Studies of fluoride retention by oral soft tissues after the application of home-use topical fluorides.

Previous studies have focused on enamel and plaque as the primary sites of fluoride (F) retention in the mouth. The present study was undertaken to evaluate the role of oral soft tissue as a site of F retention by comparing an edentulous subject panel (n = 9) with a fully dentate panel (n = 10). Unstimulated whole saliva samples were collected by having subjects pool saliva for two min. Samples were collected over a 24-hour period after application of a placebo dentifrice (PD; 0.4 ppm F), fluoride dentifrice (FD; 1100 ppm F), fluoride rinse (FR; 226 ppm F), or fluoride gel (FG; 5000 ppm F) delivered in custom trays. There was no statistically significant difference in salivary flow rate between the two panels for any of the treatments. The edentulous panel had higher salivary F levels than the dentate panel, which reached statistical significance (p less than 0.05) for the FD and FG treatments. In a separate study involving the same treatments, F levels at specific soft-tissue sites were measured over a one-hour period by use of absorbent discs placed in different soft-tissue areas of the mouth. The tongue and lower posterior vestibule retained the highest F levels, followed by the upper posterior buccal vestibule and upper anterior labial vestibule, with the lowest F levels retained in the lower anterior vestibule and the floor of the mouth. There was a strong-to-moderate correlation between whole saliva F concentration and F levels at specific soft-tissue sites. This study establishes the importance of oral soft tissue as the major site of F retention in the mouth.


Distribution of fluoride in saliva and plaque fluid after a 0.048 mol/L NaF rinse.

An ultramicro method has recently been described for measurement of plaque-fluid fluoride concentration (Vogel et al., 1990a). This method was used: (1) for exploration of the variation in fluoride concentration of plaque fluid collected from the same buccal tooth sites following a 0.048 mol/L NaF (0.2%) rinse, and (2) for examination of the distribution of fluoride in plaque fluid and saliva within one hour after this rinse. Results indicated an average coefficient of variation (CV) of 31% for plaque-fluid fluoride in triplicate samples recovered simultaneously from the buccal-proximal region of two teeth after the rinse. This was similar to the CV found for plaque-fluid fluoride from the same sites after separate administrations of the rinse. A strong linear correlation was found between salivary and plaque-fluid fluoride at 30 and 60 min after rinse administration, showing that plaque-fluid fluoride is influenced by the concentration of salivary fluoride after administration of this rinse. Plaque-fluid fluoride concentrations were higher than that in saliva at baseline, 30, and 60 min. Very large inter-site and intersubject variations in plaque-fluid distribution were observed, with the central incisors showing the slowest clearance. These variations suggest that an examination of plaque-fluid fluoride from specific tooth regions may be essential for understanding the effects of fluoride on the site-specificity of caries.


Fluoride retention in dentin after topical application of aminefluoride.

The retention of KOH-soluble and structurally bound fluoride in dentin after topical application of aminefluoride was investigated. One cylindrical dentin sample was prepared from each of 40 extracted third molars. All samples received one topical application of 1 microL of aminefluoride solution (1.23% F) for three min. Ten of them were analyzed immediately after fluoridation. The remaining 30 samples were mounted in the buccal aspects of a special mouth application which was carried by a person for five days. After one, three, and five days, 10 of the 30 samples were removed from the appliance. In all samples, the amount of structurally bound fluoride was determined in three layers (20 microns, 20 microns, 20 microns) by use of a special grinding technique. Before each grinding step, the dentin specimens were analyzed for KOH-soluble fluoride. The total amount of KOH-soluble fluoride in dentin was 48.7 +/- 14 micrograms/cm2. It decreased drastically during the experimental period. Structurally-bound fluoride increased one day after fluoridation in the first and second layers. Thus, topical application of aminefluoride resulted in a significant accumulation of KOH-soluble fluoride in dentin. This precipitate was unstable, but fluoride ions released from it could perhaps increase the amount of structurally bound fluoride.


Inhibition of plaque formation and gingivitis in beagle dogs by topical use of a degradable controlled-release system containing chlorhexidine.

The in vivo efficacy of a newly-developed dental application of a film-forming, chlorhexidine-containing system was examined in beagle dogs. A self-disintegrating film-forming solution was applied three times weekly to the dentitions of 7 out of 13 dogs, which were fed a soft-food diet. Plaque accumulation (Plaque Index) and gingival inflammation (Gingival Index) were recorded at one, two, four, six, and eight weeks. The local delivery of low-dose chlorhexidine to dogs significantly inhibited gingivitis and plaque formation. It is concluded that the dental application of a film-forming system may be a preferable method of periodontal disease prophylaxis, and may enhance supragingival plaque control in areas of isolated periodontal problems associated with obvious local predisposing factors.


Effects of chlorhexidine-containing gel and varnish on abutment teeth in patients with overdentures.

Previous experiments have shown that daily use of 1% chlorhexidine gel strongly reduced caries development in the abutment teeth under overdentures. The present experiment was designed to determine whether intermittent application of chlorhexidine, either in a varnish or in a gel, might be used as an alternative preventive method, less demanding for the patient. To this end, 31 patients were distributed among four treatment groups, with the number of mutans streptococci in plaque and saliva used as a balancing criterion. The treatments consisted of a single application of 40% chlorhexidine varnish, daily application of 1% chlorhexidine gel for one week, or the corresponding placebo treatments with varnish or gel without chlorhexidine. Patients were re-called for bacteriological and clinical examination at various intervals during an eight-week period following treatment. Chlorhexidine varnish and chlorhexidine gel applications significantly suppressed mutans streptococci on the abutment teeth for four and eight weeks, respectively. In agreement with earlier findings, the numbers of Actinomyces viscosus/naeslundii in plaque were significantly increased after chlorhexidine varnish treatment. The chlorhexidine gel reduced plaque accumulation and gingival bleeding for one week but had no long-lasting effect. The results seem to justify a long-term clinical test of intermittent chlorhexidine applications as an alternative for daily use in patients with overdentures.


Distribution of chondroitin sulfate and dermatan sulfate in normal and inflamed human gingivae.

The effect of inflammation on the distribution of chondroitin sulfate and dermatan sulfate proteoglycans was assessed after normal and inflamed human gingivae were stained with monoclonal antibodies against these extracellular matrix macromolecules. The tissues were obtained following periodontal surgery and reacted with specific antibodies after pre-treatment with chondroitinase ACII or chondroitinase ABC, and staining was visualized by the immunoperoxidase technique. The results indicated that these two proteoglycans were present in both the 4-sulfated and 6-sulfated isomeric forms. While chondroitin sulfate appeared to be uniformly distributed throughout the connective tissue, dermatan sulfate showed greater intensity of staining in the areas immediately subjacent to the epithelium. Positive staining for chondroitin sulfate was noted in the intercellular spaces of the epithelium. In inflamed tissues, there was significant staining associated with 4-sulfated dermatan sulfate and chondroitin sulfate, but this had lost the structured pattern of staining noted in normal sections. The 6-sulfated isomeric forms were greatly reduced in inflamed tissues and tended to show a predilection to be localized within the perivascular tissues. In the inflamed tissues, there was intense staining for chondroitin sulfate associated with the infiltrating inflammatory cells. These findings corroborate earlier biochemical studies on normal and inflamed gingival tissues. The specific tissue localization of dermatan sulfate and chondroitin sulfate in tissues damaged by inflammation indicates that, as opposed to the large loss of collagenous material noted during inflammation, there is not a corresponding large loss of proteoglycan. Indeed, at specific inflammatory foci, the intensity of staining for these macromolecules may intensify.


Radiometric classification of alveolar bone health.

A radiograph-based classifier for discrimination between normal and diseased alveolar bone was developed. The alveolar bone health of dry mandibles was rated, by consensus of two trained observers, as normal or diseased. Bitewing radiographs of mandibular quadrants were digitized and regions of interest (ROIs) of the alveolar bone between the first and second permanent molars outlined. Gray-scale histograms for the ROIs were computed, and a classifier based on these histograms was developed. Two observers (independently) used only the classifier to rate the bone as being normal or diseased. These ratings were compared with the original ratings of trained observers who viewed and scored the actual alveolar bone. The sensitivity (the ability to detect diseased alveolar bone), specificity (the ability to detect normal alveolar bone), and accuracy were 0.90 or greater, indicating good agreement with subjective visual assessments of dry mandibles. These results suggest that this procedure may be applicable for evaluations of bone health in humans.


Staircase assessment of the magnitude and time-course of 50% nitrous-oxide analgesia.

The analgesic effect of 50% nitrous oxide and oxygen on thermal pain sensations was evaluated in a placebo-controlled, double-blind crossover design. In a session immediately before oral surgery, 20 patients used a seven-point verbal scale to rate the intensity of pain sensations evoked by three-second thermal stimuli delivered to 14 sites on the volar forearm at 20-second intervals by a 1-cm-diameter contact thermode. Subjects rated 36 stimuli while breathing room air and then two additional sets of 36 stimuli while inhaling 50% nitrous oxide and oxygen during one set and oxygen placebo during the other. Each of these two stimulus sets was preceded by a two-minute induction of the agent, and the sets were separated by a three-minute washout period. Order of administration was randomized and counterbalanced. Stimulus temperatures were adjusted continuously by an interactive computer program so that response could be maintained at predetermined levels. This method resulted in a continuous measure of analgesia in units of stimulus intensity. Results showed that, in comparison with placebo, nitrous oxide significantly increased the stimulus temperatures (mean = 0.42 degrees C) required to make the same response [F (11,209) = 6.76, p less than 0.0001], indicating analgesia. This increase was one-third to one-half that observed with clinical doses of intravenous fentanyl. Analgesic effects were apparent at three min and wanted 10 min after termination of nitrous-oxide inhalation. These times closely correlated with previous measures of alveolar concentration, further supporting the fast but modest analgesic action of nitrous oxide.


Effect of 45,X/46,XX mosaicism on root morphology of mandibular premolars.

The effect of X chromosome mosaicism on root morphology of mandibular premolars was studied in 14 females with 45,X/46,XX chromosome constitution. Occurrences of two-rooted premolars and the morphology of the roots were examined from orthopantomograms. Six (43%) of the 45,X/46,XX mosaics had two-rooted mandibular premolars. Two-rooted first premolars were found in four (29%) and second premolars in three (21%); in one, all four mandibular premolars were two-rooted. The results indicate that the frequency of two-rooted mandibular premolars was similar in 45,X/46,XX mosaics and in 45,X females, and in both groups significantly higher than in normal 46,XX females. Compared with 45,X females, the 45,X/46,XX mosaics showed a slight tendency toward more simplified root morphology in the first premolars. The findings suggest that the presence of normal 46,XX cells among the defective 45,X cells does not affect the development of the mandibular premolar roots. Furthermore, the results do not support the earlier proposal that the presence of normal 46,XX cells in 45,X/46,XX mosaic individuals would be reflected in gradual normalization of dental development.


Demand and need for treatment of craniomandibular dysfunction in the Dutch adult population.

A nationwide survey of oral conditions, treatment needs, and attitudes toward dental health care in Dutch adults was carried out in 1986. One of the aims of the study was to investigate the perceived need and demand for treatment of craniomandibular dysfunction (CMD). A sample of 6577 persons (15-74 yrs of age), stratified for gender, age, region, and socio-economic status, was contacted. Of this sample, 4496 persons participated in the behavioral part of the study, of which 3526 were examined clinically. The CMD-treatment demand was based on (1) CMD complaints in the past, (2) CMD complaints at present, and (3) an anticipated increase of the present complaints. CMD was both anamnestically and clinically assessed, independently by different examiners. A total of 21.5% of the Dutch adult population reported dysfunction, but 85% of these perceived no need for treatment. With most of the remaining 15% either seeking or intending to seek treatment (or having had it before), a figure of 3.1% can be used to summarize the actual level of treatment need for CMD in the Dutch adult population.


A semi-empirical model for prediction of how post-retained crowns will fail under compressive loading.

The aim of this in vitro study was to determine the relative contributions to retention of the different components of the post-retained crown and the mode of failure when the crown was loaded at 50 degrees to the vertical (i.e., in an apical direction). Failure was initiated in all the specimens as a rotation of the crown about a point on the labial surface of the root at the crown-root interface with pull-out of the post. A semi-empirical model was developed to explain this mode of failure. From experimental results, it was noted that the retention provided by the post was the most significant factor in the equation. However, large variation in the maximum forces recorded from pull-out tests on 40 posts suggested that the glass-ionomer cement was acting in the manner of a brittle composite material whose failure may be attributed to defects in the structure causing stress concentrations. The probability of survival at each ultimate strength recorded experimentally was plotted for comparison with the curve generated by the derived Weibull function. Close agreement was noted. Thus, for any given force applied compressively at 50 degrees to the vertical to a post-retained crown of known dimensions, it is possible, by use of the described equation, to calculate the force, P, applied to the post. This value of P may then be inserted into the Weibull equation to give the probability of the crown failing under that applied force.


The dependence of shrinkage stress reduction on porosity concentration in thin resin layers.

The development of polymerization contraction stress was determined as a function of the surface area of porosity, so that the contribution of voids in resin composite to stress relief could be investigated. Experiments were carried out on 200-microns-thick layers of resin bonded from wall to wall in a restrained condition. The resin samples were divided into three groups: Group A was without porosity, group B contained a small number of pores, and group C contained a large number of pores in comparison with group B. For each group, porosity area, maximal stress, and stress development rate were determined. The mean maximal stress and stress development rate were inversely proportional to the mean porosity surface. These characteristics differed significantly (p less than 0.01) between group A and C. For determination of whether shrinkage stress reduction has to be ascribed to flow from the outer surfaces of the voids or to inhibition of the setting reaction by oxygen in the voids, resin containing only nitrogen bubbles was also tested. The results indicated that both aspects contributed substantially to shrinkage stress relief. Incorporation of pores by the stirring of a luting cement contributes to stress reduction and can therefore be considered as a contribution to the maintenance of marginal integrity.


Influence of tempering method on residual stress in dental porcelain.

The porcelain component of a porcelain-fused-to-metal restoration is strengthened by residual (tempering) stresses which are induced by cooling procedures followed in dental laboratories. The thermophysical properties of materials and cooling rate are the main factors which determine the residual stress. In this paper, the temperatures in the midplane of body-porcelain disks were measured from a heat-soak temperature (1000 degrees C) to room temperature during two different cooling procedures: slow cooling in air and forced-air cooling. Experimental results approximated exponential cooling wherein the cooling rates could be represented by a linear equation of temperature. Residual stresses, as affected by the tempering method and thickness of a porcelain disk, were calculated by computer simulation for regions away from the edges. The following temperature-dependent factors were incorporated into the simulation: elastic modulus, viscosity, and coefficient of thermal expansion. The cooling rate dependencies of the glass transition temperature and the temperature distribution during cooling were also included. The cooling rates used in this simulation were derived from the tempering data. The agreement between development of transient and residual stresses--calculated by computer simulation for various cooling methods, and the tendency toward failures of porcelain disks subjected to the tempering processes--was examined. Simulated residual stresses were also in good agreement with those measured by the indentation fracture method of Marshall and Lawn (1977) and Anusavice et al. (1989).


Early bond strength of luting cements to a precious alloy.

Previous studies have reported that glass-ionomer and adhesive resin cements can bond to various alloys, while zinc phosphate cements lack this adhesive property. This study evaluated the bonding properties of three luting cements during the first seven days after cementation. Thirty cylinders were cast with a high-noble porcelain-fused-to-metal (PFM) alloy and luted in pairs with one of the cements. The joints were stored in water at 37 degrees C for one, two, or seven days before being fractured in shear. The cylinders were re-used to provide 40 joints within each test group. The data were subjected to a Weibull analysis, a curve-fitting method shown to be appropriate for comparing the bond strengths of dental materials. The results showed that the zinc phosphate cement was the weakest material, whereas the adhesive resin produced the strongest joints. Microscopic observations of the fractured samples did not reveal any specific differences between the samples in terms of their mechanism of fracture. The glass-ionomer cement reached its maximum bond strength after two days, whereas storage time had no influence on the zinc phosphate cement. The adhesive resin cement was slightly, but not significantly, weaker after one week in water. We suggest that excessive loading of restorations cemented with glass ionomer should be avoided for the first two days after the placement. The use of an adhesive resin cement can be recommended on endodontically treated teeth, but further studies are needed to evaluate its biocompatibility and adhesion to dentin.


Epidemiology of snake bite in the district of Burdwan, West Bengal.

An epidemiological field survey on snake bite was conducted on 26 randomly selected villages with a population of 18,892 in the district of Burdwan, West Bengal to assess the magnitude of the problem in a decade (1980-1989). Total number of snake bite, number of presumably poisonous snake bite and deaths due to snake bite poisoning were 307, 48 and 31 respectively. The death rate among snake bite victims was 10.09%. Males (54.72%) were bitten more than females (45.23%) and highest incidence of snake bite was found in the age group of 21-30 years and during the months of July and August. Majority of the snake bites (53%) were encountered in the lower extremities. Among the snake bite patients 201 (65.47% went to the traditional healers (ozhas) and 68 (22.14%) persons received hospital treatment, while 12 (3.09%) people neither went to the ozhas nor to hospital and 26 (8.46%) persons went to hospital after consulting the ozhas. If the present data are extrapolated for the total population of the district, average number of snake bite and death per year would be 7,857 (0.16%) and 793 (0.016%) respectively. Deaths due to snake bite per 100,000 population varied from 5.28 to 31.75 (average 16.4) over 10 years.


A perforated appendix: should we drain?

The effectiveness of intraperitoneal drain was studied on patients undergoing appendicectomy for perforated appendicitis. Randomly 40 patients were allocated with drainage by corrugated rubber drains and 46 patients were without drainage. There were 5 deaths in the series, out of which 4 (10%) were in the drainage group and one (2.2%) in the group without drainage. The incidences of major wound sepsis, paralytic ileus, intraperitoneal abscess and urinary infection were observed in 55%, 42.5%, 12.5% and 15% respectively in drainage group and 50%, 28.3%, 21.7% and 15.2% respectively in non-drainage group. Occurrence of subphrenic abscess (7.5%), burst abdomen (5%) and faecal fistula (5%) were confined to drainage group only.


A study of caesarean section cases with special reference to maternal and neonatal outcome.

Two hundred cases of lower uterine segment caesarean section were studied in SSKM Hospital and IPGME&R, Calcutta (a referral hospital) during the period 1986-1987. All were unselected cases of which 192 were booked and 8 were unbooked. The maximum number of caesarean sections were done in the age group of 21-30 years ie, in 154 cases (77.00%). Of total number of cases 53.5% were primigravida, and rest were multipara. Postoperative complications were noted in 42 cases (21%). Complications were more in unbooked and emergency cases ie, 7 (87.5%) and also in cases of antepartum haemorrhage (3 out of 8 cases) and where foetal distress (12 out of 51 cases) ie, prolonged labour, difficult labour was present. Neonatal mortality and morbidity (8 and 26 out of 154 total births respectively) were high in the age group of 21-30 years. Neonatal complications following caesarean section were found in 21.8% patients in emergency caesarean section and 15.5% in elective caesarean section. Neonatal morbidity was 15% and perinatal mortality was 4% in this study. Asphyxia (11 cases) and respiratory distress syndrome (10 cases) were more dangerous complications in caesarean section. There was no maternal mortality in this series.


Role of sublingual administration of tablet buprenorphine hydrochloride on relief of labour pain.

Tablet buprenorphine hydrochloride when administered to 34 primigravida women sublingually in a dose of 6 micrograms/kg body weight during the first stage of labour, the analgesic action started 30 minutes after administration of drug and the analgesic action increased gradually and reached its peak level 3 hours after administration of drug. Analgesic action continued throughout the first stage of labour when the duration after administration of drug was 9 hours. In one case maximum analgesic action did not persist after 9 hours. The average time of delivery was 5.88 hours having cervical dilatation of 3.1 (+/- 0.13) cm and the progress of labour was not delayed by the drug. There was no cardiorespiratory depression of the subjects. None complained of nausea or vomiting. There was no change in foetal heart rate and Apgar scoring of neonates revealed the average value of 9.71 at 1 minute and 9.94 at 5 minutes.


Management of oral cancer in late stages: a review.

Sixty cases of oral cancer (2 were of stage II and other 58 were of stage III and stage IV) were treated and observed over a period of 2 years. In patients of oral cancer with bone involvement and mobile cervical nodes (44 cases) local excision which included partial or hemimandibulectomy with radical neck node dissection was performed. Out of these 44 cases, 18 cases received radiotherapy pre-operatively and 26 cases postoperatively. Better results were observed in these cases. When the growth was inaccessible and/or nodes were fixed (13 cases) radiotherapy was found to be suitable. Fistula formation and reconstructive flap necrosis were common following surgery after radiotherapy. Combined modalities of treatment with pre- and postoperative radiotherapy and radical neck node dissection showed excellent results (86.4%) in majority of cases. The remaining one patient received chemotherapy and local excision was performed in 2 cases.


Diphtheria in the eighties: experience in a south Indian district hospital.

Epidemiological and clinical analysis of 228 cases of diphtheria treated during a 10-year period from 1980-1989 is presented. No statistically significant change in the incidence over a decade was noticed. A high percentage of cases (44.74%) were noted in the age group of 5 years and above. Bilateral tonsillar and pharyngeal membranes together were seen in 60% cases. All patients were treated with diphtheria antitoxin and benzyl penicillin. Severe myocarditis (9 cases), fulminant haemorrhagic complications (2 cases), palatal palsies (11 cases) and polyneuritis and cranial nerve paralysis (2 cases) were the significant complications. Case fatality rate was 13.21%. Statistically significant increase in the mortality (p less than 0.05) was noticed in the year 1987 and onwards. In this period, myocarditis (8 out of 16 deaths) is gradually replacing laryngeal obstruction, the major cause of death in early eighties or post-tracheostomy complications (6 out of 16 deaths). Only 2 patients died of haemorrhagic diphtheria in this period.


An evaluation of inpatient consultations conducted by clinical microbiologists in a teaching hospital.

A systematic procedure for conducting consultations by clinical microbiologists requested by their clinical colleagues is described. The method was evaluated over a period of 17 months and involved sequential consultations related to 229 patients with known or probable infections. An attempt was made to elucidate the contributions of the clinical microbiologists in achieving a better understanding of the problems experienced in this particular setting and which in turn led to improved management of patients. It is hoped that this paper may provide a practical working framework for clinical microbiologists in the care of patients suffering from infection.


Urinary-tract infections in African neonates.

During a 4-year period between January 1987 and December 1990, 41 high-risk neonates with proven urinary tract infections (UTIs) were studied prospectively and compared with 55 control neonates. An incidence of 2.6 UTIs per 1000 live births was noted, amongst whom no obvious radiological abnormalities of the urinary tract were found. Significantly, more males than females developed UTIs, the ratio being 4.5:I. Low-birth-weight babies were significantly more often affected than those of normal weight (P less than 0.05). Staphylococcus aureus and Klebsiella spp. were the predominant pathogens isolated. Aetiologically, bacteraemia from sepsis was important. Most of the infants presented with a significantly higher incidence of pyrexia, abdominal distension, lethargy and jaundice (P less than 0.01). The overall mortality rate of 17.1% was closely related to these associated problems. The relatively high incidence of UTI and the rarity of radiological abnormalities of the urinary tract in the African neonate contrast with previous reports in the literature and the reason is worthy of consideration. Despite the rarity of urinary-tract anomalies, a continuous surveillance of the trend of neonatal UTI and its outcome is recommended.


Experience with Vi typhoid capsular polysaccharide vaccine in the U.K.

Adult volunteers were immunised with a single dose of typhoid Vi capsular polysaccharide vaccine. After immunisation, 96% of the 103 subjects seroconverted and 94% had antibody levels above the protective threshold. Systemic reactions were uncommon, local reactions were mild and transient.


Pneumonia due to Legionella bozemanii and Chlamydia psittaci/TWAR following renal transplantation.

Chlamydia and Legionella are recognized causes of atypical pneumonia. A case of pneumonia due to Chlamydia psittaci/TWAR and Legionella bozemanii following renal transplantation is described. Legionella bozemanii infection was diagnosed by a rise in antibodies and by isolation of the organism from bronchoscopy specimens. It is unusual to find pneumonia caused concomitantly by two such agents. This case, despite the fatal outcome, emphasises the necessity for a comprehensive approach to the diagnosis of atypical pneumonia, including culture for Legionella, especially in immunocompromised patients.


Acremonium infection in a neutropenic patient.

Acremonium species (previously Cephalosporium) are saprophytic moulds of low pathogenicity commonly found in the environment. We report a case of repeated acremonium fungaemia in a neutropenic patient, probably associated with a Hickman line. Fungaemia was accompanied by fever and a papular skin rash, both of which appeared to resolve when the neutrophil count recovered without antifungal chemotherapy, only to return when the patient next became neutropenic.


Prosthetic hip-joint infection associated with a penicillin-tolerant group B streptococcus.

We report a case of prosthetic hip-joint infection with Streptococcus agalactiae (Lancefield group B streptococcus). The infection recurred after 3 months' treatment with amoxycillin. On further investigation, the isolate was found to be amoxycillin-tolerant. Addition of gentamicin abolished tolerance in vitro and the patient has remained asymptomatic since receiving a 10-day course of amoxycillin and gentamicin followed by amoxycillin alone.


Pericarditis, pneumonia and brain abscess due to a combined Actinomyces--Actinobacillus actinomycetemcomitans infection.

A patient is described in whom there developed a pulmonary infiltrate and constrictive pericarditis caused by a combined Actinomyces and Actinobacillus actinomycetemcomitans infection, presumably originating from his poor dentition. The diagnosis was only made following repeated thoracotomy. After surgery, long-term treatment with antibiotics led to complete clinical recovery. None the less, some months later he was found to have a brain abscess which resolved during a further course of antibiotics. The variable clinical picture of actinomycosis is discussed, as well as the role of other bacteria frequently associated with actinomycotic infection, in particular Actinobacillus actinomycetemcomitans. The therapeutic implications are described.


Titres of class-specific antibodies against Shigella and Salmonella lipopolysaccharide antigens in colostrum and breast milk of Costa Rican, Swedish and Vietnamese mothers.

Enzyme immunoassays (EIA) were used to estimate titres of class-specific antibodies against purified and chemically defined phenol-water-extracted lipopolysaccharide (LPS) antigens of Salmonella serogroup B (BO), Shigella dysenteriae type I, Plesiomonas shigelloides (the same O-antigen as Shigella sonnei) and Shigella flexneri Y. Titres in colostrum and breast milk of Swedish, Vietnamese and Costa Rican mothers from various socioeconomic conditions were compared. The antibodies were mainly of the IgA isotype. IgM antibodies were also present, but only very low concentrations of IgG were found. In Costa Rican mothers, the IgA antibody titres were significantly higher (P less than 0.05) in women of low and middle socioeconomical conditions than were those in mothers of high socioeconomical level. The low titres in the last group were comparable to those found in Swedish mothers. The IgA antibody titres found in Vietnamese mothers were similar to those of Costa Rican mothers from the low and middle socioeconomic conditions, being highest against S. flexneri Y LPS. The IgM antibody titres were also highest in Vietnamese mothers, immediately followed by the Costa Rican mothers of low socioeconomic conditions. The low IgM titres in the Costa Rican women of high socioeconomic level were comparable to those seen in Swedish mothers. The results suggest that, in Costa Rica and Vietnam, S. flexneri is the most prevalent Shigella sp. causing infection and that Salmonella serogroup B infections are rare in all three countries. The results also show that the antibody repertoire in colostrum and breast milk varies. Furthermore, in addition to the prevalence of a specific micro-organism in a determined geographical area, such differences may be associated mainly with exposure to certain pathogens in particular socioeconomic conditions.


Ovine chlamydiosis in an abattoir worker.

The strain of Chlamydia psittaci causing enzootic abortion in ewes (the EAE strain) may cause serious infection in pregnant women, often resulting in hepatic and renal dysfunction, disseminated intravascular coagulation and fetal loss. The first case of such an infection in an abattoir worker is described and the possibility of human-to-human transmission considered. Direct handling of sheep or their products of conception can usually be established but this is not always so. There is much still to be learned about this uncommon but severe zoonosis.


Coxiella burneti endocarditis in a patient with positive chlamydial serology.

A 41-year-old man who habitually slept in a car park presented with a culture-negative endocarditis. Serological tests indicated infection with both Coxiella burneti and Chlamydia psittaci. He was treated with doxycycline and clindamycin and required aortic valve replacement. Culture of the excised value for both agents was negative but electron microscopy was suggestive of coxiella endocarditis.


The epidemiology and significance of Chlamydia pneumoniae.

Chlamydia pneumoniae has recently been found to be a new chlamydial species transmitted directly from man to man, obviously through the respiratory tract. It is the commonest chlamydia of mankind but fortunately the overwhelming majority of infections are mild, it has been estimated that 10% of all pneumonias are caused by this species. Since the most important chlamydial infections are chronic in nature, the question of possible chronic C. pneumoniae infections is of paramount importance. Apart from being associated with chronic inflammatory processes of the respiratory system, a quite unexpected connection to coronary heart disease has now been suggested.


Male genital Chlamydia trachomatis infections.

The role of Chlamydia trachomatis in infections of the male genital tract is reviewed. The organism is an important cause of non-gonococcal urethritis, post-gonococcal urethritis and epididymitis, but does not appear to play a major part in the pathogenesis of chronic abacterial prostatitis or in proctitis in anoreceptive homosexual men.


The laboratory diagnosis of male Chlamydia trachomatis infections--a time for change?

We carried out a two-phased study comparing the effectiveness of first-catch early morning urine (FCU) samples against urethral swabs for the detection of C. trachomatis in men. Four hundred and seventeen new and re-booked consecutive men, who attended the Department of Genito-Urinary Medicine, Bristol, having held their urine overnight, were recruited. Patients who had received antimicrobial chemotherapy in the preceding 2 months were excluded. Early morning FCU samples were obtained from 208 men followed by urethral swabs for the detection of C. trachomatis (phase I) and this order of collection was reversed for the remaining 209 patients (phase 2). A last-catch urine (LCU) was also obtained from all patients. All urethral and urine samples were examined by an amplified enzyme immunoassay (IDEIA, Dako Diagnostics Ltd). Initially, discordant samples were critically examined by direct immunofluorescence (Syva, 'Microtrak') which was used as the 'gold' standard in this study. We have shown that overall 42 and 4.7% of our symptomatic and asymptomatic male patients respectively were positive for C. trachomatis antigen by IDEIA. Furthermore 86.4 and 91.0% (phases 1 and 2) of the total C. trachomatis positive samples were detected by examination of an FCU sample. In contrast only 66.0 and 65.5% (phases 1 and 2) of the total positives were identified by examination of an urethral swab. These results show that an FCU sample not only has the advantage of being a non-invasive procedure but is also a very sensitive method, compared to swabbing the urethra for the detection of C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)


The differentiation of Chlamydia species by antigen detection in sputum specimens from patients with community-acquired acute respiratory infections.

An amplified enzyme immunoassay (IDEIA III: Dako Diagnostics Ltd) for detecting genus-specific chlamydia antigen was evaluated prospectively on 286 respiratory specimens from 275 patients presenting with community-acquired pneumonia or persistent chest infection. Nineteen patients had evidence of recent chlamydial infection, having two or more positive sputum or serological markers. Sputa from two other patients were ELISA-positive in the absence of other positive criteria and were regarded as false-positive results. When compared with a direct immunofluorescence test for chlamydial elementary bodies (EBs) using a genus-specific monoclonal antibody, the ELISA gave a positive predictive value of 91% and a negative predictive value of 99%. Non-specific problems with a wide variety of other micro-organisms isolated from the sputa were not encountered. Attempts to differentiate between Chlamydia psittaci, Chlamydia pneumoniae and Chlamydia trachomatis using genus-specific lipopolysaccharide reactive--and species-specific major outer membrane protein--monoclonal antibodies were encouraging and results were substantiated, in most patients, by the species-specific serological assays of the whole-cell-inclusion immunofluorescence or micro-immunofluorescence assays. The study demonstrated that antigen detection techniques offer scope for routine laboratories to diagnose chlamydial respiratory infections rapidly and reliably and may enable differentiation to species level. Although immunofluorescence offers marginally greater sensitivity and specificity when compared with ELISA, the latter is less subjective and less demanding. Sixty-eight per cent of these infections would have remained undiagnosed despite the general availability of ELISA tests.


Prevalence of antibodies to Chlamydia pneumoniae in a Belgian population.

To evaluate the prevalence of antibodies to Chlamydia pneumoniae in a healthy adult Belgian population a study group of 150 medical students was chosen. Sera were collected in the period between March and October 1990 and assessed by the microimmunofluorescence test. Sixty-one per cent were found to have IgG antibodies to C. pneumoniae in a titre greater than or equal to 16, which showed evidence of past infection. Twenty-one per cent had IgA in a titre greater than or equal to 8. In none were antibodies of the IgM fraction detected. The same sera were tested for the presence of antibodies to Chlamydia trachomatis. One hundred and thirty-one sera with no or low titres of antibodies to C. pneumoniae tended to have low or no detectable antibodies to C. trachomatis. Nineteen sera with high (greater than 128) titres of antibodies to C. pneumoniae had IgG antibodies in a titre of greater than or equal to 32 to C. trachomatis. This prevalence (13%) is much higher than one would expect in a population at low risk for C. trachomatis infection. The problem of possible cross-reactions between the three species in the micro-immunofluorescence test is discussed.


A comparison of the seroepidemiology of chlamydial infection in pigeon fanciers and farmers in the U.K.

A detailed comparative seroepidemiological study of antibody responses was performed in 271 pigeon fanciers and 100 farmers. Overall 73% of pigeon fanciers had IgG antibodies at a titre greater than or equal to 16 to Chlamydia pneumoniae, 39% to Chlamydia psittaci, and 6.6% to Chlamydia trachomatis. The prevalence of chlamydial antibodies was significantly lower in the farmers at 47% for C. pneumoniae, 6% for C. psittaci, and 2% for C. trachomatis. Both populations were exposed to complex microbiological and antigenic environments: 50.5% of the pigeon fanciers had antibodies to pigeon antigens, 34% to egg membrane, and 0.73% to yolk sac antigen, and 59% of the farmers had antibodies to Micropolyspora faeni, but the high prevalence of chlamydial antibodies could not be attributed to interaction with these antigens. There was considerable overlap of chlamydial antibody responses in the pigeon fanciers but not in the farmers: 36% of the pigeon fanciers had antibodies to C. pneumoniae alone, 5% to C. psittaci alone, and 31% to both agents, whereas only 3% of farmers had antibodies to both C. pneumoniae and C. psittaci. The high prevalence of antibodies to C. psittaci in the pigeon fanciers is compatible with the known avian reservoir for this infection. The particularly high prevalence of antibodies to C. pneumoniae suggests that complex interactions may be occurring in a population exposed to two chlamydial organisms, whereby infection with one species may provoke an anamnestic response against other chlamydial organisms with which the subject has previously been infected.


A family outbreak of Chlamydia pneumoniae infection.

Chlamydia pneumoniae, a newly described Chlamydia species, has been shown to be a cause of acute respiratory tract infection in both adults and children, but its role in human infection is still under investigation. Here we present a family outbreak of C. pneumoniae infection where three members of a family presented with a 'flu-like illness' and acute upper respiratory tract infection which did not improve despite penicillin or septrin therapy. No history of exposure to birds, pets or animals was obtained. As C. pneumoniae isolation from respiratory secretions is not without difficulty, diagnosis usually relies currently on serum-based tests. In this study C. pneumoniae specific IgM determined by the micro-immunofluorescence test was detected in the three clinical cases. All three cases had an elevated complement-fixing antibody titre to Psittacosis-LGV antigen, which may have suggested psittacosis, if type-specific tests had not been performed. In addition, three other members of the family had C. pneumoniae-specific IgG antibody although specific IgM was absent. These three younger members of the family had been symptomatic in the month preceding symptoms in their older sibling and their parents. All the symptomatic members of the family made a complete recovery on tetracycline therapy.


The use of transcutaneous oximetry in the noninvasive vascular laboratory.

Transcutaneous oximetry is gaining worldwide acceptance as a simple and effective means of evaluating the cutaneous circulation. Oximetry involves the use of Clark-type electrically heated oxygen-sensing electrodes that are attached to the skin; various protocols for the performance of studies (utilizing exercise, oxygen inhalation, leg elevation, and various other maneuvers) have been developed which may improve the accuracy when used in certain settings. Applications for transcutaneous oximetry are found in areas such as: (1) diagnosis of disease, (2) quantification of disease severity, (3) prediction of healing potential for skin ulcers or amputation sites, (4) assessment of microvascular disease, and (5) determination of cutaneous vasomotor status. Transcutaneous oxygen tension serves as an index of the adequacy of skin blood flow, and therefore yields valuable "functional" information not provided by noninvasive "anatomical" testing modalities such as echo-doppler ultrasound imaging.


Functional changes in canine saphenous veins after cryopreservation.

This study was designed to determine the functional characteristics of the endothelium, smooth muscle and nerve terminals of cryopreserved veins. Freshly harvested and cryopreserved canine saphenous veins were cut into rings. In some rings, the endothelium was removed. Cryopreserved veins were stored at -196 degrees C for at least 3 weeks prior to use. All rings contracted in a concentration-dependent manner to depolarization with KCl and to alpha-adrenergic stimulation; the maximal tensions were significantly less in cryopreserved than in freshly harvested veins. Calcium ionophore A23187 caused greater relaxations in rings with than without endothelium in freshly harvested and cryopreserved veins. These relaxations were reduced significantly by methylene blue and NG-monomethyl-L-arginine (L-NMMA) only in fresh veins. Cocaine-sensitive uptake of H3-norepinephrine was reduced following cryopreservation. Immediately after cryopreservation, the production of prostacyclin was elevated. The calcium ionophore A23187 stimulated production of prostacyclin only in freshly harvested veins. Tissue content of endothelin did not change following cryopreservation. These results suggest that cryopreservation of canine saphenous veins alters nerve terminals and decreases the ability of the smooth muscle to contract. The endothelium releases an endothelium-derived relaxing factor and prostanoids following cryopreservation but the ability to synthesize nitric oxide is probably reduced. These changes following cryopreservation may affect patency of the veins when used as arterial grafts.


Chronic pernio: another cause of blue toes.

It is the purpose of this report to focus attention on the clinical features, diagnosis, and management of chronic pernio. Thirty-nine patients meeting our strict criteria for a diagnosis of chronic pernio were seen at the Mayo Clinic between 1976 and 1988 and form the basis for this report. Persons with upper extremity lesions only were excluded. Twenty-eight of the patients were female, 11 were male. Age at onset of symptoms ranged from 13 to 68 years of age, with symptoms appearing from 1 to 37 years following cold injury. The lesions were bilateral in 35 (90%) of patients and symmetric in 28 (71%). Nine patients who underwent skin temperature studies following cold water immersion, showed a vasospastic response. Chronic pernio is characterized by recurring erythematous, vesicular or ulcerative lesions of the lower extremities and toes, but may present with only digital cyanosis, usually bilateral and commonly symmetrical. The diagnosis is suggested by eliciting a temporal relation between cool weather and symptom onset, particularly if there is no associated occlusive peripheral arterial disease. Treatment consists of avoidance of cold and other vasoconstrictive influences. Prazosin has been effective in the acute management and as prophylaxis against recurrences.


Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.


The prevalence of vascular occlusive disease associated with antiphospholipid syndromes.

The association of anticardiolipin antibodies (aCL) with unexplained vascular occlusive disease (VOD) is well known. We reviewed the records of 102 consecutive patients seen over a 9 months period who had positive IgG or IgM aCL to determine the frequency and types of VOD in this unselected group of patients. Lupus anticoagulant was detectable in 17 of 67 (25%) patients tested. VOD occurred in 80 of 102 (78%) aCL-positive patients comprised of 17 (16.7%) with systemic venous VOD or pulmonary embolism; 27 (26.5%) with cerebral VOD: 11 (10.8%) with systemic arterial VOD; 3 (2.9%) with coronary thrombosis; and 5 (4.9%) with visceral venous or arterial VOD. Of the 19 obstetric patients with positive aCL, 17 (89%) had at least one unexplained fetal loss and 8 of the 17 (47%) had multiple or recurrent fetal losses. Twelve (11.7%) of the 102 patients met the ACR criteria for systemic lupus erythematosus (SLE). Additionally, 12 (11.7%) patients were identified as nonSLE or undifferentiated connective tissue disease (CTD). The remaining 78 (76%) had no known underlying disease (primary antiphospholipid syndrome). We conclude that IgG and IgM aCL with or without lupus anticoagulant are associated with diverse types of VOD but cerebral VOD appears predominant. aCL-associated unexplained VOD occurs frequently in patients without evidence of CTD-65 of 80 (81%) in our series. Testing for aCL is essential for identifying patients with unexplained VOD, and it should be performed in prospective clinical studies of such patients to better define the pathogenic role of aCL in the natural history of unexplained VOD.


Occurrence of reactions, their diagnosis and management in leprosy patients treated with multidrug therapy; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

This paper reports on reactions in leprosy patients who were treated with multidrug therapy (MDT) in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Only those reactions which occurred in patients who had not been treated with dapsone before MDT and which required treatment with prednisolone were included. Until the end of the second year of MDT a reversal reaction had been diagnosed in 43.6% of 266 borderline lepromatous (BL) patients and in 19.2% of 109 lepromatous leprosy (LL) patients, and an erythema nodosum leprosum (ENL) reaction in 2.7% and 11.1% of the patients, respectively. The reversal reactions were observed in 4.9% of the BL patients and in 0% of the LL patients at the time of diagnosis of leprosy, in 26.3% and 12.8% of the patients during the first year of MDT, and in 12.4% and 6.4% during the second year of MDT. ENL reactions were seen in 0.8% of BL patients at diagnosis, 1.1% in the first year and 0.8% in the second year and 2.8% at diagnosis, 5.5% in the first year, and 2.8% in the second year for LL patients. During a 3 1/2-year period, a total of 405 reactions were diagnosed among multibacillary (MB) patients on MDT; 365 of these reactions (90.1%) were reversal reactions and only 40 (9.9%) were ENL reactions. The point in time of the reversal reactions showed that the risk of reversal reaction is highest during the first year of MDT. Thereafter there is a gradual decline, although reactions were still observed during the fifth year of MDT. A reversal reaction was diagnosed in 21.0% of 438 BT patients; in 3.4% of the patients the reaction was present at the time of diagnosis of leprosy; in 10.3% it occurred during MDT, and in 7.3% during the first year after release from MDT. During a period of 3 1/2 years a total of 183 reversal reactions were diagnosed among BT patients. The point in time showed a declining trend in the risk of reversal reaction after starting MDT. The risk is highest during MDT, followed by the first 6 months after stopping MDT. However, reactions, although few, still occurred during the fourth year after stopping MDT. The analysis of the results of prednisolone treatment in 161 patients who were treated for nerve function loss in the field showed that 142 patients (88.2%) regained complete or partial recovery of the nerve function(s), while no improvement was observed in 19 patients (11.8%).(ABSTRACT TRUNCATED AT 400 WORDS)


An analysis of current pulmonary embolism therapy.

The clinical diagnosis of venous thromboembolism, and especially pulmonary embolism, is inaccurate due to the nonspecific nature of presenting symptoms and signs which overlap with other frequently coexistent conditions. In recent years, the operating characteristics of more objective diagnostic strategies (ie, ventilation/perfusion lung scan, impedance plethysmography, venous compression ultrasound) have been more clearly defined. However, data regarding the natural history of pulmonary embolism primarily come from an era when objective diagnostic tests were unavailable which calls into question the validity of such data. Furthermore, despite a long experience there are few data regarding the clinical course of pulmonary embolism as currently treated with heparin/warfarin anticoagulation. Acute mortality correlates with the presence of systemic hypotension regardless of embolus size, suggesting that right heart functional reserve is the major determinant of acute survival. Long-term mortality has been attributed to underlying co-morbid disease. However, there are no studies of age- and sex-specific survival which control for co-morbid disease. Pulmonary embolism may be a marker for severe and imminently fatal co-morbid disease, or pulmonary embolism may add "excess mortality" over and above that co-morbid disease. Thrombolytic therapy clears pulmonary artery thrombus more rapidly than heparin and can rapidly restore normal right heart function. Current research aims to identify the ideal plasminogen activator and dosing regimen which maximizes thrombolysis and minimizes disturbance of hemostasis. In addition, more data regarding the natural history and clinical course of pulmonary embolism is needed to stratify patients into subsets with better or worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Intravascular hemolysis and acute renal failure following intermittent rifampin therapy.

Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported.


Preliminary study of cellular immunity to Mycobacterium leprae protein in contacts and leprosy patients.

Because of the good results obtained in the mononuclear cell (T lymphocyte) proliferative response in tuberculoid leprosy patients and family contacts and healthy Mitsuda-positive volunteers using Mycobacterium leprae soluble extract, we prepared different protein fractions from the soluble extract. We used the T-cell Western blot technique with separation by electrophoresis in SDS-polyacrylamide gels and transfer onto nitrocellulose membranes. Each unstained blot was converted into 18 fractions of antigen-bearing particles and tested with peripheral blood mononuclear cells from 21 individuals including Mitsuda-positive contacts, vaccinated lepromatous leprosy (LL) patients, borderline tuberculoid (BT) patients, and unvaccinated lepromatous patients. The stimulation index (SI) of the contacts was higher to the different fractions in comparison with the leprosy patients. They showed four peaks of stimulation to fractions 66-55, 45-29, 22-18, and 14 kDa. The second highest responders were BT patients, followed by vaccinated LL patients. The unvaccinated patients did not respond significantly to any of the fractions (SI less than 1).


The current role of surgical revascularization for combined renovascular hypertension and renal insufficiency.

The number of elderly patients presenting with the difficult combination of renovascular hypertension and deteriorating renal function is increasing. The majority of these patients have diffuse cardiovascular disease requiring careful preoperative evaluation and stabilization. Adequate control of hypertension and preservation of renal function frequently requires bilateral renal procedures in addition to aortic replacement in patients with significant aorto-iliac disease or aortic aneurysms. Early and late results continue to justify prompt surgical consultation and revascularization of patients with combined renovascular hypertension and renal insufficiency.


Accelerated atherosclerosis, aneurysmal disease, and aortitis: possible pathogenetic association with cocaine abuse.

Cocaine abuse and its association with vascular disease has become common in the medical literature. A variety of vascular problems have been described including neurovascular complications, cardiovascular complications, aortic dissection, venous thrombosis, mesenteric artery thrombosis, and renal infarction. The pathogenesis of these vascular complications has largely been related to increased adrenergic activity leading to vasospasm. Interaction of cocaine with the vascular endothelium resulting in thrombosis or vasculitis has also been suggested. We report a case of diffuse aneurysmal change of the aorta associated with an atypical inflammatory component consistent with possible cocaine induced vasculitis.


Sero-immunoreactivity of cloned protein antigens of Mycobacterium leprae.

Sera from 173 leprosy patients with various types of disease (tuberculoid = TT, borderline tuberculoid = BT, borderline lepromatous = BL, and lepromatous = LL), 12 intrafamilial contacts, and 40 normal healthy individuals were assayed in an indirect enzyme-linked immunosorbent assay (ELISA) using Mycobacterium leprae antigens. Recombinant clones carrying M. leprae antigens, namely, Y3184 (12 kDa), Y3179 (18 kDa), Y3164 (28 kDa), Y3180 (36 kDa), and Y3178 (65 kDa) and a cell sonicate from armadillo-derived M. leprae were used for the study. A high degree of reactivity with the 65-kDa, 36-kDa, and 28-kDa protein lysates was observed in most of the sera from multibacillary patients, with a low degree of positivity with 18 kDa and 12 kDa. Only a few sera from paucibacillary patients showed positive reactions. The majority of the contacts' sera tested showed no reactivity with these antigens.


Relationships between titers of antibodies immunoreacting against glycolipid antigens from Mycobacterium leprae and M. tuberculosis, the Mitsuda and Mantoux reactions, and bacteriological loads: implications in the pathogenesis, epidemiology and serodiagnosis of leprosy and tuberculosis.

Analysis of cell-mediated immunity [(CMI) as judged from the Mantoux, Fernandez, and Mitsuda reactions and the presence of granulomas in biopsy material] against humoral immunity (measurements of anti-PGL-I, PGL-Tb1, and SL-IV IgG and IgM antibody titers by ELISA) were performed in selected human populations. The investigations yielded data indicating that humoral (B-cell) responses preceded protective CMI in both tuberculosis and leprosy. The B-cell responses were unrelated to (unfavorable) cell-mediated delayed-type hypersensitivity (DTH). Notwithstanding the difficulty in inferring sequential events from studies in humans, it was shown that in humoral responses there was an initial rise of specific IgM immunoglobulins that switched afterward to IgG production during subclinical tuberculosis and leprosy infections. In patent tuberculosis disease the IgM-to-IgG switch was observed in the majority of patients; in patent leprosy disease the switch was impaired in the majority of patients. The clinical, immunological, and laboratory data indicated that the B-cell responses were suppressed as protective CMI was re-established in the patients during the protracted subclinical infection. According to the data, the diagnosis of subclinical tuberculosis and leprosy may be accomplished using ELISA. The yearly risk of tuberculosis in apparently healthy persons but with significant antibody titers was estimated at 44%; the yearly risk for leprosy has not yet been established. The clinical, epidemiologic, and diagnostic implications of these findings are discussed.


Human phagocyte respiratory burst by Mycobacterium bovis BCG and M. leprae: functional activation by BCG is mediated by complement and its receptors on monocytes.

We have measured the role of serum components on two parameters of the phagocytosis reaction: a) the chemiluminescence (CL) response associated with the oxidative respiratory burst in response to Mycobacterium bovis BCG and M. leprae, and b) the uptake of these two mycobacteria by healthy human monocytes. Pre-incubations of fresh or heat-inactivated serum or serum containing EGTA or EDTA indicate that these two mycobacteria activate the alternative complement pathway. Monoclonal antibodies against CR1 and CR3 inhibit the responses of M. bovis BCG and M. leprae, demonstrating that complement receptors mediate the phagocytosis of these two mycobacteria. Thus, complement and its receptors on the surface of the monocytes (CR1 and CR3) are important in the functional activation of phagocytosis of M. bovis BCG and M. leprae.


Isolation of cultivable mycobacteria from feces and lungs of armadillos infected with Mycobacterium leprae.

In the past, no cultivable mycobacteria were isolated from armadillos captured in the state of Florida, U.S.A. But recent findings of acid-fast bacilli (AFB) in the lungs of armadillos infected with Mycobacterium leprae prompted us to undertake this study to determine the correlation between systemic leprosy infection and the occurrence of cultivable mycobacteria in the lungs and stools of these animals. No AFB could be isolated from noninfected animals. Seventy percent of the infected animals developed disseminated infection, but no cultivable mycobacteria were isolated from their livers and spleens. However, cultivable mycobacteria were isolated from the lungs and stools of a large number of armadillos showing disseminated infection. The most common among these were M. gordonae, M. fortuitum, and M. avium. There was a close correlation between the development of disseminated leprosy infection and the occurrence of cultivable mycobacteria in their lungs and stools, perhaps due to the decline in the immune system in these animals in the later stages of infection.


Modulan grip-aids for leprosy patients.

Made-to-measure Modulan grip-aids were fitted to 755 articles for 155 patients with hand deformities due to leprosy. The acceptance of the grip-aids was, in general, good. No instance of contact dermatitis or skin irritation was reported. These grip-aids facilitated a normal grip with crippled hands, and thus considerably improved the quality of the patient's personal and working life. They increased the patient's self-esteem and self-confidence because he/she could handle everyday objects or tools without the help of others and could do his/her job--an important step toward social and economic rehabilitation.


Role of rifampin and clofazimine ointments in the treatment of leprosy.

The use of rifampin and clofazimine ointments alone and in combination over the patches of tuberculoid patients had a beneficial effect. In combination (rifampin and clofazimine), erythema, inflammation, and edema are considerably reduced. For some of the cases with a recent appearance of a patch, the patch completely disappeared. It is suggested that topical therapy with rifampin and clofazimine ointments would be economical and beneficial in tuberculoid leprosy.


[Study on mandibular position in occlusion during opening and closing movement in hemimandibulectomy patients--effect of difference of opening distance on mandibular position].

In the hemimandibulectomy patients the mandible is severely deviated and the occlusion is unstable, therefore the prosthodontic treatment for these patients is generally not successful. To investigate the stability of the mandibular position in occlusion of these patients, the differences of the range and the position of the mandible in occlusion between during the 5-mm opening and closing movement and during the 10-mm movement were analyzed three-dimensionally with the Jaw Movement Analyzer MM-JI-E. In this study, four hemimandibulectomy patients were selected as the subjects. The findings were as follows: 1. In three subjects, the range of the mandible in occlusion during the 10-mm opening and closing movement was larger than that during the 5-mm movement in almost all directions. On the contrary in one subject, the range of the mandible in occlusion during the 10-mm opening and closing movement was smaller than that during the 5-mm movement in almost all directions. 2. The relative relationship of the mandibular position in occlusion during the 10-mm opening and closing movement to that during the 5-mm movement varied in four subjects. In one subject, the mandible rotated horizontally towards the outside and moved upward. In another subject, the mandible rotated horizontally towards the inside and moved downward. In the other subject, the mandible moved inward and upward. In the other subject, the mandible moved outward and downward.


[Clinical and microbiological study of factors determining effective scaling and root planing].

The aim of the present study was to monitor longitudinally the clinical and microbiological parameters after root debridement in order to determine the factors affecting successful and unsuccessful results. Nine patients with moderate and severe periodontitis participated. Four sites of single root with over 5-mm periodontal pockets in each quadrant were selected. The oral hygiene was controlled in all patients, then root debridement was performed without anesthesia at the three sites of the quadrants every two weeks during eight weeks. The clinical parameters consisted of plaque index, gingival index, probing depth, clinical attachment level, bleeding on probing, tooth mobility and the value of gingival crevicular fluid (GCF). The microbiological parameters such as percentages of cocci, motile rods, non-motile rods and spirochetes and the number of microorganisms were examined and the percentages of black pigmented Bacteroides (BPB) and Actinobacillus actinomycetemcomitans as well as the number of anaerobic colonies were counted. The results demonstrated that a reduction in the probing depth was observed in all sites except four. The successful sites clinically showed a decrease of the probing depth and GCF value and, microbiologically, reduced percentages of the spirochetes and BPB. The results indicated that the decrease of the probing depth and GCF under 50 Periotoron units in coincidence with the bacterial reduction can be used to determine the successful response of root debridement.


[Anatomical observations on the attachment of human temporalis and masseter muscles].

It is very important for orthodontics to investigate the bone remodeling pattern in the area of the attachment of the masticatory muscles induced by the changing muscular function. In the present study, the insertion pattern of Sharpey's fibers and the bone structure are comparatively studied on the temporalis and the masseter muscles macroscopically, light microscopically and electron microscopically, respectively. The following results are obtained: 1) The periosteum on the squamous part of the temporal bone is thinner, while the one on the lower ridge of the zygomatic arch is relatively thicker. 2) The fine and loose Sharpey's fibers are found mostly on the squamous part of the temporal bone, while the ones on the lower ridge of the zygomatic arch are relatively coarse and dense. 3) Comparing with the squamous part of the temporal bone, the fibrous bone is thinner and also few reversal lines and resting lines are observed at the lower ridge of the zygomatic arch. These findings seem to prove the fact that the bone remodeling proceeds frequently within the limited narrow area. These differences are directly due to the differences of the anatomical site and the muscular function.


[Histological observations on structure of endomysium, perimysium and epimysium of lateral pterygoid muscle in rat].

To understand the muscle as a locomotorium, I observed the structure of the connective tissue sheaths (the endomysium, the perimysium and the epimysium) in the mature rat lateral pterygoid muscle. The following results were obtained using the macroscopy and light and electron microscopy. The lateral pterygoid muscle consists of two parts. The superior head originates from the basisphenoid and is mainly inserted into the articular disk and capsule. The inferior head originates from the lateral pterygoid processus and is mainly inserted into the condylar processus of the mandible. The perimysium is thick and bound the fasciculus secondarily as sheaths near the insertion of the superior head. The collagenous fibers are very fine in the endomysium. The collagenous fibers that make the connective tissue sheaths arrange on a skew against the muscle fibers, but parallel around the origin and the insertion. It seems that the connective tissue sheaths in the rat lateral pterygoid muscle, in view of the morphology, retain the forms of fasciculus, act as the runways for the muscle fibers in time of expansion and contraction and offer spaces for the attachment of the muscle fibers.


[Fundamental studies on biological effects of dental metals--nickel dissolution, toxicity and distribution in cultured cells].

In an oral environment, minute amounts of constituent metals dissolve from the surfaces of restorations. The uptake of the metals through the mucosa may cause systemic or local effects. The purpose of this study was to investigate these effects and mechanisms, focusing on the nickel as a dental metal. A nickel-chromium dental casting alloy was stored in 3 immersion solutions for 4 weeks and the amount of nickel dissolved was measured. NiCl2 was administrated to the cultured medium to examine the cytotoxicity for HeLa cells and periodontal ligament-derived cells as well as the nickel distribution in the HeLa cells. The results were as follows: 1. The amounts of nickel released from the alloy were 1.2 micrograms/cm2 (human saliva), 2.0 micrograms/cm2 (PBS (-)) and 2.5 micrograms/cm2 (MILLI-Q water). 2. 3.0 mM NiCl2 showed a large cytotoxicity resulting in the cell growth rate and morphological changes. 3. Incubated for 72 hours in 0.15 mM NiCl2, the amount of nickel in the 10(6) cells was 20 ng. After 24 hours of incubation with NiCl2, and the following 72 hours without NiCl2, the amount of nickel had decreased, but 30% still remained. 4. Incubated for 72 hours in 0.15 mM NiCl2, 65% of the nickel in the cells was bound by the soluble fraction. These results suggest that nickel released from the oral prosthesis may be sequestered for a long term in the cells and possibly causes some effects.


[Histological study of tissues surrounding an overloaded mandibular apatite implant and its antagonist teeth at three months].

The objective of this study is to compare the degree of the occlusal-bearing ability of 2-piece apatite implant to that of natural dentition. It is conducted by placing implants at M2 and M2 areas of adult monkey. Four months later, the occlusal vertical dimension was raised to apply the occlusal force only on the implants by inserting connected crowns on M3M2M1 and M1M2M3. Three months after loading, the tissues surrounding the implants and the antagonist teeth were histologically examined. The antagonist teeth: The connected antagonist teeth show much bone resorption on the inner surface of the alveolar wall and the roots are partly in direct contact with the bone and intruded. Implant: 1. Due to the resorption from extraction, enhanced remodeling is seen in the compact bone of the experimental site. The degree of remodeling is higher toward the coronal direction. 2. Realigned functionally oblique toward the implant, thickened trabeculae, of both the lamellae and woven bone, supported the implant. 3. Bone formed widely on the buccal and lingual surfaces of the compact bone near the implant. In the areas of close to the direct contact of the implant to the compact bone, remodeling with osteon realignment in the axial direction was observed. 4. Most embedded surfaces of the implant were covered and bound to the bone.


[Masticatory training with chewing gum on young children].

Mastication is a developmental function. It matures through learning experiences. The biting force is one of the components of masticatory function. The biting force increases with age. During the developmental stage, it is believed feasible to enhance the maturation of the masticatory function by increasing the biting force. The previous results of masticatory training for adults and school children had revealed 20% to 30% increase of the biting force. In this study, masticatory training with specially fabricated chewing gum for young (preschool) children was performed. The subjects were 5 males and 5 females from 3 years old to 5 years old. These children were instructed to bite on the chewing gum for 5 minutes, 2 times a day, for 3 months. The results show that there was a 94% average increase of biting force after 3 months of training. It was also noted that the rate of the increase of the biting force was remarkable during the first month of training.


[Studies on dimensional accuracy of working casts made by various impression techniques--influence of undercuts on dimensional accuracy].

The purpose of this research was to evaluate the clinical acceptability of various impression techniques by comparing the dimensional accuracy of their working casts. An original metallic model was designed for this experiment. It has reference points to overlap and compare the master model and the working casts for measuring their dimensional accuracy under the same condition. The amount of distortion in each area of the working casts was examined by the measuring points within the model. The master model simulated an abutment for a full veneer crown with undercuts between the adjacent teeth. It was planned so that the amount of undercuts and distances between the adjacent teeth could be changed. As a result, a small distortion of the working casts due to the undercuts was observed by the technique using an individual tooth tray and polysulfide rubber base impression material. There was no significant dimensional change in the working casts made with silicone rubber base material. For the working casts made by hydrocolloid-alginate combination technique, the dimensional change was greater and distortion was observed in the abutment cast when the undercuts of the adjacent teeth were great. However, the distortion was less when the undercuts were small.


Nitric oxide production by tumor targets in response to TNF: paradoxical correlation with susceptibility to TNF-mediated cytotoxicity without direct involvement in the cytotoxic mechanism.

Tumor necrosis factor (TNF) is selectively cytotoxic for some tumor cells in vivo and in vitro. We determined whether TNF-mediated cytotoxicity for TNF-sensitive tumor targets was related to TNF-stimulated production of NO by the tumor cell itself. We found that a cell line that was sensitive to TNF-mediated cytotoxicity produced NO in response to TNF as measured by the accumulation of nitrite in the supernatants of TNF-stimulated cells. Production of NO in response to TNF was inhibited by the competitive substrate inhibitor, NG-monomethyl-L-arginine (NMMA). The kinetics of NO production in response to TNF indicated that most of the NO was produced during the first 24 h and peaked after 48 h of culture and that TNF-stimulated NO production was dose dependent. TNF-resistant cell lines produced less NO than a TNF-sensitive cell line, and the amount of nitrite produced correlated with the relative sensitivity of each cell line to TNF-mediated cytotoxicity. In addition, recombinant interferon-gamma augmented the amount of NO produced in response to TNF by both sensitive and resistant cells and correspondingly enhanced the susceptibility of resistant cells to TNF cytotoxicity. Both sensitive and resistant cells were sensitive to NO, however, in that NO generated exogenously by culture in the presence of sodium nitroprusside was cytotoxic for both sensitive and resistant cells in a dose-dependent manner. We were unable, however, to demonstrate directly a role for NO in TNF-mediated cytotoxicity as NMMA- and arginine-free media provided little protection from TNF-mediated cytotoxicity. We tentatively conclude that the ability of adherent murine tumor cells to produce nitric oxide in response to TNF correlates directly with their level of sensitivity to TNF-mediated cytotoxicity, although NO thus produced appears not to be directly involved in the cytotoxic mechanism.


Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2.

Senescent human neutrophils undergo programmed cell death (apoptosis), leading to their recognition and phagocytosis by mature macrophages. At inflamed sites in vivo these processes may represent a neutrophil removal mechanism with the potential to limit the histotoxic capacity of these cells. Phagocytosis can provoke marked proinflammatory responses by macrophages. A macrophage proinflammatory response to the ingestion of apoptotic neutrophils would limit the efficacy of this neutrophil removal mechanism as a component of inflammatory resolution. In the present study we examined two macrophage proinflammatory responses; secretion of the granule enzyme N-acetyl-beta-D-glucosaminidase (NAG) and release of the membrane lipid-derived inflammatory mediator thromboxane A2 (TxA2, measured as TxB2). By contrast with the marked release of NAG and TxB2 elicited by phagocytosis of control particles (opsonised zymosan and immunoglobulin G-coated erythrocytes), macrophage ingestion of apoptotic neutrophils resulted in minimal release of NAG and no release of TxB2; indeed, there was a small depression of TxB2 release that was not due to a toxic effect of neutrophil uptake because macrophages ingesting apoptotic neutrophils retained marked TxB2 responses to subsequent stimulation with opsonised zymosan. Furthermore, there was significant TxB2 release in response to macrophage phagocytosis of apoptotic neutrophils that had been coated with opsonic serum, demonstrating that the lack of macrophage response was determined by the mechanism of recognition rather than the properties of the apoptotic particle itself. These observations are consistent with the hypothesis that macrophage clearance of senscent neutrophils undergoing apoptosis is an injury-limiting mechanism that favors resolution rather than persistence of the inflammatory response and are consistent with observations that the waves of apoptotic cell removal seen in embryological removal and thymic involution do not trigger an inflammatory response.


Constitutive production of PAI-II and increased surface expression of GM1 ganglioside by peripheral blood monocytes from patients with AIDS: evidence of monocyte activation in vivo.

To characterize the activation state of monocytes during human immunodeficiency virus (HIV) infection, peripheral blood monocytes (PBMs) from patients with acquired immunodeficiency syndrome (n = 10) and from healthy controls (n = 10) were cultured for 4 days. Monocyte culture supernatant (MCS) was collected daily, and levels of urokinase (UK) inhibitor PAI-II, a product of activated monocytes, released into MCS were determined (fibrin plate assay). To examine the activation state of PBMs independently, expression of GM1 ganglioside on PBMs from patients with AIDS (n = 9), patients with AIDS-related complex (ARC) (n = 8), HIV+ asymptomatic patients (n = 6), and HIV- healthy controls (n = 11) was determined (flow cytometry; living cells in suspension). Data are expressed as percent inhibition of UK, or as percent total cells. Patients' MCS collected on days 1-4 of culture contained similar levels of PAI-II because it inhibited UK in similar fashion (70-90%). In contrast, MCS from healthy controls, collected after 2 days, had decreased ability to inhibit UK (15-50%) and thus contained lower levels of PAI-II. Monocyte activation, measured by increased expression of GM1 ganglioside on PBM surfaces, directly correlated with the progression of HIV infection into the development of AIDS, since the order of magnitude of GM1 ganglioside expression on PBMs was AIDS greater than ARC greater than HIV+ asymptomatic = healthy controls. Our data indicate that PBMs from patients with AIDS are constitutively activated and suggest that activation directly correlates with disease progression.


Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation.

Blockade of phagocytosis and selective elimination of macrophages (m phi s) are generally accepted procedures for gaining knowledge about the function of m phi s in vivo. This study demonstrates that intravenous injection of gadolinium chloride (GdCl3) not only blocks phagocytosis by rat liver m phi s (Kupffer cells) but also selectively eliminates the large m phi s situated in the periportal zone of the liver acinus. Repopulation of m phi s starts at 4 days after injection. During repopulation, m phi s are less vulnerable to GdCl3. When repopulation is complete, the new m phi s show the same vulnerability as the original ones. Splenic m phi s are less vulnerable to GdCl3 because only some of the red pulp m phi s transiently disappear. The white pulp m phi s are not affected. Repopulation occurs sooner than in liver. These results indicate that administration of GdCl3 is a suitable approach to studying the in vivo function of large Kupffer cells.


Macrophage inflammatory proteins MIP-1 and MIP-2 are involved in T cell-mediated neutrophil recruitment.

Mice intraperitoneally (i.p.) infected with Mycobacterium bovis bacille Calmette-Guérin (BCG) respond to an i.p. challenge with mycobacterial antigen with an acute and extensive accumulation of neutrophils. This influx was not mimicked by the inoculation of recombinant interferon-gamma (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha). The antigen-induced recruitment of neutrophils was not affected by coinoculation of anti-IFN-gamma antibodies, was enhanced by anti-TNF-alpha antisera, and was significantly reduced by antisera against macrophage inflammatory proteins MIP-1 and MIP-2. The latter two sera had no additive effects. We hypothesize that mycobacteria-specific T cells are triggered by antigen to secrete MIP-1 and MIP-2, which directly mediate, at least partly, the influx of neutrophils that takes place in this model.


Levamisole causes differential cytokine expression by elicited mouse peritoneal macrophages.

Thioglycolate-elicited peritoneal macrophages from normal C57B1/6J mice were examined in vitro for bacterial lipopolysaccharide (LPS)-stimulated interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF) production. Macrophages from mice administered a single oral dose of levamisole (3 mg/kg) 1 to 4 days prior to macrophage harvest demonstrated a twofold enhancement of IL-1 production compared to vehicle-treated mice. In contrast, IL-6 production and TNF production by the same macrophages were inhibited up to 36 and 62%, respectively, compared to production by macrophages harvested from vehicle-treated mice. Similar results were observed when IL-1 production and TNF production were followed in peritoneal exidate cells directly stimulated with levamisole in vitro. The ex vivo LPS-stimulated IL-1 production was enhanced 4 days after macrophage elicitation, whereas TNF and IL-6 production returned to baseline by 72 h after macrophage recruitment and augmentation. No evidence could be found for the presence of inhibitors of TNF or IL-6. The specificity of the IL-1, IL-6, and TNF bioactivities was demonstrated by neutralization with specific antisera. Immunoprecipitation studies of supernatants from biosynthetically labeled macrophages also revealed augmented IL-1 production and decreased IL-6 and TNF, indicating that levamisole may have affected cytokine production at the translational level. Kinetics studies revealed that ex vivo release of IL-6 and TNF by macrophages from levamisole-dosed mice was delayed compared to production of these cytokines by macrophages harvested from mice given vehicle only. The results may explain, in part, the reported ability of levamisole to ameliorate cases of rheumatoid arthritis or other autoimmune and inflammatory diseases by affecting the relative levels of cytokines produced by macrophages recruited to sites of injury, which are associated with inflammation and acute-phase protein synthesis.


Oscillations in a model of repression with external control.

A mathematical model for control by repression by an extracellular substance is developed, including diffusion and time delays. The model examines how active transport of a nutrient can produce either oscillatory or stable responses depending on a variety of parameters, such as diffusivity, cell size, or nutrient concentration. The system of equations for the mathematical model is reduced to a system of delay differential equations and linear Volterra equations. After linearizing these equations and forming the limiting Volterra equations, the resulting linear system no longer has any spatial dependence. Local stability analysis of the radially symmetric model shows that the system of equations can undergo Hopf bifurcations for certain parameter values, while other ranges of the parameters guarantee asymptotic stability. One numerical study shows that the model can exhibit intracellular biochemical oscillations with increasing extracellular concentrations of the nutrient, which suggests a possible trigger mechanism for morphogenesis.


Dynamic models of infectious diseases as regulators of population sizes.

Five SIRS epidemiological models for populations of varying size are considered. The incidences of infection are given by mass action terms involving the number of infectives and either the number of susceptibles or the fraction of the population which is susceptible. When the population dynamics are immigration and deaths, thresholds are found which determine whether the disease dies out or approaches an endemic equilibrium. When the population dynamics are unbalanced births and deaths proportional to the population size, thresholds are found which determine whether the disease dies out or remains endemic and whether the population declines to zero, remains finite or grows exponentially. In these models the persistence of the disease and disease-related deaths can reduce the asymptotic population size or change the asymptotic behavior from exponential growth to exponential decay or approach to an equilibrium population size.


Disease transmission models with density-dependent demographics.

The models considered for the spread of an infectious disease in a population are of SIRS or SIS type with a standard incidence expression. The varying population size is described by a modification of the logistic differential equation which includes a term for disease-related deaths. The models have density-dependent restricted growth due to a decreasing birth rate and an increasing death rate as the population size increases towards its carrying capacity. Thresholds, equilibria and stability are determined for the systems of ordinary differential equations for each model. The persistence of the infectious disease and disease-related deaths can lead to a new equilibrium population size below the carrying capacity and can even cause the population to become extinct.


Rapidly converging numerical algorithms for models of population dynamics.

We propose algorithms for the approximation of the age distributions of populations modeled by the McKendrick-von Foerster and the Gurtin-MacCamy systems both in one- and two-sex versions. For the one-sex model methods of second and fourth order are proposed. For the two-sex model a second order method is described. In each case the convergence is demonstrated. Several numerical examples are given.


Application of computerized exercise ECG digitization. Interpretation in large clinical trials.

The authors report on a semiautomated program that incorporates both visual identification of fiducial points and digital determination of the ST-segment at 60 ms and 80 ms from the J point, ST slope, changes in R wave, and baseline drift. The off-line program can enhance the accuracy of detecting electrocardiographic (ECG) changes, as well as reproducibility of the exercise and postexercise ECG, as a marker of myocardial ischemia. The analysis program is written in Microsoft QuickBASIC 2.0 for an IBM personal computer interfaced to a Summagraphics mm1201 microgrid II digitizer. The program consists of the following components: (1) alphanumeric data entry, (2) ECG wave form digitization, (2) calculation of test results, (4) physician overread, and (5) editor function for remeasurements. This computerized exercise ECG digitization-interpretation program is accurate and reproducible for the quantitative assessment of ST changes and requires minimal time allotment for physician overread. The program is suitable for analysis and interpretation of large volumes of exercise tests in multicenter clinical trials and is currently utilized in the TIMI II, TIMI III, and BARI studies sponsored by the National Institutes of Health.


Conduction of early afterdepolarizations in sheep Purkinje fibers and ventricular muscle. An in vitro arrhythmia model.

To establish an arrhythmia generator model, a double-chambered bath was used in which sheep Purkinje fibers (PF) and ventricular muscle (VM) were placed. The conduction patterns of early afterdepolarization-induced triggered activations (TAs) were examined between normal segments bathed in unmodified Tyrode solution and abnormal segments bathed in ethylenediaminetetraacetate (3.3-5.0 mmol). Three types of preparations were used: PF-PF (n = 10), VM-VM (n = 5), and PF-VM (n = 13). Two types of spontaneous TAs appeared. One type was conducted to normal segments, inducing activations over the entire preparation, while the other type was not conducted. The conducting TAs had significantly more rapid mean dV/dt, larger amplitude, and higher peak transmembrane voltage as compared to nonconducting TAs. While conduction occurred in all PF-PF, VM-VM, and PF-VM preparations, conduction of TAs from abnormal segment VM to normal segment PF was impaired. A low plateau resulting from electrotonic transmission of depolarizing current from abnormal segments was recorded in normal segments near the border. This low plateau probably facilitated the transmission of TAs. In addition to spontaneous TAs, stimulated or spontaneous action potentials from NL were conducted to the not yet fully repolarized ABN and induced activations resembling TAs. These results may be relevant to clinical arrhythmias due to action potential prolongation. The arrhythmia may occur directly as a result of triggered activity or indirectly via slow conducting TAs, creating the possibility for reentry. This type of model may be useful for intervention studies, for example, by identifying agents that block abnormal segment to normal segment conduction.


Discrimination between myocardial infarct and ventricular tachycardia patients using magnetocardiographic trajectory plots and iso-integral maps.

Magnetocardiograms were recorded from 30 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 ventricular tachycardia (VT) patients. Discrimination between the groups was affected by iso-integral magnetic field mapping (MFM) and trajectory plotting of MFM extrema. Iso-integral MFM for the QRST, QRS, and ST-T intervals was created for each test group member. A polarity score, based on the number of extrema features present, was assigned to each iso-integral MFM. Differences in group mean integral of QRST map polarity scores were significant (p less than 0.05) between MI and N, between VT and N (p less than 0.005), and between MI and VT (p less than 0.05) subjects. integral of ST-T map polarity scores were significantly (p less than 0.0001) different between VT and N and between MI and VT (p less than 0.001) subjects. Discrimination between MI and VT patients, based on polarity score difference, was 56% accurate using integral of QRS maps and 73% accurate using integral of ST-T maps. For each subject, time-normalized MFM was used to construct trajectory plots of the maxima and minima in the QRS and ST-T intervals. Discrimination between MI and VT patients was based upon intergroup differences in fragmented trajectory plots. When the number of discrete trajectories and/or the total number (F) of trajectory points at which discrete trajectories coexist were considered, QRSmin trajectory plots were significantly (p less than 0.05) different for VT and N, but not for MI and N subjects. The significant (p less than 0.05) difference between MI and VT trajectory plots enabled 76% accuracy for MI and VT identification. ST-Tmax trajectory plots show significantly (p less than 0.0001) higher F values for VT patients facilitating accurate (87%) discrimination between MI and VT patients. These results suggest that the abnormalities of repolarization processes, displayed by MFM as multipolar integral of ST-T maps and/or as fragmented trajectory plots of ST-T extrema, may be useful indicators of the arrhythmia substrate/processes that characterize VT and vulnerable MI patients.


Localization of accessory pathways in Wolff-Parkinson-White syndrome by high-resolution magnetocardiographic mapping.

Fifteen patients with Wolff-Parkinson-White syndrome were studied with standard 12-lead electrocardiogram, invasive electrophysiologic study, and high-resolution magnetocardiographic (MCG) mapping. In addition, intraoperative epicardial mapping was performed in seven surgically treated patients. The MCG characteristics of ventricular preexcitation for different locations of the atrioventricular accessory pathways were described in terms of morphology and field patterns. Three mathematical source models in semi-infinite conducting space were used for localization computations: the current dipole model, the truncated current multipole model and the magnetic dipole model. Finally, the localization results of MCG and invasive mappings and electrocardiograms were compared. The mean three-dimensional distance between the localization results obtained from MCG maps and electrophysiologic study was 3.9 cm for the magnetic dipole model, 4.8 cm for the truncated current multipole model, and 7.3 cm for the current dipole model. The corresponding distances in the seven intraoperatively mapped cases were 2.3 cm for the magnetic dipole model, 5.2 cm for the truncated current multipole model, and 6.3 cm for the current dipole model. In conclusion, noninvasive MCG mapping may significantly contribute to the invasive catheter mapping for optimal preoperative localization of preexcitation site and atrioventricular accessory pathways in Wolff-Parkinson-White syndrome.


Giant negative U waves in a patient with uncontrolled hypertension and severe hypokalemia.

A 66-year-old woman with a long history of hypertension had an electrocardiogram with giant negative U waves in left precordial leads despite hypokalemia. This seems to be the first report of giant negative U waves induced by uncontrolled hypertension with hypokalemia. The occurrence of negative U waves in the presence of profound hypokalemia is an important observation because it masks the electrocardiographic manifestation of hypokalemia.