Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement.

To determine whether the Rabinov-Paulin or the long-leg venography technique should be preferred in the diagnostic management of patients with clinically suspected deep-vein thrombosis, two independent experienced radiologists blindly assessed two different series of venograms of consecutive outpatients with clinically suspected deep-vein thrombosis. Venograms were obtained from two outpatient clinics of primary referral centres. In one centre the venograms were performed according to the technique of Rabinov and Paulin with the use of 100 ml of radiographic material and spot films of the calf, popliteal and more proximal veins. In the other centre, long-leg films were obtained after the administration of 150 ml of contrast material. The percentage venograms adjudicated as inadequate by at least one radiologist and inter-observer disagreement for both series were used as the main study outcome measures. Prior to the study, both radiologists agreed on the standardized criteria for a normal, abnormal and inadequate test result using a separate set of films. An inadequacy rate of 20% was found for the Rabinov-Paulin venography series (n = 123), whereas only 2% of the 126 long-leg films were inadequate for interpretation (p less than 0.001). The inter-observer diagreement for inadequacy, presence or absence of deep-vein thrombosis was 21% for the Rabinov and Paulin venograms and 4% for the long-leg films (kappa, 0.65 and 0.92; 95% confidence intervals: 0.53 to 0.77 and 0.84 to 0.99, respectively; p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tuberculosis: a global overview of the situation today.

The overall tuberculosis situation in the world in 1990 and its recent trends are reviewed by an analysis of the case notifications to WHO and tuberculosis mortality reports. Estimates of the prevalence of tuberculosis infection and the incidence of tuberculosis disease and deaths predicted in 1990 were carried out with simple epidemiological models. Approximately one third of the world's population is infected with Mycobacterium tuberculosis. In the past decade, an average of 2.5 to 3.2 million cases were notified every year globally, the small decrease in notification rates in recent years being offset by population growth. In 1990, an estimated 8 million people developed tuberculosis worldwide and 2.6 to 2.9 million died. The majority of these cases and deaths occurred in Asia, with an increasing number among HIV-infected individuals, especially in Africa where an upward trend is clearly detectable. Data on tuberculosis cases notified by WHO Member States demonstrate the magnitude of the problem but must be interpreted with caution. Being less than the expected incidence, they reflect the inadequacies of tuberculosis control programmes. This review confirms the very high global magnitude of the tuberculosis problem and calls for an urgent revitalization of tuberculosis control programmes throughout the world.     

The use of the D-dimer test in combination with non-invasive testing versus serial non-invasive testing alone for the diagnosis of deep-vein thrombosis.

We studied the usefulness of the determination of plasma D-dimer levels (using an ELISA) in combination with non-invasive testing with impedance plethysmography (IPG) or real-time ultrasonography (US) for the diagnosis of deep-vein thrombosis (DVT), in outpatients with clinically suspected DVT. This combined approach was compared to serial non-invasive testing alone in these patients. The sensitivity of a positive D-dimer test (greater than 300 micrograms/l) for the presence of DVT was 100% (70/70 patients; 95% C.I.: 95-100%), whereas the specificity was 29% (69/239 patients; 95% C.I.: 23-34%). The proportion of patients in which a definitive decision about the presence or absence of DVT could be made on the day of referral, was calculated for both approaches. When applying the combined approach, in 42% of all referred patients the diagnosis of DVT could either be established or refuted on entry, as opposed to only 19% of patients using serial non-invasive testing alone. Also, the costs per DVT diagnosed were calculated for the two diagnostic approaches. For the diagnosis of DVT the costs using serial IPG were comparable to the costs using the combination of IPG and the D-dimer test. The same conclusion holds for the comparison of serial US with the combination of US and D-dimer testing. We conclude that for the diagnosis of DVT in symptomatic outpatients the combination of non-invasive testing with the D-dimer test might be preferred over serial non-invasive testing alone, although the safety of such an approach remains to be established in future management studies.     

A possible pain control system in a non-mammalian vertebrate (a lizard, Gekko gecko)

In a lizard (Gekko gecko) the anterograde tracer PHA-L was microiontophoretically applied to the predominantly serotonergic nucleus raphes inferior. Extensive spinal projections from the rostral magnocellular part of this nucleus were demonstrated to the superficial layers of the dorsal horn and to the intermediate zone, more sparsely to the ventral horn. But, in addition, retrogradely labeled neurons were found in and just below a periventricular cell group in tegmentum mesencephali, i.e. the laminar nucleus of the torus semicircularis, a cell group which receives spinal afferents and projects to the spinal cord as the mammalian periaqueductal gray. These data suggest the presence of a three-tiered pain control system in a lizard composed of projections from the laminar nucleus of the torus semicircularis to the rostral part of the inferior raphe nucleus which in its turn projects to the superficial layers of the dorsal horn of the spinal cord.     

Saliva, a physiological medium

Plaque and plaque fluid, rather than saliva, are of prime importance in determining the result of the interaction between tooth enamel and its environment. The concentration of calcium and phosphate ions is higher in plaque fluid than in saliva. Local supersaturation may result in the remineralization of white spot lesions or in the formation of calculus. The latter may be inhibited with containing dentifrices. Undersaturation, resulting from bacterial acids production, promotes dental caries. Fluorides are effective against caries, although the limited transporting properties of saliva would be recognized when designing caries preventive treatments. Suppleting saliva with calcium and phosphat ions through mouthrinses is another method to fight caries, while stimulation of the secretion by chewing gum is also very effective.     

Effects of glycine and GABA,and blocking actions of strychnine and picrotoxin in the hypoglossus nucleus

Summary Neutral ω-amino acids were applied iontophoretically in the hypoglossus nucleus. Intracellular recordings revealed inhibitory actions involving hyperpolarization and conductance increase of the membrane. The antidromic field potential was reduced most effectively by glycine, as judged by the comparison of iontophoretic currents. Picrotoxin, ejected electrophoretically, clearly interfered with the action of GABA, glycine effects being reduced only with rather high currents. Strychnine had very specific blocking ability against glycine actions. Supported by the Deutsche Forschungsgemeinschaft (Br 242/7).     

Tumor necrosis factor-mediated interactions between inflammatory response and tumor vascular bed

Summary: Solid tumor therapy with chemotherapeutics greatly depends on the efficiency with which drugs are delivered to tumor cells. The typical characteristics of the tumor physiology promote but also appose accumulation of blood-borne agents. The leaky tumor vasculature allows easy passage of drugs. However, the disorganized vasculature causes heterogeneous blood flow, and together with the often-elevated interstitial fluid pressure, this state results in poor intratumoral drug levels and failure of treatment. Manipulation of the tumor vasculature could overcome these barriers and promote drug delivery. Targeting the vasculature has several advantages. The endothelial lining is readily accessible and the first to be encountered after systemic injection. Second, endothelial cells tend to be more stable than tumor cells and thus less likely to develop resistance to therapy. Third, targeting the tumor vasculature can have dual effects: (i) manipulation of the vasculature can enhance concomitant chemotherapy, and (ii) subsequent destruction of the vasculature can help to kill the tumor. In particular, tumor necrosis factor α is studied. Its action on solid tumors, both directly through tumor cell killing and destruction of the tumor vasculature and indirectly through manipulation of the tumor physiology, is complex. Understanding the mechanism of TNF and agents with comparable action on solid tumors is an important focus to further develop combination immunotherapy strategies.