The inhibitory action of ethanol on the gastric mucosa and its interaction with the vagus in rats.

The influence of systemic ethanol and/or the vagus on ionic secretion and on glandular mucosal blood flow (GMBF) was studied in an ex-vivo gastric chamber preparation in rats. Sub-diaphragmatic vagotomy decreased H+ secretion and Na+ outflux from the gastric mucosa. Subcutaneous injection of 50% ethanol significantly potentiated these responses, but not the concentrations of 25% and 100%. The three doses of ethanol did not affect the secretion of both H+ and Na+ in vagus-intact animals. Ethanol, however dose-dependently reduced the GMBF in both vagus-intact and sub-diaphragmatic vagotomised rats, and the effect was greater in the latter-operated animals. It is concluded that vagus nerves greatly influence the secretion of both H+ and Na+ the gastric mucosa but the effect is unrelated to GMBF. Systemic ethanol reduced the secretion of these ions only in vagotomised animals, indicating the vagus could play a role in modulating the action of ethanol in the stomach.


The influence of age, sex and race on salivary kallikrein levels in human mixed saliva.

Variation in the level of salivary kallikrein in human saliva has been reported as a function of systemic conditions such as reduced salt intake and during the menstrual cycle. Higher levels of salivary kallikrein have been observed in subjects with tumors distant from the oral cavity when compared to control subjects. These studies have not evaluated factors, such as age, which might influence the concentration of glandular kallikrein in saliva. The purpose of the present study was to determine the variation of salivary kallikrein concentration as a function of age. Differences attributable to sex or race were also evaluated. Mixed saliva was collected from 114 subjects, ages 5-91, by paraffin stimulation. Samples were centrifuged and stored at -20 degrees C for subsequent analysis. Glandular kallikrein activity was assayed using D-ValylLeucylArginine-p-nitroanilide as the substrate. In a linear regression model which included sex, race, and age, levels only the factor of age had a significant effect on kallikrein levels. The p-value for the reduced model including only the factor of age was 0.0406 and the R-square was 0.038. Further analysis revealed that females did exhibit significantly higher kallikrein in individuals 40 years or older and that the effect of age appeared to be limited to females. It is concluded that both gender and age must be considered when evaluating salivary kallikrein changes in relationship to systemic disease.


In vitro effects of PAF on venous endothelial cell actin disposition.

Venous endothelial cells have been stained in vitro for the contractile protein actin, using an immunofluorescence technique. Semi-automated image analysis showed that treatment with platelet-activating factor (PAF 5 x 10(-7) M) caused elongation of endothelial cells and alteration in their actin-staining characteristics. These changes are prevented by the PAF antagonist BN52021 (1 x 10(-5) M and 1 x 10(-6) M) and the absence of extracellular Ca++. It is suggested that it is the resultant decrease in intracellular Ca++ levels which is responsible for preventing the effects of PAF.


Acute pulmonary toxicity of inhaled beta-1,3-glucan and endotoxin.

The number of inflammatory cells was studied in lung walls and airways after inhalation of endotoxin or beta-1,3-glucan. In the water unsoluble form, beta-1,3-glucan caused a delayed response in terms of a decrease in macrophages and lymphocytes in the lung wall, 1 to 7 days after exposure but no invasion of neutrophils into the airways. When solubilized in 0.02 N NaOH, the cell response was the same as that observed after exposure to endotoxin.


The effects of flurbiprofen on the passive transfer of adjuvant-induced arthritis.

The effect of flurbiprofen on the passive transfer of adjuvant-induced arthritis was studied to determine if flurbiprofen acted in the donor and/or recipient arms of this model. Groups of donor and recipient rats were treated with either placebo or flurbiprofen 4 mg/kg. Joint scores were markedly decreased in recipient rats treated with flurbiprofen irrespective of the whether donor animals were treated with placebo or flurbiprofen (p less than 0.01). There was also a moderate decrease in the ability of donor cells from rats treated with flurbiprofen to suppress the severity of arthritis (p less than 0.01); however, this effect was less marked than that seen in recipient animals. These data imply that flurbiprofen may act at multiple sites in adjuvant-induced arthritis, but the major site of action of flurbiprofen in this model is in the recipient animals.


Evidence that endogenous interleukin-1 is involved in leukocyte migration in acute experimental inflammation in rats and mice.

As a putative mediator of inflammation interleukin-1 has been implicated in the recruitment of leukocytes during the early stages of the inflammatory reaction. In the present report we have investigated the release of endogenous IL-1 in the rat zymosan pleurisy and in the mouse zymosan peritonitis. In both cases the release of the cytokine was maximal 4 hours after zymosan injection and appeared to be time-related to neutrophil migration into the inflammatory site. The effect of in vivo treatment with dexamethasone in rat pleurisy and with polyclonal anti-murine IL-1 beta antibody in mouse peritonitis was also assessed. The steroid reduced both cell migration and the release of IL-1-like activity as well as the formation of exudate and the release of eicosanoids. The anti-IL-1 beta serum inhibited selectively the number of neutrophil that migrated to the inflamed site (approximately 40%) and the IL-1 activity recovered in (approximately 70%) the exudate. In vitro incubation of the inflammatory exudate with polyclonal anti-murine IL-1 alpha or anti-murine IL-1 beta sera allowed the identification of the IL-1 species present. In the rat pleurisy IL-1 biological activity was mainly due to the alpha species, whereas IL-1 beta was the only species apparently present in the mouse peritoneal exudate.


Biological activity of prostaglandin E3 with regard to oedema formation in mice.

The biological activity of PGE3 with regard to oedema formation in mice was examined. Paw swelling was measured 30 minutes after injection of 10 microliters PGE2 or PGE3 into the plantar region of the hind paw. Doses investigated ranged from 1 ng-10 micrograms. Both PGE2 and PGE3 had substantial oedemogenic activity in this system.


Characterisation and pharmacological sensitivity of antigen arthritis induced by methylated bovine serum albumin in the rat.

The optimum conditions for the induction of antigen-induced arthritis in the rat have been studied. Two immunisations with methylated bovine serum albumin (mBSA) (0.5 mg) in Freund's complete adjuvant (FCA) containing 0.375 mg Mycobacterium tuberculosis followed by an intra-articular injection of mBSA (0.5 mg) led to the production of a chronic, erosive arthritis. The development of the arthritis was associated with the appearance of T lymphocytes and other inflammatory cells in the synovium. Male and female animals were equally susceptible to the disease. Prednisolone, indomethacin and methotrexate inhibited the development of the arthritis but ibuprofen and D-penicillamine were without any significant effect.


An investigation into the relationship between coal workers' pneumoconiosis and dust exposure in U.S. coal miners.

The National Study of Coal Workers' Pneumoconiosis (NSCWP) is a large, continuing epidemiologic study of the respiratory health of U.S. coal miners. By using information from the study, prevalence of coal workers' pneumoconiosis (CWP) was related to indexes of dust exposure obtained from research and compliance sampling data. Clear relationships between prevalences of both simple CWP and progressive massive fibrosis (PMF) and estimated dust exposure were seen. Additional effects independently associated with coal rank (% carbon) and age were also seen. Logistic model fitting indicated that between 2% and 12% of miners exposed to a 2-mg/m3 dust environment in bituminous coal mines would be expected to have Category 2 or greater CWP after a 40-yr working life; PMF would be expected for between 1.3% and 6.7%. The risks for anthracite miners appeared to be greater. There was a suggestion of a background level of abnormality, not associated with dust exposure, but increasing with age. Although there are certain weaknesses in the data used to derive these exposure estimates, the results are in general agreement with, but somewhat greater than, some recent findings for British coal miners.


[Sensitivity and specificity of the determination of IgE using chemiluminescence (CLA allergy test)].

We studied 80 patients. All patients underwent a thorough clinical evaluation, including a comprehensive study and physical examination of the ear, nose, throat and chest. Each patient underwent prick testing and a nasal provocation test. In addition, blood was drawn for the allergen-specific IgE test (RAST) and total serum IgE levels. We selected 11 allergens for this study: grass (Dactylis glomerata-orchard grass, Phelum pratense-Timothy grass, Lolium-raygrass), weeds (Chenipodium, Parietaria), tree (European olive), dog, cat, mites (D. pteronyssinus, D. farinae) and mould (Alternaria). To evaluate the efficiency, specificity and sensitivity of this method, test results obtained in our centre were compared to the clinical standard. Sensitivity is related to the lowest concentration of specific IgE detected by test method. Specificity is related to the antibody test's ability to detect the specific substance being measured without interference from related molecules. Chemiluminescent assay system (CLA) demonstrated a good balance between sensitivity and specificity and was consistent for the following allergens: D. pteronyssinus, D. farinae, Parietaria pollen and Gramineae pollena.


A theoretical model for respirator cartridge service life for binary systems: application to acetone/styrene mixtures.

A theoretical model, developed previously to assess respirator cartridge service life, was applied to various acetone/styrene binary assault systems. Experimental data, collected for several binary mixtures differing only with respect to the concentration of each of the two compounds, were interpreted in terms of the model. Styrene concentrations varied from 228 to 1578 ppm; the range of acetone concentrations was 92-985 ppm. The specific influence of the compound assault concentrations on respirator cartridge service life was carefully characterized, as break-through curves were generated for both acetone and styrene for each of several different binary systems. Specifically, experimental data for each system were used to determine values of the following theoretical parameters: k'1, tau 1, k'2, tau 2, and Am. These parameters were employed with the theory to generate complete theoretical breakthrough curves and to determine the time-dependence of the weight of each compound adsorbed by the respirator cartridge carbon bed. An interesting phenomenon observed for the acetone/styrene systems was the displacement (from the carbon) of previously adsorbed acetone molecules by styrene molecules. Acetone breakthrough was observed first in each of the systems studied. Following the onset of this breakthrough, the acetone breakthrough concentration was enhanced by the displacement of acetone from the carbon bed by the adsorption of styrene. The theoretical model accurately predicts both this enhancement and the associated breakthrough characteristics of styrene. In addition, the theory is capable of predicting the ratio of the number of displaced acetone molecules to the corresponding number of displacing styrene molecules. For these studies, this ratio ranged from 0.3 to 0.7. The service life of respirator cartridges exposed to acetone/styrene mixtures depends on the assault concentration of each compound and is significantly influenced (shortened) by the displacement phenomenon.


[Evaluation of the nasal provocation test in perennial allergic rhinitis. I. Rhinitis caused by mites].

Parametres of clinical usefulness of the two cutaneous tests, RAST and NPT, are analysed and compared with DPT in two series of patients. Our data show the efficacy of NPT in the diagnosis of allergic perennial rhinitis.


IgG subclass deficiencies and recurrent pyogenic infections, unresponsiveness against bacterial polysaccharide antigens.

In patients suffering from recurrent or chronic infections with encapsulated bacteria the humoral immune disorder of IgG subclass deficiencies is common (about 20%), yet insufficiently diagnosed because of the nonspecific symptomatology and the often unaffected levels of total immunoglobulin (Ig) isotypes. IgG subclass deficiency is correctly diagnosed by measurement of all four IgG subclasses. The IgG2-subclass deficiency is most frequent, often together with decreased IgG4- and/or IgA-levels. The IgG2-subclass deficiency is associated with a diminished immune response to (bacterial capsular) polysaccharide antigens. Although the anti-polysaccharide response is generally believed to be IgG2-restricted, a causal relationship between a decrease in IgG2 and disease is obscure. First, the precise meaning and contribution of IgG2 to the opsonization of encapsulated microorganisms is incompletely known. Second, several healthy individuals completely lack one or more isotype/subclasses due to (pseudo-) deletions of the genes, but still produce protective antibody titers in the residual Ig isotype or subclass. Third, young children mount protective titers of specific IgG1 antibodies against polysaccharides, whereas IgG2-subclass deficient children are prone to infection by encapsulated bacteria. In sum, decreases in IgG2 subclass levels may be merely epiphenomenal in a large group of patients who do not respond effectively to (bacterial) polysaccharides. New directions of investigation in order to obtain insight in the prevalence and pathogenesis of IgG subclass deficiencies are discussed.


Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits.

Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3 hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology].

To assess the immunoclinical effectiveness of a biological response immunomodulator, we used AM3 (glycophosphopeptide ), a glucomannan polysaccharide extracted from the cell wall of a strain of Candida utilis, in 20 children with asthmatic bronchitis. They received 2 envelopes (1 g) daily for 4 months. The results were compared with a control group of 20 untreated children with the same pathology. The following clinical and immunological parameters were assessed in all of them: cough, dyspnea, expectoration, frequency and intensity of the bronchospasm, time of administration of the symptomatic medication, and the delayed cutaneous cells response by means of the intradermal reaction of 5 antigens (Trichophyton, Candida albicans, tuberculin, E. coli and bacterial antigens). In the treated group, the immunoferon (AM3) reduced the symptoms, the intensity and frequency of the bronchospasm, and the symptomatic medication (table I, II and III). In basal conditions, the 40 children presented a state of 75% anergy; after 4 months of treatment, the treated group experienced a 45% decrease in their anergic situation, variation which was statistically significant when compared with the control group. In our 20 treated patients, AM3 behaved like and immunostimulant, improving the clinical situation and progress in patients with infectious respiratory disorders. We consider that the immunoferon constitutes a coadjuvant therapy to bacterial immunotherapy.


Use of fluidizing bed aerosol generators to establish a dust mixture of two substances at a fixed ratio for inhalation toxicity studies.

A method was developed to use two fluidizing bed generators to deliver a mixture of 1 mg cobalt + 15 mg tungsten carbide/m3 to an inhalation exposure chamber with the output from the cobalt generator split to provide the same cobalt concentration to a cobalt-only chamber. To provide a more uniform delivery of material and to minimize the amount of starting dust needed, a subsystem that produced timed bursts of compressed air was used to prevent the accumulation of dust along the aerosol transport tubes. The addition of an electrostatic precipitator placed in the exhaust lines reduced the amount of dust delivered to the high-efficiency particulate air filters, thereby reducing the number of filter changes.


Wasp sting anaphylaxis as a cause of death: a case report.

A case of death after anaphylactic reaction to a vespid is reported. The antecedent of the patient, the RAST and the RAST-Inhibition results and the geographical distribution of the vespids indicate that the responsible species was "Polistes dominulus". The pathologic finding supported that the cause of the death was an anaphylactic reaction without coexistence of any previous cardiovascular disease or other coexisting agent that could precipitate the fatal outcome.


Industrial hygiene and national health objectives for the year 2000.

Industrial hygiene can have a powerful effect on family, community, and environmental health in addition to its effect on occupational health. Contemporary industrial hygiene begins in the workplace, but its impact can spread and improve the health status of the nation in several ways. Thirteen objectives for industrial hygiene are presented in this report. Industrial hygienists should know what the objectives are, how the objectives are useful to their practice, and how they can help to achieve them to improve the health of Americans.


Long-term safety and efficacy of flecainide in the treatment of supraventricular tachyarrhythmias: the United States experience. The Flecainide Supraventricular Tachyarrhythmia Investigators.

Information about long-term safety and effectiveness is important for appropriate use of antiarrhythmic drug therapy. We report the results of an open-label, long-term (mean, 15 months) therapy extension for 66 patients with paroxysmal supraventricular tachycardia (PSVT) or atrial fibrillation (PAF) in whom short-term therapy in 2 controlled studies was deemed beneficial by both patient and investigator. Follow-up was accomplished by clinic visits and telephone calls. Results indicated excellent ongoing tolerance and safety. Only 3 (5%) of 66 patients discontinued therapy due to possible noncardiac adverse effects. Only 5 (7.6%) discontinued therapy due to inadequate clinical response. Only 1 discontinuation was ascribed to a worsening arrhythmia (increased frequency of sustained PAF). In PSVT patients, 75% of months were arrhythmia free; in PAF patients, 64% of months were attack free. No clinically significant laboratory, electrocardiographic, or physical abnormalities were ascribed to flecainide. Thus, the long-term safety and efficacy profile of the drug for treatment of PSVT and PAF is encouraging. This promising clinical experience is relatively small and so should be reinforced by larger patient trials in the future.


Long-term follow-up of patients with inducible supraventricular tachycardia treated with flecainide or propafenone: therapy guided by transesophageal electropharmacologic testing.

We report our experience with flecainide and propafenone therapy for inducible supraventricular tachycardias and paroxysmal supraventricular tachycardias due to atrioventricular (AV) nodal reentry or the Wolff-Parkinson-White syndrome. We performed an electropharmacologic test (ET) that consisted of first inducing a clinical arrhythmia by transesophageal atrial pacing (TAP) protocol. This was followed by intravenous drug administration and TAP reevaluation, either after acute intravenous administration or in oral steady-state. We used ET with flecainide and/or propafenone to study 2 groups of patients at least 3 years before the long-term clinical observation period. The first group was comprised of 58 patients with reciprocating tachycardias--due to AV node reentry in 17 (29.3%) and anomalous pathway in 41 (70.7%). Twelve (29.3%) of the latter had reciprocating tachycardias, 15 (36.6%) had atrial fibrillation, and 14 (34.2%) had both arrhythmias. During ET, flecainide was administered to 42 patients, and the ET was considered positive in 28 (66.7%). Propafenone was administered to 32 patients, with positive results in 15 (46.9%). In 15 patients, both flecainide and propafenone were tested, 8 receiving flecainide after a negative ET with propafenone, and 7 receiving propafenone after a negative ET with flecainide. In the first group, the ET was positive in 7 (87.5%), and in the second group, it was positive in 3 (42.9%). In a follow-up of 40.1 +/- 11 months, 38 (65.5%) patients had positive outcomes, 5 (8.6%) had to stop receiving the drugs because of side effects, 3 (5.2%) stopped because of inefficacy, and 12 (20.7%) dropped out.(ABSTRACT TRUNCATED AT 250 WORDS)


Flecainide in the Wolff-Parkinson-White syndrome.

The effects of flecainide on electrophysiologic parameters and arrhythmias in the Wolff-Parkinson-White syndrome were reviewed. Acute administration of flecainide blocks conduction across the accessory pathway in the anterograde direction in 40% and in the retrograde direction in 50% of cases and markedly prolongs refractoriness in the remaining cases. Flecainide has a lesser effect on refractoriness of the His-Purkinje system, atrium, ventricle, and atrioventricular node. Flecainide terminates atrioventricular tachycardia in greater than 80% of cases when given intravenously, and oral therapy prevents clinical recurrences in greater than 60% of cases, but may occasionally result in incessant tachycardia. Long-term efficacy is predicted by abolition of conduction across the accessory pathway or prevention of tachycardia induction at acute electrophysiologic testing. Concomitant administration of a beta-adrenoreceptor blocker results in greater long-term efficacy. Administered during preexcited atrial fibrillation, flecainide consistently slows the ventricular response and converts the majority of cases to sinus rhythm. Serious ventricular proarrhythmia is seen almost exclusively in patients with structural cardiac disease. Flecainide is a useful drug for the acute and chronic control of tachycardia in Wolff-Parkinson-White syndrome.


Effects of flecainide on atrial electrophysiology in the Wolff-Parkinson-White syndrome.

The effects of intravenous flecainide and propafenone (2 mg/kg) administered in random order were compared in 16 patients with Wolff-Parkinson-White syndrome. Both agents prolonged significantly the anterograde refractory period of the pathway and caused complete anterograde block in the pathway in 5 patients. Atrial fibrillation was not inducible in 7 patients following both agents. Both drugs prolonged the minimum pre-excited RR interval, but this effect was significantly greater after flecainide than after propafenone. At a pacing cycle length of 500 msec, the atrial effective refractory period was unchanged after flecainide, but the atrial monophasic action potential duration, and the atrial monophasic action potential duration of the earliest inducible atrial beat were significantly increased. These results suggest that rate-dependent prolongation of atrial repolarization does not occur following clinical intravenous doses of flecainide. The prolongation of the repolarization of ectopic beats may prevent induction of atrial arrhythmias and may also have an important role in the termination of atrial fibrillation.


Atrial fibrillation in the Wolff-Parkinson-White syndrome.

Atrial fibrillation in patients with Wolff-Parkinson-White (WPW) syndrome may lead to syncope, ventricular fibrillation, and sudden death. In a follow-up study of 241 patients with WPW syndrome in a relatively unselected population, 26 patients had documented atrial fibrillation (11%). These patients were followed up after 1-37 years (median 11 years; mean 15 years). During this period, 2 of 26 died suddenly. These 2 patients had the shortest RR interval during spontaneous atrial fibrillation (less than or equal to 220 msec), greater than or equal to 1 episodes of syncope, and a persistent delta wave in all available electrocardiograms. In comparison, sudden or tachycardia-related death was seen in 4 of the 241 patients. This difference is not statistically significant. Thus, atrial fibrillation of 26 patients with WPW syndrome was surprisingly well tolerated in our follow-up study with only 2 sudden deaths.


Flecainide acetate in the prevention of paroxysmal atrial fibrillation: a nine-month follow-up of more than 500 patients.

In order to assess efficacy, safety, and long-term tolerance of flecainide for the prevention of paroxysmal atrial fibrillation (PAF), 944 patients (555 male) were enrolled in an open multicenter study. All patients had had greater than or equal to 1 episodes of atrial fibrillation and were in sinus rhythm at the time of entry. The mean age was 65.3 +/- 11 years, and 43% of patients had no detectable heart disease. The mean daily dose of flecainide was 190 +/- 34 mg. Clinical examination, electrocardiogram (ECG) and 24-hour Holter monitoring were performed at entry into the study and on months 3, 6, and 9. Of the patients, 189 were lost to follow-up. Of the remaining 755 patients, 562 (74%) continued the treatment during the 9-month period and 193 (26%) dropped out. A total of 84 adverse effects were reported in 7.6% enrolled patients and in 9% of patients during follow-up, with treatment interruption in 50% of the cases. There were only 3 minor cardiovascular side effects, all leading to treatment discontinuation. No deaths in patients with recurrent PAF and no proarrhythmic events were reported. Flecainide appears to be effective in preventing PAF, with 65% of patients being arrhythmia-free after 9 months of treatment at a mean daily dose of 200 mg. Side effects were common, but clinically significant adverse events were infrequent.


Efficacy of flecainide for the reversion of acute onset atrial fibrillation.

The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation (AF) (present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min) was investigated. A total of 102 patients without severe heart or circulatory failure were randomized to receive either intravenous flecainide (2 mg/kg, maximum dose 150 mg; 51 patients) or placebo (51 patients) in a double-blind trial. Digoxin (500 micrograms intravenously) was administered to all patients who had not previously been receiving digoxin. The electrocardiogram was monitored continuously during the study. In 29 (57%) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 (14%) given placebo (chi square 18.9; p = 0.000013; odds ratio 8.3; 95% confidence interval 2.9-24.8). Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect. At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide group were in sinus rhythm whereas only 18 (35%) in the placebo group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67; 95% confidence interval 1.5-9.1). Significant hypotension, although short lived, was more common in the flecainide group. One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted. Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute pharmacologic conversion of atrial fibrillation and flutter: the role of flecainide, propafenone, and verapamil.

Efficacy and safety of intravenous flecainide (2 mg/kg body weight in 10 minutes), verapamil (10 mg in 1 minute), and propafenone (2 mg/kg body weight in 10 minutes) were investigated in 90 consecutive patients with atrial fibrillation (AF) or flutter (AFL). In the first 40 patients, flecainide and verapamil were evaluated; in the second 50 patients, flecainide and propafenone were compared, both in a single-blind randomized study design. The primary end point was sinus rhythm occurring within 1 hour after start of infusion. Sinus rhythm was attained in 32 of 37 patients (86%) with AF treated with flecainide and in 11 of 20 patients (55%) with AF treated with propafenone. In recent onset AF (less than or equal to 24 hours) conversion rates were 24 of 25 patients (96%) in the flecainide group and 8 of 14 patients (57%) in the propafenone group (p less than 0.05). Conversion of AFL occurred in only 1 of 8 patients (13%) in the flecainide-treated patients and in 2 of 5 patients (40%) treated with propafenone (difference not significant). Verapamil was almost ineffective, since only 1 of 20 patients (5%) responded within 1 hour. Time to conversion was 21 +/- 17 minutes in the flecainide group and 16 +/- 10 minutes in the propafenone group. QRS widening occurred in flecainide-treated patients (83 +/- 15 to 99 +/- 20 msec; p less than 0.001), but not after propafenone (83 +/- 11 to 86 +/- 12 msec). Significantly higher plasma levels were found in patients with conversion within 1 hour using propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)


Flecainide in quinidine-resistant atrial fibrillation.

Flecainide (100 mg twice daily) was used for prevention of paroxysmal atrial fibrillation (PAF) in 52 patients with frequent symptomatic attacks that were resistant or intolerant to quinidine (600-900 mg/day). Underlying heart disease was present in only 8 cases and left ventricular ejection fraction was always greater than 30%. No patient had had a myocardial infarction. Vagally induced PAF was clinically documented in 35 patients. Amiodarone, previously used and ineffective, was combined with flecainide in 33 patients. After 1-5.8 years of follow-up, complete disappearance of PAF was observed in 38 patients (73%). The success rate was slightly higher in patients with vagally induced PAF (p = 0.07). Extracardiac side effects necessitated withdrawal in only 3 cases. Permanent pacemaker was needed in 7 patients on amiodarone and flecainide because of excessive sinus bradycardia. Two patients, with previously documented atrial flutter, experienced presyncopal episodes of atrial flutter with 1:1 atrioventricular (AV) conduction and wide QRS complex. No death occurred during the follow-up. In this series, quinidine proved to be unsuccessful in 46 patients and it was withdrawn in 6. We concluded that flecainide is efficient and well tolerated for long-term prevention of PAF in patients resistant to quinidine. The possibility of 1:1 AV conduction during atrial flutter may suggest the use of verapamil or beta blockers in combination with flecainide in patients with previously documented atrial flutter.


Pharmacologic treatment of supraventricular tachycardia: the German experience.

Tachyarrhythmias that originate above the bifurcation of the bundle of His or in tissue proximal to it are classified as supraventricular tachyarrhythmias (SVTs). Primary treatment of SVT tries to influence the underlying disease. Symptomatic therapy is subdivided into drug therapy, electrotherapeutic tools (e.g., antitachycardia pacemakers, catheter ablation), and antiarrhythmic surgery. Antiarrhythmic agents that slow conduction and suppress premature beats are efficient for emergency and long-term treatment of SVTs. We evaluated some of the most relevant antiarrhythmic drugs in SVT, including propafenone, diprafenone, cibenzoline, sotalol, and diltiazem; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine, and flecainide are summarized. In 1990, the case load of supraventricular arrhythmias per physician in Germany was more than 30 patients seen per month. About 50% of them were treated with drug therapy; i.e., approximately 17 patients were treated with antiarrhythmic drugs per month per physician for supraventricular arrhythmias. The most important antiarrhythmic agents used in Germany are propafenone (40%), combination of quinidine and verapamil (23%), sotalol (12%), disopyramide (6%), flecainide (6%), and other (13%).


Performance status and outcome after coronary artery bypass grafting in persons aged 80 to 93 years.

Although coronary artery bypass grafting (CABG) effectively eliminates or diminishes symptoms of myocardial ischemia, the overall performance status and functional outcome in elderly patients undergoing CABG is poorly documented. Therefore, 86 consecutive patients aged 80 to 93 years undergoing isolated CABG were reviewed. Preoperative, intraoperative, and postoperative characteristics and pre- and postoperative performance status (Karnofsky score) were examined. Forty patients (47%) were women, and most patients had highly symptomatic coronary artery disease with class III or IV angina in 94% and unstable angina in 90%. Significant co-morbid disease was present in 49% of patients, and cardiac catheterization revealed left main or 3-vessel disease in 74% of patients. The rate of significant in-hospital complications was 29%, with infection in 14%, stroke in 9%, and respiratory failure in 8% being most frequent. Median performance status (Karnofsky score) improved from 20 to 70% (p = 0.0001) with 89% of hospital survivors being discharged home. Factors associated with failure to achieve a successful functional outcome at discharge were presence of 1 or more preoperative co-morbid conditions (p = 0.048), preoperative myocardial infarction within 7 days of operation (p less than 0.01), and postoperative low cardiac output (p less than 0.01). Survival at 30 days, 6 months, and 3 years were 90, 78, and 64%, respectively. These data demonstrate that CABG can be offered to selected elderly patients with acceptable morbidity and mortality, marked improvement in performance status, and an acceptable quality of life.


Exercise echocardiography after coronary artery bypass grafting.

Exercise echocardiography was used to assess the adequacy of regional myocardial perfusion in 125 patients who had undergone coronary artery bypass grafting. There were 108 men and 17 women (mean age 65 years) evaluated from 6 weeks to 16 years (mean 7 years) after surgery. Resting parasternal long- and short-axis and apical 4- and 2-chamber echocardiograms were recorded, digitized and stored. Maximal, symptom-limited upright treadmill exercise was then performed with continuous electrocardiographic monitoring. Repeat echocardiographic imaging and digitization were repeated within 1 minute of exercise termination. Resting and postexercise digitized echocardiograms were compared. A normal regional wall motion response to exercise consisted of improved segmental contraction and was used to predict uncompromised regional vascular supply. Unimproved or worsened segmental contraction after exercise was abnormal and was used as a predictor of regional vascular insufficiency. All patients underwent cardiac catheterization within 1 month after exercise testing. Regional coronary insufficiency was considered to exist when a segment's major vascular conduit exhibited greater than or equal to 50% luminal diameter reduction. Compared with the simultaneously acquired stress electrocardiogram, exercise echocardiography had superior sensitivity (98 vs 41%), specificity (92 vs 67%), positive predictive value (99 vs 91%), and negative predictive value (86 vs 12%) (p less than 0.001, 0.1, 0.01 and less than 0.001, respectively). In addition, exercise echocardiography correlated closely with the extent and regional distribution of compromised vascular supply. Exercise echocardiography is a highly sensitive, specific and accurate screening test for abnormal global and regional myocardial vascular supply in patients who have undergone coronary artery bypass grafting.


Normalization of impaired response of platelets to prostaglandin E1/I2 and synthesis of prostacyclin by insulin in unstable angina pectoris and in acute myocardial infarction.

The minimal inhibitory concentration of prostaglandin E1 (used as a probe for prostacyclin [PGI2]) needed to inhibit platelet aggregation (36 +/- 16 nM) in normal volunteers (n = 40) increased (64 +/- 30 nM) in patients (n = 46) with acute coronary artery disease. Bolus injection of insulin in 20 patients, 0.1 U/kg body weight 4 times a day (every 6 hours) for 7 days decreased the minimal inhibitory concentration of prostaglandin E1 from 64 +/- 30 to 26 +/- 12 nM (p less than 0.001). Twenty other patients who received only saline solution had no decrease in minimal inhibitory concentration of the prostanoid. The bolus injection of insulin also increased the plasma level of PGI2 (9 +/- 2 pM) two-fold in these patients (28 +/- 10 pM). Administration of aspirin inhibited the insulin-induced increase of plasma prostanoid level. Patients in the placebo group had no increase in plasma PGI2 level. The bolus injection of insulin administered only once to another group of patients (n = 6) demonstrated that the hormonal effects were maximally increased within an hour of insulin administration, and were directly related to the increased insulin level in plasma. These results indicated the feasibility of using physiologic quantities of insulin for controlling of platelet aggregation through resensitization of platelet response to prostaglandin and increased synthesis of PGI2 in vivo in acute coronary artery disease.


Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem. IV Diltiazem Study Group.

Diltiazem has electrophysiologic effects similar to those of verapamil. Its efficacy and safety in 4 doses for treatment of induced supraventricular tachycardia (SVT) were examined and compared with those of placebo in 87 patients (25 with atrioventricular [AV] nodal reentry tachycardia, 60 with AV reentry associated with an accessory AV connection, and 2 with atrial tachycardia). Conversion to sinus rhythm occurred in 4 of 14 patients (29%) with 0.05 mg/kg of diltiazem, 16 of 19 (84%) with 0.15 mg/kg, 13 of 13 (100%) with 0.25 mg/kg, and 14 of 17 (82%) with 0.45 mg/kg compared with 6 of 24 (25%) treated with placebo. Conversion rates in groups receiving doses of 0.15 to 0.45 mg/kg of diltiazem were superior to that in the placebo group (p less than 0.001). Time to conversion was 3.0 +/- 2.6 minutes in responding diltiazem patients compared with 5.9 +/- 6.1 minutes in responding control patients. Diltiazem administration resulted in significant lengthening of SVT cycle length, AH interval, and AV nodal effective refractory period and block cycle length. The most frequent adverse response to diltiazem was hypotension (7 of 63 patients); however, only 4 patients had symptoms related to hypotension. Thus, intravenous diltiazem in doses of 0.15, 0.25 and 0.45 mg/kg is an effective and safe treatment for the acute management of SVT.


Lack of effect of midazolam on inducibility of arrhythmias at electrophysiologic study.

Midazolam has several advantages over diazepam as a sedative agent in electrophysiologic studies, but its electrophysiologic effects in humans are unknown. Therefore, its effects were studied in 20 patients undergoing electrophysiologic studies. Electrophysiologic variables were measured before and after administration of intravenous midazolam (5 mg). There were no significant changes in the electrophysiologic variables, apart from a minor decrease in sinus cycle length (711 +/- 124 vs 647 +/- 91 ms; p = 0.005). Ease of inducibility of reentrant tachycardia was not significantly altered by midazolam, and tachycardia remained inducible in all patients. The drug was well-tolerated with no significant side effects, apart from a minor reduction (mean 18 mm Hg) in blood pressure (p less than 0.001). Good amnesic effect was achieved in 16 patients, and most patients preferred it to oral diazepam for sedation during the procedure. It is concluded that midazolam can be used safely in patients undergoing electrophysiologic studies without significantly interfering with electrophysiologic variables or the inducibility of reentrant tachycardias.


Reproducibility of a symptomatic response to upright tilt in young patients with unexplained syncope.

Serial upright tilt testing has been advocated as a possible therapeutic end point in treating patients with recurrent syncope, but the reproducibility of such testing has not been well-established in the absence of therapy. In 21 patients with recurrent syncope and a symptomatic response to upright tilt testing, tilt was repeated following a 25- to 30-minute recovery. Syncope or presyncope was reproduced in 14 of 21 patients on repeat tilt; 4 of 21 patients experienced milder symptoms, and 3 of 21 patients remained entirely asymptomatic on repeat tilt. The pattern of physiologic response was different during initial and repeat tilt in 7 of the 21 patients. Blood pressure and heart rate (before and during symptoms) were similar for the group on initial and repeat tilt. The abnormal physiologic response and associated symptoms elicited during upright tilt testing for unexplained syncope can be reproduced on immediate repeat tilt testing in most patients. However, the frequently attenuated response during repeat testing may limit its use as a therapeutic end point in individual patients.


Circadian rhythm of heart rate variability in survivors of cardiac arrest.

Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 +/- 10 vs 51 +/- 15 ms, p less than 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 +/- 7 ms2 x 10 vs 28 +/- 14 ms2 x 10, p less than 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest.


Use of telemetry functions in the assessment of implanted antitachycardia device efficacy.

Twenty patients (aged 50 +/- 21 years and mean left ventricular ejection fraction 37 +/- 17%) with recurrent ventricular arrhythmias were treated with an investigational, implantable combined antitachycardia-pacing cardioverter defibrillator. The device's telemetry capabilities include both stored (1-second snapshots) and real-time display of endocardial and device-circuit signals. The device can store these before, during and after up to 50 tachycardia and antitachycardia pacing episodes. All stored events are indexed to a 24-hour internal clock. During 10.1 +/- 5.1 months of follow-up, the device was used in 11 of 20 patients. In the entire group, antitachycardia pacing was activated on 44 +/- 14 occasions per patient (total 874) and shock delivery occurred on 8 +/- 14 occasions per patient (total 156). Reconstruction by stored telemetry of all device-therapy episodes was possible. Twenty-six percent of all shocks delivered were not appropriate and were due to atrial arrhythmias in 2 patients and dysfunction of the sensing lead in 3. The absence of a relation between symptoms and appropriate shock delivery was documented in 1 patient. Antitachycardia pace acceleration occurred in 5.3% of cases; 7% of attempts at pacing were unsuccessful and needed shock therapy. It is concluded that the enhanced telemetry available in newer antitachycardia devices enables more accurate assessment of device use and enhances diagnosis of inappropriate therapy delivery.


Exercise hyperventilation chronic congestive heart failure, and its relation to functional capacity and hemodynamics.

The ventilatory response to exercise was evaluated in 26 normal sedentary men and 68 patients with chronic heart failure using the slope of the relation between minute ventilation (VE) and carbon dioxide production (VCO2). All subjects underwent maximal upright bicycle cardiopulmonary exercise testing; 33 patients also underwent right-sided cardiac catheterization. The slope of VE/VCO2 was calculated by linear regression analysis using data from all the exercise tests and the first 60% of exercise duration; a high correlation was seen between these results (r = 0.83; p less than 0.001). The slope of VE/VCO2 was significantly, though weakly, related to peak exercise work load, oxygen consumption and ventilatory threshold (r = -0.49, -0.56 and -0.49, respectively), several peak exercise hemodynamic parameters and peak exercise dead space/tidal volume ratio (r = 0.70). With use of multivariate analysis, the only independent determinants of the slope were peak exercise dead space/tidal volume ratio and cardiac index. Thus, in patients with heart failure, exercise hyperventilation can contribute to the impairment of functional capacity and can be considered a compensatory response to abnormal hemodynamics and lung blood distribution in order to keep blood gas concentrations normal.


Exclusion of coronary artery disease by exercise thallium-201 tomography in patients with aortic valve stenosis.

In many patients with valvular aortic stenosis (AS), management decisions may be possible without invasive studies if coexistent coronary artery disease (CAD) can be ruled out noninvasively. The use of thallium-201 single-photon emission computed tomography to the exclusion of CAD was studied in 44 patients aged 41 to 78 years with AS. In addition to cardiac catheterization and selective coronary angiography, patients underwent a cardiac ultrasound study and thallium-201 myocardial perfusion imaging at rest and after bicycle ergometer exercise. Two thirds of the patients had critical AS (valve area index less than or equal to 0.5 cm2/m2) but none had left ventricular systolic dysfunction. Twenty-one patients had angiographically significant CAD (greater than or equal to 50% diameter stenosis in greater than or equal to 1 coronary artery), whereas 23 had either a fully normal angiogram (n = 17) or mild (less than 50%) stenoses (n = 6). Each patient with significant CAD had an abnormal thallium-201 tomogram, either a strictly segmental perfusion defect (n = 19), or a patchy nonsegmental abnormality (n = 2); however, 10 of 23 patients free of significant CAD had similar results. Thus, the sensitivity and specificity of an abnormal scintigram were 100 and 57%, respectively. If only segmental perfusion defects typical of CAD had been considered abnormal, then the sensitivity of the test would have been 90% and the specificity 70%. Patients with false abnormal scintigrams had more severe AS and more angiographically nonsignificant CAD than those with true normal findings.(ABSTRACT TRUNCATED AT 250 WORDS)


Immediate effects of percutaneous transvenous mitral commissurotomy on pulmonary hemodynamics at rest and during exercise in mitral stenosis.

Hemodynamics were evaluated during exercise in 33 patients with mitral stenosis who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC was performed using an Inoue balloon. Each patient underwent a supine ergometer exercise test before and on the day after PTMC. Ergometer work load was started at 20 W and increased in increments of 20 W at 3-minute intervals until terminated by the patient's fatigue or shortness of breath. Mitral valve area increased by 0.8 +/- 0.4 cm2 (1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.001). Mean mitral pressure gradient decreased (12 +/- 5 to 6 +/- 2 mm Hg, p less than 0.001). Pulmonary arterial pressure significantly decreased and the cardiac index significantly increased both at rest and during exercise after PTMC. Before PTMC, the increases in pulmonary arterial pressure, total pulmonary resistance and pulmonary arteriolar resistance during exercise were greater in patients with a mitral valve area less than 1.0 cm2 than in patients with an area greater than or equal to 1.0 cm2. After PTMC, total pulmonary resistance still increased during exercise. However, pulmonary arteriolar resistance did not change during exercise in patients with a mitral valve area greater than or equal to 1.5 cm2, whereas it increased in patients with an area less than 1.5 cm2. An enlarged mitral valve area greater than or equal to 1.5 cm2, which may prevent pulmonary vasoconstriction and permits a greater increase in pulmonary blood flow during exercise, is considered a good result immediately after PTMC.


Comparison of the cardiotoxicity of ethanol in women versus men.

Subclinical left ventricular (LV) dysfunction is a common occurrence in alcoholic men but has been claimed to be absent or very rare in alcoholic women. M-mode echocardiography was performed to study LV size, mass and systolic function, and Doppler ultrasound to study LV filling in 14 chronic female alcoholics aged 24 to 48 years and in 2 age-matched control groups consisting of 17 healthy women and 22 alcoholic men. Compared with healthy women, female alcoholics had no differences in heart rate or blood pressure but a shorter LV end-diastolic diameter (mean +/- standard deviation, 46 +/- 4 vs 48 +/- 3 mm, p less than 0.05), lower fractional shortening (31 +/- 6 vs 34 +/- 3%, p less than 0.05), increased wall thickness to radius ratio (0.43 +/- 0.08 vs 0.37 +/- 0.05, p less than 0.05), reduced peak early diastolic transmitral velocity (45 +/- 11 vs 68 +/- 7 cm/s, p less than 0.001), reduced deceleration of the early diastolic velocity (-274 +/- 69 vs -572 +/- 107 cm/s2, p less than 0.001), and an increased atrial filling fraction (35 +/- 12 vs 27 +/- 5%, p less than 0.05). Although alcoholic men had a longer duration of heavy drinking than alcoholic women (median 19 vs 5 years, p less than 0.001), and a higher systolic blood pressure (140 +/- 17 vs 120 +/- 17 mm Hg, p less than 0.001), there were no statistically significant differences between the sexes either in LV diameters, wall thickness or mass normalized to body area, or in indexes of systolic or diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)


Altered cardiac hemodynamic and electrical state in normal sinus rhythm after chronic dual-chamber pacing for relief of left ventricular outflow obstruction in hypertrophic cardiomyopathy.

Dual-chamber (DDD) pacing relieves left ventricular (LV) outflow tract obstruction in patients with hypertrophic cardiomyopathy. The reduction in LV outflow gradient persists in some patients after cessation of pacing. Twelve-lead and signal-averaged electrocardiograms were obtained before and after 12 weeks of DDD pacing in 18 patients with obstructive hypertrophic cardiomyopathy to determine whether the altered hemodynamic state after chronic pacing is accompanied by electrical changes. Hemodynamic studies were performed at baseline and at follow-up. Signal-averaged electro-cardiograms were obtained using a Corazonix Predictor and bidirectional filters at 25 Hz to a noise level of less than 0.5 microV. At follow-up, LV outflow tract gradients were reduced significantly during DDD pacing and with cessation of pacing in sinus rhythm by 56 +/- 10 and 47 +/- 10 mm Hg, respectively (p less than 0.001). There was no simple relation between changes in LV outflow tract gradient and in the electrocardiogram. For example, amplitude of the R wave in V5,6 was reduced by greater than or equal to 0.5 mv in 4 patients, unchanged in 12 and increased in 2. Similarly, the S wave in leads V1,2 was reduced in 7 patients, unchanged in 7 and increased in 4. The T wave became more negative (greater than or equal to 0.1 mv) in leads II, III, aVF and V5,6 in 13 patients and more positive in leads I and aVL in 12.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy.

The long-term results of patients undergoing myotomy/myectomy of the ventricular septum for obstructive hypertrophic cardiomyopathy are documented in 31 patients (15 women, 16 men, age range 21 to 80 years [mean 55]) with mean New York Heart Association functional class III to IV congestive heart failure, who underwent radical myotomy/myectomy at the Brigham and Women's Hospital from 1972 to 1991. Preoperative gradients by catheterization or echocardiography ranged from 26 to 240 mm Hg (average 96). There were no operative deaths. Two patients developed early postoperative complete heart block requiring a transvenous pacemaker. Clinical follow-up was 1 to 14 years (mean 6.5). All surviving patients were restudied by echocardiography and clinical examination. The mean postoperative functional class was II. Postoperative gradients ranged from 0 to 30 mm Hg (mean 4.5) (p less than 0.001 compared with preoperative values). There were 5 late deaths (low cardiac output in 2, stroke in 2, and acute respiratory failure in 1); 4 of 5 deaths occurred in patients with concomitant coronary artery disease. Survival at 10 years was 86 +/- 9%. There were no reoperations for subaortic obstruction.


1,000 consecutive children with a cardiac malformation with 26- to 37-year follow-up.

The current status of 997 of 1,000 consecutive children with a cardiac malformation initially evaluated between 1952 and 1963 was determined. Of the 1000, 285 have died and the survivors have been followed up for periods of 26 to 37 years. Six hundred thirty-two are in excellent or good clinical condition, being asymptomatic and without planned need for further treatment. The other 80 have significant abnormalities, although 63 of these have few symptoms. Infective endocarditis occurred in 12 of 10,000 susceptible patient-years, with a lower rate in the past decade. Only 22 of the survivors are currently receiving cardiac medication. These data are derived from a group of patients initially seen during a period of time that cardiac surgery was being developed for congenital heart disease. Thus, the outlook should be even better for children who are currently undergoing treatment.


Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events.

This study compares the value of transthoracic (TTE) and transesophageal (TEE) color Doppler and contrast echocardiography for detecting a patent foramen ovale (PFO). A total of 238 patients were studied: 74 patients with a history of otherwise unexplained ischemic stroke, transient cerebral ischemic attacks or peripheral embolic events (group A), 48 with a history of similar episodes explained by other cardiac abnormalities (group B), and 116 with no embolic events (group C). A PFO was detected by contrast TEE in 50 of 238 patients (21%) compared with 45 patients (19%) by color Doppler TTE. In a subgroup of 198 patients, TEE results could be compared with TTE findings. No patient had a PFO identified by color Doppler TTE. Contrast TTE detected a PFO in 15 patients (8%) compared with contrast TEE which demonstrated a PFO in 44 of 198 patients (22%) (p less than 0.001). Prevalence of PFO by TEE was 22, 21 and 22% in groups A, B and C, respectively. A PFO was present in 50% of patients aged less than 40 years and otherwise unexplained ischemic stroke; this percentage was higher (p less than 0.05) than corresponding values found in all other groups. Thus, contrast and color Doppler TEE are significantly superior to TTE for detecting PFO. The prevalence of PFO is significantly increased in young adults with otherwise unexplained ischemic stroke.


Hyperventilation syndrome and the assessment of treatment for functional cardiac symptoms.

Three methods of breathing retraining (guided breathing retraining, guided breathing retraining with physiologic monitoring of thoracic and abdominal movement plus peripheral temperature, and guided breathing retraining with physiologic monitoring of thoracic and abdominal movement, peripheral temperature and end-tidal carbon dioxide) were compared with a no-treatment control group to determine the effectiveness of breathing retraining on modifying respiratory physiology and reducing functional cardiac symptoms in subjects with signs associated with hyperventilation syndrome. Of 41 subjects studied, 16 were diagnosed with mitral valve prolapse. Results demonstrated that all 3 methods of breathing retraining were equally effective in modifying respiratory physiology and reducing the frequency of functional cardiac symptoms. Results determined that respiratory rate and subject's perception that training had generalized were the best predictors of treatment success. Furthermore, it was found that subjects with mitral valve prolapse responded as well to treatment as did those without prolapse.


Percutaneous pericardial catheter drainage in childhood.

The clinical course of 41 consecutive pediatric patients (mean age 7.6 +/- 5.8 years, weight 27 +/- 22 kg) who underwent percutaneous pericardial drain placement during a 3-year period were reviewed. The most common diagnoses were malignancy (20%), postpericardiotomy syndrome (17%), aseptic pericarditis (12%), and patients recovering from a Fontan type of operation (12%). Indications for drainage included increasing effusion size determined by 2-dimensional echocardiogram (48%), clinical deterioration (33%) and echocardiographic evidence of hemodynamic compromise (12%). Only 3 (7%) patients had clinical evidence of cardiac tamponade. Drainage catheter placement was accomplished percutaneously from the subxiphoid approach. Insertion was successful in all but 1 patient (98%) and successful evacuation of the pericardial space was achieved in 93% of patients. There was 1 death in a critically ill 2-week-old infant and 4 complications, 3 of which occurred in patients aged less than 2 years. Drainage catheters remained in position from 1 to 18 days (mean 3 +/- 3 days) with no late complications. There were 3 instances (7%) of drainage catheter occlusion. These data support the notion that placement of a percutaneous pericardial catheter is safe and effective in providing definitive drainage of the pericardial space in the pediatric age group. Children younger than age 2 years may be at increased risk for complications.


Breast carcinoma simulating fibroadenoma or fibrocystic change by fine-needle aspiration. A study of 16 cases.

The cytologic features of fine-needle aspiration specimens from 16 breast carcinomas that closely simulated benign lesions were analyzed and compared to smears from fibroadenomas and fibrocystic change. No combination of features was found that accurately separated all benign and malignant cases. Many nuclei with discernible small nucleoli in smears with many single bipolar nuclei indicated a benign lesion, whereas nuclear hyperchromasia indicated a malignant one.


Sialosyl-Tn antigen. Its distribution in normal human tissues and expression in adenocarcinomas.

In normal adult human tissues, sialosyl-Tn antigen, detected by monoclonal antibody TKH2, was uniformly found in the bronchus, uterus, salivary gland, palatine tonsil, testis, stomach, duodenum, and capillary endothelium of several organs. It was also sporadically found in the small intestine, appendix, colorectum, gallbladder, urinary bladder, skin, and esophagus. The antigen was absent in the other organs. Even in the organs showing positive findings, the antigen was observed only in the limited areas. In contrast, sialosyl-Tn antigen was expressed in a large number of adenocarcinomas in many kinds of organs. It was expressed in more than one half the adenocarcinomas of the pancreas, ovary, uterus, stomach, colorectum, and gallbladder, but not in hepatocellular carcinomas, renal cell carcinomas, and papillary carcinomas of the thyroid gland. Sialosyl-Tn antigen expression also was observed in intestinal metaplasia of the stomach and in transitional mucosa adjacent to the colorectal carcinoma, which are considered to be cancer-related lesions. These results indicate that sialosyl-Tn antigen is a useful tumor marker, especially in adenocarcinomas of the mucin-producing organs, and suggest that the regulation of sialosyl-Tn antigen synthesis in adenocarcinomas is different from that in normal tissues.


Content and design of laboratory report forms for human immunodeficiency virus type 1 antibody testing.

In a pilot study involving proficiency testing for human immunodeficiency virus, markedly diverse and potentially confusing test report forms were encountered among participating laboratories. Therefore, a comprehensive study of human immunodeficiency virus type 1 report forms was conducted from state-licensed testing laboratories in California. Participants analyzed three serum samples of known human immunodeficiency virus type 1 antibody reactivity and reported their results on forms that they would normally submit to clinicians. Report forms from 84 laboratories were evaluated for content, design, and clarity. Differences were found among commercial, hospital, and public health laboratories. The significance of these findings is discussed. This technique also may be applied to evaluate laboratory report form design and content for other diagnostic test results.


Acute megakaryoblastic leukemia in infants with t(1;22)(p13;q13) abnormality.

Six infants with acute megakaryoblastic leukemia and a translocation (1;22)(p13;q13) were studied. There were five female infants and one male infant, and the age at initial examination varied from 0.8 to 6.5 months (median, 2.3 months). All the patients had hepatosplenomegaly and anemia (6 to 8.3 g/dL), and four patients had thrombocytopenia (9,000 to 63,000/mm3). The bone marrow showed prominent fibrosis in five cases and reticulin fibrosis in one patient at presentation. Crush artifact often made the histologic sections difficult to interpret, but typical megakaryoblasts could be identified in the smears. Biopsy specimens of the liver and lymph node were suggestive of a nonhematopoietic malignant condition because of the cohesiveness of the tumor cells, stromal fibrosis, and the prominent sinusoidal and vascular pattern of infiltration. Immunophenotyping of peripheral blood mononuclear cells was helpful in identifying the blasts as belonging to the megakaryoblastic lineage. Using a panel of mononclonal antibodies, it was also possible to confirm the nature of the infiltration in paraffin sections and to differentiate it from other childhood small round cell tumors, especially neuroblastoma in paraffin sections (typical staining pattern: CD45-, CD43+, vW Factor, Ulex europeus I+, CD20-, CD45RO-, synaptophysin-, chromogranin-, cytokeratin-, desmin-). This special type of infantile acute leukemia can be recognized with confidence if one is aware of its clinical features, peculiar pathologic characteristics, the morphologic features and immunophenotype of the megakaryoblasts, and the unique cytogenetic abnormality.


Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration.

A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line.


Proficiency testing of platelet counting in Ontario.

Proficiency testing results provide data for interlaboratory comparisons. The Laboratory Proficiency Testing Program of Ontario, Canada, has tested platelet counting for a decade and other hematology parameters for 15 years. Despite the fact that all testing programs are compromised by the type of testing material used, for platelet count testing, conclusions are possible. The data indicate that most laboratories in Ontario have greater difficulty performing reproducible platelet counting as compared with other components of hematologic cytometry. A major contributor to this shortfall is the method used by the laboratory. It was not a surprise that manual counting had a high coefficient of variation. Unexpectedly, the semiautomated methods used in the mid-1980s also displayed a high coefficient of variation.


Imprecision of prothrombin time monitoring of oral anticoagulation. A survey of hospital laboratories.

Prothrombin time monitoring of oral anticoagulation is highly dependent on the tissue thromboplastin used. In the United States, patients have received a higher level of anticoagulation because of the use of a less sensitive thromboplastin. Many advocate the use of an International Normalized Ratio to rectify this problem. Laboratory supervisors from all acute care hospitals in Massachusetts were surveyed to determine the disparity in thromboplastin use and reporting practices for prothrombin time testing. Eighty-eight of 103 (86%) hospitals responded. Fifty-eight lots from six manufacturers of thromboplastin were in use. The International Sensitivity Index of these lots ranged from 1.89 to 2.74. Ninety-nine percent of hospitals reported prothrombin times in raw seconds. Only 5% reported an International Normalized Ratio. Sixteen different coagulation instruments were in use. Close to 70% of laboratory supervisors had little or no understanding of the significance of an International Sensitivity Index or an International Normalized Ratio. The management of oral anticoagulation appears far less precise than had been believed. Prothrombin times in the same individual from different laboratories may have poor correlation. Based on the level of understanding of laboratory supervisors, extensive education will be necessary to change practices and improve accuracy and comparability of prothrombin time testing.


Clinically significant heparin carryover on the ACL 300R.

Investigation of a patient with an unexpected prolonged activated partial thromboplastin time showed on repeat testing that the patient had normal coagulation times, but had been preceded on the automated coagulation analyzer run (ACL 300R--Instrumentation Laboratory, Lexington, MA) by a heparin-contaminated apheresis line sample taken from a different patient. Heparin carryover was suspected, and subsequent experiments showed that ex vivo heparinization of normal plasmas will produce similar effects in following normal plasma samples in a test series. This effect increases with the baseline activated partial thromboplastin time and the heparin concentration. It is recommended that coagulation analyzers that are susceptible to carryover be cleaned after testing of plasmas likely to have heparin concentration of more than 5 x 10(3) U/L. Furthermore, when using analyzers of this type, investigation of an unexplained activated partial thromboplastin time must include a review of the preceding samples tested, particularly when duplicate testing has been discontinued.


Evaluation of serum immunoglobulins by protein electrophoresis and rate nephelometry before and after therapeutic plasma exchange.

One hundred fourteen pre- and postplasma exchange (PE) serum protein electrophoretograms and serum IgG, IgA, and IgM levels obtained during a 4-month period from 23 patients were evaluated. The interval between PE sessions varied from once daily to approximately once monthly. Typically, post-PE patterns had decreased alpha-1, decreased alpha-2, decreased beta, and decreased gamma fractions. The average percentage decreases of the immunoglobulins subsequent to PE were as follows: IgG, 52%; IgA, 55%; and IgM, 51%. There was a high linear correlation between the pre- and post-PE concentrations of IgG and IgA, whereas correlation of pre- and post-PE IgM concentrations was much lower. All IgG, IgA, and IgM levels (100%) returned to their respective reference intervals before subsequent PE when procedures were scheduled at least 2 weeks apart. When procedures occurred 1 week apart or less, only 1 IgG level (1%) returned to its reference interval, whereas 68 IgA (73%) and 74 IgM levels (80%) returned to their respective reference intervals. During this study, a faint monoclonal band was discovered in each of two patients. One had a normal baseline serum protein electrophoretogram before initiation of PE therapy, and the gammopathy was of uncertain significance. In the other patient, a vertebral plasmacytoma was discovered. It is concluded that PE reduces IgG, IgA, and IgM by approximately the same percentages; however, reference interval levels of IgA and IgM are restored more rapidly than IgG levels. Because monoclonal proteins may be present before or may appear during PE therapy, patients should be monitored by baseline and subsequent periodic serum protein electrophoresis.


Dental and orthopedic effects of high-pull headgear in treatment of Class II, division 1 malocclusion.

In the present study a prospective cephalometric investigation was undertaken to examine the skeletal and dental effects of the high-pull extraoral appliance, when the resultant force was directed through the level of trifurcation of the maxillary molars. Twelve adolescent patients with Class II, Division 1 malocclusions were selected for the study. Each patient wore the headgear for a 6-month period, an average of 12 hours a day. A group of untreated adolescent patients with Class II, Division 1 malocclusions who were in a similar age range, as well as skeletal and dental characteristics were chosen as controls. Lateral cephalometric films were taken before and after the 6-month treatment period, and before and after the observation period in the control group of patients. Our data indicate that by directing the force of the headgear approximately through the center of resistance of the maxillary molars, it is possible to accomplish simultaneously a substantial distal movement of the molars (2.6 +/- 0.6 mm), as well as significant intrusion (0.54 +/- 0.54 mm). In addition, our results demonstrate that the applied force of 500 gm was sufficient to initiate maxillary orthopedic changes in the treated patients. These changes include relative restriction of horizontal and vertical maxillary growth, as well as distal movement (mean: 0.8 mm) of the maxillary anterior border in the treatment group relative to an untreated control group. Such orthopedic changes have been previously described only in association with much higher force levels.


Shear peel bond strengths of esthetic orthodontic brackets.

Anecdotal reports of bracket fracture and tooth damage associated with the use of certain esthetic orthodontic brackets have been reported in the literature. With the advent of new esthetic orthodontic brackets, the need has arisen to test the claims of the manufacturers. The objectives of this study were to determine: (1) shear peel bond strengths (SPBS) of various debonded orthodontic brackets, (2) SPBS of these rebonded esthetic brackets with and without use of silane, and (3) fracture sites of all groups examined. Seventy-five noncarious human premolar teeth were randomly divided into five groups (A through E). The teeth were cleaned, stored in 70% ethyl alcohol, and mounted for testing in the Instron machine. The following brackets were bonded to the teeth with Ortho-Concise bonding resin: (A) metal brackets, (B) Silkon brackets, (C) Transcend 2000 brackets, (D) debonded Transcend 2000 brackets, and (E) debonded silanized Transcend 2000 brackets. After wet storage at 37 degrees C for 7 days, the SPBS of brackets were recorded, and fracture sites observed. There were statistically significant differences between the SPBS of metal brackets when compared with the Transcend 2000 and the Silkon brackets. These groups exhibited clinically acceptable SPBS. Debonded silanized Transcend 2000 brackets showed clinically unacceptable SPBS. Fracture sites of metal and Transcend 2000 brackets were resin-bracket, whereas Silkon brackets fracture sites were predominantly resin-enamel.


The role of the condylar cartilage in mandibular growth. A study in thanatophoric dysplasia.

A new approach to evaluate the role of the condyle in mandibular growth could be its study in chondrodysplasias. The growth of the condylar cartilage and the mandible has not previously been reported in thanatophoric dysplasia (TD), a lethal osteochondrodysplasia. We have studied the light microscopic, histomorphometric, and radiologic findings in four infants affected by TD and in four control infants. The diagnosis was made on the basis of clinical, radiographic, and pathologic criteria. All the measured radiographic parameters of the patients' mandibles showed a normal longitudinal growth in TD, despite the severe disturbance of the condylar cartilages. The lesions in the chondroblastic cells and the extracellular matrix were similar to those observed in growth plate cartilages in TD. Marked membranous ossification spread from the cartilage canals of the condyles. The articular and prechondroblastic layers were histologically normal. Histomorphometry demonstrated that condylar cartilages were twice as thick as normal in TD, mainly because of the thickening by the chondroblastic layer. Present results support the hypothesis that condylar cartilage is a secondary growth site instead of being a primary growth center.


Mandibular remodeling measured on cephalograms: 2. A comparison of information from implant and anatomic best-fit superimpositions.

This study quantifies the differences in the perceived pattern of mandibular remodeling when two different methods are used to superimpose roentgenographic images of the mandible. Lateral cephalograms for a group of subjects with metallic implants of the Björk type were superimposed twice; first on the metallic implants and then independently on mandibular anatomic structures according to a common "best fit" rule. In this article, we compare the between-superimposition differences in the perceived displacements of condyle, gonion, menton, pogonion, and Point B. Mean differences between the two superimpositional techniques were smaller than had been anticipated. For the 7-year time interval between 8.5 and 15.5 years, the largest mean differences between methods were 2.70 mm in the horizontal direction at condyle, 1.90 mm in the vertical direction at condyle, and 1.52 mm in the vertical direction at gonion. None of the other between-superimposition differences had a mean value in excess of 1 mm. The individual case variability between the two methods was, however, quite considerable, a finding that we believe has bearing on the confidence that can be placed in individual case analyses in clinical orthodontics. A preliminary attempt has been made to represent and discuss the magnitude of this problem.


Evaluation of an anamnestic questionnaire as an instrument for investigating potential relationships between orthodontic therapy and temporomandibular disorders.

A group of 100 patients who received orthodontic treatment, between the ages of 16 to 31 years, were asked to complete the TMJ Scale (an anamnestic temporomandibular disorder [TMD] questionnaire) and undertake a simple clinical TMD examination, the Helkimo clinical dysfunction index. The purpose of this study was to compare the TMJ Scale and the Helkimo clinical dysfunction index to validate the use of the TMJ Scale as a potential method with which to examine whether there is any relationship between TMD and orthodontic therapy. Comparisons between TMJ Scale scores from the orthodontically treated group were made with previously reported TMJ Scale data. In addition, comparisons were made between various treatment and malocclusion groups identified within the orthodontically treated sample. On the basis of the TMJ Scale global scale scores for the orthodontically treated group and two normative nontemporomandibular disorder groups described by Levitt, Lundeen, and McKinney, no differences were observed. Similarly, TMJ Scale comparisons between various treatment and malocclusion subgroups showed no statistically significant differences. The results of this study support the use of the TMJ Scale as a valid instrument with which to determine whether there is any relationship between orthodontic therapy and TMD.


Arch length considerations due to the curve of Spee: a mathematical model.

Arch length analysis should consider discrepancies not only within the sagittal plane but also within the vertical and transverse planes. The vertical deviation of the occlusal plane from a flat plane is known as the curve of Spee. The purpose of this study was to produce a mathematical model of the mandibular arch form in three planes of space and to determine the effect that the curve of Spee has on arch circumference. Two mandibular arch forms, the catenary and the Bonwill-Hawley, were examined. The curve of Spee was modeled as a cylinder perpendicular to the midsagittal plane centered on the arch anteroposteriorly. A mathematical distance formula was used to calculate arch circumferences from the central fossa of the first molars for 10 arches with curves of Spee ranging from 0 to 10 mm. This procedure was repeated for arch circumferences extending from the central fossa of the second molars. Plots for the difference in arch circumferences verses depth of the curve of Spee showed that the relationship between these two variables is not linear and is less than one to one. This model showed that clinical practice of allowing 1 mm of arch circumference for leveling each millimeter of curve of Spee overestimates the amount of arch circumference needed to flatten the curve of Spee.


The effects of infraocclusion: Part 1. Tilting of the adjacent teeth and local space loss.

The normal arrangement of the transseptal fibers in the dentition is one of a completely horizontal system that links the mesial and the distal aspects of each tooth within the dental arch, from the most distal tooth of one side to the most distal tooth of the other, across the midline. This continuous fiber band is parallel to the occlusal plane, being attached to each tooth coronal to the level of the interradicular alveolar bone crest and apical to the cementoenamel junction. Alteration of the occlusal plane will be mirrored by a similar change in the plane of the transseptal fiber system. From the clinical observation of young people with infraoccluded deciduous teeth, over many years, the regular and concomittant occurrence of certain other, well-defined phenomena appears to be the rule. It was thought that these phenomena could be explained in terms of the inclusion of a vertical component (infraocclusion) into this horizontal system. Two of these phenomena are discussed here. The first and most obvious of these relates to the exaggerated tipping that affects the adjacent tooth mesially and distally. The second parameter measures the amount of actual horizontal (mesiodistal) space change that occurs locally, within the dental arch, between the two teeth adjacent to the infraoccluded tooth, measured at both the occlusal level and at the level of their root apices. With a high degree of statistical validity, it was found that infraocclusion is related to severe tilting of the two adjacent teeth toward the affected tooth, with minimal space loss in the dental arch at the occlusal level, but a wide separation of root apices.


Relations between verbal behavior of the orthodontist and communicative cooperation of the patient in regular orthodontic visits.

A study of interrelationships between orthodontist and patient communication characteristics on the basis of audiotape recordings is reported. The subjects were 66 patients from an orthodontic outpatient clinic who were treated by seven orthodontists. Strong relationships (partial correlations) were found between clinicians encouraging behavior (listener signals and symmetrical answering) and patient communicative cooperation (speech volume, detailed answering, questions, initiatives); whereas orthodontists guiding behavior showed lower correlations, only the clinicians' direct questions were significantly related to patient participation. For communication content, relations to patient activity depended on how strongly orthodontists discussed social or therapy topics. Discussion characteristics of both parties were not related to the patient's age, sex, and duration of therapy. However, patient communication differed with the personality of the dentist. Results are discussed with reference to literature, orthodontic consulting practice, and future research.


Correction of a superiorly displaced impacted canine due to a large dentigerous cyst.

One of the more difficult situations dealt with by orthodontists is the treatment of impacted maxillary canines. This case report describes an impacted canine positioned near the floor of the orbit that was brought into a normal position. Diagnostic records revealed impacted and displaced teeth resulting from a large radiolucent lesion. The patient was referred to an oral surgeon. The lesion was diagnosed as a dentigerous cyst and marsupialized over 12 months. After decompression of the cyst, the impacted teeth were exposed and orthodontically brought into their proper position.


Angle classification revisited 2: a modified Angle classification.

Edward Angle, in his classification of malocclusions, appears to have made Class I a range of abnormality, not a point of ideal occlusion. Current goals of orthodontic treatment, however, strive for the designation "Class I occlusion" to be synonymous with the point of ideal intermeshing and not a broad range. If contemporary orthodontists are to continue to use Class I as a goal, then it is appropriate that Dr. Angle's century-old classification, be modified to be more precise.


Positional asphyxiation in adults. A series of 30 cases from the Dade and Broward County Florida Medical Examiner Offices from 1982 to 1990.

Over a 9-year period, 30 cases of positional (or postural) asphyxia were identified in the Dade and Broward County (Florida) Medical Examiner Offices. The victims had an average age of 50.6 years with no significant sex or racial differences as compared with the general medical examiner population. Chronic alcoholism or acute alcohol intoxication was a significant risk factor in 75% of cases and these had an average postmortem ethanol concentration of 0.24 g%. Signs of mechanical asphyxiation (petechiae and/or combined lung weights greater than 900 g) were present in 93% of cases. Victims were commonly (43%) found in a restrictive position producing hyperflexion of the head and neck. Two deaths involved restraint vests ("poseys") in elderly, demented, wheel-chair-confined victims. Scene photographs of the undisturbed decedent are extremely helpful in confirming a suspicion of postional asphyxia.


An unusual accidental death from reverse suspension.

Deaths involving prolonged suspension head downwards have received little or no attention in the English-language literature, doubtless because they are extremely rare. An example, involving alcoholic intoxication as the sole complicating factor, is reported. The mechanism of death is also considered since this is plainly a subject of some interest and likely to provoke further thought and discussion.


Death by power car window. An unrecognized hazard.

The unusual accidental asphyxial death of a 26-month-old girl involving a car power window is reported. The circumstances and investigation results are discussed, as well as how such tragedies may be avoided.


Atypical autoerotic deaths.

So-called "typical" autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas "atypical" autoeroticism involves sexual self-stimulation by other means. We present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.


Does advancing age modify the presentation of disease?

A group of patients who had died of either cardiac tamponade due to ruptured myocardial infarct, perforated peptic ulcer, or diverticulitis with perforation were studied to determine the effect that age has on the presentation of these three potentially fatal diseases. With advanced age, a decrease in the number of patients who had symptoms typical for the disease that was ultimately the cause of death was found. We also noted a number of patients who did not experience any symptoms, and some patients who experienced symptoms that were not typical of their disease. In many instances, the disparity between disease severity and symptoms had resulted in the disease not being diagnosed either because the patient did not seek medical advice or because the doctor was unable to make the appropriate diagnosis from the patient's symptoms.


The development of forensic medicine in the United Kingdom from the 18th century.

Forensic medicine in the United Kingdom includes both forensic pathology and clinical forensic medicine on the living. It began at the end of the 18th century, long after its development in Germany, Italy, France, and other countries in Europe. Initial beginnings were in Scotland, where a program began at the University of Edinburgh with the establishment of a chair in Forensic Medicine by Prof. Andrew Duncan Sr. The development in England began in London's Kings College Medical School with a chair held by Prof. William A. Guy. Later chairs in Forensic Medicine were established in Glasgow, Aberdeen, and in London, where Forensic Medicine was taught at St. Mary's Hospital Medical School, Guy's Hospital Medical School, London Hospital Medical School, Charing Cross Hospital Medical School, St. Thomas Hospital Medical School, and St. George's Hospital Medical School. In other cities in England, Wales, and Northern Ireland, departments were founded in Leeds, Manchester, Cardiff, and Belfast. Many textbooks were prepared during this time by professors from these medical schools and by others working in nonacademic areas. The development of coroner activities and those of the police surgeons is also part of the study of forensic medicine.


Sudden death due to self-treatment of peripheral edema with rubberband tourniquet.

A 70-year-old white male alcoholic with a history of congestive heart failure associated with peripheral edema was found dead in a pool of blood with a circumferential laceration of his right leg. A rubberband was found around the leg deep within the wound. The decedent reportedly refused medical treatment for his cardiovascular condition and treated himself by applying rubberbands and bandages around his legs to stop the spread of edema and infection.


Esophageal-atrial fistula resulting in systemic "meat and vegetable" emboli.

An 85-year-old demented woman died in the state hospital and her death was investigated by our office, based on allegations of neglect. At autopsy, a feeding catheter was found passed through an esophageal-atrial fistula into the left atrium. Fragments of striated muscle and plant wall (cellulose) embolized to the systemic organs including heart, kidney, and brain. Her dilated esophagus suggests a premortem esophageal motility disorder that contributed to the formation of the fistula. This is the first reported case of an esophageal-atrial fistula in the medical literature.


Body packing with a twist. Death of a salesman.

Reported cases of death due to oral ingestion of lidocaine are rare. We report the case of a known cocaine dealer who died after swallowing a small packet of white powder, thought to be cocaine, during a relatively routine arrest. The authors describe how the deceased differed from the usual "body packer" and alert the forensic community to be wary of what may first appear to be another "garden-variety" cocaine death.


Forensic anthropology in the 1990s.

Forensic anthropology has undergone considerable change over the past 10 years. Today it is utilized by most law enforcement, coroner, and medical examiner systems. The techniques for determination of age at death, sex, race, and stature from skeletal remains have been modified and greatly expanded. The role of the forensic anthropologist within a medicolegal context is much broader than in previous years. In addition to establishing individual identity, forensic anthropologists are now consulted for trauma analysis, facial reconstruction, photographic superimposition, determination of time interval since death, and crime-scene recovery. Not all physical anthropologists are forensic anthropologists. Qualified individuals are certified, through rigorous examination, by the American Board of Forensic Anthropology. A list of board-certified forensic anthropologists may be obtained through the American Academy of Forensic Sciences.


The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. II. Analysis of the incidence rate and its many variations.

We have analyzed suicide data of the Forensic Psychiatric Program of the Oregon State Hospital in terms of the various ways of expressing occurrence rates that are found in the literature. All of these rates are ultimately based upon either (a) the average daily population, computed from occupancy rates of institutional beds, or (b) a measure of the total number of individuals at risk (that is, all who were in the study population during the time frame of the study). We discuss reasons for the use of these different rates. We have also calculated the risk of suicide for each of two factors: (a) the primary psychiatric diagnosis and (b) the type of legal commitment under which these patients were admitted to the Forensic Psychiatric Program. We discovered that virtually the entire risk of suicide in this program was borne by patients whose primary diagnosis was that of chronic schizophrenia and who were committed there because of diminished criminal responsibility for a crime of which they were found guilty in a court of law.


The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. III. A 25-year overview of unnatural deaths in the mental and correctional facilities.

I document 25 consecutive years (1963-1987) of unnatural deaths within the State of Oregon's mental and correctional institutions in Marion County. This study includes 93 unnatural deaths in the Oregon State Hospital, 18 in the Forensic Psychiatric Program, 52 in the Fairview Training Center, and 45 in the Corrections Department facilities. These institutional unnatural deaths are compared with the 2,618 unnatural deaths that occurred during this same period in Marion County (exclusive of these state facilities). Death rates are shown in five 5-year blocks of time to illustrate death trends. Accidents and suicides were the predominant types of unnatural death in the Oregon State Hospital; suicides predominated in the Forensic Psychiatric Program and the corrections facilities; and accidents predominated in the Fairview Training Center. Extremely high total unnatural death rates were found in the Oregon State Hospital (approximately 520/100,000 or 8.46 times that found in Marion County) and the Forensic Psychiatric Program (approximately 561/100,000 or 9.13 times that found in Marion County). The overall accident death rate for the Fairview Training Center was approximately 119/100,000 or 2.84 times that found in Marion County. The overall total unnatural death rate for the corrections facilities was approximately 75/100,000 or 1.23 times that found in Marion County. I compare these data with those of other investigators in the United States, Canada, and western Europe. The total unnatural death rate appears to represent a valid criterion of violent death within a community.


Diffuse axonal injury by simple fall.

Diffuse axonal injury (DAI) is the second most common lethal head trauma after subdural hematoma and probably the most frequent cause of traumatic coma in the absence of an expanding intracranial mass lesion. Though it occurs most often in traffic accidents, it may occasionally result from falls from a height. Previously, it has not been associated with a simple fall or a fall of a distance not more than the victim's own height. We report herein a case of DAI from a simple fall.


Positional asphyxia during law enforcement transport.

Three cases of positional asphyxia are described that occurred while victims were in a prone position in rear compartments of police patrol cars. These deaths are attributed to positional asphyxia. Autopsy findings and specific scene and circumstantial correlations of the investigation are discussed with emphasis placed on the limitations of interpretation of the anatomic changes at autopsy.


The perils of investigating and certifying deaths in police custody.

Procedures leading to the proper investigation and certification of deaths occurring in police custody are discussed. The importance of training and experience, of interchange of information between investigator and forensic pathologist, and of common sense in the pursuit of fairness toward this end is emphasized.


Prevalence of coronary heart disease in subjects with normal and impaired glucose tolerance and non-insulin-dependent diabetes mellitus in a biethnic Colorado population. The San Luis Valley Diabetes Study.

The prevalence of coronary heart disease was studied in 1984-1988 in 1,092 individuals with normal glucose tolerance, 173 individuals with impaired glucose tolerance, and 429 individuals with non-insulin-dependent diabetes mellitus, who were age 25-74 years and were from a biethnic community in the San Luis Valley, Colorado. Glucose tolerance was classified using the World Health Organization criteria, and coronary heart disease prevalence was assessed using the Rose Questionnaire and a resting electrocardiogram. Compared with normal glucose tolerance, coronary heart disease was significantly more prevalent in diabetic non-Hispanic white women (odds ratio (OR) for all end points combined = 3.2, 95% confidence interval (Cl) 1.8-5.5) and men (OR = 1.9, 95% Cl 1.1-3.3) and in diabetic Hispanic women (OR = 1.7, 95% Cl 1.1-2.5), but not men (OR = 1.0, 95% Cl 0.6-1.7). Among diabetic men, the prevalence of possible myocardial infarction was lower in Hispanics than in non-Hispanic whites (OR = 0.4, 95% Cl 0.2-0.7). Similar patterns of coronary heart disease were observed in individuals with impaired glucose tolerance. The paradoxically low prevalence of coronary heart disease in Hispanics with non-insulin-dependent diabetes mellitus, especially men, may be due to unknown protective factors, increased case fatality, or competing mortality in this group.