The role of heavy metals and polychlorinated biphenyls (PCBs) in the oncogenesis of head and neck tumors and thyroid diseases: a pilot study.

Previous literature has highlighted the mechanisms of molecular toxicity induced by substances such as arsenic, cadmium, chromium, nickel, lead, barium and PCBs. The research was carried out on 20 volunteers, all the patients gave their consent to the research: the aim of the study was to evaluate the presence of metals and PCBs in these different matrices (blood and hair), correlating the biochemical data to pathological conditions present, and also to the area in which patients resided. Various quantitative determinations were carried out on samples of blood and hair for 14 heavy metals and on blood samples for 12 PCBs. For the 11 patients the results indicated that blood levels for half of the 14 displayed heavy metals measured considerably higher compared to the reference values, whilst the levels measured in hair evidenced some positive values significantly higher than the maximum reference. Of the 12 PCBs assayed in blood some showed higher positive values compared to the maximum tabular reference (although there is no clear reference quantified in the WHO-2005 report). In the 9 healthy patients heavy metals in the blood were within the expected target range, with those showing positive results (≤ 3 out of 14 heavy metals for each patient) having values only slightly higher than the reference maximum. The levels of 14 heavy metals measured in hair were below thresholds, and levels for the 12 PCBs measured in blood showed negativity or positivity with values close to the minimum benchmarks. The analyses carried out on biological matrices have uncovered important and significant differences between healthy and unhealthy subjects, both qualitative and quantitative differences with respect to heavy metals and PCBs. All patients with head and neck cancer enlisted for the study had heavy metal and PCB blood levels at least twice the maximum reference level. The levels of heavy metals in hair were at least double the maximum reference. In contrast, all healthy volunteers enrolled showed no significant levels for either metals or PCBs.

Minor stroke and major vascular occlusion. A case report.

Occlusion of middle cerebral artery (MCA) is generally associated to severe stroke and poor prognosis; however a few patients with mild to moderate presentation and long-term reversibility of neurological deficits have been reported. A 66-year-old male presented with left-side weakness and dysarthria (NIHSS score 7), which progressively resolved within a few days; ischaemic lesion of the anterior arm of the right internal capsule was found at brain CT obtained 72 h after presentation. Transcranial Colour Doppler showed absence of flow of the right MCA. Cerebral angiography showed occlusion of the right MCA that was retrogradely revascularised by leptomeningeal collaterals. Non-invasive intracranial vascular examinations could identify major intracranial artery lesions in patients who present with mild to moderate stroke symptoms. These patients could be identified and followed to clarify their best treatment and prognosis.

Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope.

Syncope as an initial presentation of pulmonary embolism occurs in 10% of patients. We compared clinical and instrumental parameters in patients with syncope as the presenting symptom of pulmonary embolism and in patients with documented pulmonary embolism without syncope. Seventy patients with the diagnosis of pulmonary embolism and apparently stable clinical conditions were evaluated. They were divided in two groups: 10 patients with syncope as the presenting symptom of pulmonary embolism (group 1) and 60 patients without syncope (group 2). Patients with syncope showed a more pronounced tendency to present with main pulmonary artery embolus than patients without syncope (contingency coefficient = 0.301, p < 0.04; one-tailed). However, despite the evidence that patients with syncope have significant reductions in systolic and/or diastolic blood pressure, shock was not observed in any patient. In no case was thrombolytic treatment given and all patients received standard anticoagulation with unfractioned heparin and oral anticoagulant. We suggest that syncope in the setting of non-massive pulmonary embolism may be due to vaso-vagal mechanism that can lead to a reduction of arterial blood pressure when central artery thrombosis is involved.

The rat shorn mutation (shn) maps between D7Got143 and D7Rat94.

The recessive shorn (shn) mutation in the rat generates an almost complete absence of normal hair. Previous analysis of 85 backcross rats typed for shn-generated hypotrichosis located this marker between the telomere and D7Mgh1 on distal rat Chromosome 7. Here, we present a microsatellite polymorphism analysis of a 184-member backcross panel-including 99 new rats-that places shn within a 2.7cM interval between markers D7Got143 and D7Rat94. In addition, this analysis has allowed meiotic ordering of 18 microsatellite markers-including 10 D7Got markers previously positioned only by radiation reduced hybrid analysis-across the 16.8cM region between D7Mit16 (Cyp2d4) and D7Rat94. Our inability to meiotically separate shn from 8 microsatellite markers (mapped by others over some 2-4cM or more than 40cR of genetic distance) suggests that the shn mutation may result from a chromosomal rearrangement that suppresses recombination throughout this interval.

Hyperthyroidism and pulmonary hypertension.

In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension (PH). This observational study was designed to evaluate the incidence of PH in hyperthyroidism and was set in a department of internal medicine and pulmonary diseases with an out-patients department of endocrinology. Thirty-four patients, 25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty had Graves' disease and 14 had a nodular goitre. The patients were divided into two equally matched groups: those with a recently diagnosed hyperthyroidism, taking no drugs (group 1; n = 17) and those in a euthyroid state taking methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressurements of (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli equation. Measurements of triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also taken. We found a mild PH in seven patients of group 1 and in none of group 2. The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1 and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in group 1. These findings indicate the presence of a frequent association between PH and hyperthyroidism. We suggest that hyperthyroidism be included in the differential diagnosis of PH.

Pulmonary function in non-insulin-dependent diabetes mellitus.

BACKGROUND: In type I diabetes mellitus, lung function has been investigated in several clinical studies, but there are few data concerning pulmonary function abnormalities in patients with non-insulin-dependent diabetes mellitus (NIDDM). OBJECTIVES: The aim of this study was to assess the presence of pulmonary function abnormalities in patients with NIDDM and to verify the possible associations between diabetic renal microangiopathy, retinopathy and diabetes control. METHOD AND PATIENTS: Thirty patients with NIDDM were collected and divided into two similar groups: subjects with retinopathy and/or diabetic glomerulopathy (group 1, n = 15) and patients without any complications (group 2, n = 15). 17 were males and 13 females, aged from 45 to 81 years. They had had diabetes for 3-23 years and were studied at the Division of Internal Medicine, with an outpatient service for diabetic patients. All patients were non-smokers. The presence of diabetic glomerulopathy was determined by measuring the 24-hour protein excretion rate using the nephelometric method. The presence of retinopathy was determined by using ophthalmoscopy. Glycosylated hemoglobin was measured as an indicator of glycemic control. We performed a global spirometry and measured pulmonary diffusion capacity by the single-breath method corrected by alveolar volume. RESULTS: We found a significant reduction in lung diffusion capacity for carbon monoxide (DL(CO)) in the group of patients with other signs of diabetic microangiopathy (p < 0.005) and a significative correlation between DL(CO )and the grade of albuminuria (r = -0.83, p < 0.001). CONCLUSIONS: Pulmonary function abnormalities, in particular a reduction in diffusion capacity, are common in patients with NIDDM and signs of diabetic microangiopathy. A possible explanation is related to an impaired pulmonary microvasculature and alveolar epithelial basal lamina.

Changes in the carbon monoxide diffusing capacity of the lung in ulcerative colitis.

The aim of this study was to investigate lung function in patients with ulcerative colitis and to assess the incidence of latent pulmonary involvement in subjects with active and inactive disease. After full colonscopic assessment with multiple mucosal biopsy, the clinical disease activity of each patient was quantified, using the simple index of Harvey and Bradshaw. The patients were divided into 2 equal groups: subjects with active disease (group 1; n=16); and those with inactive disease (group 2; n=16). Global spirometry was then performed. A latent pulmonary involvement was found in 17 of 32 patients (53%), the incidence was higher in the group 1 patients (81%). The majority of patients presented a reduction in the carbon monoxide diffusing capacity of the lungs (DL,CO). The mean DL,CO value was 73.87+/-14.87 in group 1 and 87.31+/-11.23 in group 2. The DL,CO and KCO reduction correlated significantly with intestinal histopathological grading in the group of patients with active disease (r=0.87, p<0.001; r=0.603, p=0.015). To conclude, a high incidence of pulmonary function abnormalities were identified, despite the lack of radiological alterations (High Resolution Computed Tomography) and pulmonary symptoms, in ulcerative colitis patients. These alterations were more common in patients with active disease. The strong correlation between DL,CO values and histopathological grading suggests that this test may reflect bowel disease activity.

[Hypo-osmolar hyponatremic syndromes: physiopathology and clinical aspects]. / Sindromi iposodiemiche ipoosmolari: fisiopatologia e clinica.

Hyponatremia in virtually all patients results from water retention due to an inability to excrete ingested water. In most cases, this defect represents the persistent secretion of ADH (such as in effective circulating volume depletion, and in the syndrome of inappropriate ADH secretion), although free water excretion can also be limited in disorders in which ADH levels may be appropriately suppressed (such as in advanced renal failure, and in primary polydipsia). The symptoms of hyponatremia primarily reflect neurologic dysfunction induced by cerebral edema and are related both to the severity and to the rapidity of reductions in the plasma sodium concentration. The degree of cerebral edema which occurs in acute hyponatremia is much less with chronic hyponatremia, because the brain cells lose solutes, leading to the osmotic movement of water out the cells and less brain swelling. In general, hyponatremia is corrected acutely by giving Na+ to patients who are volume-depleted and by restricting water intake in patients who are normovolemic or edematous. The optimal rate of correction should be defined to prevent the risk of central demyelinating lesions.

Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I.

In recent classifications of gastric endocrine tumors, tumors arising in patients with multiple endocrine neoplasia type 1 (MEN-1) are regarded to be regulated by the concomitant hypergastrinemia resulting from to pancreatic or, most commonly, duodenal gastrinomas and to have a benign behavior. In this article, we report on two cases of MEN-1 gastric neuroendocrine tumors having a fatal course. Case 1 was a young male with hyperparathyroidism and Zollinger-Ellison syndrome and with florid development of multiple gastric carcinoids and multiple duodenal gastrinomas. Metastases occurred in the liver, of exclusive gastric origin, in periduodenal lymph nodes, of exclusive duodenal origin, and in perigastric lymph nodes, of mixed origin. The patient died 48 months after diagnosis. Case 2 was an adult female patient with hyperparathyroidism, adrenocortical disorders, and gastric tumors but no hypergastrinemia. The patient died 3 months after tumor diagnosis. At autopsy, the stomach showed multiple benign carcinoids and two independent neuroendocrine carcinomas not reported before in MEN-1 and massively metastatizing to lymph nodes, liver, and peritoneum. Multiple islet cell tumors mostly producing pancreatic polypeptide were found, whereas gastrinomas were seen in neither the pancreas nor the duodenum. Allelic losses at the MEN-1 gene locus in chromosome 11q13, the mechanism responsible for tumor development in MEN-1 syndrome, were demonstrated in the carcinoid tumors of case 1 and in the neuroendocrine carcinoma of case 2. We conclude that gastric neuroendocrine tumors in patients with MEN-1 may have a poor outcome, they have the same genetic mechanism as MEN-1 tumors in other organs, and they may be independent of the trophic effect of hypergastrinemia.

Effects of reduced preload on diastolic filling in essential hypertensive patients with increased left ventricular mass.

Doppler-derived indices of diastolic filling are widely used in the routine evaluation of essential hypertensives. However, these indices are affected by loading conditions and systolic performance. This study aimed at monitoring the transmitral flow pattern and indices of left ventricular systolic function during acute nonpharmacological isolated reduction of preload in essential hypertensives with left ventricular hypertrophy. Nine essential hypertensive patients with left ventricular hypertrophy and nine age- and sex-matched normotensive controls underwent echocardiographic and Doppler evaluation of both systolic function and diastolic filling indices at baseline and during lower body suction at -40 mm Hg. Lower body suction caused a similar decrease in end-diastolic volume index, stroke volume index, and midwall fractional shortening in the normotensives and hypertensives. Circumferential end-systolic stress was unaffected in both groups. Acceleration time of early diastolic filling and isovolumic relaxation time increased in the normotensives but not in the hypertensives. Deceleration time of early diastolic filling increased in both groups. The ratio of peak velocities during early filling and at atrial contraction decreased in the normotensives, whereas it was unchanged in the hypertensives; this was due to the fact that early filling velocity decreased in both groups, whereas peak velocity at atrial contraction decreased only in the hypertensives. We conclude that Doppler-derived diastolic filling indices are not affected by a reduction of preload in essential hypertensives with left ventricular hypertrophy.

Treatment of biguanide-induced lactic acidosis: reproposal of the "physiological" approach and review of the literature.

We report a case of severe biguanide-induced lactic acidosis which did not respond to symptomatic alkali treatment via either intravenous bicarbonate infusion or bicarbonate-dialysis. We thus initiated a therapeutic strategy based on insulin and thiamine only in order to reactivate the pyruvate oxidative pathway, in which both drugs play important roles as cofactors. This original "physiological" approach proved effective, and further alkali administration was unnecessary. Our results prompted a review of the literature on the treatment of biguanide-induced lactic acidosis, a situation in which the absence of precise therapeutic rules can undoubtedly affect both the evolution and the prognosis of the syndrome.

[Adherence to dietetic treatment, the nutritional metabolic status and the progression of chronic kidney failure]. / Aderenza al trattamento dietetico, stato metabolico nutrizionale e progressione dell'insufficienza renale cronica.

Effects of two protein restricted diets on dietary compliance, nutritional and metabolic state, and progression of chronic renal failure (CRF) were investigated. Twenty-one patients with CRF were randomly assigned to either a conventional low protein diet (0.6 g of protein/kg b.w./day) or to a very low protein diet, providing 0.4 g of protein/kg b.w./day, supplemented with a mixture of essential amino acids which contained HIS, TYR and a high proportion of branched chain amino acids. Nutrition, assessed by body weight, anthropometry, serum protein levels and nitrogen balance studies, was maintained in all patients. Some metabolic abnormalities of CRF (i.e., secondary hyperparathyroidism, glucose intolerance) improved in both groups. The supplemented diet provided better adherence to protein prescription, corrected the depletion of VAL and LEU in muscle and was more effective than conventional diet in slowing the rate of progression of CFR.

[Mandibular laterodeviation of surgical significance]. / Le laterodeviazioni mandibolari di interesse chirurgico.

The Authors look at the mandibular laterodeviations and their classification. They speak about the combined surgical-orthodontic treatment of this pathology and show some clinical cases from their clinical experience.

[Brodie's syndrome]. / La sindrome di Brodie.

The authors, after having completed a wide bibliographic research on this subject, examine the etiopathogenesis of Brodie's syndrome, and distinguish a congenital from an acquired form. The different therapeutic possibilities, orthodontic or surgical, have been examined and discussed.

A comparative clinical study on the effects of cardiopulmonary bypass with different flows and pressures on skeletal muscle cell metabolism in patients undergoing coronary bypass grafting.

This study compares the effects of cardiopulmonary bypass with different flows and pressures on intracellular energy metabolism, acid-base equilibrium, and muscle water compartments in two groups of patients undergoing coronary artery bypass grafting. Eighteen patients (16 men and two women aged 54 +/- 7 years, New York Heart Association class I-II) undergoing low flow (flow rate 1.5 L/min/m2 at 26 degrees C), low pressure (mean arterial pressure 40 to 60 mm Hg) cardiopulmonary bypass, as well as 10 age-matched and sex-matched patients undergoing normal flow (flow rate 2.2 L/min/m2 at 26 degrees C), normal pressure (mean arterial pressure 60 to 80 mm Hg) bypass were studied. Intracellular acid-base equilibrium (intracellular pH and intracellular bicarbonate), cell energetics (adenosine triphosphate, diphosphate, and monophosphate, phosphocreatine, and lactate), and muscle water compartments were evaluated in specimens of the quadriceps femoris muscle obtained by needle biopsy before and at the end of cardiopulmonary bypass. In both the low flow-low pressure and normal flow-normal pressure groups, adenosine triphosphate levels were unchanged at the end of bypass, whereas phosphocreatine concentration was decreased; muscle total water and extracellular water increased without variations of intracellular water; muscle and plasma lactate increased as intracellular bicarbonate decreased; intracellular pH values remained unchanged. The present study suggests the following: (1) Cardiopulmonary bypass is associated with the overall preservation of intracellular compartment metabolism in skeletal muscle (about 40% of body cell mass) of patients undergoing coronary bypass grafting, even though low phosphocreatine values and increased plasma and muscle lactate values found at the end of bypass could be an expression of cell functional reserve exhaustion; (2) the effects of cardiopulmonary bypass on cell metabolism are comparable, regardless of the flows and pressures used.