Apical root canal anatomy in the dog.

240 permanent teeth from 8 different dogs aged 1, 3, 8, 10, 15 years, were used for an anatomic study. The teeth were cleaned, their root canal system was stained with dye, then the teeth were decalcified and cleared to determine the root canal anatomy. The apical root canal anatomy in dogs can be described as a "sprinkler-rose" anatomy: at the tip of the pulpal canal, the canal is divided in numerous narrow channels radiating peripherally through the dentin and the cementum and ending in numerous apical foramina on the cementum surface. This architecture constitutes a very complex apical delta.


Rigidity of various fixation methods used as dental splints.

Horizontal and vertical rigidity of teeth fixed with seven types of dental splints were evaluated by two tooth mobility measuring devices. Altogether 21 dissected sheep mandibles including soft tissues were used for the experiments in which Fermit, flexible wire-composite, Kevlar, Fiber, Protemp, rigid wire-composite and Triad Gel splints were applied to four incisors. The mean rigidity of the central incisors within the splint was measured by means of Mühlemann periodontometer (horizontal mobility) and Periotest (horizontal and vertical mobilities). Mobility values of teeth before splinting were used as covariants and the values with the splints were illustrated as adjusted mobility. Statistical significance between the rigidity of various splints was analyzed by an unpaired t-test. It was shown that the most rigid splints both in horizontal and vertical directions were Triad Gel, rigid wire-composite and Fermit splints. Kevlar and Fiber splint allowed more horizontal movement than other splints. Protemp and flexible wire-composite splints proved to produce adequate lateral support for the fixed teeth and allowed vertical flexibility which is experimentally known to improve periodontal healing of luxated teeth.


Toxic effects of various retrograde root filling materials on gingival fibroblasts and rat sarcoma cells.

The aim of this in vitro study was to evaluate the effect of amalgam, glass ionomer, composite and titanium on the growth of gingival fibroblasts (GF) and rat sarcoma cells (UMR) in vitro. The cells were either obtained from gingival biopsies taken during deliberation of unerupted canines (GF) or were of commercial origin (UMR). Equal numbers of cells were placed on culture dishes and incubated for a period of two weeks with the freshly prepared test materials. The cultures were photographed through a light microscope after 7 days incubation and finally counted after 14 days. It was shown that the proliferation of gingival fibroblasts was less disturbed by titanium, being approximately 96% of the control value (cell cultures without test particles), followed by composite, amalgam and glass ionomer (61%, 49% and 35% of the control value respectively). The number of UMR cells after 14 days incubation with the various materials was 76% of the control value with titanium, 12% with composite and 5% with both amalgam and glass ionomer. Inhibition of cell growth (UMR) around the test particles was most prominent around amalgam and glass ionomer, followed by composite and titanium. These effects were noted only with freshly prepared components however, so that the toxic reaction was less pronounced or minimal in a second incubation using the same particles sterilized in between. The results demonstrated that potential retrograde root filling materials have a variable toxic effect on gingival fibroblasts and rat sarcoma cells. The fact that the influence on proliferation disappeared when the test was performed with materials already tested once may be of clinical importance when estimating the biocompatibility in vivo.


Histologic evaluation of three endodontic instrument/preparation techniques.

33 curved canals were prepared to quantify both the increase in canal area and predentin removal in the apical region. Compared were three different file designs/instrumentation techniques, that is "stepback" with K-flex file, "balanced force" with Flex-R file, and the Canal Master system. Following canal preparation and histological processing, cross-sections at 1 and 3 mm levels were examined using the Bioquant image analysis system. Results showed that, at the 3 mm leve, the mean increase in canal area and predentin removal showed no statistically significant difference (p > 0.05) between the techniques. At 1 mm, the step-back technique (with K-flex files) resulted in a significant increase in canal area and greater predentin removal than did the "balanced forces" (with Flex-R files) or the Canal Master system. However, although there were statistical differences, the actual differences were small; these may not translate to clinically significant differences in the 3 techniques.


Traumatic gemination--triple tooth. Survey of the literature and report of a case.

Gemination and twinning are two rarely encountered developmental abnormalities. Although the precise etiology remains unknown, genetic predisposition is often suggested in the process. In the present study a maxillary incisor with three crowns of conical shape and three roots which were presumed to be the gemination of the tooth due to trauma, is reported.


Apical closure of an immature root subsequent to apical curettage.

A 7-year-old female presented with a history of trauma to the mandibular central incisor resulting in pulpal necrosis and soft tissue swelling. During apexification treatment, an ultrasonic file was separated and lodged in the periapical tissues. Surgical retrieval of the broken instrument resulted in complete curettage of the periapical tissues. Apical closure occurred following intracanal calcium hydroxide therapy. The findings suggested that hard tissue barrier formation occurred despite the absence of Hertwig's epithelial root sheath and local periapical tissues.


Oral defense factors in the elderly.

Continuously increasing proportion of elderly people in the human population creates new challenges for the dental care. Because the microbial etiology of the most common oral diseases, dental caries, endodontal and periodontal diseases, is not substantially different in different age groups, the altered host response during aging may modify the progression of these diseases. Most prevalent and severe change in the oral defense is hyposalivation or xerostomia but aging as such does not seem to reduce neither parotid nor whole salivary flow rate. However, submandibular and minor salivary glands produce less saliva at old age which may be the reason for the frequently reported symptoms of oral dryness even if the stimulated flow rate is normal. Concomitantly to the changes in the flow rate the daily output of many saliva-mediated defense factors declines but age-related impairment has been described only for specific IgA response to external antigens, for salivary opsonic activity, and for T-lymphocyte function. The non-immunoglobulin defense factors seem to act with full capacity over the entire life-span. Therefore, elderly people with normal salivary flow rate possess no special risk group for the development of oral diseases.


Effectiveness of different endodontic files for preparing curved root canals: a scanning electron microscopic study.

In this study, the effect of using four endodontic files from different manufacturers on the final shape of 80 prepared curved root canals of extracted single-rooted teeth were comparatively analyzed with scanning electron microscopy. The instruments tested were Tri-files, Flex-R files, Flexofiles and conventional K-type files. All files were used with in and out linear movements with a circumferential motion starting with a size 15 file. Final preparation of the apical thirds was performed with a size 30 file. Shaping effectiveness of the tested files was qualitatively evaluated in terms of respect for conservation of the apical constriction and the presence or absence of ledging, specially in the apical third of the root canals. A well-centered and tapered preparation without apical transportation or ledging was detected when Tri-file or Flex-R files were used. Conversely, the use of Flexofile or conventional K-type files resulted in frequent alteration of the initial pattern of the root canals, showing an hour-glass preparation with alteration of the apical constriction and ledge formations.


Functional hepatocellular heterogeneity for the production of plasma proteins.

It is now well established that hepatocytes are the main liver cells responsible for the synthesis of plasma proteins produced by the liver. That these cells are not specialized in the production of the different plasma proteins is also well established. Presently the point still debated is whether a functional hepatocellular heterogeneity exists for plasma protein synthesis as for many other hepatocyte functions. Several physiological and pathological situations suggest that this heterogeneity takes place in the hepatocytes of two opposite hepatic lobular zones, the periportal and centrilobular zones. However, this zonal difference, which supposes different regulatory mechanisms, must be confirmed by techniques other than the now classical immunocytochemistry or the in situ hybridization technique recently proposed for the demonstration of mRNAs in hepatocytes. Another hepatocellular heterogeneity, the intercellular heterogeneity, which can be observed in the same lobular zone, is more difficult to analyze, but shows that from hepatocyte to hepatocyte a variation exists in the synthesis of a given plasma protein.


Liver cell heterogeneity: functions of non-parenchymal cells.

The normal hepatic sinusoid is formed or lined by four different cell types, each with its specific phenotypic characteristics, functions and topography. Endothelial cells constitute the closed lining or wall of the capillary. They contain small fenestrations to allow the free diffusion of substances, but not of particles like chylomicrons, between the blood and the hepatocyte surface. This filtering effect regulates the fat uptake by the liver. Sinusoidal endothelial cells also have a pronounced endocytotic capacity which makes them an important part of the reticuloendothelial system. They are also active in the secretion of bioactive factors and extracellular matrix components of the liver. Recently, a zonal heterogeneity of the endothelial lining has been reported with regard to its filtering capacity (fenestration) and binding capacity for lectins and cells. Kupffer cells are intrasinusoidally located tissue macrophages with a pronounced endocytotic capacity. They are potent mediators of the inflammatory response by the secretion of a variety of bioactive factors and play an important part in the immune defense. A zonal heterogeneity has been established with regard to the endocytotic capacity and cytotoxic function. Pit cells are now known to represent a liver-associated population of large granular lymphocytes. They have the capacity to kill tumor cells and probably also play a role in the antiviral defense of the liver. In addition, pit cells may have a growth-regulatory function of the liver. They are known to be numerically more prominent in the periportal region, as is also the case for Kupffer cells. Fat-storing or Ito cells are present in the perisinusoidal space of Disse and are thought to represent the main hepatic source of extracellular matrix components. They are also the main site of vitamin-A storage. Fat-storing cells are more numerous in the periportal region than in the central region of the hepatic acinus. The periportal cells also store higher amounts of vitamin A. Sinusoidal cells may be considered to represent a functional unit at the border line between the hepatocytes or parenchymal cells and the blood. They participate in various liver functions and liver pathologies and our knowledge about this is growing. The heterogeneity of these cell types and possible cooperations between them and the hepatocytes may add to our understanding of liver functions.


Hepatocyte heterogeneity in the metabolism of carbohydrates.

Periportal and perivenous hepatocytes possess different amounts and activities of the rate-generating enzymes of carbohydrate and oxidative energy metabolism and thus different metabolic capacities. This is the basis of the model of metabolic zonation, according to which periportal cells catalyze predominantly the oxidative catabolism of fatty and amino acids as well as glucose release and glycogen formation via gluconeogenesis, and perivenous cells carry out preferentially glucose uptake for glycogen synthesis and glycolysis coupled to liponeogenesis. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of carbohydrate metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes in carbohydrate metabolism has been well characterized. In vivo evidence is provided by the complex metabolic situation termed the 'glucose paradox' and by zonal flux differences calculated on the basis of the distribution of enzymes and metabolites. In vitro evidence is given by the different flux rates determined with classical invasive techniques, e.g. in periportal-like and perivenous-like hepatocytes in cell culture, in periportal- and perivenous-enriched hepatocyte populations and in perfused livers during orthograde and retrograde flow, as well as with noninvasive techniques using miniature oxygen electrodes, e.g. in livers perfused in either direction. Differences of opinion in the interpretation of studies with invasive and noninvasive techniques by the authors are discussed. The declining gradient in oxygen concentrations, the decreasing glucagon/insulin ratio and the different innervation could be important factors in the zonal expression of the genes of carbohydrate-metabolizing enzymes. While it is clear that the hepatocytes sense the glucagon/insulin gradients via the respective hormone receptors, it is not known how they sense different oxygen tensions; the O2 sensor may be an oxygen-binding heme protein. The zonal separation of glucose release and uptake appears to be important for the liver to operate as a 'glucostat'. Thus, zonation of carbohydrate metabolism develops gradually during the first weeks of life, in part before and in part with weaning, when (in rat and mouse) the fat- and protein-rich but carbohydrate-poor nutrition via milk is replaced by carbohydrate-rich food. Similarly, zonation of carbohydrate metabolism adapts to longer lasting alterations in the need of a 'glucostat', such as starvation, diabetes, portocaval anastomoses or partial hepatectomy.


Hepatocyte heterogeneity in the metabolism of amino acids and ammonia.

With respect to hepatocyte heterogeneity in ammonia and amino acid metabolism, two different patterns of sublobular gene expression are distinguished: 'gradient-type' and 'strict- or compartment-type' zonation. An example for strict-type zonation is the reciprocal distribution of carbamoylphosphate synthase and glutamine synthase in the liver lobule. The mechanisms underlying the different sublobular gene expressions are not yet settled but may involve the development of hepatic architecture, innervation, blood-borne hormonal and metabolic factors. The periportal zone is characterized by a high capacity for uptake and catabolism of amino acids (except glutamate and aspartate) as well as for urea synthesis and gluconeogenesis. On the other hand, glutamine synthesis, ornithine transamination and the uptake of vascular glutamate, aspartate, malate and alpha-ketoglutarate are restricted to a small perivenous hepatocyte population. Accordingly, in the intact liver lobule the major pathways for ammonia detoxication, urea and glutamine synthesis, are anatomically switched behind each other and represent in functional terms the sequence of the periportal low affinity system (urea synthesis) and a previous high affinity system (glutamine synthesis) for ammonia detoxication. Perivenous glutamine synthase-containing hepatocytes ('scavenger cells') act as a high affinity scavenger for the ammonia, which escapes the more upstream urea-synthesizing compartment. Periportal glutaminase acts as a pH- and hormone-modulated ammonia-amplifying system in the mitochondria of periportal hepatocytes. The activity of this amplifying system is one crucial determinant for flux through the urea cycle in view of the high Km (ammonia) of carbamoylphosphate synthase, the rate-controlling enzyme of the urea cycle. The structural and functional organization of glutamine and ammonia-metabolizing pathways in the liver lobule provides one basis for the understanding of a hepatic role in systemic acid base homeostasis. Urea synthesis is a major pathway for irreversible removal of metabolically generated bicarbonate. The lobular organization enables the adjustment of the urea cycle flux and accordingly the rate of irreversible hepatic bicarbonate elimination to the needs of the systemic acid base situation, without the threat of hyperammonemia.


Liver architecture.

The development of liver parenchyma starts from entodermal cells which grow out from the gut into the mesenchyma of the septum transversum. In the definitive organ this close association of epithelial cells (hepatocytes) and mesenchyma-derived nonparenchymal cells is maintained. The liver, and with it each hepatocyte, acts in two directions: the vascular poles of the hepatocytes serve in an ingestive sense, while at their biliary poles secretory functions are exerted. Hepatic microvascularization comprises two afferent vessels (arterial and portal terminal branches), the sinusoids and the terminal hepatic venule. Sinusoidal cells surround the capillaries but also have highly specialized functions with regard to filtration, phagocytosis, fat storage and defense. The autonomic innervation plays an important role in the regulation of metabolic functions. Above the cellular level the proper architecture of the liver parenchyma has been the object of controversial discussions for centuries. The concept of the liver lobule, the portal unit, the liver acinus and other structures are presented and discussed. Finally, the liver parenchyma is described as an irregular interdigitating system of regions related to the terminal blood vessels.


Hepatocyte heterogeneity in bile formation and hepatobiliary transport of drugs.

In the past two decades many studies have been devoted to the involvement of the periportal (zone-1) and perivenous (zone-3) hepatocytes in bile formation and hepatobiliary transport of endogenous and exogenous compounds. It became clear that such a heterogeneity in transport function can, in principle, be due to the different localization of the cells in the acinus with respect to the incoming blood, to intrinsic differences between the cells or to both. In this review we first discuss the techniques used to study hepatocyte heterogeneity in hepatobiliary transport function. Combinations of such techniques can be used to discriminate between cellular heterogeneity due to acinar localization as opposed to intrinsic differences. These techniques include: normal and retrograde perfusions of isolated perfused livers; autoradiographic, fluorimetric and histochemical localization of injected substrates; separation of isolated hepatocytes into fractions enriched in periportal and perivenous cells; measurements of fluorescent surface signals with microlight guides; selective zonal toxicity, and pharmacokinetic modelling and analysis. Subsequently, for each of the rate-limiting steps in the hepatobiliary transport of organic compounds, the basic mechanisms are summarized and the available knowledge on the involvement of the cells from the various zones in these transport steps is discussed. The available literature data indicate that heterogeneity in transport function is often due to the localization of the cells in the acinus: the periportal cells are the first to come into contact with the portal blood and are thus exposed to the highest substrate concentration. Consequently they obtain the most prominent task in further disposition of the particular compound. It follows that the extent of involvement of the perivenous cells in drug disposition is implicitly determined by the activity of the periportal cells. Because of the potential saturation of elimination processes in the periportal cells, the involvement of perivenous cells may vary with the input concentration. In addition, real intrinsic differences have been established in the hepatobiliary transport of some substrates. These are probably based on differences in the cellular content of carrier- and receptor-binding and/or metabolizing proteins. In some cases these intrinsic differences may be secondary to existing sinusoidal gradients of endogenous compounds, such as O2, amino acids, bile acids or monosaccharides. Yet, data on the heterogeneity of hepatocytes in the various transport steps are far from complete or are even totally lacking, especially for human liver. A multi-experimental approach and advanced technology will be needed in the future to gain more insight into the acinar organization of bile formation and hepatobiliary transport of drugs in the human.


Survival of hypertensive subjects identified on screening: results for sustained and unsustained diastolic hypertension.

Casual readings of blood pressure predict mortality and may reflect either the risk of sustained hypertension, additional components of 'white coat' hypertension or variable blood pressure. This study investigated mortality in 442 men and 360 women with a diastolic pressure (Phase IV) of 90 mmHg and over, unsustained on two subsequent monthly visits, followed for an average of 11 years and compared with a matched control cohort with an initial diastolic pressure (DBP) of less than 90 mmHg. Subjects were identified between 1975 and 1979 by screening 28,257 subjects aged 18-65 years on the lists of general practitioners in seven practices in the United Kingdom. Additionally, 912 men and 844 women with sustained hypertension (DBP > 90 mmHg on at least two out of three occasions) were identified and matched with normotensive controls. In men with sustained hypertension the relative risk (RR) for death from circulatory disease was 1.76, P < 0.01, 95% confidence interval 1.21, 2.58 and in women 1.85, P < 0.05, 95% confidence interval 1.06, 3.24 respectively, while in men with unsustained hypertension the RR = 1.52, P = 0.2, 95% confidence interval 0.81, 2.84. Few circulatory deaths occurred in women with transient hypertension or their controls (five and seven respectively). Despite the screening programme and further treatment, newly discovered subjects with sustained hypertension, both men and women, remain at high risk of cardiovascular mortality. The 95% confidence interval for men with transient hypertension does not exclude a similar adverse effect.


Height: a risk marker for ischaemic heart disease: prospective results from the Caerphilly and Speedwell Heart Disease Studies.

The predictive power of height for future ischaemic heart disease (IHD) was examined in 4860 men from two communities in South Wales and the West of England. At follow-up, men in the shortest fifth of the height distribution had experienced twice as many incident IHD events (fatal and non-fatal myocardial infarction) as was the case for men from the tallest fifth. Adjustment for age, social class and smoking habit failed to alter these relationships significantly. In the data from South Wales, determinants of height were examined; birth rank and number of siblings showed a trend with height. This trend was found only in men whose fathers were manual workers and may be related to inadequate nutrition in the higher birth ranks and larger families. These results support the suggestion that early childhood factors may be relevant to IHD in middle age and possible mechanisms are discussed.


Reproducibility of electrocardiographic criteria for left ventricular hypertrophy in hypertensive patients in general practice.

Before changes in ECG voltage criteria can be accepted as evidence for changes in LVH, the variability of ECG measurements must be known. Here we report on the results of a study, on the variability of electrocardiographic single lead voltage parameters and (voltage) criteria for left ventricular hypertrophy in hypertensive patients in general practice. Two electrocardiograms were recorded, from 64 patients at an interval of 2 min, to measure the minute-to-minute variability. From 77 patients, two electrocardiograms were recorded at an interval of one week to measure the day-to-day variability. The coefficient of variation of voltage parameters for single leads ranged in the day-to-day group from 9.2% in R/I to 42% in T/V1, and the coefficient of variation for voltage combinations in this group ranged from 10.0% for the Sokolow-Lyon criteria to 13.7% for Gubner-Ungerleider criteria. The reclassification percentages in the day-to-day group ranged from 0% for Gubner-Ungerleider to 17% for Minnesota code criteria. A factor analysis showed that studies which use the Romhilt-Estes score, the Sokolow-Lyon or the Minnesota criteria to detect ECG-LVH are not comparable with studies which use the Cornell or Gubner-Ungerleider criteria.


Prognosis after recovery from myocardial infarction: the relative importance of cardiac dilatation and coronary stenoses.

In order to further define clinical and angiocardiographic predictors of long-term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end-diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta-blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction.


ST segment analysis for assessment of coronary artery patency: comparison of surface ECG and Holter recordings.

In a prospective trial in 124 patients with acute myocardial infarction, Holter and surface ECG recordings were obtained simultaneously and compared for their ability to assess thrombolysis-induced ST segment changes. Accuracy in predicting patency of the infarct-related artery was evaluated in both methods. Success or failure of thrombolysis was determined angiographically 90 min after the start of therapy. For both methods, sensitivity, specificity, and positive predictive value for correct prediction of the perfusion status ranged between 64% and 92%. However, the negative predictive value was considerably lower (40-53%). There were no significant differences in any parameter evaluated for either method. Thus, two surface ECG recordings before and 2 h after the start of therapy yield the same predictive value as continuous Holter monitoring with respect to thrombolysis-induced coronary artery reperfusion. However, for triage of patients to early coronary interventions, more sophisticated methods are needed for non-invasive prediction of coronary artery patency due to the low negative predictive value of ST segment analysis.


Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate?

The objective of this blinded, randomized, prospective study was to assess whether supplementation of normal diet with omega-3 polyunsaturated fatty acids can reduce angiographically defined restenosis following coronary angioplasty. The study included all patients undergoing coronary angioplasty in this institution between January 1988 and January 1989. One hundred and twenty patients enrolled, 60 in each treatment group. All were randomized to either supplementation of normal diet with 3 g of omega-3 polyunsaturated fatty acids per day started 1-2 days prior to angioplasty and continued for 6 months (treatment group), or to receive standard therapy only (control group). Quantitative angiographically defined restenosis was assessed at 6 months post angioplasty. Restenosis occurred in 27.8% (95% CI 18.0-37.7%) of lesions in the treatment group and in 28.3% (CI 16.9-39.7%) of lesions in the control group, but the difference was not statistically significant. The study showed that diet supplemented with 3 g of omega-3 polyunsaturated fatty acids started 1-2 days preceding angioplasty does not reduce angiographically defined restenosis rate.


Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease.

The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolated single coronary artery: a review of 50,000 consecutive coronary angiographies.

Single coronary artery is a rare congenital anomaly of the coronary arteries where only one coronary artery arises from the aortic trunk by a single coronary ostium, supplying the entire heart. A database consisting of the angiographic reports of 50,000 consecutive coronary angiographies performed in adult patients in the University Hospital of Leuven between March 1973 and August 1991 was searched for the diagnosis of single coronary artery. All films concerned were reviewed and classified according to their anatomical type. Thirty-three cases of single coronary artery were retrieved, yielding an incidence of 0.066%. Patient characteristics and clinical data are described, with a discussion on the pathological importance of this finding.


Lack of platelet-activating factor release during reversible myocardial ischaemia.

Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production.


Anticardiolipin antibodies and coronary heart disease.

Arterial or venous thrombotic events have been described as complications in patients with positive anticardiolipin antibodies (aCL), affecting various organs including the heart. In order to see whether aCL could be, among others, a predisposing factor for coronary artery occlusions and whether it could serve as a prognostic marker for coronary heart disease, 232 patients enrolled in the European Concerted Action on Thrombosis Angina Pectoris Study were studied. aCL and various other haemostatic parameters were determined at time of admittance in order to see whether a relationship existed between haemostasis at baseline and extent or prognosis of the cardiovascular disease. A follow-up at 12 and 24 months after angiography included information about relapsing coronary or other thrombotic events, treatment and outcome of the disease. aCL were not found to be a marker of either progressive cardiovascular disease or recurrent thrombotic events. No correlation was found, either in aCL positive or in aCL negative patients, between high levels of haemostasis activation markers, such as beta-thromboglobulin, platelet factor 4 or fibrinopeptide A and recurrent cardiovascular disease.


Therapy for acute vascular complications in percutaneous transluminal coronary angioplasty with the autoperfusion balloon catheter.

Prolonged dilatation with an autoperfusion balloon catheter (APBC) (High-Flow-CPC-Mainz (Schneider) in 23 cases and Stack Perfusion (ACS) in 50 cases) was carried out in 73 patients (60 men, 13 women, mean age 59.3 +/- 8.8 years) with acute vascular complications occurring during PTCA (25 occlusive dissections (34%), five thrombotic occlusions (7%), 42 non-occlusive dissections (58%) and one non-occlusive thrombus with reduction of flow (1%)) in order to avoid stent implantation or emergency bypass surgery. On average 1.5 +/- 0.8 inflations were carried out per patient with a mean maximum inflation time of 14.1 +/- 8.4 min and a mean total inflation time of 16.8 +/- 12.3 min. In 61 patients (83.5%), the vascular complication could be controlled successfully with APBC, but in 12 APBC was not successful. Eight patients (11%) had emergency surgery. A stent was implanted in three patients (4.1%), and one suffered an acute myocardial infarction. Out of the 61 patients with positive result after prolonged dilatation, the hospital phase was uncomplicated in 53 (86.9%), five (8.2%) suffered an infarct with a maximum rise in CK of 350 U.l-1, two with multivessel disease had elective operations and one was dilated a second time because of a subacute reocclusion. Our experience indicates that when an acute vascular complication occurs, prolonged dilatation with an APBC is good interventional therapy avoiding stent implantation or emergency bypass surgery. However, new techniques cannot always replace surgery so an emergency bypass operation may still be necessary.


Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis.

Normal gestation is associated with a hyperdynamic adaptive state. The circulatory changes represent an additional burden on the cardiovascular system of women with rheumatic mitral stenosis (MS). Life-threatening complications can occur in pregnant women with severe MS. We successfully performed percutaneous balloon mitral valvotomy (PMV) in eight pregnant patients (mean age 28 +/- 6.9 years, range 21-38 years). Pregnancy mean age was 24.6 +/- 6.5 weeks. Five patients were in NYHA functional class III and three patients were in class IV. Emergency PMV seemed to be life saving to both mother and foetus in one case. All patients but one had pliable valves. PMV was achieved using the double balloon transseptal technique. To protect the foetus from radiation, the patient's pelvic-abdominal area was shielded and left ventriculography was not performed. The total mean time of PMV was 72 +/- 19 min and that of fluoroscopy was 16.6 +/- 7.8 min. Gorlin's mitral valve area increased from 0.83 +/- 0.15 to 2.4 +/- 0.34 cm2 and the cardiac index from 3.1 +/- 0.77 to 4.2 +/- 0.79 l.min-1.m-2. Left atrium pressure decreased from 29 +/- 10 to 14 +/- 5 mmHg and mitral valve gradient from 21 +/- 7 to 6 +/- 3 mmHg. There were no complications or residual MS. At a mean follow-up of 13.2 +/- 9.4 months, all patients were in NYHA class I and had a normal course of pregnancy. The eight women delivered healthy full-term babies. At 1-25 months post-partum follow-up, the eight infants had shown normal growth and development.(ABSTRACT TRUNCATED AT 250 WORDS)


On-line quantification of ventricular function during dobutamine stress echocardiography.

To develop an approach for on-line quantification of left ventricular size and function during pharmacological stress testing we employed echocardiographic automatic edge detection via integrated backscatter imaging during dobutamine infusion in 27 patients. Ventricular cavity areas, fractional area change and rate of cavity area change were obtained on-line with instantaneous graphic display of the data. When compared to baseline image data, patients with a normal response exhibited modest (15%) reduction in end-diastolic cavity areas at peak dobutamine level, but marked (33%) reduction in systolic areas yielding a 52% increase in fractional area change (n = 13; P < 0.001). The second group of patients (n = 14) had an abnormal response characterized by limited changes in measured parameters of ventricular function and reduced fractional area change (P < 0.05). On-line quantification during pharmacological stress echocardiography is a promising addition to the test for surveillance and objective instantaneous evaluation of global cardiac responses.


Assessment of left ventricular volumes by magnetic resonance in comparison with radionuclide angiography, contrast angiography and echocardiography.

The present study shows that for assessment of LVEF, MRI and the standard methods seem to provide information of similar value. For absolute volume measurements, MRI and RNA are superior to single plane angiography and 2 DE using the modified Simpson-rule. The time consuming transversal MRI method does not seem to be superior to the oblique multislice method, when apical aneurysms can be ruled out. MRI thus seems to be an accurate method for determination of LV stroke volume as well as for determination of LVEF and hence for diastolic and systolic volumes. MRI, however, depends of a good image quality, which is crucial especially in dilated ventricles containing stagnant or slowly moving blood.


The acute effects of intravenous nisoldipine on left ventricular function within 24 h after acute myocardial infarction.

Nisoldipine is a calcium antagonist with potent coronary vasodilating effects in patients with chronic stable angina pectoris. We studied the acute effects of nisoldipine in six patients within 24 h (mean 14 +/- 4 h) after the onset of myocardial infarction. Nisoldipine was administered as a 4.5 micrograms kg-1 intravenous bolus over 3 min followed by intravenous infusion of 0.2 microgram kg-1 min-1 during 60 min. Radionuclide angiography, cardiac output and intra-arterial blood pressure measurements were performed before and during nisoldipine. Left ventricular ejection fraction increased from 48.3 +/- 10.3% to 55.3 +/- 11.8% (P = 0.034) during nisoldipine infusion. Regional wall motion score changed during nisoldipine infusion from 3.3 +/- 2.5 to 1.8 +/- 2.6 (P = 0.027). Cardiac output increased from 5.5 +/- 1.0 to 7.3 +/- 1.3 l min-1 (P = 0.0001). Heart rate increased from 78 +/- 12 to 88 +/- 11 beats.min-1 (P = 0.004). Mean arterial blood pressure decreased from 91.7 +/- 20.2 to 78.7 +/- 13.1 mmHg (P = 0.038). The rate-pressure product did not change significantly during nisoldipine infusion. It is concluded that nisoldipine improves global and regional left ventricular function in patients with acute myocardial infarction within the first 24 h. Our findings suggest that this effect is achieved without increasing myocardial oxygen demand.


Six-month survival in 20,891 patients with acute myocardial infarction randomized between alteplase and streptokinase with or without heparin. GISSI-2 and International Study Group. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto.

This 6-month follow-up of the patients recruited into the GISSI-2 Study and the International Study substantially confirmed the in-hospital results. The aim was to compare the effectiveness and safety of alteplase (tPA) and streptokinase (SK), and of heparin and no heparin, in patients with acute myocardial infarction in an open multicentre randomized trial with a 2 x 2 factorial study design. Six-months' mortality rates were similar for patients randomized to tPA or SK (12.3% vs 11.7%, RR = 1.06, 95% CI 0.97-1.15) and for patients randomized to heparin or no heparin (11.9% vs 12.1%, RR = 0.98, 95% CI 0.90-1.07). Mortality rates were also similar between randomized treatments in the pre-defined subgroups: sex, age above and below 70 years, with and without previous myocardial infarction, Killip class at entry and randomization within 3 h or between 3 and 6 h from onset of symptoms. Reinfarction and cerebrovascular accidents were similar in all treatment groups. Adjusted analysis (Cox model) indicated that age and higher Killip class were the most important predictors of a poor prognosis. Previous myocardial infarction, female sex and longer delay from onset of symptoms were also indicators. Patients treated with SK plus heparin have a statistically significant better survival than the others, although the statistical significance of the remaining absolute difference disappears once the substantial proportion of patients dying in the first 12 h is excluded, when, by design, no heparin was given.


The mechanisms underlying the increased ventilatory response to exercise in chronic stable heart failure.

Chronic heart failure is a common clinical condition with a high mortality and morbidity. Patients with the condition suffer from shortness of breath and fatigue on exercise. This article reviews the recent advances made in the understanding of the pathophysiology of chronic heart failure and explores further possible research options.


Deletion of mitochondrial DNA in the endomyocardial biopsy sample from a patient with Kearns-Sayre syndrome.

A 15-year-old boy with Kearns-Sayre syndrome is reported. The deletion of mitochondrial DNA in the endomyocardial biopsy sample from the patient was confirmed by the polymerase chain reaction method, and was identified to that in the skeletal muscle.


Concurrent post-streptococcal carditis and glomerulonephritis: serial echocardiographic diagnosis and follow-up.

The two non-suppurative post-streptococcal events, acute rheumatic fever and acute glomerulonephritis, rarely occur simultaneously. We describe such a patient, a 16-year-old male who was admitted with fever, agitation and confusion. Blood work-up showed high antistreptolysin O titre, raised serum creatinine and low complement levels. Urinalysis showed RBC casts. Echocardiographic examination demonstrated markedly impaired left ventricular systolic and diastolic function and three large thrombi in the apex. Serial echocardiographic examinations revealed improvement of cardiac function and the resolution of the thrombi and both cardiac and renal function returned to normal after 3 weeks of treatment.


Right atrial thrombus migration during echocardiography: a case for urgent intervention.

A 65-year-old woman presented with increasing shortness of breath, chest pain and ST-T wave abnormalities on the electrocardiogram suggestive of unstable angina. Cross-sectional echocardiography performed to assess wall-motion abnormality and left ventricular function revealed a pedunculated right atrial thrombus prolapsing into the right ventricle which suddenly dislodged and migrated into the pulmonary circulation during the examination. A diagnosis of recurrent pulmonary thromboembolism was made, necessitating urgent pulmonary angiography with infusion of streptokinase. The patient made an uneventful recovery.


Right atrial invasive thymoma with protrusion through the tricuspid valve.

A patient with superior caval vein compression due to malignant thymoma with infrequent intracavitary cardiac growth is presented. Diagnostic accuracy of cardiac involvement was higher using transesophageal echocardiography compared to transthoracic echocardiography. The majority of the rare intracavitary cardiac thymomas seem to be confined to the right side of the heart.


The heart as a bass organ.

Many florid physical signs of aortic regurgitation have been described. We describe a florid investigational finding of virtually monotonous intracardiac reverberation originating at the aortic valve leaflets.


Eosinophilia-myalgia syndrome: coming to grips with a new illness.

In late October 1989, over 1,500 cases of an unusual illness involving severe myalgia and striking peripheral eosinophilia were reported in the United States and several other countries. Other clinical manifestations included pulmonary involvement (interstitial infiltrates and pleural effusions), skin rash and edema, axonal polyneuropathy, perimyositis, and possible adverse neurocognitive effects. Because of the primary manifestations of the illness, it was named "eosinophilia-myalgia syndrome" (EMS) by the Centers for Disease Control. Epidemiologic studies clearly linked illness to the ingestion of tryptophan produced by a single manufacturer in Japan, and the time course of the epidemic was most consistent with its being caused by a product contaminant. Epidemiologic analysis of plant operating conditions and data obtained from chemical analyses of case- and control-associated lots implicated 1,1'-ethylidene-bis(tryptophan) (EBT) as a candidate for the compound that causes EMS. However, the etiologic significance of EBT is still uncertain. Factors found to increase a person's risk for EMS included higher tryptophan dose and older age. Although cases occurred predominantly in women and patients had frequently been taking other medications concurrently with tryptophan, sex and use of several categories of other medications were not shown to influence the risk of illness. Few patients recovered rapidly and fully from the disease. Many were treated with glucocorticoid medications, and although they may have benefited from therapy in the short term, the development of chronic sequelae of EMS appears not to have been prevented. Public health practitioners currently depend on the reports of alert clinicians to detect this type of outbreak. In this case, state and federal government epidemiologists, once they were notified, were able to develop substantial basic information about the epidemic in a relatively short time. Control measures were introduced rapidly, effectively stopping the epidemic.


Epidemiology of pertussis and reactions to pertussis vaccine.

It remains clear that pertussis is a dangerous infectious disease that is well-controlled in industrialized countries by widespread immunization. In the developing world, it remains a source of high morbidity and mortality because of previously inadequate immunization programs. However, because of the intense efforts of the World Health Organization's Expanded Programme on Immunization, the effects of pertussis have already been ameliorated and show promise of being within a decade of approximating the situation in the developed world. Pertussis can be controlled only by immunization; other measures such as antimicrobial therapy offer negligible benefit. A problem that has been addressed in recent years is the excessive reactivity of whole-cell pertussis vaccine, which undoubtedly includes components of the organism that are irrelevant to the induction of immunity and are excessively reactive. Although epidemiologic studies appear to have largely, if not completely, absolved pertussis vaccine of responsibility for inducing death or permanent neurologic disability, a less reactive vaccine is highly desirable, not only to promote acceptance of a full course of immunization for the world's children but also for simple humanitarian reasons. Additionally, it has become evident that, because of waning immunity, pertussis increasingly occurs in adults. A less reactive vaccine would offer opportunity for reinforcement of immunity beyond childhood. The development of better, though as yet incomplete, understanding of the biology of Bordetella pertussis and its relation to humanity offers the opportunity for the production of less reactive vaccines free of irrelevant components. Acellular pertussis vaccines have been used exclusively in Japan for more than 10 years, and one such preparation, combined with diphtheria and tetanus toxoids, was licensed in the United States in late 1991 for use as the fourth and fifth doses of DTP, given at 15 months and prior to school entry. Field trials of this and other acellular DTP preparations are currently under way to determine their clinical efficacy in infants. It is probable that, within a very few years, whole-cell pertussis vaccine will be replaced by these newer preparations and that, in addition, the acellular product will be combined with other antigens, such as Haemophilus influenzae type b vaccine.


Connectedness versus separateness: applicability of family therapy to Japanese families.

This article, a product of the two authors' multicultural experiences, contrasts British and Japanese families in order to examine the applicability of the Western model of family therapy to Japanese families and therapists. Areas where the Western model is incompatible are identified, and modifications to fit the Japanese indigenous model are suggested. The most significant difference in value systems between the two cultures is the Japanese preference for connectedness. The Japanese person is seen as a part of the embedded interconnectedness of relationships, whereas British norms prioritize separateness and clear boundaries in relationships, individuality, and autonomy. This value orientation is manifested in the Japanese language, hierarchical nature of the family structure, the family life cycle, and the implicit communication style. Systemic thinking, which deals with the pattern of relationships, is valid for all families regardless of cultural differences. But therapists should note that the preferred direction of change for Japanese families in therapy, is toward a process of integration--how a person can be effectively integrated into the given system--rather than a process of differentiation. An authoritative therapist style, the use of individual sessions, silence, and other nonverbal techniques are relevant to bringing about the desired change toward better integration of the individual with his or her networks.


Families with adolescents: escaping problem lifestyles.

Using the concepts of "restraints" and reciprocal patterns, a specific approach for understanding and working with families of adolescents is offered. The organizing idea is the "restraint" that revolves around a difficulty both parents and youngsters have in making a distinction between what parents want for their youngsters and what the young person might want. This difficulty may come from the parents' ideas and beliefs about parenting and from their own growing-up experience, from the adolescent's "not completely storied" lives, and/or from societal discourse about adolescence. Restraint of ideas can be constructed as reciprocal patterns and located in dominant narratives that families may have about themselves. A restorying process allows families to separate from the problem pattern and focus on the youngsters' willingness to have ideas for themselves.


Working with projective identification in couples.

Couples therapists spend considerable time focused on the recurring patterns of anger and misunderstanding that occur in their sessions. These patterns usually represent projective identification sequences in which one partner disavows disturbing thoughts and feelings, and, instead, unconsciously induces similar thoughts and feelings in the other partner by behaving in such a way as to stimulate them. Conflict and misunderstanding surround the partners' shared efforts to avoid identifying with the undesirable thoughts and feelings. The underlying problem is each individual's inability to contain the disturbing material and provide holding for the other partner. This article offers a technique for interrupting the process and helping each partner to identify with and contain the disturbing material.


The importance of similarity in the marital relationship.

Concepts such as "agreement," "consensus," "understanding," and "shared meaning" are very familiar to clinicians. It is argued in this article that similarity in perceptions between spouses is a crucial dimension of the family system underlying these concepts. Findings are presented that support the idea that families vary along a dimension of similarity of perceptions, with more functional families characterized by high similarity between spouses' perceptions of their marriage and their family. In addition, the structure of this similarity was stable over 2 years and little change occurred in the mean level of similarity. Of three sets of predictor variables--psychological stress, marital cohesion, and structural variables--marital cohesion was the most powerful predictor of marital similarity. The importance of similarity of perceptions between family members in clinical work is discussed.


Lives in a balance: perceived family functioning and the psychosocial adjustment of adolescent cancer survivors.

Childhood cancer patients have a greater likelihood of long-term survival than ever before. This study examined both the perceived family functioning of adolescents who had successfully completed treatment for pediatric cancer and the relationship between family functioning and post-treatment adjustment. Eighty-eight adolescent survivors of hematologic malignancies were assessed regarding their family functioning, mental health, self-esteem, global competence, and problem behaviors. Contrary to expectations about the influence of cancer on these families, adolescent cancer survivors reported lower levels of family cohesion than the normative sample of healthy adolescents and their families. While current age, gender, age at diagnosis, and time since treatment completion were generally not associated with adolescents' adjustment, perceived family cohesion and adaptability were strongly related to post-treatment psychological adjustment.


The California Family Health Project: IV. Family structure/organization and adult health.

This research explores the relationships between each of four "domains" of family life and the health of husbands and wives in a community-based sample of 225 families. In this article we report the association between Family Structure/Organization and adult Health. This family domain refers to the architecture of the family or the structural frame of roles and rules within which the family operates. Interrelationships among 13 self-reported, family Structure/Organization scales are described, using principle components analysis (PCA) and multidimensional scaling analysis (MDS). Derived, joint-spouse or couple Structure/Organization variables also were created using inter-battery factor analysis. The PCA yielded a poor solution, whereas the MDS yielded a good two-dimensional solution, which roughly displayed the scales in a circular pattern for both husbands and wives. The analyses indicated that no single dimension or set of separate subdimensions adequately described the Structure/Organization variables. All 13 scales than were associated with a battery of 14 adult health scales for husbands and wives separately, using canonical correlation. Different aspects of family Structure/Organization were correlated with health for husbands and wives: Organized Cohesiveness, Sex Role Traditionalism, Role Flexibility and Shared Roles for husbands; and Organized Cohesiveness and Differentiated Sharing for wives. Different patterns of health scores also emerged by gender, with behavioral indicators, such as Smoking and Drinking, more salient for husbands, and mood indicators, such as Anxiety and Depression, more salient for wives.


The California Family Health Project: V. Family problem solving and adult health.

This article explores the relationship between family Problem Solving and the Health of adults in a community-based sample of 225 families. Family Problem Solving refers to the ways in which the family conducts itself to resolve a shared problem. Sixteen observer ratings of family Problem-Solving behavior during a 30-minute task were developed, based on the Simulated Family Activity Measure (SIM-FAM), and good interrater agreement was achieved. Principal Components Analysis (PCA) yielded a set of three well-constructed, interpretable dimensions: Problem-Solving Effectiveness, Problem-Solving Style, and Sociomotor Activity. Multidimensional scaling analyses (MDS) suggested that family problem-solving behavior involved an organized, means-end sequence of family behaviors in which aspects of style served problem-solving effectiveness. All 16 Problem-Solving variables were analyzed with a set of 14 health variables, for husbands and wives separately, using canonical correlation. No subset of Problem-Solving variables was significantly associated with a subset of Health variables for either husbands or wives, although there was a significant association between the two sets of variables when taken as a whole. Given previous research on family Problem Solving, we conclude that the absence of significant associations between particular aspects of family Problem Solving and Health may be due to our use of a community-based rather than a stressed or clinical sample. Associations between Family Problem Solving and Health might best be viewed in the context of other family variables.


The therapeutic system as viewed by depressive inpatients and outcome: an expanded study.

In an expansion of a previous study, we examined in which way depressive inpatients' views of psychiatrists' and significant others' attitudes toward the severity of their illness were related to outcome. Fifty-six patients were asked a two-part question--"Who regards your illness as being more severe: (a) you or your significant others; (b) you or your psychiatrist?" Two subsamples of patients were identified: those who viewed the psychiatrists' and significant others' attitudes as similar and those who viewed them as dissimilar. Both groups showed substantial and significant improvement during hospital treatment; but the group that viewed the attitudes held by psychiatrists and significant others as dissimilar had significantly fewer depressive symptoms by the end of a 3-month followup period. The findings were consistent with those of the original study, and with the hypothesis as derived from the Mental Research Institute brief therapy principles.


The chemical morphology of the vitreous.

The water of the vitreous is stabilised by an ordered meshwork of very fine collagen fibrils that are tied together in loosely parallel bundles or sprays by bridges of sulphated glycosaminoglycan. Some fibril bundles run at right angles to other bundles. In these respects vitreous resembles a very dilute corneal stroma. The glycosaminoglycans of the vitreous (hyaluronan and chondroitin sulphate) aggregate with themselves and with each other in solution. The protein cores of the proteoglycans are attached to collagen fibrils. Thus, a three-component cross-linked structure is formed: collagen fibril-->proteoglycan protein core-->glycosaminoglycan chain-->glycosaminoglycan chain-->protein core-->collagen fibril. Hyaluronan can aggregate directly with chondroitin-6-sulphate, or with aggregated glycan cross-links, thus entering into an infinite meshwork.


Mathematical modelling of the elastic properties of retina: a determination of Young's modulus.

The retina can be regarded as an elastic membrane or sheet which stretches and deforms when a force is applied to it. Isolated bovine retina was taken and a graded traction force applied to determine retinal profile as a function of force. The resulting profile can be modelled mathematically and the model then used to determine a value for the elastic constant. The value of the elastic constant obtained by this method is approximately 2 N/m. This value of the elastic constant, combined with the observed retinal thickness, yields a value of Young's modulus for retina of approximately 2 x 10(4) Pa, which is about 2 orders of magnitude weaker than typical rubber. This value can then be used in modelling retinal behaviour in vivo when forces are applied to detached retina.


Thrombospondin as a component of the extracellular matrix of epiretinal membranes: comparisons with cellular fibronectin.

We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co-distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes.


Removal of scleral explant elements: a 10-year retrospective study.

There are several studies in the American literature on the incidence and causes of retinal redetachment following removal of explants. This is, to our knowledge, the first such study from Britain and differs in its findings from the American experience. The reason for removal of explants, the time of removal after initial detachment surgery and the consequences of removal were reviewed for the 10-year period from 1980 to 1990. During this period 1898 retinal detachment operations were performed at this centre, with an explant removal rate of 3.2% (61 eyes). Extrusion of the element was the cause in 74%. Of these 8% subsequently suffered a redetachment. In two eyes no retinal break was identified at initial surgery. Both of these suffered a redetachment following removal of the explant. Contrary to previous reports, redetachment was not related to short periods of explant or to infection of the explant. This study suggests that explant removal is a safe procedure. However, there is a significant risk of redetachment after explant removal if no breaks are identified at the time of initial surgery.


Four-quadrant local anaesthesia technique for vitreoretinal surgery.

We report our experience of a recently described local anaesthetic technique which seeks to avoid risk of perforation of the globe, damage to the optic nerve, or injection into the subarachnoid space, whilst providing prolonged and reliable anaesthesia. A prospective series of 19 patients who underwent vitreoretinal surgery using this technique were compared with 19 patients who had retrobulbar anaesthesia for cataract extraction. The vitreoretinal group had excellent akinesia and very good anaesthesia, allowing prolonged retinal reattachment surgery lasting up to 3 hours. Patient evaluation of discomfort or pain experienced in the two groups was assessed using a visual analogue pain score chart. The pain scores for the two groups were not significantly different (p = 0.03) and 16 of 19 patients in each group (84%) experienced only slight pain or less. Satisfaction with local anaesthesia, in both groups, was also assessed by asking patients which method of anaesthesia they would prefer if future surgery were to be performed. In the vitreoretinal group, 18 of 19 patients expressed a preference for local anaesthesia and in the cataract group 17 ot 19 also favoured local anaesthesia. The vitreoretinal patients' median pain score was 0 compared with 1 for the cataract patients. This study demonstrates that local anaesthesia provides pain relief for vitreoretinal surgery which is comparable to the experience of patients undergoing cataract surgery by retrobulbar anaesthesia. The technique described can provide successful local anaesthesia for vitreoretinal procedures. The success of this technique for pain relief and akinesia calls for a reappraisal of the number of patients suitable for vitreoretinal surgery under local anaesthesia.


Tumour fluorescence and tumour-associated fluorescence of choroidal melanomas.

'Tumour fluorescence' occurs within the tumour itself and is inversely related to the degree of pigmentation of the tumour, whereas 'tumour-associated fluorescence' occurs within the retinal pigment epithelium and retina as a result of degenerative changes in these structures; these secondary changes can collectively be termed 'tumour-associated retinal pigment epitheliopathy'. Tumour fluorescence should be differentiated from tumour-associated fluorescence so as not to confuse naevus with melanoma and to facilitate the interpretation of angiographic changes after radiotherapy or photocoagulation of choroidal melanomas.


Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid.

Sensitisation to retinal S-antigen has been implicated in the pathogenesis of several clinical forms of posterior uveitis. S-antigen-like molecules have recently been demonstrated in the brain and choroid plexus of experimental animals. We used a panel of four monoclonal antibodies (MAbs), MAbF4-C1, MAbC10-C10, MAbA2-G5 and MAbA9-C6, which define specific epitopes in the amino, mid and carboxyl terminal portions of S-antigen in order to identify an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid (CSF). Three MAbs, MAbF4-C1, MAbC10-C10 and MAbA9-C6, localised an S-antigen-like molecule to the cytoplasm of the epithelial cells of the human choroid plexus. Polymerase chain reaction of cDNA from choroid plexus verified the presence of S-antigen homologues in the choroid plexus. The presence of an S-antigen-like molecule in the CSF was demonstrated by western blots in seven CSF samples from patients with a variety of neuropathological disorders. It is proposed that immunological cross-reactivity and biochemical similarity between retinal S-antigen and an S-antigen-like molecule in human choroid plexus and CSF could form a basis for neurological manifestations observed in certain clinical forms of uveitides.


Results of early surgery for infantile esotropia in normal and neurologically impaired infants.

A prospective study was performed over a 4-year period of 56 infants presenting with infantile esotropia to assess development of binocularity after surgical alignment before 2 years of age. In 50% of cases infantile esotropia was associated with neurological problems or prematurity. Forty-three cases have undergone surgery (mean age 15.7 months +/- 3.46); 86% were aligned (+/- 10 dioptres) at 2 years. Eighty-seven per cent of normal children and 74% of children with neurological problems or prematurity were aligned at last follow-up (mean 27.2 months since surgery). Tests of fusion and stereopsis have to date been possible upon 21 'successfully' aligned infants and although most have evidence of peripheral sensory fusion none showed stereopsis to more than one test. Although early surgery achieves a good cosmetic result in normal children and those with neurological problems, our findings question its ability to promote the development of even gross stereopsis in most children.


Can retinoscopy be used to screen infants for amblyopia? A longitudinal study of refraction in the first year of life.

One hundred normal babies were refracted by two observers in a double-masked study within 24 hours of delivery and 30 minutes after instillation of 1% cyclopentolate. The procedure was repeated at 6 weeks, 3 months, 6 months and 1 year. At birth agreement between the two refractionists to within 1 dioptre spherical equivalent was 82%, rising to 94% at 1 year. Astigmatism of greater than 1 dioptre increased from 10% at birth to 42% at 6 months but decreased to 15% at 1 year. Myopia was uncommon (4%) but 80% of eyes were hypermetropic more than +2 dioptres and 25% more than +4 dioptres at birth, although these percentages decreased to 5% and 3% at 1 year. Anisometropia of more than 1 dioptre between the two eyes was uncommon but in the two cases where it persisted in the presence of high hypermetropia, reversible amblyopia was encountered in both cases.


Standardised echography in the differential diagnosis of extraocular muscle enlargement.

Standardised echography is well documented for its use in the evaluation of enlarged extraocular muscles in orbital disease, but is still a largely underdeveloped imaging method in Britain. This paper demonstrates the technique of muscle ultrasound scanning and the characteristic echographic findings in a variety of extraocular muscle diseases, as illustrated by five case reports. The role of echography in the management of such cases is discussed.


A prospective study examining the changes in factors that affect visual acuity following trabeculectomy.

Many patients report subjective changes in vision following trabeculectomy. In a prospective study of 16 eyes, we have tried to determine the causes of these visual changes. Ninety-four per cent of eyes showed a change in uncorrected Snellen acuity 1 week following surgery. This change was due to a myopic shift in refraction secondary to changes in the anterior chamber depth. A 1 mm change in anterior chamber depth results in approximately a 2 dioptre change in refractive sphere. Visual acuity starts to return to pre-operative levels by the third post-operative week, from which point no eyes showed a deterioration in corrected acuity of more than one line of Snellen. The vertical corneal radius of curvature is reduced in the early post-operative period and there is a with-the-rule change in corneal astigmatism. This resolves over longer follow-up and the possible causes of this are discussed. No changes were noted in corneal thickness and there was no evidence of macular oedema over the follow-up period. Patients should be warned of these possible visual changes pre-operatively as many will have normal acuity prior to surgery.


Fields, DVLC and panretinal photocoagulation.

Laser panretinal photocoagulation (PRP) reduces visual loss in proliferative diabetic retinopathy but decreases peripheral retinal function. The Driver and Vehicle Licensing Centre (DVLC) states that when a patient volunteers that he or she has had photocoagulation, a questionnaire will then be sent to the patient's diabetic physician who can refer the patient for formal field testing. Of 30 patients who had PRP, 15 failed DVLC visual field regulations using the Esterman binocular field test on the Humphrey field analyser. The failures were more likely to have had treatment with a xenon laser, but there was no difference between the groups as regards age, number of burns or whether an argon or diode laser was used. The patients who failed were more likely to be hypertensive (p = 0.04). Two patients with unilateral PRP could not meet the driving regulations because of other field defects. Diabetes itself causes field defects, and therefore even with small amounts of laser, formal field testing may be necessary.


Comparison of small-incision phacoemulsification with standard extracapsular cataract surgery: post-operative astigmatism and visual recovery.

A prospective study compared post-operative astigmatism and visual acuity (corrected and uncorrected) following phacoemulsification and extracapsular surgery. Fifty eyes had implantation of a 7 mm diameter optic intraocular lens (IOL) following conventional extracapsular cataract extraction (ECCE) with a 10 mm corneal incision. Forty-seven eyes were implanted with a 5 x 6 mm optic IOL through a 5 mm scleral incision after phacoemulsification. Uncorrected visual acuity of 6/9 or better was achieved in 25% of eyes on the first day following phacoemulsification, 36% at 1 week and 57% at 12 weeks. These results (and also the best corrected acuity) were significantly better than those following ECCE. Less astigmatism was induced by phacoemulsification than extracapsular surgery, measured at all post-operative time intervals.


Corneal autoimmunity in patients with peripheral ulcerative keratitis (PUK) in association with rheumatoid arthritis and Wegener's granulomatosis.

Serum antibodies to the cornea were investigated in patients with peripheral ulcerative keratitis (PUK) in isolation or in association with a systemic disease (rheumatoid arthritis or Wegener's granulomatosis). Indirect immunofluorescence on bovine corneal sections demonstrated that antibodies bound to epithelial antigens in two distinct patterns: a lattice-like pattern, probably staining intercellular membrane antigens, and a diffuse pattern covering the entire surface of the epithelium. Both patterns were associated with PUK rather than systemic disease whilst the presence of the lattice pattern was more associated with the onset of the PUK. Immunoblotting of sera to corneal epithelial protein extracts demonstrated that a number of corneal antigens were targeted by antibodies. Two antigens, 54 kDa and 70 kDa, were of particular interest. Antibodies to the 54 kDa antigen, the major corneal-specific antigen, were also detected by enzyme-linked immunosorbent assay (ELISA). Longitudinal studies showed that these antibodies often first occurred after an episode of PUK. Antibodies to the 70 kDa antigen were related to the Wegener's granulomatosis rather than the PUK.


A morphological study of rabbit corneas after laser keratectomy.

We have examined the morphology of the collagen and proteoglycans in rabbit corneas that have undergone excimer laser photorefractive keratectomy using a clinical, 193 nm excimer laser. The photoablation was carried out to a stromal depth of 100 microns and a diameter of 6 mm. All ablated corneas developed a haze that was most intense between week 4 and week 8 and which showed no improvement after week 16. The corneas were stained with the cationic dye cuprolinic blue to visualise proteoglycans and were then processed for transmission electron microscopy. The ultrastructural location of proteoglycans (keratan sulphate and dermatan sulphate) was observed in the corneal wounds at different time intervals. Corneas that had undergone steroid treatment post-operatively were also examined. In the healing tissue proteoglycan filaments of abnormal size were observed, which became most prominent after 2 weeks. As healing progressed these abnormal filaments decreased but after 45 weeks some were still present, indicating that the proteoglycan content had not returned to normal.


Immunocytochemical analysis of blood lymphocytes in uveitis.

We studied the surface expression of activation markers IL2-R, HLA-DR and CD45-RO on peripheral T-lymphocytes in two groups of patients (n = 26) with idiopathic uveoretinitis, compared with controls. Thirteen patients were analysed by alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry, which demonstrated a significant rise in expression of HLA-DR and IL2-R surface markers. Flow cytometric analysis was performed on a further 13 patients, which confirmed a significant rise in IL2-R expression in uveitis patients. Within this group systemic activation was confined to patients with idiopathic retinal vasculitis. Dual flow cytometry confirmed a CD4+,IL2--R+ T--lymphocyte phenotype. A further 4 patients with retinal vasculitis who had been treated with cyclosporin A demonstrated a 32% reduction in IL2-R expression over a 3-month period. Analysis of CD45-RO and CD5+ cells was found to be uninformative in this study. We have demonstrated activated peripheral lymphocytes in patients predominantly with retinal vasculitis, the significance of which is discussed.


Plasminogen activator in human tears.

Measurements were made of the nature and levels of plasminogen activator in human tears using, as a model of inflammation, patients undergoing cataract surgery. Tissue plasminogen activator (t-PA) but not urokinase plasminogen activator (u-PA) was found in tears. A wide variation in the range of t-PA in pre-operative tears was found. In those patients not receiving per-operative subconjunctival betamethasone a significant rise in t-PA was found in tears on the first post-operative day over pre-operative levels. A significant fall was noted in those receiving per-operative subconjunctival betamethasone.


A scoring method for Hess charts.

A new scoring system for Hess charts is described. Scores for both horizontal and vertical deviations are calculated from the displacement of individual points on the Hess chart, using weighting factors for the centre, inner and outer zones. The scoring system was validated in a group of 24 patients undergoing surgery for paralytic or restrictive strabismus. Subjective scores were obtained from patients both before and after corrective surgery, and corresponding Hess charts were scored using the new system. There was a good correlation between the changes in subjective and objective score. Our scoring system has applications in both research and clinical practice, allowing objective analysis of changes in muscle balance in a variety of motility disorders.


Experience with the Astra dental implant system.

The Astra Dental Implant System appears to be a relatively successful and economical method of osseointegration. This article lists its clinical components, explains how the system is fitted and discusses the preliminary results.


Computer-aided diagnosis.

The author advocates the use of computers to increase the accuracy of diagnosis. Their ability to rapidly sift through large amounts of information and calculate probabilities quickly could provide a useful adjunct to human skills.


Oral problems and the dentist's role in the management of paediatric oncology patients.

Child cancer patients require a great deal of intensive treatment and support. This paper provides an account of the dental problems a practitioner will encounter with these children and discusses how they may be managed.


Food and oral health: 2. Periodontium and oral mucosa.

Dental schools tend to teach only the rudiments of this subject and this does not provide a good basis for dentists to advise patients and combat the misinformation surrounding the topic. The first article in the two-part series examined nutrition as it applies to dental caries, while part two discusses some of the general principles of nutrition in relation to oral health, periodontal disease and the oral mucosa.


Prevention in orthodontics--a review.

Increasing numbers of patients are being orthodontically treated by specialist and general dental practitioners, after postgraduate courses and clinical assistantships. The potential for iatrogenic damage to the teeth and supporting structures has, therefore, also increased. This paper examines these problems and outlines measures for their prevention.


Fusion of mandibular third and supernumerary fourth molars.

Fusion of the permanent molars is a relatively uncommon dental anomaly. In this article, a case of fusion of a symptomatic mandibular third molar with a supernumerary fourth molar is reported. The differentiation with other forms of 'double teeth' is explained and the possibility of the initial panoramic radiograph view being misinterpreted as an artefact is discussed.


Guided tissue regeneration--why, when and how?

Chronic periodontitis results in the destruction of the collagen fibre attachment to cementum, apical migration of the epithelial attachment, contamination of the exposed root surface by plaque and loss of alveolar bone. Regeneration can be defined as the restitution of lost tissues to a state which existed before destruction. As such, it is an ultimate and ideal goal and in most circumstances is currently beyond our capabilities. However, research in periodontology over the last 10 years or so has made considerable advances and is perhaps unique in proposing a new and fundamental treatment modality--guided tissue regeneration.


Orthodontic/restorative interface.

There have been many advances in orthodontic and restorative procedures. These can be combined to provide a very powerful tool in providing the optimum results. This article describes when a combined approach would be appropriate and discusses how the various problems are overcome.


Some problems with anticoagulants in dental surgery.

Anticoagulants have been used to reduce the risk of embolic and thrombotic complications in patients at risk since the discovery of the coumarin drug warfarin sodium in 1941. Since then, both the spectrum of disease for which anticoagulation is recommended and the range of anticoagulants has widened. In addition to treatment with conventional anticoagulant drugs, many patients nowadays have an additional bleeding defect due to the therapeutic use of daily low-dose aspirin therapy, either alone or in combination with other drugs. The aim of this report is to highlight some of the important aspects of anticoagulant therapy and its relevance to dental treatment.


Selected issues on care and management of the ageing patient: 1. Utilization and decision making.

The elderly are a vulnerable and expanding group of patients who are retaining their teeth longer. Even simple dental care in these people can become invasive and require the use of a local anaesthetic. Part 1 assesses the factors which may influence the ability of the patient to receive treatment and establishes treatment priorities. It also describes the particular problems that may arise when dealing with the elderly and indicates the adjustments of a practice which would help in the care of these patients. Part 2 will discuss prevention and treatment.


Continuing education--an approach to organizing a course.

The importance of continued education for the general dental practitioner is being increasingly emphasized. This paper describes the review of a prosthetic dentistry course which endeavoured to involve local practitioners to increase its appeal and relevance.


Conservative treatment for anterior dislocation of the meniscus.

Anterior dislocation of the meniscus is classified as an internal derangement of the temporomandibular joint (TMI). The pathogenesis and clinical syndromes of anterior dislocation have been described fairly frequently. Conservative treatment for this painful, clicking joint is the treatment of choice. This article presents the results of the simple conservative treatment of a case with clinical manifestation which are classical as an early stage of anterior dislocation without reduction of the meniscus.


Plasma and tissue hormones in the dog after administration of the prostaglandin analogue, misoprostol.

Dogs were given a prostaglandin analogue, misoprostol, at a dose that significantly increases gastrointestinal epithelial cell proliferation. Both basal and postprandial concentrations of gastrin were significantly higher in the misoprostol-treated dogs and more than doubled after the meal in both the controls and in the test group. Plasma enteroglucagon, cholecystokinin, insulin and glucose-dependent insulinotrophic peptide all increased postprandially, with no effect of misoprostol. Tissue concentrations of bombesin, gastrin and somatostatin were unaffected by misoprostol, but the fundic glucagon-like immunoreactivity was significantly increased. Thus high doses of misoprostol have only minor effects on gastrointestinal regulatory peptides, suggesting that the trophic effect of prostaglandins on the intestinal tract may be direct.


Two weeks of oral synthetic E2 prostaglandin (Enprostil) improves the intestinal morphological but not the absorptive response in the rat to abdominal irradiation.

Enprostil, a synthetic E2 prostaglandin, was administered in a dose of 5 micrograms/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal's body weight, but does not prevent the malabsorption of glucose.


Effect of zinc sulfate and acetylcysteine on experimental gastric ulcer: in vitro study.

A small ulcer produced in vitro by monopolar electrocoagulation on endoscopically obtained human antral biopsies and incubated in Trowel T-8 medium at 37 degrees C for 8 h has many histologic features of chronic gastric ulcer in man. Zinc sulfate and acetylcysteine in low concentrations had a significant healing effect in this ulcer model. Since the beneficial effect of zinc sulfate and acetylcysteine was counteracted by N-ethylmaleimide, a known blocker of sulfhydryl compounds, the beneficial effect of these two compounds probably was mediated through sulfhydryl compounds. Using special stain, N-(4-aminophenyl)maleimide, the sulfhydryl groups were localized in the epithelial cells of the surface layer and gastric glands.


Effect of chronic ethanol feeding on factors leading to inappropriate intrapancreatic activation of zymogens in the rat pancreas.

In rats fed control and ethanol-containing Lieber-DeCarli diets for a period of 12 months, the bile did not contain any enterokinase, the pancreatic juice did not contain any plasmin or thrombin, but in animals fed high fat diet with ethanol, trypsinogen and chymotrypsinogen were significantly increased and trypsin inhibitor decreased. In the tissue, free trypsin and cathepsin B were increased. Composite profile of trypsinogen in gel segments obtained from the pancreatic juice and the tissue showed higher peaks of cationic and anionic variants of trypsinogen in animals fed ethanol. There was no evidence of mesotrypsinogen or of enzyme Y in the juice or the tissue. These studies show that serine proteases and cathepsin B may play a major role in the pathobiology of alcoholic pancreatitis.


Effects of gastric fundectomy and antrectomy on the colonic mucosa in the hamster.

The effects of gastric fundectomy and antrectomy on the colonic mucosa were studied in hamsters over 5 and 25 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly increased after fundectomy and significantly decreased after antrectomy. Five days after fundectomy, there was a significant increase in scintigraphically determined colonic tissue [3H]-thymidine uptake and [3H]-thymidine labeling index of goblet cells, both of which were reduced 5 days after antrectomy. After fundectomy, the labeling index was maximal in differentiating-proliferative cells in the midportion of the colonic crypts, whereas the labeling index of the immature proliferative cells at the base of the crypts did not differ from that in the controls. On day 25, the crypt size and the number and percentage of goblet cells in the crypts were significantly increased in fundectomized animals. The number and percentage of goblet cells in antrectomized animals were significantly reduced on day 25. It is concluded that fundectomy in the hamster induces colonic mucosal hyperplasia with goblet cell proliferation, whereas antrectomy leads to retardation of colonic goblet cell proliferation.


Effects of phosphatidylcholine and phosphatidylinositol on acetic-acid-induced colitis in the rat.

The therapeutic effects of exogenous phosphatidylcholine and phosphatidylinositol on acetic acid-induced colitis in rats were evaluated. A uniform colitis developed 4 days after instillation of 4% acetic acid for 15 s in an excluded colonic segment, also resulting in a 6-fold increase in mucosal permeability. Instillation of 12.5 mg phosphatidylcholine once daily from the day after acetic acid instillation and for the following 2 days prevented partially the development of colitis causing partial mucosal restoration. By increasing the phosphatidylcholine dose to 25 and 50 mg, a better preventive effect was achieved. By starting the phosphatidylcholine instillation immediately after the acetic acid exposure, almost complete prevention of the colitis could be obtained. Similarly, 50 mg phosphatidylinositol in each instillation with the first administration immediately after acetic acid administration resulted in complete prevention of the colitis and a significant decrease in mucosal permeability expressed as a plasma exudation into the colonic lumen. Similar results were obtained when phosphatidylcholine was administered immediately after acetic acid, but the drug then had to be applied twice daily. In contrast, a single application of the same total dose (150 mg) of the two different phospholipids, either 30 min before or immediately after acetic acid administration, could not prevent the development of colitis. It is concluded that both phosphatidylcholine and phosphatidylinositol have a therapeutic effect on the development of acetic acid-induced colitis in the rat.


Effect of teprenone on acute gastric mucosal lesions induced by cold-restraint stress.

The effects of intragastric administration of teprenone on acute gastric mucosal lesions induced by cold-restraint stress was investigated using a model of obstructive jaundice. Rats received teprenone 200 mg/kg/day for a week before stress; nontreated rats served as controls. Teprenone suppressed stress-induced depressions in defensive factors (blood flow, transmucosal potential difference, hexosamine content and lectin staining of carbohydrate residues) and suppressed increases in lesion-enhancing factors (gastric mucosal lysosomal enzyme activity and thiobarbituric acid reactants showing lipid peroxidation). Intragastric pH did not change significantly with teprenone but the ulcer index decreased. These results showed that teprenone protects gastric mucosa against stress, even in the presence of obstructive jaundice.


Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial.

According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain.


Study of the effect of neurotensin on meal- and cerulein-induced gallbladder contraction.

We studied the effect of a low dose of neurotensin (2.5 pmol/kg/min) on meal- and cerulein-induced gallbladder contraction in 11 healthy volunteers by means of real-time ultrasonography. Ingestion of a meal caused a significant reduction in gallbladder volume which reached a maximum of 57 +/- 2% of the basal value at 60 min after the meal. The infusion of neurotensin caused a slight but not significant attenuation of the contractile response of the gallbladder to the meal (maximal reduction of 49 +/- 6%). Increasing doses of cerulein (10, 20 and 40 ng/kg/h, for 30 min at each dose) caused progressive reductions in gallbladder volume of 18 +/- 5, 72 +/- 5 and 89 +/- 4% with the three respective doses of cerulein used. The simultaneous administration of neurotensin did not significantly modify the gallbladder response to cerulein. The results indicate that neurotensin, at a dose of 2.5 pmol/kg/min, does not influence the gallbladder contraction stimulated by food or cerulein.


Sucralfate, ranitidine and no treatment in gastric ulcer management--a multicenter, prospective, randomized, 24-month follow-up with a study of risk factors of relapse. GISU (Interdisciplinary Group for Ulcer Study).

This multicenter, prospective, randomized, open, long-term study compares sucralfate (2 g daily) with ranitidine (150 mg daily) and no treatment in gastric ulcer (GU). We report the results of the second year of a scheduled 3-year follow-up, the outcome of the 1st year has been reported earlier. The 24-month follow-up was completed by 142 patients who were continuously either treated with the drug randomly assigned at the beginning of the study or left untreated (i.e. 32 patients took 150 mg ranitidine at bedtime, 29 took 1 g sucralfate twice daily and 81 were left untreated, 23 of whom came from the ranitidine group, 19 from the sucralfate group and 39 from the untreated group). Seven patients dropped out and 26 subjects relapsed (5 under ranitidine, 4 under sucralfate and 17 untreated cases). Ranitidine versus previous ranitidine, sucralfate versus previous sucralfate and each one versus no treatment showed comparable relapse rates. An additional study, using Cox's models, showed that three variables have a significant correlation with relapse during the 1st year of follow-up: therapy carried out (p = 0.0025), symptoms (p = 0.0047) and family history of ulcer (p = 0.0392). In conclusion, both ranitidine 150 mg and sucralfate 2 g proved effective in reducing GU relapse as compared with no treatment, an effect which does not seem to persist during the 2nd year of therapy, when the 'no treatment' option may be taken into account.


Time course study on the action of 5-hydroxytryptamine on gastric secretion and mucosal blood flow and on ethanol-induced gastric mucosal damage in rats.

The effects of 5-hydroxytryptamine (5-HT; given i.p. in doses of 1 or 10 mg/kg) on gastric secretion and mucosal blood flow (GMBF) and on ethanol-induced gastric mucosal damage were studied in rats over a period of 30-450 min. The blood pressure was also examined, in relation to the changes in GMBF. 5-HT, 10 mg/kg, given 30 min before ethanol administration markedly worsened lesion formation and this potentiating action was present for a further 90 min; a significant protective effect was seen only at 450 min after 5-HT injection. The lower dose of 5-HT, 1 mg/kg, did not affect the severity of gastric damage. 5-HT (10 mg/kg) also decreased GMBF at 30 min after injection and this lasted up to the end of 120 min, but the depressive action of ethanol on GMBF was reversed at 450 min. The basal gastric secretory volume was depressed from 30 to 120 min but acid output fell from 75 to 120 min after the higher dose of 5-HT; this reduction of acid secretion was followed by an increase from 360 to 450 min. 5-HT decreased the mean blood pressure in a dose- and time-dependent manner. The heart rate was unaffected by either dose level of 5-HT. The present study not only demonstrates the ulcerogenic action of 5-HT but also the protective nature of the amine. The reduction in secretory volume and lesion formation, but not acid secretion, seems to be related to GMBF depression, whereas the protective action depends on the maintenance of GMBF.