Cytokine regulation of macrophage apo E secretion: opposing effects of GM-CSF and TGF-beta.

Biosynthesis of apolipoprotein (apo) E has been previously demonstrated to be regulated in macrophages by intracellular free cholesterol levels as well as by macrophage activating factors. In this report, the regulation of apo E secretion by cytokines detected within atherosclerotic lesions has been investigated. Granulocyte macrophage-colony stimulating factor (GM-CSF) stimulated macrophages had a 3-5-fold reduction in apo E secretion, comparable to that observed for gamma interferon (IFN gamma), while tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) resulted in a 2-fold decrease. In contrast to the reduction in apo E secretion by these cytokines, transforming growth factor beta (TGF-beta) stimulated macrophages secreted 3-fold greater amounts of apo E than controls. The reduced secretion of apo E by GM-CSF was reversible, heat labile, dose dependent, maximal 48 h after cytokine exposure and was coincident with an increase in fibronectin secretion. The opposing effects of GM-CSF and TGF-beta on apo E secretion were consistent with similar changes detected in apo E mRNA levels. Cytokine effects on apo E secretion in cholesterol loaded macrophages were also investigated and found to be similar to the non-loaded cells with GM-CSF decreasing and TGF-beta increasing apo E secretion. The observed differences in apo E secretion did not correlate with any significant changes in either cellular cholesterol distribution in the non-cholesterol loaded macrophages or in basal ACAT activity. In addition to changes in apo E secretion, cytokine treated macrophages pulsed with [14C]oleate and acetylated LDL for 2-6 h had a 2-fold increase (GM-CSF) or decrease (TGF-beta) in cholesterol esterification. Therefore, GM-CSF and TGF-beta mediated changes in apo E secretion may occur through a mechanism independent of changes in cellular free cholesterol levels. These results suggest that cytokines expressed within an atheroma may play an important role in the modulation of macrophage mediated reverse cholesterol transport.


Adrenaline increases the uptake of low-density lipoproteins in carotid arteries of rabbits.

The uptake of low-density lipoprotein was compared in carotid arteries of anaesthetized male New Zealand rabbits after infusing alternate carotids with adrenaline, or with saline as a control. The infusions were at approximately 2% of the carotid blood flow, the adrenaline being at approximately 10 nM in the carotid blood. Human low density lipoprotein, methylated to prevent recognition by the high affinity receptor (m-LDL), was labelled with 125I and injected intravenously. Adrenaline infusions for 2 or 4 h significantly increased m-LDL radioactivity in the carotid walls. The radioactivity of reinjected red cells labelled with 51Cr was the same in the walls of both carotids. This excluded the possibility that the excess LDL radioactivity in adrenaline infused carotids was accounted for by increased amounts of blood in the arterial wall. It also made it improbable that the excess LDL resulted from decreased elimination through a vasoconstriction effect of adrenaline on the vasa vasorum, which should have decreased the amount of radioactivity due to red cells. The results, therefore, suggest that adrenaline at its pathophysiological blood concentrations accelerates the uptake of LDL by large arteries in rabbits.


The variability of and associations between measures of blood coagulation, fibrinolysis and blood lipids.

Hemostatic variables are increasingly recognized as atherothrombotic risk markers and their susceptibility to lifestyle changes has therefore considerable interest. To study this subject knowledge of the spontaneous variability of measures of coagulation and fibrinolysis is required. We monitored 17 young male adults with constant lifestyles for a year and here present characteristics of the observed variability of factor VII coagulant activity (F VIIc), fibrinogen, fibrinolytic variables and blood lipids. The variables differed considerably with regard to total variability (range of CV (%): 13-54) and with respect to relative size of the inter- and intrapersonal components of variation. None of the variables showed seasonal changes of biological significance. Descriptive statistics of the same variables measured in 74 young healthy adults (19 women, 55 men) are also reported. These values may be used as a reference for comparable groups of individuals. Serum triglycerides were significantly associated with F VIIc (Spearman's Rs = 0.24, P < 0.05) and plasma concentrations fo the plasminogen activator inhibitor type I (Spearman's RS = 0.23, P = 0.05). An increased thrombotic tendency with elevated triglyceride levels was thus indicated. Serum cholesterol was not associated with hemostatic variables, except for plasminogen activator activity (Spearman's Rs = 0.31, P < 0.05).


Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease.

Familial defective apolipoprotein B-100 is a recently identified, dominantly inherited genetic disorder caused by a G to A mutation in exon 26 of the apolipoprotein B gene. This creates a substitution of glutamine for arginine in the codon for amino acid 3500 and results in reduced affinity of low density lipoprotein (LDL) to the LDL receptor. We have integrated already published data with hitherto unpublished data from 8 countries and a total of 135 affected individuals from 56 families, in an attempt to focus on the range of expression of this mutation on lipid and lipoprotein levels and on coronary artery disease. The frequency of this mutation may be as high as 1 in 500 to 1 in 700 in Europe and in North America. The vast majority of affected heterozygotes have total and LDL cholesterol levels well above the 95th centile for age and gender; in contrast, high density lipoprotein cholesterol, very low density lipoprotein cholesterol and plasma triglycerides are not affected by the mutation. The risk of premature coronary artery disease in the carriers of the mutation is increased to levels as high as those seen in patients with clinical familial hypercholesterolemia; at age 50, about 40% of males and 20% of females heterozygous for the mutation have developed coronary artery disease. Familial defective apolipoprotein B-100 is thus a significant cause of hypercholesterolemia and premature coronary artery disease in Western societies.


Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.


Binding of modified high density lipoproteins to endothelial cells: relation with cellular cholesterol efflux?

Human endothelial cells (EA.hy 926 line) were enriched with cholesterol using cationized low density lipoprotein (LDL). Cholesterol-loaded cells interacted with native apolipoprotein (apo) E-free high density lipoprotein3 (HDL)3 as well as with dimethyl suberimidate-modified HDL3 (DMS-HDL3). At 4 degrees C both HDL preparations showed a saturable high affinity binding with a KD of 31 and 50 micrograms of protein/ml and a Bmax of 226 and 436 ng/mg cell protein for native HDL3 and DMS-HDL3 particles, respectively. Competition of binding of 5 micrograms apo E-free 125I-labelled HDL3/ml by unlabelled DMS-HDL3 and tetranitromethane-treated HDL3 (TNM-HDL3) was very poor, whereas unlabelled native HDL3 competed very effectively with 125I-labelled HDL3 binding. Thus, both types of modified HDL did not compete for the high affinity binding sites for native HDL. Unlabelled native HDL3 and unlabelled DMS-HDL3 both competed for the binding of 125I-labelled DMS-HDL3 very effectively. These experiments indicate that there are two distinct high affinity binding sites for HDL on cationized LDL-loaded EA.hy 926 cells: one specific HDL binding site, which only binds native HDL, and a second binding site for both native HDL and DMS-HDL. The modified HDL fractions were used to study the relation between HDL binding and HDL-mediated efflux. Efflux of cell cholesterol was measured as the increase of cholesterol mass in the medium after 24 h of incubation with 0.2 mg native HDL3/ml, or the same amount of modified HDL3. DMS-HDL3-mediated efflux was identical to efflux mediated by native HDL3. TNM-HDL3 also induced efflux of cell cholesterol; however, efflux induced by TNM-HDL3 was only 45-50% of the amount obtained with native HDL3. So both DMS- and TNM-modified HDL3 induced efflux of cholesterol, although these particles do not bind to the specific high affinity sites for native HDL. These results do not indicate a link between binding of HDL to specific receptors for native HDL and HDL-mediated efflux of cholesterol from loaded endothelial cells.


Inhibition of intimal thickening of the carotid artery of rabbits and of outgrowth of explants of aorta by probucol.

The effect of administration of probucol in preventing intimal thickening of rabbit carotid artery after balloon catheter injury and the mechanism of action of the drug were studied. Groups of 6 male New Zealand-White rabbits were given normal diet (Group I), high cholesterol diet (Group II) or high cholesterol diet plus probucol (Group III) for 4 weeks. Balloon catheter injury was made in week 2 and animals were killed in week 4. No significant differences in the total cholesterol levels in Groups II and III were found in week 4. The medians of areas of the intimal layer in cross-sections of the carotid arteries of Groups I, II and III were 0.237, 0.475 and 0.309 mm2, respectively. Thus high-cholesterol diet increased the thickness of the intimal layer and probucol reduced its effect. There were no significant differences in the areas of the medial layers in these 3 groups. For the examination of the mechanism of the effect of probucol, rabbits were given chow containing 0.5% cholesterol with and without 0.5% probucol (7 rabbits each) and then the numbers of explants from their aortas showing outgrowth were compared. The plasma total cholesterol levels of these two groups were the same. The probucol concentrations in the plasma and aorta of the former group were 18.6 +/- 13.2 micrograms/ml and 7.3 +/- 5.4 micrograms/g wet tissue, respectively. The number of explants showing outgrowth on day 14 was suppressed by 34% in the probucol-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential regulation of hepatic apolipoprotein A-I and A-II gene expression by thyroid hormone in rat liver.

Apolipoproteins A-I and A-II (apo A-I, apo A-II) are major protein components of high density lipoproteins. Thyroid hormone has a differential effect on the expression of the apo A-I and apo A-II genes in rat liver. Apo A-I gene expression is stimulated by thyroid hormone, whereas apo A-II mRNA abundance is decreased in chronic hyperthyroidism. To determine the regulatory steps involved in this differential effect of thyroid hormone on hepatic apo A-I and apo A-II gene expression, we studied the effect of short term and chronic hyperthyroidism on apo A-I and apo A-II gene transcription rates, nuclear RNA abundance and total cellular mRNA levels. After a single receptor saturating dose of L-triiodothyronine (T3) apo A-II gene transcription was transiently increased to 164% +/- 13% of basal values (P < 0.05) without affecting nuclear apo A-II RNA abundance. Apo A-I gene transcription, however, increased to 158% +/- 8% of baseline levels (P < 0.05) and remained elevated for at least 24 h. Nuclear and total cellular apo A-I mRNA increased more than expected from the increased transcription rate suggesting nuclear RNA stabilization and/or more efficient processing of the primary transcripts. In chronic hyperthyroidism, total cellular apo A-II mRNA abundance decreased to 62% +/- 18% (P < 0.05) and apo A-II gene transcription and apo A-II nuclear RNA were moderately reduced. By contrast, apo A-I nuclear and total cellular RNA were increased several fold by post-transcriptional mechanisms, whereas apo A-I gene transcription was drastically decreased. We conclude that the apo A-I and apo A-II genes in rat liver respond differently to both acute and chronic hyperthyroidism and that their expression is regulated at transcriptional and posttranscriptional levels.


Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden.

Association studies were carried out on a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms (PvuII, HindIII and Serine447-Stop) at the lipoprotein lipase (LPL) gene locus on among-individual differences in plasma lipid traits and progression of atherosclerosis. Significant linkage disequilibrium was detected between any two of these polymorphisms, with the Stop447 allele being only found on the same chromosome as the rare alleles (no cutting sites) of the PvuII and HindIII polymorphisms. In the healthy individuals, weak associations were found between genotypes of the HindIII polymorphism and triglycerides and the PvuII polymorphism and high density lipoprotein cholesterol explaining 7.4% and 5.6% of sample variance (P = 0.03 and 0.09), respectively. No associations were found between these traits and genotypes of the Serine447-Stop substitution, and thus it is unlikely to be the cause of the associations seen with the PvuII and HindIII polymorphisms even though it truncates the enzyme amino acid sequence. The presence of the rare allele, H-, of the HindIII polymorphism was associated with a smaller variance in triglycerides and both cholesterol and triglycerides in the very low density lipoprotein fraction, and with larger interdependent variation between these lipid traits, and also between LPL activity and these lipid traits. This implies that the H- allele, rather than the Stop447 allele, has the major impact on interdependence between traits which are directly or indirectly influenced by LPL activity. In the healthy individuals who were carriers of the apolipoprotein E2 allele, the inter-dependence between LPL activity and lipid traits was significantly smaller, and that between high density lipoprotein cholesterol and both cholesterol and triglycerides in the very low density lipoprotein fraction was much larger compared with non-carriers (P < 0.05). No significant associations were found between lipid traits or lipase activity and genotypes of the Serine447-Stop substitution. However, in the patients, global severity of coronary atherosclerosis at the first angiography was significantly associated with haplotype combinations of the HindIII and the Serine447-Stop polymorphisms, with the H-Stop haplotype being associated with the highest median score (P = 0.02). The data suggest that variation at the LPL gene locus is associated with a pleiotropic effect, that is not directly mediated by changes in lipids, on severity of coronary atherosclerosis.


Structural and functional properties of apolipoprotein B in chemically modified low density lipoproteins.

The structural and compositional changes occurring during in vitro chemical modification of apolipoprotein B-100 (apo B), the apolipoprotein component of low density lipoproteins (LDL), were investigated in this study. The functional properties of chemically modified apo B and especially its potential to induce accumulation of cholesterol esters in macrophages were related to the structural changes of apo B. Acetylation, maleylation or malondialdehyde conjugation did not significantly affect the lipid composition of LDL. However, the unsaturated cholesteryl esters content, especially that of cholesteryl arachidonate was significantly decreased through Cu-oxidation. The number of reactive lysine residues in apo B was decreased by Cu-catalyzed LDL oxidation, acetylation, maleylation and by malondialdehyde conjugation. The number of free cysteines decreased from six in native apo B-100 to three in Cu-oxidized LDL. The tryptophan fluorescence intensity decreased most in malondialdehyde-conjugated LDL and in Cu-oxidized LDL, compared with acetylated and maleylated LDL. The secondary structure of native and chemically modified LDL was measured by attenuated total reflection infrared spectroscopy and by circular dichroism. No significant changes were observed in the secondary structure of any of the modified LDL. These data suggest that neither acetylation, malondialdehyde treatment or even Cu-oxidation substantially altered the secondary structure of apo B, in spite of significant modifications in the primary structure. Incubation of chemically modified LDL with J774 macrophages induced an accumulation of cellular cholesteryl esters and foam cell formation. The highest cholesterol accumulation was induced after malondialdehyde treatment of LDL. These data suggest that the cellular uptake and accumulation of modified LDL is not modulated by changes in the apo B structure. Rather it seems dependent upon the net charge of the apo B protein and probably involves the modification of critical lysine residues.


On the accumulation of D-aspartate in elastin and other proteins of the ageing aorta.

Ageing and degenerative changes of the human aorta are associated with medial thinning and a reduced dry weight content of elastin. The metabolic stability of cross-linked elastin was investigated by measuring the accumulation of D-aspartate with ageing in insoluble elastin isolated from human aorta. D-Aspartate accumulation in elastin was compared with D-aspartate accumulation in aortic collagen and an elastin bound glycoprotein fraction. The D-aspartate content of elastin, purified from infrarenal aorta; increased linearly with age from 3% of the total aspartate in youth to 13% in the mid 80s. In contrast the D-aspartate content of aortic collagen remained invariant (3-5% of the total aspartate) from youth to old age. The apparent first order rate constant for the racemization of L-aspartate in elastin was 1.14 x 10(-3). The D-aspartate content of the elastin bound glycoproteins increased by only a small amount, from 3% in the mid 30s to 6% in the mid 80s. These results argue for the metabolic stability of aortic elastin as compared with the fibrillar collagens of the human aorta. Both the rate of racemization and the specific accumulation of D-aspartate in elastin, but not collagen, indicates that mature cross-linked elastin is not synthesized in the adult aorta.


Ultrasonography in the detection of Achilles tendon xanthomata in heterozygous familial hypercholesterolemia.

We have examined the usefulness of ultrasound (US) in the detection of Achilles tendon (AT) xanthomata in heterozygous familial hypercholesterolemia. Our study is based on 30 adult subjects with heterozygous familial hypercholesterolemia (FH) (16 men, 14 women), 27 subjects with other non-familial forms of severe hypercholesterolemia (non-FH) with serum total cholesterol levels > or = 8 mmol/l (13 men and 14 women) and 31 subjects without marked hypercholesterolemia of the same age (control group; serum total cholesterol < 8 mmol/l) (15 men, 16 women). The three groups were comparable with respect to age, sex and body mass index. In the control group the mean sagittal thickness of AT was 4.5 mm (95% CI 3.2, 5.9 mm) and the mean coronal breadth of AT 11.0 (95% CI 9.0, 13.0 mm). Mean thickness of AT was 4.9 (range 4-7) mm in the non-FH group and 11.1 (5-16) mm in the FH group. The mean breadth of AT was in these groups 12.0 (10-17) mm and 19.2 (12-27) mm, respectively. Using the upper 95% confidence interval cut-off point in the control group as a criterion for normal AT thickness and breadth, 6 (22%) of non-FH and 29 (97%) of FH patients had increased AT thickness and 5 (19%) vs. 26 (87%) patients had increased AT breadth, respectively. The sensitivity of AT thickness for identifying FH was 0.97, specificity 0.78 and positive predictive value 0.83. The sensitivity of AT breadth in identifying FH was 0.87, specificity 0.81 and positive predictive value 0.84. None of the control subjects and none of the non-FH patients showed structural abnormalities of AT in the US, whereas 89% of FH-patients showed hypoechogenicity of AT. FH-score obtained by summing up the number of abnormal US findings gave a sensitivity of 0.93, a specificity of 0.96 and a positive predictive value of 0.96 for AT US in discriminating FH from non-FH. In conclusion, US examination of AT is a useful method in the detection of AT xanthomata and thus of help in the diagnosis of heterozygous FH.


DUI pre-arrest alcohol purchases: a survey of Sonoma County drunk drivers.

Based on a sample of 1,052 drunk drivers in northern California, less than 1% (0.80%) of those arrested for DUI had purchased and consumed alcohol prior to arrest from a convenience/gas store (gasmart). Data from both "on-sale" (on-premises consumption) and "off-sale" (off-premises consumption) alcohol outlets were compared. When off-sale outlets were compared only 2% of the DUI offenders had purchased and consumed alcohol from gasmarts prior to the arrest event. Gasmarts were the least frequent source of DUI-offender alcohol purchases. This report also describes the distribution of alcohol outlets for Sonoma and San Diego counties with respect to type of license and activity. Convenience stores that sold gas and alcohol concurrently were not overrepresented in either county.


Perineurial permeability to sodium during Wallerian degeneration in rat sciatic nerve.

In rat sciatic nerves, the effect of Wallerian degeneration on the rate of transperineurial passage of sodium between the endoneurium and the epineurial extracellular space was investigated. In nerves transected and ligated at the sciatic notch, an in situ technique was used to measure the permeability coefficient-surface area product (PS) of the mid-thigh portion of the perineurium to 22Na. Sampling times ranged from one day to sixteen weeks after the lesion. Additionally, endoneurial water content (an indicator of nerve edema) was also measured in transected, degenerating nerves at the same sampling times. Endoneurial water content increased significantly by the fourth day after transection, peaked at four weeks, and then remained elevated through 16 weeks of post-lesion measurement. The PS of the perineurium to 22Na on the 4th day after transection was significantly greater than that of control animals. This increase then declined to normal levels through the 2nd week, and finally increased to values that were 3-fold to 4-fold of control values for the remainder of the observation period. The earlier, short lasting increase in perineurial PS is probably associated with the inflammatory response to nerve section, and proliferation of perineurial layers and cells. The later increase in perineurial permeability is proposed to play a role in the dissipation of endoneurial hydrostatic pressure and clearance of myelin debris from the endoneurium. In view of the complex changes in perineurial permeability described herein, it would seem inappropriate to consider these phenomena merely as passive breakdowns of the barrier properties of the perineurium.


Acute vibration--its effect on digital blood flow by central and local mechanisms.

In order to establish underlying mechanisms responsible for the vasospastic disorder vibration white finger (VWF), the acute effect of vibration on digital blood flow was assessed. Thirteen patients with primary Raynaud's phenomenon (RP), 15 patients with WVF and 13 controls were exposed to acute vibration in the middle digit of one hand for 1 and 3 minutes. Blood flow was measured in that digit and in the middle finger of the contralateral hand using strain gauge plethysmography before and after vibration. The measurements were then repeated following digital nerve blockade using 2% Lignocaine in the vibrated digit. The results demonstrate that vibration affects digital blood flow through two independent mechanisms. Vibration appears to cause both an axonal vasoconstrictor reflex and an active local vasodilation phenomenon. In patients with established vasospastic disorders this vasoconstrictor reflex is exaggerated.


Venous haemodynamics--a consideration of macro- and microvascular effects.

In health, valves in the deep veins function unidirectionally permitting blood flow towards the heart. This function is often degraded following deep vein thrombosis leading to venous hypertension and disturbed haemodynamics in the legs of the patient. Hypertension, in turn, promotes venous ulceration through a series of degenerative pathological steps. Traditional methods of treatment include leg elevation and compression using elasticated garments or bandaging. These techniques manage the problem with varying success but do not cure it. Recent advances in surgical research suggest that novel techniques are being developed for treating valve incompetence. In these circumstances, vascular scientists should be examining methods of addressing both the macro- and the microcirculation so that changes in these consequent to venous hypertension may be measured. This review examines existing methods of measuring the macrocirculation as well as the potential techniques to study effects of venous haemodynamics in the microcirculation.


Engineering design of vascular prostheses.

The replacement and bypass of arteries of diameter greater than 6 mm with textile vascular prostheses has proved very successful since they were first introduced forty years ago. Although manufacturers continue to improve their products and make them of consistent quality for increased safety and performance and to facilitate their use by surgeons, most of the research work in this area is concerned with the development of small-diameter prostheses. Current expanded PTFE and textile prostheses do not perform satisfactorily when their diameters are reduced to less than 6 mm. For the small-diameter prostheses it will be necessary to develop less thrombogenic materials and to design the structure of the prostheses more closely to match the mechanical properties of the natural arteries. The purpose of this paper is to discuss the design requirements and to review the development of large- and small-diameter vascular prostheses.


The measurement of blood flow waveforms from X-ray angiography. Part 1: Principles of the method and preliminary validation.

The principles and implementation of a method for measurement of blood flow waveforms from X-ray angiography are described. Contrast medium mass values are obtained at multitudinous positions along individual vessels and from numerous images in a time sequence. These values are represented as a matrix of grey levels in a parametric image. This image is normalized to represent contrast medium concentration, and the movement over time of isoconcentration portions of the contrast bolus is recovered to determine blood flow. Preliminary validation has been undertaken using parametric images generated in two ways: synthesis from a computer model of vascular pulsatile flow and analysis of cine-angiograms of physical models (plastic and perspex tubes) carrying known pulsatile flows. Two distinct methods for interrogation of parametric images by digital image processing were employed; both provided accurate flow measurements.


The measurement of blood flow waveforms from X-ray angiography. Part 2: Application to video recordings of digital subtraction angiography.

A method of measuring blood flow from X-ray angiograms recorded on cine film, by obtaining contrast mass values at numerous positions along individual vessels and at multiple instants of time, has been previously reported. In the present work it was hypothesized that the signal-to-noise limitations of recordings on video tape could be overcome by recording already-subtracted angiograms from a digital subtraction angiographic (DSA) system and that the spatial resolution of video was adequate to use a similar measurement method. Validation experiments were recorded, in which flows measured using a calibrated electromagnetic flowmeter passed through tubes of 4-7 mm diameter, during injections of 2-5 ml contrast medium. The video sequences were computer analysed and produced angiographic flow measurements agreeing with the electromagnetic flows to within 5 per cent. A case study of a clinical carotid artery DSA in a patient with secondary carcinoma metastases in the brain is described. It is concluded that accurate flow measurements can be made from DSA video recordings.


Determination of the arterial flow fraction in normal and diseased livers using constrained deconvolution.

There is some evidence that the ratio of the blood flow to the liver through the hepatic artery to the total flow to the liver through the hepatic artery and portal vein (the hepatic arterial flow fraction, AFF) is altered in the presence of cirrhosis. Several methods have been published that seek to provide an index of this ratio. These indices are dependent on factors other than the AFF and cannot provide a true measure of it. The impulse retention function of the liver has two components and these may be derived using a model-driven deconvolution of the arterial tracer concentration curve and the curve of tracer concentration in the liver. The AFF may then be obtained from the relative heights of these two components. Simulation studies show that the AFF calculated using this method is reasonably accurate and a small clinical series shows that it is capable of appropriate clinical classification of patients into cirrhotic and non-cirrhotic groups.


Liver blood flow: non-invasive estimation using a gamma camera.

A non-invasive radioisotope technique for the measurement of total liver blood flow (TBF) is described. The method requires the use of two intravenously administered tracers, 99mTc (technetium 99m) human serum albumin (HSA) and 99mTc colloid. Computer analysis of first-pass time activity curves for HSA for liver and lung tissues yields values for the arterial and portal contributions to liver blood flow, from which TBF can be determined. These values are then corrected for attenuation using the images of the colloid distribution. The use of the method is illustrated in 17 subjects. Assumptions, limitations and possible applications of the technique are discussed.


Anatomy and pathophysiology of the popliteal tendon area in the lateral meniscus: 1. Arthroscopic and anatomical investigation.

An arthroscopic and anatomical investigation was performed to define the abnormal conditions of the popliteal tendon area in a lateral meniscus. Arthroscopic findings for 100 patients and anatomical observations of 10 amputated knees were analyzed. Five of the 10 dissected menisci were also examined histologically. Menisco-tibial coronary ligaments were classified into two types, as follows: type I--a coronary ligament covering an entire popliteal tendon beneath the meniscus; type II--a popliteal tendon visible beneath the meniscus through defects of the coronary ligament. Twenty-one of 100 cases were classified as type I, and 79 were classified as type II. Three of the 10 anatomical dissections were type I, and the remaining 7 were type II. Menisci in which the type I coronary ligaments were thought to be torn and menisci with type II coronary ligaments showed a rather marked mobility, but no conclusion could be reached.


Anatomy and pathophysiology of the popliteal tendon area in the lateral meniscus: 2. Clinical investigation.

Treatment of abnormal mobility of the popliteal tendon area of the lateral meniscus is described. Twenty-seven patients who exhibited an abnormally mobile posterior segment with no obvious ruptures in the lateral meniscus were directly examined by us after an average of 4 years and 3 months from the time of the arthroscopic procedure. The main complaints associated with this condition before the surgery were pain and locking during deep knee flexions. The patients were divided into three groups according to surgical method: partial meniscectomy, subtotal meniscectomy, or meniscal repair. The subtotal meniscectomy and repair groups showed significantly higher scores than the partial meniscectomy group. A locking phenomenon recurred in one case of the meniscal repair group. In this case, the menisco-femoral coronary ligament posterior to the popliteal tunnel could not be sutured.


Cellular repopulation of deep-frozen meniscal autografts: an experimental study in the dog.

This study evaluated the cellular repopulation of deep-frozen meniscal autografts. Medial menisci of adult dogs were excised, deep-frozen in liquid nitrogen (-196 degrees C) for 10 min, and orthotopically reimplanted into the joint. Deep-freezing was found to effectively kill all the cells within the meniscus as determined by the absence of Na(2)35SO4 incorporation. Following orthotopic replacement within the knee joint, menisci were repopulated with cells that seemed to originate from the adjacent synovium. These cells migrated over the surface of the meniscus and began to invade the deeper layers of the tissue. However, even after 6 months, the central core of the meniscus remained acellular. While the new cells appeared to modulate into cells that are similar in appearance to meniscal fibrochondrocytes, the exact phenotypic expression of these newly differentiated cells has yet to be determined. Histological alterations, as manifested by a loss of normal orientation of the collagen architecture of the superficial layers of the meniscus; was evident at 6 months and suggests that a remodeling phenomenon may be associated with the cellular repopulation. While biomaterial studies have not been carried out on these specimens, the morphologic alterations observed in the collagen orientation would suggest a possible alteration in the material properties of the repopulated meniscus. The clinical implication of this study is that the structural remodeling associated with the cellular repopulation of deep-frozen meniscal allografts may make the transplanted meniscus more susceptible to injury.


The effect of inflammatory synovial fluid on the breaking strength of new "long lasting" absorbable sutures.

The effect of inflammatory synovial fluid upon several absorbable sutures potentially useful for arthroscopic procedures, e.g., meniscus repair and shoulder stabilization, was studied by implanting lengths of these sutures into unstable, arthritic rabbit knees and testing their breaking strength after varying time periods (up to 18 weeks). Polyglyconate (Maxon) sutures retained no significant strength at 6 weeks. Polydioxanone (PDS) sutures began to lose breaking strength at 3 weeks, retained only 40% of their original strength 6 weeks after implantation, and had no measurable strength at 9 weeks. Polycaprolactone (LTS) sutures showed a slow reduction in strength and retained approximately 90% of their original breaking strength after 18 weeks of implantation. Green braided polyester (Mersiline) sutures showed no loss of breaking strength over the testing period. Measurements of inherent viscosity were made to give an indirect indication of the decline in molecular weight of these sutures. These data paralleled the breaking strength decline in every case. The surgeon selecting an absorbable suture must consider the length of time the suture will hold the target tissue. This information should be helpful to surgeons considering an absorbable suture for procedures such as meniscus repair and shoulder stabilization.


The intraoperative evaluation of the neurosensory function of the anterior cruciate ligament in humans using somatosensory evoked potentials.

Most of the investigation of the properties of the anterior cruciate ligament (ACL) has focused on its biomechanical functions. There has been increasing interest in the study of the possible neuroreceptor function of the ACL and its role in providing important proprioceptive feedback. Anatomic and histologic studies in humans have shown the presence of neuroreceptors within the anterior cruciate ligament. Indirect evidence exists that proprioception is diminished in the ACL-deficient knee. However, direct evidence in humans of the actual origin of the afferent impulses from within the ACL itself is lacking. Measurement of direct electrical afferent activity, occurring on stimulation of the ACL, should provide this evidence. Somatosensory evoked potentials (SEP) measure the electric potentials evoked in the cerebral cortex upon stimulation of a peripheral neuroreceptor. Carried by the posterior columns of the spinal cord, they reflect activity of the proprioceptive fibers. During arthroscopic procedures performed on nine patients, the normal ACL was stimulated by the use of electrodes applied to the femoral end, midsubstance, and tibial end, and cortical potentials thus evoked were recorded. In all cases, SEPs were recorded at the cerebral cortex upon stimulation of the ACL. The greatest potentials were reported upon stimulation of the midsubstance of the ligament. These findings provide direct evidence for, and strongly support the presence of, active proprioceptive receptors within the intact anterior cruciate ligament of the human knee.


Blood loss from arthroscopic autogenous patellar tendon anterior cruciate ligament reconstruction.

Thirty patients who had arthroscopically assisted autogenous patellar tendon anterior cruciate ligament reconstructions were retrospectively reviewed to determine the blood loss associated with this procedure. On average, a 1.5 U blood loss (9-point hematocrit decrease) occurred with this procedure. The amount of blood lost was not affected by use of an intraoperative tourniquet. Blood loss was minimally increased by extra-articular iliotibial band surgery and was unrelated to surgical timing, in the acute versus chronic phase of the injury.


The biomechanical effects of geometric configuration of bone-tendon-bone autografts in anterior cruciate ligament reconstruction.

This study provides biomechanical support for a new technique of autograft anterior cruciate ligament reconstruction featuring circular bone plugs and endosteal interference fit fixation. Six matched pairs of fresh frozen human knees were utilized. Femoral interference fit pull-out strength was determined from material-testing-machine-generated oscillograph recordings at a strain rate of 100%/s. Circular bone plugs, obtained with a circular oscillating saw, provided 19.9% greater interference fit pull-out strength compared with identically fixed trapezoidal bone plugs. Different geometric defects were compared in three- and four-point bending on an Instron machine with frozen patellae and an artificial bone composite. Circular defects have 107% greater strength than matched trapezoidal patellar defects in three-point bending. In a bone composite, circular defects are 53% stronger than triangular and 25% stronger in four-point bending than trapezoidal defects. A new technique of harvesting bone plugs with endosteal interference fit fixation is described and biomechanically supported. To date, this technique has been performed on over 500 cases clinically without evidence of patellar fracture or fixation failure. This study demonstrates the efficacy of this simple and reproducible technique compared with previously reported procedures.


Classification of the suprapatellar septum considering ontogenetic development.

At the end of the 4th fetal month, the suprapatellar septum completely separates the knee joint cavity from the suprapatellar bursa. A perforation of the septum normally occurs at the end of the 5th fetal month. Mechanical factors, such as the pressure and friction of the quadriceps tendon on the condylar surface, are said to determine the form and extent of the perforation. Anatomic studies of adult knee joints revealed four variants in the further development of the suprapatellar septum, namely, a completely preserved septum (complete septum), a perforated septum with the communication between suprapatellar bursa and knee joint cavity differing in localization and number (perforated septum), a residual septum in the form of a fold that is almost always in a medial localization (residual septum), or a completely involuted septum (extinct septum). The clinical term "suprapatellar synovial plica" should not be used as a synonym for the expression "suprapatellar septum." The suprapatellar synovial fold corresponds to the residual septum and thus is only one of the four types of the suprapatellar septum.


Patellofemoral relationships and distal insertion of the vastus medialis muscle: a magnetic resonance imaging study in nonsymptomatic subjects and in patients with patellar dislocation.

The correlation between the insertion level of the vastus medialis muscle and lateral patellofemoral angle (LPA), lateral patellar displacement (LPD) and tilt (LPT), and the height of the patella (LT/LP) was analyzed by magnetic resonance imaging (MRI) in patients with patellar dislocation (n = 10) and in control subjects (n = 10). Images were produced in 0 degrees and 20 degrees of knee flexion. The insertion level to the patella was also analyzed with the knee in extension. No significant correlation was noted between the insertion level and different patellofemoral indexes, but multiple-regression analysis showed that the best predictor for the insertion level was the LPA with the knee in extension. The insertion level was significantly more proximal in patients with patellar dislocations than in normal subjects.


Ligament strain and ankle joint opening during ankle distraction.

To determine the efficacy of ankle distraction and to investigate possible complications of the procedure, the strain on four ankle ligaments and the tibiotalar joint opening resulting from distraction force and various foot positions were studied. We mounted strain gauges on the deltoid, calcaneofibular, tibiofibular, and anterior talofibular ligaments of six fresh human cadaver ankles. An Acufex ankle distractor was used to apply forces of 45, 90, 135, and 180 N at 20 degrees dorsiflexion, neutral, and 10 degrees plantar flexion. The ankle distractor proved to be effective in opening the joint space for better visualization, but complications of pin bending, excessive ligament strain, and bony destruction did occur within the clinically recommended range. Based on the observed results, the safest method of distraction was to use forces < 135 N in the neutral position.


Osteochondritis dissecans of the lateral femoral condyle in the adult.

In osteochondritis dissecans, 15% of the lesions occur in the lateral condyle. In order to understand the significance of these lesions, 27 were studied prospectively from 1983 to 1990 and compared with 20 consecutive cases of lesions of the medial femoral condyle. Lesions of the lateral femoral condyle were larger, and often comprised the entire width of a condyle and resulted in deformation of a significant segment of the femoral condyle. They lay further posteriorly and commonly were associated with mechanical symptoms including buckling or locking. A discernible clunk was unique to these lesions. In addition, lateral lesions were more fragile, often having multiple bony islands that were prone to fragmentation, making replacement difficult if not impossible. Lateral lesions occurred directly within the main force-bearing areas of the condyle, disrupting normal contact areas and possibly leading to more rapid joint deterioration once segments are lost. This has prompted concern for reinsertion of articular fragments or reconstruction with osteochondral allografts.


Early degenerative joint disease simulating impingement syndrome: arthroscopic findings.

Eighteen patients who underwent shoulder arthroscopy for impingement syndrome were shown at operation to have coexisting glenohumeral degenerative joint disease (DJD) which was not apparent during preoperative clinical and radiographic evaluation. Because traditional ("open") techniques of anterior acromioplasty do not allow inspection of the glenohumeral joint, it is almost certain that this pathology would have been missed at operation if open acromioplasty had been performed. We conclude that arthroscopic subacromial decompression (ASD), by allowing easy inspection of the glenohumeral joint, offers a distinct advantage over traditional acromioplasty. Furthermore, arthroscopic evaluation of some of these patients' glenohumeral joints provided us with evidence supporting the existence of subluxation arthropathy. We have also developed a new clinical test, the "compression-rotation" test, which has been helpful in distinguishing patients with both impingement syndrome and early DJD syndrome from those with isolated impingement syndrome. Although patients in this study appeared to be doing well at short-term follow-up status post-ASD and glenohumeral debridement, no long-term results are yet available.


Biceps tendon and superior labral injuries.

Twenty-two patients sustained injury to the biceps tendon, rotator cuff interval, or superior labrum. Seven patients with "interval lesions" underwent biceps tenodesis, one biceps repair, and three subscapularis repairs. All were satisfied, although one tenodesis failed with distal biceps retraction. Key arthroscopic findings included biceps or subscapularis fraying. Thirteen patients with "S.L.A.P. (superior labrum anterior to posterior) lesions" underwent labral debridement. All but one obtained pain relief. Eight cadaveric shoulders exhibited extreme anatomic variability of the bicipital origin/superior labral attachment. Biomechanical study showed anterior-superior and posterior-superior labral strain with simulated biceps contraction to be greatest in shoulder abduction (p < 0.01). Biceps tendon strain was greatest in shoulder adduction (p < 0.05). A continuum of injuries to the biceps tendon exist, from the rotator cuff interval to the labral attachment. Key arthroscopic findings may assist in the difficult diagnosis of interval lesions. Individual anatomy and mechanism of injury may determine the site of the lesion.


Arthroscopic elbow findings: correlation with preoperative radiographic studies.

Correlation between arthroscopic findings and preoperative radiographic studies (plain radiographs and arthrotomograms) was performed in a consecutive series of 37 elbows. Arthrotomograms added significant diagnostic information unavailable from plain radiographs alone, thereby improving the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficiency (accuracy) in the evaluation of elbow joint surface changes, marginal spurs, and loose bodies. Arthrotomograms gave 85% accuracy for bone spurs, 89% accuracy for joint surface abnormalities, and 89% accuracy for loose bodies (88% accuracy overall), whereas plain radiographs demonstrated 69% accuracy for bone spurs, 71% accuracy for joint surface abnormalities, and 75% accuracy for loose bodies (72% accuracy overall). The arthrotomograms had 100% sensitivity for loose bodies as well as a 100% negative predictive value for loose bodies. Arthrotomograms are indicated when additional preoperative diagnostic accuracy is necessary. These radiographic studies approached only 90% accuracy, confirming that diagnostic arthroscopy adds additional information.


Microarthroscopic study of the morphologic features of normal and pathological synovial membrane.

The complex symptoms occurring in several internal knee diseases are usually related to changes in the synovial membrane, causing diagnostic and therapeutic problems. The conventional arthroscope, useful in establishing the diagnosis of internal derangement, is of questionable value in the differential diagnosis and evaluation of the stages of arthritis. With magnifying arthroscopy, it is possible to better show various forms of synovitis. Between 1983 and 1989, 3,000 knee joints were studied with conventional arthroscopy. In 400 of these joints, magnifying arthroscopic examination (microarthroscopy) was performed: 34 were normal, 57 had meniscal and ligamentous lesions, 220 had osteoarthritis, and 89 had inflammatory synovitis. We used two types of arthroscopes, Hamou-Storz and Microview-Wolf, adapted from a microhysteroscope, which provided a x 150 magnification of the conventional field. Referring to established microarthroscopic aspects of the synovial membrane in normal and pathological conditions, we have suggested microarthroscopic criteria for the differential diagnosis of synovitis in various pathological disorders. We believe that there are new applications for microarthroscopy because the instruments appear to have great potential value for both research and diagnosis.


Arthroscopic anterior cruciate ligament reconstruction with patellar tendon.

Anterior cruciate ligament reconstruction using a bone-patella tendon-bone free autologous graft was performed with an arthroscopic technique in 73 patients with chronic insufficiency. Sixty-nine (94.5%) were available for personal follow-up 3-5 years after the operation. Six patients (8%) had had postoperative difficulties in regaining a complete range of motion. Symptoms of giving-way were cured in 97% of the cases, and 89% had returned to vigorous activities. Residual anterior laxity (defined as pivot shift 2+, and/or Lachman 2+, and/or KT-1000 > 5 mm at the manual maximum) was found in 13% and was more frequent in patients with an uncorrected varus laxity. Patellofemoral crepitus was present in 17% of the knees and was associated with pain and/or swelling in a further 4%; it correlated with radiographic evidence of patellofemoral incongruence (p = 0.009). Comparison of the results with those of a previous series performed by arthrotomy revealed a decreased incidence of limited range of motion, severe patellar symptoms, and changes in patellar height. Stability was the same.


Arthroscopic treatment of flexion deformity after ACL reconstruction.

After anterior cruciate ligament (ACL) reconstruction, one frequent complication is the restriction of the range of motion and loss of extension. In addition to the presence of adhesions in the suprapatellar pouch, it is possible to detect two different pathological findings in the intercondylar notch: a misplacement of graft causing an intercondylar impingement, or the presence of hypertrophic tissue originating from the graft that blocks the last degrees of extension, causing an "anterior impingement." We reviewed 18 consecutive cases treated by arthroscopic release. All patients had knee range-of-motion restriction after an ACL procedure. The follow-up at 1 and at 6 months shows that good results have been obtained in cases of anterior impingement, whereas in cases of intercondylar impingement a restricted range of motion, especially of flexion, did remain. In all cases, after arthroscopic treatment the postoperative extension was between 5 and 10 degrees, but this deficit regressed after 6 months in 12 patients, whereas a dropout case was necessary in the remaining 6 patients.


Microvasculature of the human medial meniscus: operative findings.

The purpose of our study was to weigh the probability of a successful meniscus repair on the basis of the microvasculature of the human medial meniscus. In a series of 105 patients who underwent an anterior cruciate ligament reconstruction between January 1985 and December 1986, we chose the 40 patients who had a subtotal medial meniscectomy (38%) to study the microvasculature of the human medial meniscus adequately; the other patients had either an intact meniscus (23%), a meniscus repair (29%), or an already removed meniscus (10%). Forty medial menisci, from 40 male patients with an average age of 27 years, having an anterolateral and/or anteromedial chronic knee laxity and an associated meniscal pathology, were subdivided into two groups: (a) 20 tears restricted to the posterior horn, and (b) 20 bucket-handle tears observed under light microscopy. Meaningful capillary plexuses penetrating into the meniscal stroma were found in 18 of 40 menisci (45%). They were easier to identify in posterior horn tears (55%) than in bucket-handle tears (35%), and were found especially in younger patients (22 years on the average). Therefore, we encourage meniscus repairs even in chronic tears, particularly in younger patients and in posterior-horn tears.


Lateral discoid meniscus: treatment and results.

Forty-six patients (47 knees) who had symptomatic discoid lateral menisci were operated on between August 1981 and May 1989. The patients were categorized according to Watanabe's classifications: complete (80.8%), incomplete (10.6%), and Wrisberg type (8.5%). The treatment of the discoid meniscus is based on total or partial meniscectomy, achieved by the percutaneous or arthrometric technique. Of the 47 knees, 30 underwent a follow-up evaluation. Using Ikeuchi's knee scale, 27 cases (90%) had either excellent or good ratings, and 3 (10%) received fair ratings. There were no poor outcomes. The results in the knees treated by partial meniscectomy were better than those in the knees treated with total meniscectomy.


Role of arthroscopic lateral release in the treatment of patellofemoral disorders.

The results of 50 arthroscopic lateral releases are reported. The average follow-up period was 36 months with a range of 18-52 months. Satisfactory results were achieved in 71% of 21 patients with patellar pain alone and in 76% of those (Betz RR, Lonergan R, Patterson R. The percutaneous lateral retinacular release Orthopaedics 1982;5:57-62) with instability. Patients with patellofemoral osteoarthritis or patellar dislocation were excluded from the series. Postoperative hemarthrosis occurred in 10%. Unsatisfactory results could be related to incomplete release, severe chondromalacia, or insufficient rehabilitation. Lateral release is capable of producing high rates of success with a low incidence of complication when used to treat patellar pain with tight retinaculum, patellar instability, and subluxation.


Operative arthroscopy of the ankle.

The long-term results of 30 operative arthroscopies of the ankle performed from 1983 to 1989 are the basis of this study. The most frequent lesions are synovitis and osteochondral defects of the talus. The treatment consists of lavage, synovial debridement, osteochondral debridement, and the removal of loose bodies. Of the 30 cases, 86.7% obtained excellent or good results and 88% of the athletes returned to their sport.


Recurrent atraumatic superior dislocation of the patella: case report and review of the literature.

Recurrent atraumatic superior dislocation of the patella with spontaneous reduction prevented by interlocking osteophytes has not been previously reported. Eight previous case reports were noted in the literature with single episodes of interlocking by osteophytes in a superior dislocation, none with recurrence, and all treated by closed reduction. The presentation of a 60-year-old woman with recurrent atraumatic superior dislocation of the patella on three separate occasions required closed reduction due to interlocking patella and trochlear osteophytes that were preventing spontaneous reduction. Arthroscopic debridement of these osteophytes resulted in no functional limitation or recurrence of dislocation at 28-month follow-up. This case demonstrates successful arthroscopic treatment of this previously unreported condition. In light of the increasingly active aging population with coexistent patellofemoral joint osteoarthritis, this presentation may become more frequent.


Arthroscopic release of a posttraumatic flexion contracture in the elbow: a case report and review of the literature.

Open arthrotomy has been the standard of treatment for posttraumatic flexion contractures of the elbow. Utilizing standard arthroscopic techniques combined with electrocautery, anterior capsulotomy was performed without complication. Immediate improvement in extension was demonstrated. Multiple cadaveric dissections evidenced the safety of the approach as the humeral capsular attachment is isolated from the neurovascular structures by the brachialis muscle. This technique serves to underscore the utility of elbow arthroscopy in patients with dysfunction previously only amenable to open joint procedures.


The role of screening in the fight against breast cancer.

Breast cancer, a significant cause of mortality, can often be tackled effectively if detected at an early stage. This may be achieved by mammography, physical examination by skilled practitioners, or self-examination of the breasts. However, the value and feasibility of these methods vary with the age of the subject and with economic and cultural circumstances.


Preparing the young to look after the old.

In Malaysia the steady rise in the proportion of people aged 60 or more, and an awareness of their complex psychosocial, economic and health care needs, have led medical faculties to introduce geriatrics as an essential subject in their curricula. The efforts made in this field by the School of Medical Sciences of the Universiti Sains Malaysia are outlined in the present article.


Rehabilitation technicians for remote rural communities.

A programme is described in which indigenous personnel are trained to provide culturally appropriate rehabilitation services for islanders of the Pacific Basin. The disabling conditions most commonly dealt with are associated with stroke, diabetes, arthritis, trauma, and back and neck pain. The programme could be adapted to meet needs in other remote rural communities lacking suitably trained carers.


Health care for nomads too, please.

Pastoral nomadism, a way of life in many developing countries, especially in Africa, has received little attention from planners, economists and governments, partly because the communities in question present what are perceived as difficult logistical problems. Yet it is incumbent on the authorities to develop practical and feasible approaches to the delivery of primary health care for nomadic populations.


What health system for nomadic populations?

In Niger, independent mobile health units intended to meet the needs of nomadic populations have proved ineffectual and excessively costly. Primary health care services should be based on fixed structures with a reasonably wide radius of coverage and sufficient flexibility and mobile capacity to fulfil their obligations to all sectors of the population.


Patterns and problems of alcohol consumption in Japan.

The authors trace the roots of Japan's drinking culture and show how socioeconomic developments, especially in the cities, have led to increased alcohol consumption and associated problems. Measures taken by both the state and nongovernmental bodies to combat alcohol abuse and rehabilitate alcoholics are outlined.


What technologies for health care in developing countries?

In order to decide whether a health technology is suitable for introduction into a developing country it is first necessary to assess both it and the infrastructural conditions in which it would have to function. The present article examines the rationale for establishing national health technology assessment programmes and outlines how they might be conducted.


Intoxicants: no gateway to happiness.

Intoxicants may have symbolic and ritualistic significance and they are widely used to provide excuses for social ineptitude, poor performance, bad behaviour and various other kinds of failure. There are no grounds for attributing to their pharmacological properties any feelings of well-being or joy that may be associated with their use.


Removing the "magic" from drugs.

Following training courses, young people in Sri Lanka are demonstrating that the subjective influence of alcohol and other drugs, and the behaviour they allegedly induce, can be changed by undermining widely held beliefs on their effects. Support is thus emerging for the view that the "magic" or pleasurable experiences commonly ascribed to drugs have little to do with their chemical action.


PCR-based analysis of the TCR repertoire in human autoimmune diseases.

Characterization of T cells at sites of autoimmune damage has been difficult. Now, however, polymerase chain reaction (PCR)-based methods are being used to analyse T-cell receptor (TCR) gene expression in such lesions. Here, Christopher Marguerie, Claudio Lunardi and Alex So summarize and interpret the most recent findings and describe the current understanding of TCR usage in autoimmune diseases.


A strategy to improve the efficacy of vaccination against tuberculosis and leprosy.

The pathogens responsible for leprosy, tuberculosis and the leishmaniases can induce different classes of immunity, but protection is provided only by a cell-mediated response. Here, Peter Bretscher proposes a strategy to achieve an immunological imprint that ensures a stable cell-mediated response upon natural infection.


The role of hsp90 in fungal infection.

The immunodominant antigens of many microbial pathogens are heat shock proteins (hsps). In systemic candidal infections, a major target of protective antibody is an epitope shared with human hsp90. Here, Ruth Matthews and James Burnie suggest that fungal hsp90 plays a key pathogenic role in systemic infection by either binding to certain serum proteins, causing them to malfunction, or by mimicking the functional activity of other proteins.


Islet cell antigens in insulin-dependent diabetes: Pandora's box revisited.

A major goal of research into IDDM has been the identification of the 'causative antigen'. As described in this article by Len Harrison, this reductionist aim is confounded by the fact that numerous candidate islet cell antigens have been described. He scrutinizes the credentials of these candidates and discusses the problem of using autoantibodies to identify causative antigens in a T-cell-mediated disease.


The echinoid immune system and the phylogenetic occurrence of immune mechanisms in deuterostomes.

In this article, Courtney Smith and Eric Davidson reinterpret the published data on immune function in lower deuterostomes and primitive chordates. It leads them to a new model of immune system phylogeny in which MHC-directed T-cell responses are the last to evolve and are not derived from subchordate self-nonself recognition systems.


Guidelines for the PhD degree in immunology. International Union of Immunological Societies Education Committee.

The International Union of Immunological Societies, recognizing the need for internationally acceptable standards for the PhD degree in immunology, commissioned the IUIS Education Committee to prepare recommendations on the subject. This document, the result of a two-year study of PhD programs in many countries, presents these recommendations.


Secondary structural changes of metmyoglobin and apomyoglobin in anionic and cationic surfactant solutions: effect of the hydrophobic chain length of the surfactants on the structural changes.

Secondary structural changes of metmyoglobin and apomyoglobin were examined in solutions of sodium alkylsulfates with hydrocarbon numbers of 8 and 12, and alkyltrimethylammonium bromides with hydrocarbon numbers of 10, 12, 14, and 16. The relative proportion of alpha-helical structure was estimated by the curve-fitting method of circular dichroic spectrum. The helical proportions of metmyoglobin and apomyoglobin were 82 and 63%, respectively. The shorter the hydrocarbon chain the surfactant had, the higher the concentration necessary to disrupt the secondary structures of these proteins. However, the helical proportion had a tendency to decrease down to lower values in solutions of the cationic surfactants with short hydrophobic groups. On the other hand, the alpha-helical structure of apomyoglobin was disrupted in lower concentrations of each cationic surfactant than that of metmyoglobin, although the disruptions of the same structures in both the proteins occurred in the same concentration range of each anionic surfactant. It appeared likely that the removal of the heme group unstabilized the myoglobin conformation only in the cationic surfactant solutions.


Identification of tissue proteins by amino acid analysis after purification by two-dimensional electrophoresis.

Mouse brain proteins were separated by two-dimensional electrophoresis (2-DE). The proteins of a section of the 2-DE pattern were blotted onto hydrophobic membranes and 43 of them were excised and hydrolyzed by liquid-phase hydrolysis. The amino acid composition of these proteins was determined by orthophthaldialdehyde precolumn derivatization and compared with the compositions of known proteins stored in the NBRF sequence database. An identification program named ASA was developed for this purpose. The ASA program includes correction and weighting factors, data reduction by molecular weight windows, and exclusion or inclusion of certain organisms as desired. As a control, eight test proteins and five well-known proteins from mouse brain, all separated by 2-DE, were correctly identified by the program. Out of the 43 brain proteins selected, 19 were identified with high confidence.


Solubility and reactivity of caseins and beta-lactoglobulin in protic solvents.

The study of the solubility of unstructured proteins (alpha s1-, beta-, and kappa-casein) and well-structured globulin (beta-lactoglobulin) in low water binary solvent systems demonstrated the crucial importance of solvent polarity and neutralization of protein polar functions on the final outcome of solubility experiments. The solubilities up to 38, 56, and 96% in CHCl3/CH3OH (1/1, v/v) acidified with HCl and up to 5, 10, and 25% in CHCl3/CH3OH (1/1, v/v) in the presence of triethylamine (TEA) were obtained for kappa-, alpha s1-, and beta-casein, respectively. The importance of protein charge neutralization was apparent when the solubilization was performed in basified CHCl3/CH3OH media, giving the optimal results when the studied proteins were brought before to their isoionic point. The maximum solubility of beta-casein at its pI in 30-70% methanol in CHCl3 was reaching 50-60% with triethylamine (TEA) added. beta-lactoglobulin could be solubilized up to 70% in CHCl3/CH3OH (7/3, v/v) acidified with HCl and up to 40% in CHCl3/CH3OH (3/7, v/v) in the presence of TEA. The observed yield of reductive alkylation of beta-lactoglobulin was much higher (98%) when performed in studied solvent system than in aqueous conditions (75%). Apparently, steric hindrance of the well-folded beta-barrel (in aqueous conditions) structure masks the portion of epsilon-NH2 groups. In the case of unstructured aqueous media beta-casein, 90% alkylation yields were obtained in organic and aqueous conditions.


Prediction of the tertiary structure of parathyroid-hormone-related protein (residues 1-34) by the island model.

Prediction of the tertiary structure of a 34 residue N-terminal fragment of parathyroid-hormone-related protein was carried out by the island model. This peptide is known as a major causative agent of humoral hypercalcemia of malignancy, but structural information studied by X-ray diffraction has not been reported. We adopted the secondary structure determined by NMR and packed on the basis of island model of protein folding developed by us. Predicted structure is discussed in connection with the interaction of active sites.


Primary structure of chain I of the heterodimeric hemoglobin from the blood clam Barbatia virescens.

The blood clam Barbatia virescens has a heterodimeric hemoglobin in erythrocytes. Interestingly, the congeneric clams B. reeveana and B. lima contain quite different hemoglobins: tetramer and polymeric hemoglobin consisting of unusual didomain chain. The complete amino acid sequence of chain I of B. virescens has been determined. The sequence was mainly determined from CNBr peptides and their subpeptides, and the alignment of the peptides was confirmed by sequencing of PCR-amplified cDNA for B. virescens chain I. The cDNA-derived amino acid sequence matched completely with the sequence proposed from protein sequencing. B. virescens chain I is composed of 156 amino acid residues, and the molecular mass was calculated to be 18,387 D, including a heme group. The sequence of B. virescens chain I showed 35-42% sequence identity with those of the related clam Anadara trapezia and the congeneric clam B. reeveana. An evolutionary tree for Anadara and Barbatia chains clearly indicates that all of the chains are evolved from one ancestral globin gene, and that the divergence of chains has occurred in each clam after the speciation. The evolutionary rate for clam hemoglobins was estimated to be about four times faster than that of vertebrate hemoglobin. We suggest that blood clam hemoglobin is a physiologically less important molecule when compared with vertebrate hemoglobins, and so it evolved rapidly and resulted in a remarkable diversity in quaternary and subunit structure within a relatively short period.


Comparative study on the thermostability of collagen I of skin and bone: influence of posttranslational hydroxylation of prolyl and lysyl residues.

Pepsin-solubilized collagen I from skin and bone was analyzed with regard to its thermal stability as a triple helical molecule in solution and after in vitro fibril formation. Collagen I from human control bone was compared with samples showing deficiencies or surplus in the degree of hydroxylation of lysine. The helix to coil transitions were studied by circular-dichroism measurements and limited trypsin digestion. Melting of fibrils from standardized in vitro self-assembly was investigated turbidimetrically. Human control bone collagen I has a maximum transition rate (Tm) at 43.3 degrees C in 0.05% acetic acid. This is 1.9 degrees C above control skin (Tm = 41.4 degrees C), most likely, due to a higher degree of prolyl hydroxylation--0.48 in bone vs. 0.41 in skin collagen I. Lysyl overhydroxylation of human and mouse bone collagen I appears to reduce the Tm slightly (approximately 1 degree C). Underhydroxylated bone collagen has a Tm which is 2 degrees C below control. Melting temperatures of in vitro formed fibrils are an indication for higher thermostability in parallel with an increase of lysyl hydroxylation. Accordingly, the melting temperature of such fibrils from human control skin, 49.3 degrees C, exceeds control bone by 1.4 degrees C. The degree of lysyl hydroxylation in these samples is 0.14 and 0.10, respectively. Further underhydroxylation (0.06) reduced it down to 45.4 degrees C, while extensive overhydroxylation did not continue to increase the thermal stability of fibrils.


Binding of benzo(a)pyrene, ellipticine, and cis-parinaric acid to beta-lactoglobulin: influence of protein modifications.

The binding of benzo(a)pyrene, ellipticine, and cis-parinaric acid to native, esterified, and alkylated beta-lactoglobulin was followed by enhancement of the ligand fluorescence. Three studied ligands bind to native or modified beta-lactoglobulin in apparent molar ratios varying between 1/8 and 2/1, with apparent dissociation constants in the range of 10(-8) M for ligand/beta-lactoglobulin complexes. The studied, chemically modified beta-lactoglobulin derivatives display higher binding affinities for all studied ligands, cis-parinaric acid excluded. The reductive alkylation of epsilon-NH2 lysyl residues of beta-lactoglobulin increases the apparent molar ratios of benzo(a)pyrene and cis-parinaric acid, and decreases it for ellipticine. The esterified and native beta-lactoglobulin complexed to the investigated ligands display similar stoichiometries. Dynamic light scattering study of ligand-beta-lactoglobulin complexes in solution shows the formation of aggregates: the apparent hydrodynamic radius value of beta-lactoglobulin dimer (3.4 nm) reaches 49, 46, and 74 nm upon addition and binding of benzo(a)pyrene, ellipticine, and cis-parinaric acid, respectively.


Chemical modification of interleukin-1 beta: biochemical characterization of a carbodiimide-catalyzed intramolecular cross-linked protein.

We have modified recombinant human Interleukin-1 beta using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide at pH 6.5, resulting in the formation of an internally cross-linked protein. The major product (30% yield) of the reaction (17 kD; pI = 6.2) was purified and fully characterized by peptide mapping using Endoproteinase Lys C. When digests were conducted under nondenaturing conditions, we found that the modified protein is different from the native protein. The native protein yielded 14 peptides after digestion, whereas only two large peptides and a tetrapeptide, Asn-Tyr-Pro-Lys, were released from the cross-linked protein (i.e., cleavage occurs only at residues Lys88 and Lys92). Using gel filtration, the two peptides were found to co-elute as a single species (15 kD), which represent a noncovalent complex of the amino terminal and C-terminal portions of the molecule. Further analysis of the modified protein by peptide mapping under denaturing conditions and by FAB MS analysis showed that Glu111 and Lys138 were internally cross-linked. The cross-linked protein had bioactivity (T-cell proliferation), fluorescence, and circular dichroism spectra similar to native IL-1 beta. In contrast, while having similar secondary structure, the digested cross-linked protein had less than 1% of T-cell proliferative activity of the undigested protein. These data show that the structural integrity surrounding and perhaps including the Asn-Tyr-Pro-Lys region may be crucial for the biological activity of rIL-1 beta and may be important for the binding of IL-1 to its receptor.


Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 145-151 (antigenic site 5) of myoglobin.

Monoclonal antibodies of predetermined specificity were prepared by immunization with a free (i.e., without coupling to any protein carrier) synthetic peptide representing region 145-151 of sperm whale myoglobin (SpMb) and their cross-reactions with eight Mb variants were determined. Five Mbs--bottle-nose dolphin myoglobin (BdMb), pacific common dolphin myoglobin (PdMb), horse myoglobin (HsMb), dog myoglobin (DgMb), and badger myoglobin (BgMb)--have an identical sequence in that region. Nevertheless, these Mbs exhibited very different cross-reactivities. BdMb and PdMb exhibited cross-activities which were comparable to that of the reference antigen, SpMb; while the reactivity of HsMb was remarkedly decreased, DgMb and BgMb showed almost no cross-reactions with these mAbs. Since the region 145-151 has an identical sequence in all the five Mbs, it is concluded that the differences in their antigenic reactivities with anti-region 145-151 mAbs are due to the effects of amino acid substitutions outside the region 145-151. Another pair of myoglobins, echidna myoglobin (EdMb) and chicken myoglobin (ChMb), have the same sequence in that region, but reacted very differently with anti-region 145-151 mAbs. The reactivity and affinity of EdMb were substantially decreased while those of ChMb were almost completely absent, relative to SpMb. It is concluded, contrary to popular assumptions, that when an amino acid substitution influences the binding of a protein variant to a mAb, it is not necessary for that substitution to be an actual contact residue (i.e., a residue within the antigenic site where the mAb binds). Such effects, which are often very drastic, could be due to indirect influences of the substitution on the chemical and binding properties of the site residues. Furthermore, residues which had been postulated, on the basis of these assumptions, to constitute discontinuous antigenic sites in SpMb, were found [from the present studies and those recently reported with mAbs against the other four antigenic site of Mb (regions 15-22, 56-62, 94-100, and 113-120 of SpMb)] to merely be exerting indirect effects on the known five antigenic sites of Mb. The effects of substitutions, which can happen even in the absence of conformational changes, are determined by many factors, such as the chemical nature of the substitution, its environment, its distance from the site, and the nature of the site residue(s) being affected.


Enkephalin is a competitive antagonist of cholecystokinin in the gastrointestinal tract, as predicted from prior conformational analysis.

Prior calculations based on ECEPP (Empirical Conformational Energies for Peptides Program) of the low energy minima for cholecystokinin (CCK) and Met-enkephalin have demonstrated that significant structural features of these two peptides are identical. This result suggested the possibility that Met-enkephalin, as well as other enkephalin analogues of similar structure, could associate with receptors for CCK. To test this theoretical result, we examined the ability of Met-enkephalin and its analogues to bind to peripheral CCK receptors in the rat gastrointestinal tract; in particular, we measured the ability of the opiate peptide to inhibit the effects of CCK in a physiological assay system which we have previously characterized: CCK-induced contraction of the isolated rat pyloric sphincter. We find that Met-enkephalin is an antagonist of the CCK-8-induced contraction, with a IC50 of 110 nM. Furthermore, antibodies against CCK were found to cross-react with Met-enkephalin and its analogues in a manner which suggests a distinct structure-activity relationship. These experimental results strongly support the theoretical results of conformational analysis showing structural similarity between enkephalin and CCK. They further suggest that enkephalins could modulate the response of CCK systems under physiological conditions.


Guanine-nucleotide binding activity, interaction with GTPase-activating protein and solution conformation of the human c-Ha-Ras protein catalytic domain are retained upon deletion of C-terminal 18 amino acid residues.

A truncated human c-Ha-Ras protein that lacks the C-terminal 18 amino acid residues and the truncated Ras protein with the amino acid substitution Gly-->Val in position 12 were prepared by an E. coli overexpression system. The truncated Ras protein showed the same guanine-nucleotide binding activity and GTPase activity as those of the full-length Ras protein. Further, the same extent of GTPase activity enhancement due to GTPase-activating protein was observed for the truncated and full-length Ras proteins. In fact, two-dimensional proton NMR analyses indicated that the tertiary structure of the truncated Ras protein (GDP-bound or GMPPNP-bound) was nearly the same as that of the corresponding catalytic domain of the full-length Ras protein. Moreover, a conformational change around the effector region upon GDP-->GMPPNP exchange occurred in the same manner for both proteins. These observations indicate that the C-terminal flanking region (18 amino acid residues) of the Ras protein does not appreciably interact with the catalytic domain. Therefore, the truncated Ras protein is suitable for studying the molecular mechanism involved in the GTPase activity and the interaction with the GTPase-activating protein. On the other hand, an active form of the truncated Ras protein, unlike that of the full-length Ras protein, did not induce neurite outgrowth of rat pheochromocytoma PC12 cells. Thus, membrane anchoring of the Ras protein through its C-terminal four residues is not required for the interaction of Ras and GAP, but may be essential for the following binding of the Ras-GAP complex with the putative downstream target.


Calcium-binding proteins in the dentate gyrus.

Calbindin D28k (CaBP) is present throughout the entire cell volume of all dentate granule cells in the rat and its appearance is a useful indicator of their development and maturation. Kindling induces a dramatic reduction of granule cell CaBP content but does not make granule cells any more susceptible to the effects of ischemia in adult rats. Others have reported that the levels of CaBP are regulated by corticosterone but our results (in adrenalectomized Wistar or hypophysectomized Sprague-Dawley rats) suggest that any effect is small and transitory. Parvalbumin (PV) is located quite specifically within the entire cell volume of a subpopulation of GABAergic neurons both in the granule cell layer and hilar zone. It appears quite late in the development of the neurons. Reports that kindling induces an increase in PV immunoreactivity in neurons within the hippocampal formation are not supported by the direct measurement of PV levels by radioimmunoassay. Hypophysectomy resulted in a significant fall in PV levels in a number of brain areas including the combined dentate gyrus/CA3 region of the hippocampal formation.


Morphological changes in the dentate gyrus in human temporal lobe epilepsy.

Multiple morphological and neurochemical changes are found in the dentate gyrus of humans with temporal lobe epilepsy (TLE). Three basically different types of changes will be discussed and some interrelationships considered. Neuronal loss in several regions of the hippocampal formation in human TLE has been recognized for many years, but only recently have the polymorph or hilar neurons been evaluated as a distinct group of neurons, and cell loss in this region is now being documented in many cases with severe TLE. Reorganization of afferents within the molecular layer of the dentate gyrus is also found in a high percentage of TLE specimens. The apparent reorganization of mossy fibers from the dentate granule cells is particularly striking, and aberrant innervation of the inner part of the molecular layer by zinc- and dynorphin-containing mossy fibers has been reported in human tissue by several groups of investigators. In a subpopulation of TLE specimens, there is also disorganization of the granule cell layer. Rather than being arranged in the compact, highly organized layer that is characteristic of control tissue, the granule cell bodies in some TLE cases are dispersed. In some additional cases, a bilaminar pattern of granule cells is observed. Each of these changes could contribute to altered circuitry within the dentate gyrus of humans with TLE, and such alterations could influence seizure susceptibility within the hippocampal formation.


Information processing in the dentate gyrus.

The dentate gyrus is viewed as playing a major role in the generation of epileptiform activity. The ramifications of disrupted neuronal activity in the dentate gyrus are discussed with emphasis on the role of the dentate gyrus in processing sensory information. Several features of conditioned auditory-evoked potentials reflective of activity in the perforant path are described with respect to the activity of dentate granule cells. Comparisons of the sequential changes which occur in the perforant path synaptic activity and dentate granule cell discharge reveal an inverse relationship between synaptic input from the perforant path and degree of cell firing on any given trial. This inverse relationship is addressed in terms of extra-hippocampal projections to the cortex as well as recurrent connections to the enthorhinal area and the cells of origin of the perforant path. It is concluded that the perforant path regulates the response of the dentate granule cells to sensory input from the neocortex by decreasing synaptic drive when granule cell activity is high and increasing that synaptic drive when granule cell activity is low. This extra-hippocampal control of perforant path activity serves to 'clamp' the dentate granule cell response rate within a tightly controlled range to guarantee that granule cells will have some response capacity to 'unexpected' sensory experiences.


[Metabolism of trace elements in healthy and sick children. I. Health status].

The oligo-elements or trace elements have acquired a major importance in the knowledge concerning corporal composition and in the comprehension of their metabolic participation in organic processes. Today, thanks to the technological and scientific progress reached by modern pediatrics, the studies made at cellular level have advanced to a molecular level, which will in the future be, without doubt, the bridge that will lead into the atomic level. In addition, this review will briefly summarize several facts of the knowledge accumulated up to now, regarding: 1. The nutritional aspects of these oligo-elements; 2. Its biological functions in healthy condition, especially in children; 3. Their respective nutritional requirements.


[Differential physical growth during the 1st year of life. II. Growth of the head].

The corporal segment that display the major growth velocity before and after born is the head; that is, once a baby is born, it represents the fourth part of the stature, it has the greater corporal circumference, and their development is superior than other corporal segments. However, the growth shape of the craniofacial structures is different; so, the growth gradient of brain, is the responsible of the morphological view described previously; the facial structures follow the general growth curve; moreover, the facial bone that contributes with the growth of brain, describes mixed growth gradients. This complex shape of the head growth, requires the existence of growth standards for these structures. The present paper describes the results of longitudinal research on head growth. We studied 200 children of both sex and ages from 0 to 1 year of extrauterine life. We got 18 growth measures of the head, such as: head circumference, head length and width, minimum frontal diameter; head, total facial, upper facial, and nose height; bizygomatic, bigonial, external bipalpebral, internal bipalpebral and nose widths; length and width of lips and ear. Moreover, we report the final increments and the differences on sexual dimorphism.


[Protection of health personnel against hepatitis B by DNA recombinant vaccine].

Hepatitis B (HVB) is a worldwide spread health problem. It has been assessed that there are more than 300 millions of carriers. HVB has a special concern for health care workers (HCW's) due to the high risk among them of getting the infection in clinic-setting areas. According to some estimation, the risk for hepatitis B among HCW's is 2 to 10 times higher than the risk for general population. The risk is related to the degree of direct contact with blood and body fluids, as well as, with the frequency of traumatic exposure in the work place. The control of this infection is based on the observance of universal precautions and the vaccination, since there is not treatment against this disease. The results of an efficacy-evaluation of DNA recombinant vaccine against hepatitis B are reported; 174 HCW's were studied; three dosages of vaccine were administered (0.1st and 6th month) by I.M. via. In addition, three serum samples were collected at 0, 1st and 9th month after vaccine administration. We did not find carriers of surface antigen of hepatitis B. With regards to seroconverted individuals we observed the following results: there were a satisfactory response to the vaccine in 163 individuals (93.7%); however, 8 (4.6%) persons did not reach titles of protective antibodies and 3 (1.7%) did not show seroconversion at all. Therefore, 11 persons (6.3% of the total) did not result immunized. The secondary reactions to the vaccines were low in frequency and mainly of local presentation. Among the study population we did not find chronic carries of hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)


[Usefulness of endoscopy in the differential diagnosis of hemorrhage of the upper digestive tract in children].

One hundred and sixty two patients with upper and intermediate gastrointestinal hemorrhage studied under a prospective protocol are reported. Upper endoscopy revealed lesions of the upper gastrointestinal tract in 137 patients (89%); a barium swallow performed to 92 of them failed to confirm the endoscopic diagnosis in 66 (71.7%). In 99m Tc scan suggested ectopic gastric mucosa in 9 cases; Meckel's diverticulum was confirmed by laparotomy in 7 and gastrointestinal duplication in two of them. Selective mesenteric arteriography demonstrated bleeding ileo-cecal varices in one patient. The main causes of gastrointestinal hemorrhage in the current series were duodenal ulcer (22.8%), esophageal varices (14.8%), stress ulcers (14.2%), reflux esophagitis (7.4%), aspirin-induced gastritis (6.8%), gastric ulcer (5.6%) and ectopic gastric mucosa (5.6%). These diagnosis were characteristically distributed according to pediatric age-groups. The source of bleeding could be detected in 90% of the patients studied. A clinical approach to differential diagnosis of patients with gastrointestinal bleeding is presented.


[Prevalence of dental caries and rampant caries in a preschool population].

The results from a study on prevalence of ordinary dental caries and rampant caries in a children population are presented. The study was carried out at Dentistry Out patient Service in the Children Hospital "San Juan de Aragón" of the Federal District Department. The DMF index was obtained and its was proposed another one, in order to classify the different degrees of rampant caries in function of dental damage. An interview was applied to the fathers of the children of the study group in order to determinate hygiene oral habits, eating and familiar antecedents that could influence in the process of the ordinary and rampant caries and to compare between them. Serum and saliva were analyzed to determinate levels of albumin and IgM, IgG and IgA; there were also others factors tested that could indicate caries development.


[Right pulmonary hyperplasia with bronchoesophageal fistula].

The pulmonary hypoplasia with bronchoesophageal fistula is a rarely-seen disease which can be confused with total pulmonary agenesis. This case study concerns to one day old male newborn which was hospitalized in our hospital with respiratory difficulties, accompanied by pulmonary opacity of the right side. After having carried out diagnosis studies, including bronchography, we concluded that it was a case of pulmonary agenesis. The patient died from persistent pulmonary hypertension. The anatomopathologic diagnosis, was right pulmonary hypoplasia with bronchoesophageal fistula. This pathology originated during early embryonic stage when the bronchoplastic and esophagoplastic tissue are incompletely separated an thus a fistula between the esophagus and the principal bronchus is formed. The presence of a fistula could not be proven by bronchography. However, esophagography or esophagoscopy would have proven the presence of the fistula.


[Becker's melanosis: a case report].

Becker melanosis is a dermatosis characterized by hyperpigmentation and hypertrichosis in absence of cells nevus; its frequency is unknown an its presentation is rare in the infancy; appearance usually during puberty. In the last years its association to anomalies of development increase the importance of this entity. We present the case of 4 years old girl considered the youngest report in the literature, with affection of trunk and right leg associated to minimum shorten of right leg.


[Septic shock in newborn infants].

Systemic bacterial infections continue to be a main cause of death in newborns at neonatal intensive care units (NICU), worldwide. Bacteria causing neonatal septicemia are mainly the gram-negative, which possess endotoxin and are responsible for endotoxic shock. However, gram-positive bacteria are also able to induce septic shock, especially in immunocompromised hosts, like the newborns. Diagnosis and treatment of neonatal septic shock are quite difficult. Furthermore, there is not sufficient knowledge about its real frequency in Latin-american countries. The hyperdynamic phase of septic shock in newborns can be short and the hypodynamic phase is rapidly established, which increases the mortality. Since few years ago, some important aspects of physiopathology in septic shock have been studied and, at the same time that our knowledge about immunologic soluble mediators is increasing, new therapeutic modalities have been discovered. Such is the case of the therapeutic potentialities of cytokines, receptor antagonists and monoclonal antibodies, which is very encouraging at the present time.


Effect of post-training unilateral labyrinthectomy in a spatial orientation task by guinea pigs.

The effects of unilateral labyrinthectomy in guinea pigs have been studied on an angular orientation task consisting, in an open field, of running to a hidden goal oriented at 45 degrees with respect to the cephalocaudal axis of the animal placed in a starting-box. The task was conducted in light but in an homogeneous environment, i.e. without visual, auditory or olfactory cues indicating the location of the goal. A second group of animals was submitted to a similar task running to a hidden goal but the place of the goal was indicated by a colored card. All the animals were trained before the lesion and tested in their respective task for 1 month after the lesion. In the task conducted without conspicuous cues, animals were dramatically disturbed. In contrast, animals pretrained in the visually guided task were not impaired after the lesion. These results point out the important role of vestibular information in performing spatial tasks based on angular estimation, since, even if proprioceptive and visuokinesthetic information remain available, subjects seemed not able to maintain a correct angular trajectory. The trajectories being not disturbed in the visually guided task, one can exclude the hypothesis that such deficit was due to a purely motor disturbance.


Regulatory behaviour, exploration and locomotion following NMDA or 6-OHDA lesions in the rat nucleus accumbens.

The effects of bilateral, N-methyl-D-aspartate (NMDA)-induced lesions of the nucleus accumbens (N.Acc.) on regulatory and behavioural responding were studied in rats and compared with the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions. After postoperative body weight, food and water intake had been monitored for a period of 4 weeks, rats were tested in an exploration-choice box. Spontaneous locomotion and the locomotor and stereotypy responses to different doses of dopaminergic agonists were measured subsequently. Detailed assessment of NMDA-induced lesion volumes showed that on average 81.53% of total N.Acc. area was damaged, depending on excitotoxin dose. Tyrosine hydroxylase immunohistochemistry was used to confirm loss of mesolimbic dopamine neurones following 6-OHDA. Analysis of the behavioural data showed that NMDA N.Acc. lesions significantly enhanced exploratory behaviour, spontaneous locomotor activity and the locomotor response to a low dose of D-amphetamine. By comparison, 6-OHDA lesions did not affect exploration and spontaneous locomotion but significantly attenuated the locomotor response to a low dose of D-amphetamine. Regulatory responses were unaffected 28 days after surgery, although NMDA-lesioned rats took longer to recover from postoperative hypodipsia. The results suggest that NMDA N.Acc. lesions induce a deficit in the control of general locomotor output and are consistent with the hypothesis that the N.Acc. functions as an interface between sensory input and locomotor output and that it is needed to channel activity levels appropriately.


Opponent-process theory and drug conditioning: an assessment for conditioned stimulant-induced movement.

Opponent-process theory occupies an important place in drug conditioning because it accounts for conditioned drug effects which are opposite to those induced by the drug itself. It has not been established, however, whether there is an opponent-process component to stimulant drug induced conditioned effects. In the present study the unilateral 6-hydroxydopamine (6-OHDA) rat model was used to examine this issue. Two groups of Sprague-Dawley rats with equivalent 6-OHDA lesions were administered five apomorphine treatments (0.05 mg/kg s.c.) either paired or unpaired to a 10-min test chamber placement. Apomorphine induced vigorous contralateral rotation and suppressed all ipsilateral rotation. While the apomorphine-induced contralateral rotation response can be conditioned to the test environment cues, the critical test of opponent-process theory in the present study was whether the opposite response of ipsilateral rotation would also become conditioned as a latent opponent-process response to the exteroceptive test environment cues associated with the apomorphine drug state. The postacquisition saline test for conditioning showed that the paired group exhibited higher rates of contralateral and ipsilateral rotation compared to the unpaired group. In addition, when the animals were subsequently tested with the dopaminergic receptor antagonist, haloperidol (0.5 mg/kg), unexpectedly, contralateral rotation was enhanced in the paired group, whereas, ipsilateral rotation was suppressed in both groups. While these findings are, in part, compatible with an opponent-process mechanism, the data supported a simpler explanation; namely, the mechanism of differential habituation in the two groups due to a blocking effect of apomorphine on habituation selectively in the paired group.(ABSTRACT TRUNCATED AT 250 WORDS)