Altered surfactant synthesis and function in rats with diet-induced hyperlipidemia.

Altered lung function in hyperlipidemic patients has been reported by many authors. An alteration of surfactant synthesis has been suggested. Isolated lungs of rats rendered hyperlipidemic by suitable diets display an increased distensibility at maximal inflation and a higher degree of alveolar stability during deflation. These alterations are related to modifications of surfactant properties. Lung lavage fluid obtained from hyperlipidemic rats displays an increase in percent content of phosphatidylglycerol and a decrease of phosphatidylethanolamine. The percent content of phosphatidylglycerol correlates with the circulating levels if free fatty acids (FFA). It is suggested that FFA might affect the activity of enzymes operating in lung phospholipid synthesis. The reported increase of surfactant phosphatidylglycerol might explain the increment of alveolar stability observed in hyperlipidemic rats.

Is serum PSA measurement a good test for early diagnosis of prostate cancer? Results of a pilot study and cost analysis.

Over the last years--late 1970s to early 1990s--the incidence of prostate carcinoma has nearly doubled, even though many more patients die suffering from prostate cancer than because of it. This finding, together with the slow growth of this tumor and the absence of a controlled trial that would suggest a benefit from screening, makes early diagnosis of this disease quite questionable. On the other hand, it is well known that prostatic carcinoma is curable as long as it is intracapsular, and that there is an ever increasing encouragement to early detection in all diseases. The costs of screening and the difficulty in balancing the benefits of screening against its negative effects, such as psychological impact and overtreatment, must be taken into account as well. In our opinion, one of the advantages of early diagnosis should be that the patients' quality of life improves, because the stage at diagnosis and, as a result, the number of patients suffering from bone metastasis decrease, and unknown benign pathologies can be cured. These observations are not at all negligible. Our study aims to demonstrate that by using PSA as an initial test, the screening costs are reasonable and the disease incidence is just as expected.

Evaluation of the circulating glycoprotein CA549 in mammary cancer and other malignancies.

A prospective study was carried out on a recent marker for breast cancer, CA549, a mucine-like acid glycoprotein present in the fat membranes of human milk. Fifty healthy control subjects and 91 with benign conditions, 103 mammary cancer patients and 256 patients with other types of malignancy were studied. For comparison, CEA and CA15-3 were also investigated. The CA549 cutoff was 11 U/ml. In breast cancer the marker was below the cutoff in 9 cases (92.8%); in malignancies other than breast cancer it was above the cutoff in 5 to 50% of patients. In breast cancer it was raised in 83.3% of cases (CA15-3 showed 82.9% and CEA 50%). In breast cancer after radical surgery, CA549 was normal in patients who were in TNM stage I but above the cutoff in 57.1% of those at more advanced stages. The follow-up study is ongoing among these patients. In all the study conditions, CA549 favorably compared to CA15-3 values, with sensitivity and specificity greater than CEA.

Reduction of humeroulnar congenital elbow luxation in 8 dogs by using the transarticular pin.

The purpose of this study was to evaluate the clinical and radiographic outcome in 8 dogs of surgical reduction of congenital humeroulnar luxation by using the transarticular pin. Five cases were bilateral and 3 were unilateral, for a total of 13 elbows. The treatment was performed in animals between 45 and 150 days of age. Articular stabilization was achieved by using a transarticular pin driven from the caudal aspect of the olecranon into the body of the humerus or into the distal condyle and distal metaphysis of the humerus. The follow-up period was between 1 and 19 months. There were 5 postsurgical reluxations, 3 related to the insertion of the pin into the humeral condyle and 2 related to the insertion into the humeral body. These animals needed further surgery. Six animals showed near normal return to limb function and 2 had lameness. We conclude that the use of the transarticular pin is an effective and simple method for the treatment of humeroulnar congenital elbow luxation.

Musical creativity and suicide.

The different abilities involved in artistic creativity may be mirrored by differences among mental disorders prevalent in each artistic profession, taking poets, painters, and composers as examples. Using suicide rates as a proxy for the prevalence of mental disorders in groups of artists, we investigated the percentage of deaths by suicide in a sample of 4,564 eminent artists who died in the 19th and 20th centuries. Of the sample, 2,259 were primarily involved in activities of a linguistic nature, e.g., poets and writers; 834 were primarily visual artists, such as painters and sculptors; and 1,471 were musicians (composers and instrumentalists). There were 63 suicides in the sample (1.3% of total deaths). Musicians as a group had lower suicide rates than literary and visual artists. Beyond socioeconomic reasons, which might favour interpretations based on effects of health selection, the lower rate of suicides among musicians may reflect some protective effect arising from music.

Reduction of blood pressure in obese hyperinsulinaemic hypertensive patients during somatostatin infusion.

Hypertension in the obese may be related to hyperinsulinaemia. To investigate this relationship further, we infused somatostatin (250 micrograms/h in 100 ml saline) or saline, single-blind and in a random order, for 10 h in seven obese hyperinsulinaemic hypertensive patients and in seven normo-insulinaemic hypertensive controls. Every 2 h, blood pressure, plasma insulin, glucose, sodium, potassium, renin, cortisol and aldosterone concentrations and the urinary sodium:creatinine ratio were determined. Two hours after the somatostatin infusion was started, mean arterial blood pressure was significantly reduced in the obese hyperinsulinaemic patients (from 128 +/- 11 to 114 +/- 11 mmHg, P less than 0.05) but not in the controls and this reduction persisted throughout the study. The somatostatin infusion reduced plasma insulin and increased plasma glucose similarly in both groups. Plasma sodium, potassium, renin, cortisol and aldosterone concentrations and the urinary sodium:creatinine ratio were unchanged after the somatostatin infusion. These results suggest that hyperinsulinaemia could help sustain the blood pressure rise in obesity.

Total vertebrectomy for stabilisation of chronic spinal lumbar luxation in a paraplegic dog without nociception.

An adult male crossbred dog was referred with a history of a road traffic accident that took place 1 month earlier. Neurological examination revealed paraplegia with absent nociception in the pelvic limbs. On epaxial palpation, significant curvature of the anatomical axis of the spine between the third and fourth lumbar vertebrae was observed, with the presence of a bone end almost piercing the dog's skin. Survey radiographs of the lumbar spine revealed severe dislocation between L3 and L4 vertebrae. During surgery, the spinal cord was not visible between the dislocated segments. Because of difficulties in reducing the lumbar luxation during surgery, vertebrectomy and vertebral shortening were performed. After alignment between vertebrae L3 and L5, eight cortical orthopaedic screws and bone cement were used for fixation. After 30 days, the dog started to use a wheelchair and was considered by its owner to have a good quality of life with no evidence of pain. To the authors' knowledge, this is the first case of severe luxation treated by total vertebrectomy and spine shortening in a dog. This surgery can be considered as an option in the management of severe spine luxation when the spinal cord is physically transected.

Evidence of enhancement of the ras oncogene protein product (p21) in a spectrum of human tumors.

Using a direct binding liquid competition radioimmunoassay, the amount of the ras oncogene protein product, p21, was quantitated in a variety of human tumors and adjacent apparently normal tissues. In 48 of 50 matched tumor and normal tissue biopsy specimens from 50 patients, more ras p21 was detected in the tumor than in its normal counterpart. Twenty-five of 28 breast tumors demonstrated more ras p21 than the average of the values obtained for fibroadenomas. Furthermore, in 17 of the 19 cases studied, over 20% more ras p21 was observed in breast carcinomas compared with their respective normal counterparts. More ras p21 was also demonstrated in the majority of tumors of the stomach, lung, colon and bladder compared with their respective adjacent normal tissues. Our data therefore indicate that ras p21 expression is quantitatively enhanced in many human tumors originating from several different tissue types.

Metabolic effects of glucagon in endogenous hypertriglyceridemia.

The metabolic effects of glucagon, administered i.v. in doses of 1 microgram/kg, were evaluated in two groups of patients with endogenous hypertriglyceridemia (Types IV and V according to Fredrickson) with normal and reduced glucose tolerance and in a control group. Glucagon had a lipolytic effect, evaluated as the plasma increase of free fatty acids (FFA) during the first 20 min in normal subjects, but not in the two hyperlipemic groups. A negative correlation was observed between fasting IRI level and FFA mobilization. The ketogenic and hypotriglyceridemic effects of glucagon were demonstrated in normal and hyperlipemic groups. It would seem, therefore, that at the pharmacological doses injected, there is no resistance to the hypotriglyceridemic effect of glucagon in endogenous hypertriglyceridemia.

[Activity and number of lymphocyte beta adrenergic receptors after protracted treatment with mepindolol sulfate of patients with essential arterial hypertension]. / Attività e numero dei recettori beta-adrenergici linfocitarî dopo trattamento protratto con mepindololo solfato in pazienti con ipertensione arteriosa essenziale.

beta-Blockers are widely used in the treatment of high blood pressure. To study clinical and pharmacological role of beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA), lymphocyte beta 2-adrenoceptor density, assessed by 3H-dihydroalprenolol binding, was investigated in 10 hypertensive patients (8 male, 2 female) aged 20-62 years before and after treatment with mepindolol (5 mg o.i.d.). After 3 months of therapy, both systolic (from 169.7 +/- 28.3 mmHg to 146.5 +/- 17.6 mmHg) and diastolic (from 108.7 +/- 17.5 mmHg to 93.6 +/- 8.7 mmHg) blood pressure decreased significantly. Similarly heart rate decreased after treatment (from 76.5 +/- 10.1 b/min to 62.7 +/- 3.4 b/min). Mepindolol treatment decreased beta 2-adrenoceptor density from 1112.2 +/- 459.6 sites/cell to 295.1 +/- 131.2 sites/cell. Plasma noradrenaline values did not correlate with lymphocyte beta 2-receptor number both before and after treatment. Our results show that ISA may play an important role in modulating beta 2-adrenoceptor density on lymphocyte surface. This biological effect could be relevant in reducing the so called "propranolol rebound effect".

Hormonal and metabolic characteristics of genetically obese Zucker and dietary obese Sprague-Dawley rats.

The endocrine-metabolic plasma pattern and the capacity of isolated perfused livers to produce triglycerides and ketone bodies have been studied in genetically and diet-acquired obese rats (Zucker and Sprague-Dawley obese rats), and in control groups of the same strains. An increased plasma insulin/glucagon molar ratio with hyperinsulinaemia and hypoglucagonaemia was associated with hypertriglyceridaemia, normal ketonaemia, elevated free fatty acids and normal or slight hyperglycaemia in obese rats. During oleate perfusion, the livers of Zucker and Sprague-Dawley obese rats showed an increase in triglyceride output and liver triglyceride content. The ketone body output as well as the mitocondrial carnitine palmitoyl transferase activity were normal or slightly decreased. In our rat population, a positive correlation between the insulin/glucagon molar ratio and triglyceride output has been found.

Effect of lipid loading on fetal uptake of free fatty acids, glycerol, and beta-hydroxybutyrate.

The possibility of influencing the fetal uptake of free fatty acids (FFA), beta-hydroxybutyrate (beta-OH), and glycerol was demonstrated by enhancing the maternal blood level of these substances by means of 10% intralipid infusions to the mothers during delivery. The FFA uptake, which was not significant in fetuses of control mothers, became positive in fetuses born after maternal infusion with intralipid. The uptake of beta-OH and glycerol, which were positive in normal conditions, increased in fetuses from intralipid-infused mothers. These studies demonstrate that, after intralipid infusions to the mothers, the fetal FFA uptake could be correlated with the FFA concentration difference between maternal arterial, and fetal umbilical arterial blood. Since the fetal uptake of FFA subsequent to intralipid infusions is not negligible, we consider the possibility that lipid infusions to the mothers could be an approach to the treatment of the fetus with poor intrauterine growth.

[The role of the absolute value and "density" of the prostate-specific antigen estimated echographically in the selection of patients to undergo a biopsy in suspected prostatic carcinoma. A comparison between PSA, palpation and echography in 95 patients undergoing echo-guided endorectal prostatic biopsy]. / Ruolo del valore assoluto e della "densità" dell'antigene prostatico specifico, valutata ecograficamente, nella selezione dei pazienti da sottoporre a biopsia nel sospetto di carcinoma prostatico. Confronto tra PSA, palpazione ed ecografia in 95 pazienti sottoposti a biopsia prostatica endorettale ecoguidata.

We retrospectively reviewed the findings relative to 95 patients with known prostate specific antigen (PSA) values who had undergone digital rectal examination, transrectal US and US-guided biopsy for suspected prostate carcinoma. Histology (48 adenocarcinomas, 26 BPHs, 12 inflammations and 9 negatives) was compared with results from rectal examination, prostate US, PSA values and "density" (PSA/prostatic volume, as measured with US). PSA values < 4 ng/ml exhibited 90% negative predictive value and PSA > 10 ng/ml 70.8% positive predictive value. In the intermediate range (4-9.9 ng/ml) the positive predictive value of PSA was 44.4% and its negative predictive value was 55.5%. PSA density did not affect predictive values in the two groups with PSA < 4 and > 10 ng/ml, while in the intermediate 4-9.9 ng/ml group, positive predictive value raised to 62.5% and negative predictive value to 81.8%, thus increasing the specificity of PSA values and US findings. Our results suggest that PSA should be the examination of choice in the patients with prostatic disease. Follow-up with PSA dosage after one year may be suggested when PSA < 4 ng/ml. PSA density can be helpful in patients with PSA values ranging 4-9.9 ng/ml; biopsy should be performed when the index > 0.15, while follow-up at 6 months should be performed when the index < 0.15. PSA values > 10 ng/ml require further evaluation with rectal examinations, prostate US and US-guided biopsy. Random biopsies are suggested when PSA values are > 20 ng/ml.

Prevalence and determinants of carotid atherosclerosis in a general population.

BACKGROUND AND PURPOSE: The aim of this study was to assess the prevalence of asymptomatic carotid atherosclerotic lesions and their relation to principal risk factors. The importance of the relation between asymptomatic carotid atherosclerotic lesions, stroke, and coronary atherosclerosis has been widely discussed, but there are few transversal and longitudinal studies on a general population. METHODS: A noninvasive examination was carried out using high-resolution B-mode ultrasonography, which has been shown to be a reliable tool for epidemiological studies. We examined 630 men and 718 women aged 18-99 years (participation rate, 74.9%). RESULTS: The global prevalence of carotid atherosclerosis was 25.4% in men and 26.4% in women. Intimal-medial thickening was found in 9.4% of men and 11.7% of women. Plaque prevalence was 13.3% in men and 13.4% in women; prevalence of stenotic plaques was 2.7% and 1.5%, respectively. Subjects aged < or = 39 years showed a very low prevalence of any asymptomatic carotid atherosclerotic lesions. In the multiple logistic regression, the analysis of subjects aged > or = 40 years showed a positive significant association between the severity of carotid atherosclerotic lesions (plaques and stenosis) and age (p < 0.001), systolic blood pressure (p < 0.01), cigarette smoking (p < 0.0001), and the protective effect of high density lipoprotein cholesterol (p < 0.037). This analysis did not provide evidence of a clear-cut association between risk factors and intimal-medial thickening. CONCLUSIONS: This population study shows the high prevalence of asymptomatic carotid atherosclerotic lesions in a general population (approximately 25% of adults) and its relation with the classic risk factors. It emphasizes the value of ultrasonography in the detection of early atherosclerotic lesions.

Effects of fat mass reduction by dieting and by lipectomy on carbohydrate metabolism in obese patients.

The interrelation of enlarged body fat mass (BFM) with reduced carbohydrate tolerance and hyperinsulinemia was studied in obese subjects with chemical diabetes. These patients were subjected to lipectomy following weight loss induced by a low-calorie, low-carbohydrate diet. An improvement in glucose tolerance and in insulin sensitivity and a reduction in insulin release during OGTT was observed after a diet-induced BFM loss of 9.9 +/-1.2 kg. Subsequent surgical reduction of BFM by 6.0 +/- 0.5 kg had no further effect upon carbohydrate tolerance, insulin release or insulin sensitivity though a marked decrease in basal plasma FFA values was observed. These findings suggest that fat mass enlargement per se has no effect on blood glucose homeostasis after oral or i.v. loading. The improvement in carbohydrate tolerance and in insulin resistance usually observed following diet-induced loss of BFM seems to be due to the reduction in calorie and carbohydrate intake rather than to decrease of BFM.

Atrial natriuretic peptide and hemodynamic changes after concentrated ascitic fluid reinfusion in cirrhotic patients.

In order to assess the role, if any, of atrial natriuretic peptide (ANP) and hemodynamic changes in diuretic response to concentrated ascitic fluid reinfusion (CAFR) in cirrhotic patients, we studied 10 patients with liver cirrhosis before and after aspiration, concentration and intravenous reinfusion of their ascitic fluid. Basal ANP levels were higher than in normal subjects, but not related to the degree of water and sodium excretion. CAFR induced a variable degree of ANP changes and diuretic response, and these two parameters were strictly correlated to each other. No major changes of cardiac output and systemic vascular resistances were observed after CAFR. In conclusion, the apparent resistance to ANP diuretic action observed in basal condition in cirrhotic patients seems to revert after expanding blood volume by CAFR.

Longitudinal evaluation of prostate-specific antigen levels in a case-control study.

BACKGROUND: Over the last period--late 1970 to early 1990--the incidence of prostate carcinoma has nearly doubled, even though many more patients die with prostate cancer rather than of it. This finding, together with the slow growth of this tumor and the absence of a controlled trial, makes early diagnosis for this pathology quite questionable. On the other hand, it is well known that prostatic carcinoma is curable as long as it is intracapsular and that there is an ever increasing encouragement for early detection in all diseases. Since prostatic pathology increases its incidence as age advances, the first step in early diagnosis is to be able to discriminate between healthy, benign prostatic hyperplasia and cancer cases with a well-accepted and easily understandable method. The problem is to find the best method to do it. METHODS: We measured serum prostate-specific antigen (PSA) levels in 435 men participating in an epidemiological study, at first in 1987 and again in 1992. Men with PSA levels above 4 ng/ml (in 1992) were invited to undergo other diagnostic tests (digital rectal examination, transrectal ultrasonography, biopsy) in sequence on the basis of the results of the previous tests. The pathological findings from biopsies were the reference test to determine the presence or absence of prostate cancer (2.5% of the population). RESULTS: We divided PSA concentrations into three categories, according to the most used cutoffs ( < 4, 4-10, > 10 ng/ml); in the meantime, we took into account the change rate in PSA concentration in time, defined as delta PSA. By the comparison between PSA categories and delta PSA, we found out that the first one does not discriminate between benign and malignant pathologies, while the use of delta PSA strongly discriminates them (p < 0.001). CONCLUSION: On the basis of our results, we think that delta PSA might be the best parameter to indicate the presence of prostate cancer cases in an asymptomatic population.

Standardization of assay for cytokeratin-related tumor marker CYFRA21.1 in urine samples.

The determination of tumor markers in urine samples has been proposed as an effective diagnostic tool in bladder cancer. The aim of the present investigation was to validate in urine samples the assay of the CYFRA21.1 cytokeratin-related marker, the serum concentrations of which showed promising diagnostic utility in patients with bladder cancer. First-voided urine samples were collected from patients with different malignancies. CYFRA21.1 was assayed with a commercially available enzyme immunoassay (Boehringer Mannheim). Different centrifugation patterns, the use of different buffers and nonionic detergents, and pH variations were evaluated. We demonstrated that: (a) cells and cell debris contain a large amount of CYFRA21.1 and must be eliminated by centrifugation; (b) storage at -20 degrees C causes amorphous precipitate, which may aspecifically bind CYFRA21.1; (c) the latter behavior may be prevented by diluting fresh urine samples with phosphate buffer with nonionic detergent added; (d) pH variations within the range 4.9-8.2 do not significantly affect CYFRA21.1 assay results. Provided that samples are diluted with buffer containing nonionic detergent, the CYFRA21.1 assay showed good precision and accuracy characteristic in urine samples. We therefore propose a standard protocol for the collection of urine samples for CYFRA21.1 assay. In a preliminary clinical evaluation, CYFRA21.1 concentrations in 16 patients with primary bladder cancer were higher than in healthy subjects. In the urine collected in the follow-up of patients treated for bladder cancer, CYFRA21.1 tended to be higher in relapsed patients than in those without evidence of disease. These preliminary data induced us to extend the clinical trial to establish the actual role of this assay in routine use.