blood mononuclear cells (iPBMC) were unable to stimulate the clones, indicate that the response of these clones was directed to a liver membrane antigen in association with class II or class I MHC molecules on the surface of the hepatocytes. All the CD8+ T clones and 5 CD4+ T clones expressed high cytotoxic activity in a lectin-dependent cell-mediated cytotoxicity assay; 10 CD8+ and 3 CD4+ T clones also showed natural killer (NK)-like function. The cytolytic machinery was also present in those clones (both CD8 and CD4) recognizing the HLA-matched hepatocytes. All liver-derived T clones were able to produce high amounts of interferon (IFN)-gamma, as well as being capable of secreting IL2, following PHA stimulation.
Plasma atrial natriuretic peptide (ANP) behavior was evaluated in 26 untreated essential hypertensives, 21 normotensives, and 20 normotensives with hypertensive heredity under normal sodium intake (120 mEq of Na+/day). All subjects were men, mean age 22.1 +/- 1.9 years. Plasma ANP was evaluated by radioimmunoassay on samples collected in supine position upon waking and again after 1 h of orthostatism. Resulting data showed that ANP in hypertensives (supine = 44.5 +/- 19.4 pg/mL, orthostatism = 24.1 +/- 11.6 pg/mL) was at higher levels than in controls (supine = 38.3 +/- 19.4 pg/mL, orthostatism = 19.9 +/- 10.6 pg/mL) or in normotensives with hypertensive heredity (supine = 42.1 +/- 16.8 pg/mL, orthostatism = 23.2 +/- 10.8 pg/mL). Mean ANP level was higher in the latter group than in the control group (supine = +9%; orthostatism = +14.2%). In conclusion, plasma ANP is raised in young essential hypertensives, resulting in slightly elevated levels in normotensives with hypertensive heredity.
We performed an epidemiological study on the atrial natriuretic factor pattern in a young population. Subjects were recruited in the Ospedale Militare Principale of Rome among young men liable to conscription, whose hospitalization was due either to essential hypertension or to other pathologies (not influencing our study, such as headache etc.). The recruitment lead to the formation of three different groups: normotensives, normotensives with family history of hypertension (mother and/or father) and hypertensives. On the morning of the study (after 7 days of pharmacological wash-out, under a diet containing 120 mEq of Na+/die), blood samples were taken. Plasma atrial natriuretic factor, renin activity and aldosterone were assayed by RIA. Digoxin-like immunoreactive substance was assayed by a solid-phase radioimmunoassay, following the extraction of plasma. Serum creatinine, sodium, potassium and urinary sodium and potassium (24 h before the study) were assayed by standard methods. Urinary kallikrein was assayed by chromogenic substrate S-2266. So far, we have studied 60 subjects (26 hypertensives, 21 normotensives and 13 normotensives with family history) and we wish to discuss in this article the preliminary results concerning the atrial natriuretic factor and its relationship with renin activity, aldosterone and blood pressure. Our results show that the mean plasma levels of atrial natriuretic factor in the hypertensive group were higher, although not significantly, than those of the other two groups and that the normotensives with family history had slightly higher levels as compared to normotensives (Delta % = + 7.4).(ABSTRACT TRUNCATED AT 250 WORDS)
Factor VII and prekallikrein activities were studied in 37 patients with liver cirrhosis who were in a decompensated state. Sixteen of them died 30-70 days after admission; 21 survived and were discharged after 30-80 days. Seven who died and six survivors had signs of hyperfibrinolysis: factor VII activity differentiated the two groups independently of the presence of hyperfibrinolysis. The presence of hyperfibrinolysis significantly reduced prekallikrein activity, which did not differentiate clearly survivors from non-survivors. Long term follow up of survivors showed a good correlation between factor VII and prekallikrein activities with long term survival. Hyperfibrinolysis seemed to influence the clinical course of patients: 87% of patients with hyperfibrinolysis who died had fatal haemorrhagic episodes. Low factor VII activity may be a precursor of terminal liver insufficiency.
Peripheral blood mononuclear cells (PBMC) from 'responders' recently boosted with hepatitis B vaccine, were studied for synthesis in vitro of antibody to hepatitis B surface antigen (anti-HBs Ab) when stimulated with pokeweed mitogen (PWM) or HBsAg. HBsAg alone can induce an antigen-specific anti-HBs Ab response in vitro; this antibody synthesis is T cell-dependent. In some responders both allogeneic T4+ cells (in absence of PWM or HBsAg) and mixed leucocyte culture supernatants (MLC/SN) (without T cells and antigen) can help responder B cells to produce anti-HBs Ab. Thus, in some immunized subjects, B lymphocytes involved in anti-HBs Ab synthesis are in an advanced phase of differentiation and require only non-antigen specific T cell signals (B cell growth factor or B cell differentiation factor or interleukin 2, etc) to differentiate into antibody-secreting cells. Moreover, the concentration of the antigen necessary to suppress anti-HBs Ab production induced by HBsAg was five times lower than that necessary to suppress antibody production induced by PWM. T cell help for antigen induced anti-HBs Ab could be different from T cell help for the PWM-induced anti-HBs Ab response. Moreover, the finding that the low HBsAg doses inhibiting specific response did not affect the PWM-driven anti-HBs response suggests that antigen-specific T suppressor cells could play a role in this context.
Normotest, serum albumin, prekallikrein (Prekk), and Factor VII plasma activity were investigated in 64 patients with chronic liver disease--13 with type I chronic active hepatitis (CAH), 10 with type II CAH, 16 with compensated liver cirrhosis (LC), and 25 with decompensated LC--and in 20 matched-for-age healthy individuals. All of these blood parameters were reduced significantly as a result of liver damage. Patients with type II CAH and compensated LC had similar blood coagulation values. Eight decompensated LC patients, who died 30 to 45 days after the last blood coagulation parameter measurements, showed significantly low Prekk and Factor VII values compared with eight matched for sex and age survivors of decompensated LC. Prekk and Factor VII values of nonsurvivors did not overlap those of the survivors. This striking difference was not detected if Prekk and Factor VII were studied 2 to 4 months before death. These data suggest that Prekk and Factor VII are very sensitive to liver damage and could be useful prognostic indexes of liver insufficiency.
Peripheral blood lymphocyte subsets involved in cytotoxicity to autologous hepatocytes have been characterized by isolation on antibody-coated Petri dishes in autoimmune and HBsAg-positive chronic active hepatitis (CAH). In autoimmune CAH and in HBsAg-positive CAH without HBcAg in liver tissue, cytotoxicity is sustained by non-T lymphocytes and is confined to M1-positive cells bearing Fc receptors: M1 cytotoxicity inhibition by adding aggregated IgG suggests that these cells are responsible for an antibody-dependent cell-mediated mechanism (ADCC). Moreover, when T-enriched fractions were separated in T4, T8 and 5/9 positive subsets, only the first one showed a significant cytotoxicity: T4 positive cells might act as cytotoxic T cells or might be involved in delayed type hypersensitivity (DTH) reactions. Cytotoxic T lymphocytes in HBsAg-positive CAH with HBcAg in liver tissue are confined in T8 positive subset, while helper/inducer T cells (T4 positive or 5/9 positive) seem to play an important role only in the induction of cell-mediated injury against hepatocytes. The inhibition of T cell-cytotoxicity by preincubating liver cells with monoclonal antibody (Mab) anti-HLA AB and not with Mab anti-HLA DR or aggregated IgG supports the involvement of the class I major histocompatibility complex (MHC) expressed on the hepatocyte surface.
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In contrast to convalescent hepatitis B patients, who exhibit the ability to elicit a specific immune response to HBsAg, patients with chronic hepatitis B virus (HBV) infection are markedly hyporesponsive to HBsAg and show a decrease in the normal ratio of OKT4-positive (helper/inducer) to OKT8-positive (suppressor/cytotoxic) lymphocytes. In this study the role of OKT4-positive and OKT8-positive cells on cellular immune response to HBsAg was evaluated in patients with chronic HBV infection and the ability of such patients to develop antigen-specific suppressor lymphocytes after in vitro sensitization to HBsAg. Elimination of OKT8-positive cells markedly improved the in vitro lymphocyte proliferative response to HBsAg without altering the reactivity of cells from the same donor to PPD or Candida. In contrast, the degree of responsiveness to HBsAg was not affected by the depletion of OKT4-positive cells. In vitro co-culture experiments, performed in the seven chronically HBV-infected patients who showed a proliferative response when their PBM were cultured with purified HBsAg or PPD, have demonstrated that lymphocytes from chronic HBV carriers, stimulated with HBsAg, inhibit the response of autologous PBM to HBsAg but not to the unrelated antigen PPD.
Platelet aggregation (PA) and plasma beta-thromboglobulin (beta TG) values were evaluated in 40 patients affected by chronic airway obstruction (CAO). PA and beta TG were significantly higher than those observed in normal subjects. Beta TG plasma levels were inversely correlated with PaO2, directly with PaCO2 and [H+]. Two h after a venesection of 300-400 ml, no change of beta TG and PA was seen in 10 healthy subjects, while a significant increase of beta TG and PA values was observed in 29 patients. The investigation suggests that in patients with CAO in vivo platelet activation is present.
Immunoregulatory mechanisms in chronic HBsAg carriers have been investigated through the study of in vitro proliferative responses to HBsAg by allogeneic coculture experiments between T lymphocytes from HBsAg + chronic active hepatitis (CAH) patients (HBsAg no responder) and PBMC from subjects boosted with anti-hepatitis B vaccine (high responder). When high-responder PBMC have been challenged with the hepatitis B surface antigen (HBsAg) in the presence of HBsAg no-responder T lymphocytes, HBsAg no-responder T lymphocytes caused an antigen specific, dose-dependent, suppression of the responsiveness of high-responder PBMC. On the other hand, T cells from patients with autoimmune CAH did not exert any suppressor effect in our system. The suppressor T lymphocytes were mitomycin C resistant and were positive for OKT8, but were negative for OKT4. When T8 + cells were depleted from HBsAg no-responder PBMC, the in vitro immunoproliferative response to HBsAg in chronically HBV infected patients was markedly improved. Out data clearly demonstrate the existence of T8 + suppressor T lymphocytes that can control low responsiveness to HBsAg in chronic HBV patients.