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Despite huge progress in acidbase knowledge, several confusing, irrational and controversial issues still remain. Acid-base disturbances have been usually evaluated with the traditional Henderson-Hasselbach method and with BE evaluation that seem inadequate since they define the magnitude of metabolic acidosis rather than its cause. Some studies have shown that the traditional approach is often not able to highlight the complicated acid-base disorders in critically ill patients; in these subjects, the possibility to identify tissue acids could offer a greater prognostic value than the evaluation of traditional parameters. An alternative approach is the Stewarts physiochemical method that defines the aetiology of a metabolic acidosis by quantifying the tissue acids. But the clinical utility of this method is limited due to its mathematical complexity. Therefore, some parameters of simplification were proposed in order to allow greater clinical applicability of this system. Specifically, it was observed that in the presence of metabolic acidosis, the chloride/sodium ratio (Cl-/Na+ ratio) or the sodium-chloride difference (DiffNa-Cl) would be useful indicators of the presence of unmeasured anions (UMA) and/or lactate.

Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis. In subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable at onset, is correladed with mortality. An early assessment of blood and tissue lactate levels could play a role in the therapeutic management as well as in outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would act also as "signal molecule" and as a promoting factor in angiogenesis and tumor progression. In the presence of risk factors for LA the role of metformin may be overrated. Despite the doctrinal progress to understand the pathogenesis and pathophysiology, there is not univocal consensus on the therapeutic treatment of LA. The identification and the attempt to remove the cause of acidosis are main aims; treatment with sodium bicarbonate is a matter of debate as the data on the cardiovascular effects and mortality are unclear. The therapy with carbicarb, dichloroacetate or THAM has shown no specific advantages in terms of mortality. In experimental models of LA and shock the use of sodium-hydrogen exchanger-1 (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines synthesis; it also improves cardiac performance and decreases mortality.

Sodium, the most important extracellular fluid electrolyte, is the focus of several homeostatic mechanisms that regulate fluid and electrolyte balance. Hyponatremia is a common electrolyte abnormality caused by an actual sodium deficiency or extracellular compartment fluid excess. Clinical symptoms are related with acuity and speed with which this abnormality is established. The symptoms are mainly neurological and neuromuscular disorders (headache, confusion, stupor, seizures, coma) due to brain cells edema. Hyponatremia due to sodium deficiency is caused by sodium loss from kidney (nephritis, diuretics, mineralocorticoid deficiency) and / or extrarenal (vomiting, diarrhea, burns). Hyponatremia due to water excess seems to be the most common and it is attributable to cirrhosis, nephrotic syndrome, heart failure, infusion 5% glucose solutions and drugs that stimulate ADH secretion. It was recently highlighted the role of inflammation and IL-6 in the non-osmotic ADH release. Hyponatremia is considered also marker of phlogosis. Acute (<48 h) and severe (<125 mEq/ L) hyponatremia is a medical emergency that requires prompt correction. Patients with chronic hyponatremia have a high risk of osmotic demyelination syndrome if rapid correction of the plasmatic sodium occurs. In combination with conventional therapy, a new class of drugs, vasopressin receptors antagonists (AVP-R antagonists) would be able to increase the excretion of electrolyte-free water and the serum sodium concentration.

Exercise Associated Hyponatremia (EAH) is an occurrence of endurance sports that can cause severe clinical manifestations such as cerebral edema or respiratory failure. EAH is a dilutional hyponatremia, variant of SIADH, characterized by a plasma concentration of sodium lower than 135 mEq/l. Female gender and the duration of the competitions are associated with higher risk of hyponatremia. The incidence of hyponatremia, in fact, increases with duration, especially 4-8 hours after the start of the race. Women seem to be at greater risk than men. The pathophysiological mechanisms include increased loss of sodium through sweating and excessive intake of hypotonic fluids during and after the sporting event. In the genesis of EAH seems to have a decisive role the inadequate secretion of AVP by non osmotic stimuli, including IL-6. Indications for the prevention of hyponatremia include education of athletes for adequate consumption of fluids and monitoring of changes in body weight. Following the identification of electrolyte imbalance, the treatment requires a water restriction and infusion of hypertonic solutions 3%, especially in cases of severe hyponatremia. The effectiveness of the V2 receptor antagonists needs further investigation.

Endothelial dysfunction and oxidative stress are the main pathophysiological mechanisms of several diseases such as hypertension, atherosclerosis, dyslipidemia, diabetes mellitus, cardiovascular disease, renal failure and ischemia-reperfusion injury. Reactive oxygen species (ROS) can modulate cellular function, receptor signals and immune responses in physiological conditions, but when present in excess, they mediate progressive endothelial damage through growth and migration of vascular smooth muscle and inflammatory cells, alteration of extracellular matrix, apoptosis of endothelial cells, activation of transcription factors (NFkB, AP-1), over-expression of inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1 , E-selectin). Recent evidences suggest that the major source of ROS is the NADPH-oxidase, especially activated by angiotensin II, shear stress and hyperglycemia. The unbalance between production of free radicals and the ability to neutralize them by antioxidant systems causes a condition of "oxidative stress". ROS alter vascular tone by increasing concentration of cytosolic calcium and especially causing a decreased availability of nitric oxide, the principal agent of endothelial function with vasodilating action. The data emerged from experimental and clinical studies confirm that endothelium-dependent vasodilation is altered in many diseases.

Adhesion molecules play a significant role in leukocyte migration across the endothelium and are also involved in regulating immune system. It is shown that diabetic patients have an increase of soluble adhesion molecules (sICAM-1, sICAM-2, sVCAM-1, sE-selectin, sL-selectin, sP-selectin) considered an integral part of inflammatory state. This inflammation is responsible for the increased cardiovascular risk of these patients. There is a close link between hyperglycemia, oxidative stress, coagulopathy and inflammation and between these factors and the vascular damage. Various studies have showed the potential role of adhesion molecules in the pathogenesis of diabetic vasculopathy. They promote leukocyte recruitment, which is one of the initial steps in the genesis of atherosclerotic plaque. Adhesion molecules are also involved in the pathogenesis of diabetes mellitus type 1; sICAM-1 would have a particular immunomodulatory role in the process of destroying beta-cells and could be used as a subclinical marker of insulitis. Plasma levels of soluble adhesion molecules correlate with hyperglycemia, insulin resistance, dyslipidemia and obesity; they are associated with the development of nephropathy, retinopathy, myocardial infarction, stroke and obliterant peripheral arterial disease in diabetic type 1 and 2. Given the role of these molecules in endothelial dysfunction genesis and tissue damage associated with diabetes, they could constitute a therapeutic target for the prevention of genesis and progression of chronic complications of diabetic disease.

In the period 1997-2001, 466 sentinel lymph nodes from 342 lymphatic basins in 322 melanoma patients were examined at the Health Unit of Florence. The lymphatic mapping was performed through pre-operative lymphoscintigraphy using technetium-labelled nano-colloid, intradermal injections of vital blue dye and intra-operative gamma-probe. The examined patients were 182 females and 140 males. Sentinel lymph node was one in 65.2% of cases; two sentinel lymph nodes were detected in 27% of cases and more than 2 sentinel nodes were detected in 7.8% of cases. Melanoma metastases in one or more sentinel lymph nodes were found in 61/322 patients (18.9%). Lymphatic basins resulted to be involved by melanoma metastases were 64/342 (18.7%); sentinel lymph nodes containing metastatic melanoma deposits were 73/466 (15.6%). No metastasis was found in patients with melanoma thickness < or = 1 mm. One or more positive sentinel lymph nodes were found in 7.5% of patients with melanoma thickness > 1.00 and < or = 1.50 mm, in 27.7% of patients with melanoma > 1.50 and < or = 3.00 mm, in 38.2% of patients with melanoma > 3.00 and < or = 4.00, and in 60.7% of patients with melanoma > 4.00 mm. Frozen section analysis of sentinel lymph nodes, performed in 59/61 patients with nodal metastases, detected nodal involvement in 21 patients (35.6%). Metastases were identified by routine hematoxylin-eosin staining in 57/64 positive lymphatic basins; in 7 cases (11%) metastases were detected by immunohistochemical stainings (S100 and HMB-45). A nodal nevus was found in 3/466 sentinel lymph nodes (0.6%). Our data are analyzed and compared to previously data of the literature. The value of frozen section analysis and the major problems in the diagnosis of melanoma micrometastases in sentinel lymph nodes are discussed. The importance of the sentinel node biopsy for the detection of occult metastases and for the correct staging of melanoma patients are stressed, according to the new TNM melanoma classification.

An analysis of Homer's Iliad shows that a great number of anatomic references are contained in the text. Anatomic structures mentioned in the poem include: encephalon, spinal cord, trachea, lung, heart, liver, bowel, urinary bladder, tongue, diaphragm, cranial bones, cervical vertebrae, clavicle, acetabulum, ankle joint, aorta and external carotid artery. This suggests that a conspicuous complex of anatomic notions was included in the Homer's age culture.

Two cases of hyperplastic polyp of the appendix are reported. Its association with other appendiceal and extraappendiceal lesions and its relationship with appendiceal mucocele are briefly considered.

A rare case of syringomatous carcinoma of the breast in a 64-year-old female patient is reported. The tumor, occurring in the left breast, measured 1 cm. A quadrantectomy was performed and the patient presented no further recurrence or metastasis. Histologically, the neoplasm was composed of small tubules, often dilated, sometimes with a "tadpole" appearance, lined by epithelial flattened cells, and of keratinizing squamous cysts embedded in a desmoplastic stroma. Some tumors occurring in other anatomic sites show histologic features similar to those of syringomatous carcinoma of the breast: infiltrating syringomatous adenoma of the nipple, syringomatous carcinoma of the skin, syringomatous adenocarcinoma of minor salivary glands; such lesions seem to be part of a group of neoplasms characterized by local infiltrative growth, absence of metastasis and characteristic histologic features (syringomatous tumors).

A 51-year-old woman suffered from an increase in body temperature from 37 degrees to 38.4 degrees C after physical exercise. She did not sweat. The patient also had labile hypertension with maximum values reaching 210/130 mmHg. Tests were carried out to explore the possibility of a link between the increase in body temperature and her hypertension. Evaluation of the patient's blood pressure and temperature changes after exercise and after environmental modification suggests a pathogenetic link between hyperthermia and hypertension.

The infiltration of the epidermis by malignant melanocytes is a characteristic phenomenon of cutaneous melanoma. A series of consecutive unselected cutaneous melanomas was histologically reviewed in order to study the frequency and the characters of epidermal infiltration. Such a feature was found in 86% of tumors (93% in superficial spreading melanomas); it was extensive in 65% of cases, focal in 35%; topographically, it was central and peripheral in 67%, peripheral in 30%, central in 3%. Results show that epidermal infiltration, albeit inconstant, is a useful feature in the histological diagnosis of melanoma (especially in SSM), provided that it is distinguished from pseudoinfiltration, a histologically similar, but intrinsecally different, feature observed in some benign melanocytic lesions.

A hypothesis on the Achaean disease. Analyzing the text in the light of the modern medical knowledge, the article traces a profile of the mortal illness described in the first book of Homer's Iliad. The disease was a severe, acute epidemic zoonosis, rapidly bringing death. First, it affected mules and dogs, then it involved men; the infection spread quickly and the number of deaths was high. These elements suggest that the illness occurred among the Achaeans can be identified with glanders, an infectious disease affecting primarily mules and horses that can be transmitted to man by contact with these animals.

Histopathologic parameters in predicting lymph node metastasis of supraglottic laryngeal carcinoma. A systematic clinical-pathological study was performed on fifty-three resected cases of supraglottic laryngeal squamous cell carcinoma, followed up for at least 5 years. The aim of the research was to evaluate histopathologic parameters in predicting lymph node metastasis (N+) as expression of biological malignancy of the neoplasm. The following neoplastic microscopical features were studied: histopathologic and cytologic grading, pattern of growth, peritumoral inflammatory infiltrate, stromal reaction, tumoral necrosis. The results are as follows: stromal reaction and cytologic grading are not useful to identify N+ and N- cases. Cases with high and low degree of differentiation (Broder's grading) are significantly correlated respectively to low (14.3%) and high (70%) incidence of lymph node metastasis (p less than 0.03). A clear correlation is present between the pattern of growth "pushing" and lacking of node metastasis (84.6%). A favorable prognosis significance seems to be linked with the presence of peritumoral lymphoplasmocytic infiltrate, which results to be a marker of cases in which lymph node metastasis incidence is very low (5.5%; p less than 0.001). On the contrary lymph node metastasis incidence increase when tumoral necrosis is present (76.5%; p less than 0.001).

Eight cases of melanoma of the lower female urogenital tract are presented. The lesions were located 5 in the vulva, 2 in the vagina and 1 in the urethra. Patients had a mean age of 58.3 (range 43-80). Most of vulvar melanomas were polypoid and black, 3 of them arose in the major labium, 2 in clitoris area; histologically, four tumors were superficial spreading melanomas and one unclassifiable. Grossly, one vaginal melanoma was nodular, one polypoid, both were black and arose in the lower vagina. Urethral melanoma arose in the distal part of the organ. Prognosis of gynecological melanoma is severe, as 5 out of 8 patients died in 5-52 months.

A case of Dermatofibrosarcoma Protuberans (DFSP) with unusual cystic features is described. It is difficult to evaluate the actual incidence of this feature on the basis of literature; on the other hand we observed it only once in a series of 27 patients studied from 1975-1989.

The diagnostic category "malignant acrospiroma" includes acrosiryngeal-derived sweat gland malignant neoplasms. Many terms are usually employed to indicate different histologic types of such tumours, lacking a definitive classification. We describe a patient suffering from malignant acrospiroma (malignant poroma) with unusual clinico-evolutive presentation.

Histological analysis of intraepidermal melanocytic proliferation in the peripheral areas of superficial spreading melanoma. The intraepidermal melanocytic proliferation in the areas adjacent to the invasive component of 100 superficial spreading melanomas of the skin (levels III and IV) was studied. Three patterns were identified: 1) melanoma in situ type (MIS); 2) melanocytic dysplasia type (DYS); 3) normal skin or increased number of typical melanocytes (0). The different distribution of these patterns in the areas adjacent to the invasive melanoma led to a histological classification of the tumors into 4 topographical models. Two models showed MIS areas and contiguous normal skin (A1, A2); two models showed MIS areas adjacent to DYS areas, that in turn were contiguous to normal skin (B1, B2). In all cases, however, in centrifugal sense, more severe alterations preceded less severe ones. These observations suggest that superficial spreading melanoma grows horizontally by induction of neighbour cells (neoplastic recruitment). The neoplastic transformation seems to progress in two ways: directly to melanoma in situ or through an intermediate phase (melanocytic dysplasia).

Two rare cases of laryngeal paraganglioma are reported. The first patient was a 14-year-old girl, that had a new laterocervical paraganglioma, 4 years after the excision of a laryngeal tumor. The other patient was a 33-year-old man. In both the cases, the diagnosis was made on histopathological ground and the tumors displayed the typical histological pattern of paragangliomas: epithelioid tumor cell arranged in nests (Zell-ballen) in a vascular stroma. Neoplastic cells were found to contain argyrophil granules and chromogranin. Laryngeal paragangliomas reported in the literature are 73, they generally are supraglottic, show no sex predilection and prefer the V-VII decades of age.