Biomarker-guided drug development provides value for patients, payers and drug developers: lessons learned from 25 years in the biomarker industry.

Introduction: There is an urgent, persistent, need for better biomarkers in clinical drug development. More informative biomarkers can increase the likelihood of drug advancement or approval, and implementing biomarkers increases the success rate in drug development. Biomarkers may guide decisions and allow resources to be directed to the projects most likely to succeed.

The return of austerity imperils global health.

Recognising the world's lack of preparedness for the COVID-19 pandemic, international organisations like the World Health Organization, World Bank, and International Monetary Fund are calling for extensive additional funding to strengthen pandemic preparedness and response systems in low-income and middle-income countries, including through domestic resource mobilisation. This article examines the prospects of national health budgets increasing in such a context, drawing on new International Monetary Fund projections on public spending around the world. We show that by 2024 public spending will be lower than the 2010s average for almost half of all low-income and middle-income countries.

Prevalence of metabolic syndrome, insulin resistance, and microvascular angina pectoris in 500 consecutive patients referred to coronarography.

Objective: This work was aimed to evaluate the prevalence of insulin resistance (IR) and metabolic syndrome in a large cohort of 40-60 years old patients with cardiovascular symptoms.

Methods: A total of 500 consecutive males and females referred to coronarography and coronary catheterization, because of spontaneous or after load precordial pain plus denivelisation of ST segment by electrocardiography, were included. Besides standard clinical examinations, ergometry, echocardiography, fundamental laboratory tests, and several other laboratory examinations were also performed, including oral glucose toleration test (OGTT), total and high-density lipoprotein (HDL) cholesterol, triglycerides, apoprotein A1 and B, apolipoprotein (a), uric acid, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), cytokines (tumor necrosis factor α, TNFα, interleukin-1, IL-1, interleukin-6, IL-6), endothelin-1, as well as hormones (insulin, C peptide, leptin, growth hormone, cortisol).

The prevalence of cigarette smoking and its relation to certain risk predictors of cardiovascular diseases in central-Slovakian Roma children and adolescents.

The objective of the study was to determine some Cardiovascular Disease (CVD) risk factors in relation to cigarette smoking in 174 Roma children and adolescents (88 males and 86 females) and 131 non-Roma probands (males and females) aged 7-18 in central Slovakia. In this biethnic study, 26.4% of the Roma children and adolescents (more than twice contrary to the control group) were smokers.

Cardiovascular risk predictors in central Slovakian Roma children and adolescents: regional differences.

The objective of the study was to determine some Cardiovascular Disease (CVD) risk factors in 174 Roma children and adolescents (88 males and 86 females) aged 7-18 in 3 Central Slovakian cities (44 from Zilina, 39 from Bansk, Bystrica and 91 from Rimavská Sobota). Venous blood samples were drawn in the morning, after a 12 hour overnight fast for biochemical analysis. Total cholesterol (TC) and triglycerides (TG) were determined enzymatically.

Some cardiovascular risk factors in Gypsy children and adolescents from Central Slovakia.

Background: Atherosclerosis could develope in the presence of CVD risk factors in early age.

Objective: To determine some risk factors of Cardiovascular Disease in Gypsy children and adolescents from Central Slovakia.

Participants: Study population (Gypsy/Caucasian ethnicities) consisted of 198 Gypsy children and adolescents (101 males and 97 females) aged 7-18 and 140 non-Gypsy children and adolescents (72 males and 68 females) from 3 Central Slovakia cities.

Characteristics of the aging rat mandible.

The study evaluates the effect of age and sex on the physical characteristics of rat mandible. Wistar derived rats were divided into four groups; young male (4-6 months old), old male (23-25 months old), young female (4-6 months old) and old female (23-25 months old). Mandibles were removed and cleaned of soft tissue, placed on a dental X-ray film and exposed together with an aluminium stepwedge 0.

[Difficult diagnosis in a case of pulmonary epidermoid carcinoma].

We present a case of a 66 years old male patient, from urban area, smoker for 54 years, without special antecedents, hospitalized in our service with a pulmonary right lower lobe abscess, whose onset was 4 months ago, persistent under treatment in another pneumology service. Clinically and radiologically we suspected a pulmonary excavated right lower lobe neoplasia, but unsustained by fiber-bronchoscopy and thoracic computer tomography. By this reason the patient underwent exploratory thoracotomy and the diagnosis was confirmed by the biopsy of the resected specimen: pulmonary epidermoid carcinoma.

[Rare histological type of pulmonary adenocarcinoma--two clinical cases].

Two cases of primary signet-ring cell adenocarcinoma of the lung are presented. The patients were: a 53-year-old man with a left lung mass and a 40-year-old woman with a right lung mass. Endobronchial biopsy performed after fiber-bronchoscopy reveal this rare histological type for pulmonary localizations of neoplasms.

The levels of soluble adhesion molecules in diabetic and nondiabetic patients with combined hyperlipoproteinemia and the effect of ciprofibrate therapy.

Cell adhesion molecules are thought to play a role in atherosclerosis. Several clinical trials have shown that fibrate treatment leads to a reduction in coronary events, although the mechanisms are not fully understood. Soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin plasma concentrations were measured in 10 obese dyslipidemic men (group A), in 10 obese dyslipidemic type 2 diabetic men without coronary artery disease (CAD) (group B), and in 10 dyslipidemic type 2 diabetic men with angiographically documented CAD (group C) before and after 12 weeks of treatment with ciprofibrate.

[Homocysteine--a routine biochemical parameter in cardiovascular diseases?].

An elevated level of total homocysteine (tHcy) in blood-hyperhomocysteinemia, is prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral and peripheral vessels and for thromboembolism (arterial and venous). Elevated total homocysteine confers a graded risk with no threshold, is independent of but may enhance the effect of conventional risk factors. Hyperhomocysteinemia seems to be a particularly strong predictor of cardiovaskular mortality.

[Relation between cytokines (TNF-alpha, IL-1 and 6) and homocysteine in android obesity and the phenomenon of insulin resistance syndromes].

TNF-alpha (so-called cachectin), IL-1 and 6 are important regulating agents in the homeostasis of energy in the organism, as among others they control processes of apoptosis and thus also the volume of adipose and muscular tissues. They are produced not only in immunocompetent cells but also in adipocytes and muscle cells. The cytokine system is then activated not only in tumours and infections but elevated values were found also in obesity, NIDDM, in myocardial infarction and in advanced decompensated cardiac patients.

[Insulin resistance and the coronary syndrome].

The different diseases associated with the insulin resistance syndrome--diabetes mellitus or impaired carbohydrate tolerance, atherogenic lipoprotein phenotype, arterial hypertension and central type of obesity are the main risk factors of atherosclerosis. The reduced sensitivity of target tissues to the metabolic action of insulin (insulin resistance) is considered at present a separate risk factor. The authors analyze on the basis of a group of 210 coronarographic patients the influence of insulin resistance and associated etiopathogenetic risk factors on coronary lesions evaluated by the method of quantitative coronarography.

[Relation between levels of leptin, insulin and cortisol in persons with the 5H (X) syndrome].

Leptin levels in subjects with android obesity with the insulin resistance syndrome (syndrome X, 5H) are in general elevated, as compared with non-obese subjects and correlate with the BMI, with the percentage of body fat, WHR, IRI levels and sex (they are higher in women), as it is the case in the general population. In the elevated leptin level in syndrome 5H (association of hyperinsulinism, hyperglycaemia-NIDDM, hyperlipoproteinaemia with android obesity, arterial hypertension and hirsutism in females with the polycystic ovaries syndrome) participate in a significant way also elevated basal IRI and cortisol levels as well as an elevated postprandial IRI response during oGTT despite the fact that leptin and endothelin-1 levels do not rise significantly during oGTT despite hyperinsulinaemia. Leptin levels were however higher in men (liminally significant in women) with an hyperinsulinaemic response during oGTT, as compared with probands with a normal insulin response.

[Functions and dysfunctions of the vascular endothelium].

Endothelium represents a large paracrine gland with an enormous reactive surface. By means of its numerous vasodilation and vasospastic factors it manages the basal and working tonus of vessels and thus also the regional flow and the access of target tissues to hormones and metabolic substrates. It manages also the proliferation and migration of myocytes of the vascular wall and thus its adaptation to overload.

[Not Available].

Endothelium represents a large paracrine gland with an enormous reactive surface. By means of its numerous vasodilation and vasospastic factors it manages the basal and working tonus of vessels and thus also the regional flow and the access of target tissues to hormones and metabolic substrates. It manages also the proliferation and migration of myocytes of the vascular wall and thus its adaptation to overload.

Follow-up of the long-term effect of intraarterial vasodilator administration in patients with PAOD by means of changes in resting arterial and venous lactate and pyruvate levels, and in ABB parameters.

The aim of the study was to assess, on the basis of changes in the resting arterial and venous values and arteriovenous difference of pH, pCO2, pO2, lactate, pyruvate and the lactate/pyruvate ratio in blood collected from the common femoral artery and vein before and after therapy, and at 4 weeks after therapy, the long-term effect of intraarterial vasodilator administration in 42 lower extremities with the chronic ischaemic syndrome in stages IIb, III and IV according to Fontaine. Ten intraarterial vasodilator infusions containing 300 mg trimecaine and 60 mg papaverine in 200 ml of saline led to an increase in oxygen extraction from circulating blood, as demonstrated by a statistically significant rise in arteriovenous pO2 difference persisting as long as 4 weeks after termination of therapy. The finding of increased CO2 release and the permanent drop in venous lactate levels suggest stimulation of aerobic metabolism of the chronically ischaemic tissue of the lower extremity induced by intraarterial vasodilator administration.

[Nocturnal bruxism. Contributions to the detection and assessment of involvement in the craniomandibular pain dysfunction syndrome].

The authors review the most updated information concerning the etiopathogenesis of nocturnal bruxism, stressing the co. destructive role of psychosomatic factors and of traumatogenic ones, of the type of premature dental contacts, and of occluding interferences, with evident direct implications in the buccal cavity and at a distance, giving rise to hypnic masticatory automatism, with painful hypercontraction of the masticatory muscles, and stress exerted on the temporomandibular articulations. On the basis of original studies of the interdisciplinary type (prosthetic gnathology and neurophysiology), with the aid of polygraphic investigations during sleep carried out in subjects with nocturnal bruxism it was possible to demonstrate that this oral parafunction may determine sleep disturbances at a central level which makes necessary a complex stomatologic and neuropsychiatric medical therapy.

Importance of arterial, venous and arteriovenous values of ABB parameters and glucose metabolites for assessment of resting lower extremity metabolism in healthy individuals and in patients with peripheral arterial occlusive disease.

The study deals with assessment of the extent of tissue ischaemia and disorders of aerobic metabolism on the basis of comparison of resting arterial, venous values, and the arteriovenous differences in pH, pCO2, pO2, lactate, pyruvate and glucose levels and the lactate/pyruvate index in 32 extremities of 16 healthy individuals and in 42 extremities of 38 patients with chronic ischaemic syndrome of the lower extremity in stages IIb, III and IV according to Fontaine. The group of patients showed significantly higher values of lactate, pyruvate, glucose and the lactate/pyruvate index and lower pH levels than controls. Changes in pCO2, pO2 and pyruvate levels were not significant.

Holography.

Research on holography has now grown to such dimensions that we have not been able to mention each of the numerous authors who have made significant contributions to it. Investigators from Bell Telephone Laboratories, the RCA, Xerox, and Westinghouse laboratories, Conductron Corporation, GC-Optronics, IBM, TRW Systems, the University of Michigan, and Stanford University have made particularly significant early contributions in the United States. Especially notable were the efforts of R.