Giorgio Zavagli

Platelet Activation and Fibrinolysis in Large Bowel Cancer

Four coagulation indices [fibrinopeptide A (FpA), X degradation products (XDPs), platelet factor (PF4), beta-thromboglobulin (beta-TG)] were assessed in 38 patients affected by large bowel cancer at different stages before surgery, 7 and 30 days after it, to evaluate the capacity of such neoplasia to influence coagulation. The reported study showed that (1) FpA levels were elevated in nearly all cases both before and after surgery (thus it is a useful index for the diagnosis of such neoplasia, although its levels are not influenced by the presence of metastases), (2) increased levels of XDPs were found in a significantly (p < 0.05) higher percent of patients 7 days after surgery (no significant differences were observed in relation to the cancer stage), (3) PF4 levels were in the normal range throughout the study, and (4) beta-TG levels were increased throughout the study in a high percentage of cases. It may be inferred that large bowel cancers may affect coagulation in either way(s), by triggering platelet activation and/or fibrinolysis. The most useful index for the diagnosis and follow-up of this neoplasia is FpA, although its levels are unaffected by the presence of metastases. The comprehensive evaluation of the four above-mentioned coagulation indices may give rise to the suspicion of large bowel cancer.

Life-threatening hyponatremia caused by vinblastine.

Some days after the administration of a third bolus of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) a patient affected by immunoblastic lymphoma underwent a neurotoxic crisis. The episode lasted 1 week and was followed by a dramatic fall in plasma sodium (104 mEq I−1, associated with a proportionally lesser decrease in plasma chloride and phosphate. Despite the lowest plasma osmolality, detectable levels of circulating ADH were present.After 36 h the hyponatremic episode improved after the infusion of hypertonic sodium chloride. Nevertheless the patient lapsed into a hypotonic coma. The urinary concentrations of the main tubular enzymes (γ-glutamyltranspeptidase,N-acetyl-glucosaminidase, α-glucosidase) proved very high and successively decreased slowly.The most likely cause of such hyponatremic episode is vinblastine. The drug acted through: (a) an already known inappropriate release of ADH, and (b) a hitherto unreported tubular lesion, which impaired the reabsorption of sodium and other coupled solutes.

Coagulation Disorders and Tumor Markers in the Diagnosis of Pancreatic Cancer

Twenty patients (42-80 years old of whom 9 women) affected by instrumentally ascertained pancreatic cancer (7 cases were operated on) were studied. In all of them the following coagulation indices (fibrinopeptide A, FpA; beta-thromboglobulin, BTG; platelet factor IV, PF4; fibrinogen degradation products, XDP) and tumor markers (gastrointestinal cancer associated antigen, GICA; tissue polypeptide antigen, TPA; carcinoembryonic antigen, CEA; alpha-fetoprotein, or AFP) were assessed at the time of diagnosis, and 10 and 30 days after diagnosis, to test whether and which of the above parameters are more sensitive for entertaining the underlying affection. In both operated and nonoperated patients FpA was shown to be the most sensitive index. Lesser sensitivity was shown by XDP, GICA, and BTG. AFP proved to be quite useless as its serum levels constantly fell within the normal range.

Specificity of carcinoembryonic antigen, gastrointestinal cancer-associated antigen, tissue polypeptide antigen, fibrinopeptide A and gamma-glutamyltransferase in the diagnosis and follow-up of gastric cancer.

The usefulness and specificity of the main tumor markers (carcinoembryonic antigen, CEA; gastrointestinal cancer-associated antigen, GICA; tissue polypeptide antigen, TPA; fibrinopeptide A, FpA; gamma-glutamyltransferase, gamma-GT) have been investigated in the diagnosis and follow-up of the circumscribed and disseminated gastric cancers (GCs). The comprehensive evaluation of all of these markers has given the most reliable results. For the diagnosis and follow-up of GCs, the present study has shown that the sensitivity and specificity of the above markers have the following decreasing order: FpA, TPA, GICA, CEA, gamma-GT. However gamma-GT has proved to be a reliable index of the presence of hepatic metastases.

Red Cell 2,3-Diphosphoglycerate Contents and Oxygen Affinity in Heterozygous Beta-Thalassaemia

Red cell 2,3-diphosphoglycerate and whole blood P50 have been found to be significantly higher in β -thalassaemia heterozygotes than in normal controls. Such increases cou

Specificity of tumor markers (CEA, GICA, TPA, α-FP, FpA, γ-GT) for the diagnosis of hepatic metastases from large bowel cancers

In 98 patients affected by colorectal cancer (43 patients with colon cancer, 55 patients with rectosigmoid cancer) the specificity of some tumor markers (CEA, GICA, TPA, α-FP, FpA, γ-GT) has been tested in evidencing the coexistence of liver metastases and the site of the primary tumor, i.e. the rectosigmoid region (rectum + 15 cm of the adjacent sigmoid colon) vs the rest of the colon. Liver metastases, present in 19 patients with colon cancer and in 24 with recto-sigmoid cancer, were previously ascertained by various instrumental investigations.Unlike previous studies which indicated CEA or α-FP as the most reliable markers to suggest the coexistence of liver metastases in such patients, the reported results allow the following sequence, in decreasing order of sensitivity, to be proposed: gg-GT; FpA; CEA and GICA to a similar degree; TPA, which increases only when liver metastases from colon cancer are present; lastly, α-FP, which rises only in very few cases of massive hepatic involvement.

Specificity of fibrinopeptide a (FpA) as a marker for gastrointestinal cancers before and after surgery

In 70 patients affected by gastrointestinal malignancies the plasma fibrinopeptide A (FpA) levels were assessed both before and at various intervals after the operation. At the same time other more commonly used tests of coagulation were carried out.In all the patients plasma FpA levels were shown to be variously elevated, so that they could give useful clues to the diagnosis, treatment, prognosis and follow-up of the gastrointestinal malignancies. In all the patients the coagulation tests fell into the normal ranges. However in the patients affected by recto-sigmoid adenocarcinoma an increase of circulating fibrin degradation products (FDPs) was observed which paralleled the increase of plasma FpA.In conclusion, in gastrointestinal malignancies the increase of plasma FpA levels suggests the cancer-induced start of the coagulation cascade. The assay of this peptide proves to be a reliable marker for these diseases.

An easy diagnostic approach to primary aldosteronism

The infusion of 40 mEq potassium (aspartate) in 250 ml isotonic 1-fructose at a rate of 20 mEq/h into 5 patients (34-56 years old) with aldosteronoma and 2 patients with bilateral primary aldosteronism consistently raised their mean arterial pressure by 15-20 mmHg. Their pressure values returned to the baseline levels 4-5 h after the infusion. In contrast, in controls (10 patients with idiopathic arterial hypertension, matched for age, sex, and magnitude of the untreated hypertension, and 7 patients with inactive adrenal nodules as incidental findings on upper abdomen ultrasound or computerized tomography) the same procedure caused negligible arterial pressure changes. The cause of the rise in blood pressure observed uniquely in patients with primary aldosteronism after infusion of potassium (aspartate) cannot be accounted for by an increase in plasma aldosterone, blood volume, or plasma angiotensin II. The cause of this response thus remains obscure; nonetheless, this simple procedure may prove useful in differentiating primary aldosteronism from idiopathic hypertension, in excluding the adrenal disorder, and in revealing even its mildest forms.

Why inclusion bodies do assume different locations in thalassaemic erythrocytes

SummaryThe reported scanning (SEM), transmission (TS), and freeze-etching (FE) electron microscopic studies have agreed in confirming that in thalassaemic erythrocytes, previously incubated with brilliant cresyl blue (BCB), the unpaired alpha chains precipitate in the central portions of the cell whereas excess beta chains locate in the submembranous regions. This is due to the fact that beta chains, possessing two thiols instead of only one (as in alpha chains), are more liable to bind to similar groups contained in the inner red cell leaflet. Less soluble alpha chains tend to form inter-chain bridges and thus precipitate centrally. SEM observations have given evidence that on the surface of the affected red cells denaturated alpha chains give rise to large and shallow invaginations whereas denatured beta chains lead to a diffuse wrinkled appearance. The causes of the different SEM aspects have been suggested.

Survival and Significance of PNH Erythrocytes: a Scanning Study

The SEM study of PNH erthrocytes which survived incubations with decreasing dilutions (from 1:640 to 1:20) of fresh compatible serum in isotonic sucrose has indirectly evidenced that spherocytes and spherostomatocytes are the most sensitive population to the complement lytic action; swelling is an osmotic consequence of their membrane hypersusceptibility. In such functional abnormality the swollen red cells are closely followed by the cribrous and pitted erythrocytes. A relationship has been found between percentage of the swollen cells and frequency of PNH haemolytic bouts: these are most likely to occur when spherocytes and spherostomatocytes are above 40% of cells. On the contrary, SEM evaluation of swollen erthrocytes does not allow to express any longer-term prognosis about the severity and the course of PNH, owing to the constantly variable marrow production of abnormal erythrocytes.