Sodium currents in single cardiac Purkinje cells.

The sodium (Na) channel is the fundamental unit of excitability in heart muscle. This channel has been very difficult to study in detail, because the major experimental tool, the voltage clamp, has been difficult to use in multicellular tissue. In the absence of more direct studies in the heart, it has been assumed that the sodium channel in the heart was the same as that in nerve tissue, where it could be studied quantitatively. However, the sodium channel is not likely to be the same as in nerve, because it responds differently to local anesthetics and to other drugs such as tetrodotoxin. It is essential to learn the details of the cardiac sodium channel, because it is the membrane process that underlies many lethal cardiac arrhythmias, and it is the molecular site of action of the most effective antiarrhythmic drugs. Single cardiac Purkinje cells were dialyzed at room temperature through a large bore pipette, and their Na+ currents were studied under voltage clamp control. The peak currents were 0.5 to 1.0 mA/cm2, assuming a 1 mu farad/cm2 membrane. Peak currents near 0 mV were achieved in less than 1 ms. The decay of the Na+ current did not correspond to a single exponential process. This result and the observation that recovery from inactivation occurred with a latency are inconsistent with the original Hodgkin-Huxley model, but they qualitatively fit a model with two sequential inactivated states or a model with two kinetically different types of Na+ channels. The steady state inactivation curve shifted in the negative direction after initiation of intracellular dialysis, stabilizing with a half-availability voltage of -115 mV.

Electrophysiological changes in the canine atrium and ventricle during progressive hyperkalaemia: electrocardiographical correlates and the in vivo validation of in vitro predictions.

The electrophysiological response to hyperkalaemia was reinvestigated in the whole dog for several reasons including: the paucity of comparative electrophysiological and electrocardiographical studies in which atrial and ventricular tissues were simultaneously investigated; the contrast between the clarity of findings in previous in vitro studies as compared with the rather conflicting results in earlier in vivo investigations; and the difficulty in validating the extrapolation from in vitro results and theory to the in vivo situation because of deficiences in the literature. Biphasic alterations in atrial and ventricular conduction times as well as excitability in response to progressively increasing hyperkalaemia were documented. The alterations in conduction times were reflected quite accurately by relevant electrocardiographical changes. Experiments in the whole animal were designed to test predictions based on membrane theory: the results offering strong support for the validity of extrapolating from the in vitro to the in vivo situation. The results of this study should help clarify and render interpretable many of the seemingly conflicting results in the literature.

Measurement of intracellular calcium ion activity with neutral exchanger ion sensitive microelectrodes.

Micropipettes filled with the neutral liquid ion exchanger ETH 1001 can be used to make microelectrodes that are sensitive to cytoplasmic levels of Ca2+. They are high resistance electrodes, so that care is required in order to record the low current signal. The electrodes often yield 10-15 mV change between intracellular Ca2+ activities of 10(-6) and 10(-7) M, according to a log relation. The microelectrodes are non-destructive, even in rather small cells, and can be used to monitor Ca2+ changes during experimental interventions.

Megatrends in medical education.

Several major financial trends affecting medical education are delineated and their implications described. To channel these new economic forces in a productive manner, the curriculum of undergraduate and, especially, graduate medical education need to be reevaluated to ensure that medical training is accomplished in an efficient manner and reflects career opportunities of graduates in an era of excess physician supply.

A laboratory study of spontaneous platelet aggregation.

During studies on platelet aggregation using the EEL platelet aggregation meter, 8% of the individuals tested were found to have platelets which aggregated spontaneously when citrated, platelet-rich plasma was stirred at 37 degrees C. The EEL aggregation meter differs from other machines in that it incorporates a vertical stirrer which subjects platelets to greater mechanical force. When using this machine it is suggested that spontaneous platelet aggregation is related to increased mechanical fragility of the platelets and low levels of plasma ADP-inhibitor.

Dental caries in South African black and white high school pupils in relation to sugar intake and snack habits.

DMFT scores, total sugar intakes and snacks habits were determined in 1918 South African Black pupils (923 rural, 995 urban) and 724 White pupils (English and Afrikaans speaking) aged 16-18 years inclusive. Mean DMFT scores of school groups of Black pupils (both sexes) ranged from 0.9 and 2.0 in rural areas, to 4.2-6.7 in urban areas (where data were far higher than such obtained 7 years ago), and were 9.2 and 10.2 for White pupils. Corresponding mean daily sugar intake were - rural Blacks, 69 g and 97 g, urban Blacks 118-141 g, respectively (all slightly higher than previously); and Whites 102 g and 123 g. Mean DMFT scores of girls were higher than those of boys; yet while mean sugar intakes of Blacks girls and boys were somewhat similar, White girls' intakes were much lower than those of White boys. In the ethnic-sex groups studied, mean DMFT scores for pupils in upper, compared with lower, third of sugar intake, were higher in nine of the 14 sub-groups. Mean DMFT scores in upper, compared with lower, third of exposure to snack practices were higher in 11 of the 14 groups. However, most of the differences were slight. In further research, more intensive enquiries should be pursued on roles of ethnic and familial factors, as well as on roles of inter-acting dietary components additional to sugar and sugar-containing foods.

Diagnosing and comanaging patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome, or OSAS, is a common, but underdiagnosed, disorder that potentially is fatal. It is characterized by repetitive episodes of complete or partial upper airway obstruction leading to absent or diminished airflow into the lungs. These episodes usually last 10 to 30 seconds and result in loud snoring, a decrease in oxygen saturation, and chronic daytime sleepiness and fatigue. The obstruction is caused by the soft palate, base of the tongue or both collapsing against the pharyngeal walls because of decreased muscle tone during sleep. Potentially fatal systemic illnesses frequently associated with this disorder include hypertension, pulmonary hypertension, heart failure, nocturnal cardiac dysrhythmias, myocardial infarction and ischemic stroke. CLINICAL IMPLICATIONS: The classic signs and symptoms of OSAS may be recognizable by dental practitioners. Common findings in the medical history include daytime sleepiness, snoring, hypertension and type 2 diabetes mellitus. Common clinical findings include obesity; a thick neck; excessive fat deposition in the palate, tongue (enlarged) and pharynx; a long soft palate; a retrognathic mandible; and calcified carotid artery atheromas on panoramic and lateral cephalometric radiographs. CONCLUSIONS: Dentists cognizant of these signs and symptoms have an opportunity to diagnose patients with occult OSAS. After confirmation of the diagnosis by a physician, dentists can participate in management of the disorder by fabricating mandibular advancement appliances and performing surgical procedures that prevent recurrent airway obstruction.

Panoramic dental radiography: an aid in detecting individuals prone to stroke.

Stroke (cerebrovascular accident, CVA) is the third leading cause of death and an important cause of hospital admission and long-term disability in England and Wales. Atherosclerotic lesions at the bifurcation of the common carotid artery are the most common cause of stroke. On occasion, these lesions are partially calcified and visible on a conventional panoramic dental radiograph. The atheroma may appear either as a nodular radiopaque mass or as two radiopaque vertical lines within the soft tissues of the neck at the level of the lower margin of the third cervical vertebra (C3). These opacities are separate and distinct from the hyoid bone and variably appear above or below it. Dentists should scrupulously review the panoramic radiographs of all individuals over the age 55 with medical histories (hypertension, diabetes mellitus, hypercholesterolaemia, coronary artery disease) and behaviours (smoking, alcohol abuse, dietary indiscretion, overweight, sedentary life-style) known to be associated with atherosclerosis and stroke.

Dentistry's role in the diagnosis and co-management of patients with sleep apnoea/hypopnoea syndrome.

The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by repeated upper airway narrowing or collapse during sleep. The obstruction is caused by the soft palate and/or base of tongue collapsing against the pharyngeal walls because of decreased muscle tone. These episodes are accompanied by hypoxaemia, surges in blood pressure, brief arousal from sleep and pronounced snoring. Individuals with occult disease are at heightened risk of motorway accidents because of excessive sleepiness, sustained hypertension, myocardial infarction, and stroke. The signs and symptoms of SAHS may be recognisable in the dental practice. Common findings in the medical history include daytime sleepiness, snoring, hypertension, and type 2 diabetes mellitus. Common clinical findings include male gender, obesity, increased neck circumference, excessive fat deposition in the palate, tongue (macroglossia) and pharynx, a long soft palate, a small recessive mandible and maxilla, and calcified carotid artery atheromas on panoramic and lateral cephalometric radiographs. Dentists who recognise these signs and symptoms have an opportunity to diagnose patients with occult SAHS. After confirmation of the diagnosis by a physician, dentists can participate in the management of the disorder by fabricating mandibular advancement appliances that enlarge the retroglossal space by anterior displacement of the tongue and performing corrective upper airway surgery that prevents recurrent airway obstruction.

Identification of stroke prone patients by panoramic radiography.

Stroke (cerebrovascular accident, CVA) is the third leading cause of death and an important cause of hospital admission and long term disability in Australia. Atherosclerotic lesions at the bifurcation of the common carotid artery are the most common cause of stroke. On occasion these lesions are partially calcified and visible on a conventional panoramic dental radiograph. The atheroma may appear either as a nodular radiopaque mass or as two radiopaque vertical lines within the soft tissues of the neck at the level of the lower margin of the third cervical vertebra (C3). These opacities are separate and distinct from the hyoid bone and variably appear above or below it. Dentists should scrupulously review the panoramic radiographs of all individuals over age 55 with medical histories of hypertension, diabetes mellitus, hypercholesteraemia and coronary artery disease, or whose behaviour includes smoking, ethanol abuse, or dietary indiscretion coupled with overweight and a sedentary lifestyle which are known to be associated with atherosclerosis and stroke.

The electrophysiologic effects of tolamolol (UK-6558-01) on the passive membrane properties of mammalian cardiac Purkinje fibers.

Tolamolol (UK-6558-01) is a relatively cardioselective beta receptor antagonist which is effective clinically in the treatment of supraventricular and ventricular arrhythmias. Animal studies suggest tolamolol may have significant antifibrillatory properties. The effect of tolamolol on the passive membrane properties of sheep cardiac Purkinje fibers was studied using multiple microelectrode techniques. In sodium-deficient Tyrode's solution, we measured the resting transmembrane voltage (Vr) at differing external potassium concentrations (K+]0, investigated current-voltage relationships and per formed cable analysis. Tolamolol was found to hyperpolarize the membrane in the presence of a large driving force [i.e., when (Vr - VK) was significantly greater than zero, where VK is the potassium equilibrium voltage ]; to hyperpolarize fibers with a Vr decreased due to stretch at [K+]0 = 4.0 mM; to increase membrane chord and slope potassium conductance; to decrease the membrane length constant; and to decrease the membrane time constant. In normal sodium Tyrode's solution, tolamolol could suppress automaticity. These results suggest that tolamolol increases membrane potassium conductance within the range of the pacemaker potential. This action can account, in part, for its ability to suppress automaticity and for its ability to prevent reentrant arrhythmias. In normal sodium Tyrode's solution, tolamolol suppressed oscillatory and sustained rhythmic activity occurring at a low transmembrane voltage which may be related to its alleged antifibrillatory effects.

Utilization of MEDFILE--a preprinted medical literature filing system.

To facilitate the creation of a personal medical literature filing system, we developed MEDFILE, a noncomputerized, preprinted medical literature filing system. A graduating medical school class that had access to MEDFILE and a control group of incoming interns were studied to ascertain satisfaction, usage, utility, and implementation of MEDFILE in comparison with traditional literature filing systems. Data were obtained from 52 recent graduates of the site school and 25 graduates of other institutions. MEDFILE users had a significantly higher satisfaction level (7.3 +/- 1.5 vs 4.5 +/- 2.7, p less than .0001, two-tailed t-test), a more extensive filing system (p less than .02, chi square), and greater confidence that their filing system would remain useful during residency (p less than .0001, Fisher's exact test) than new graduates who had created their own filing systems. The data indicate that MEDFILE is an efficient, effective, and inexpensive method of organizing medical reprints. It may be particularly useful for physicians entering primary care disciplines that require information processing over a wide range of clinical topics.

Students evaluate MEDFILE, a preprinted medical literature filing system.

Medical professionals are highly dependent on personal libraries and reprint files as their sources for current information. A large population of practising doctors have poorly organized medical literature data bases in their professional environment. To expedite the development of a personal library data base by medical students, we created MEDFILE, a preprinted, cross-indexed file folder system for organizing the medical literature. This paper reports the results of two surveys performed in connection with the distribution of the MEDFILE system. One hundred per cent of the students who used MEDFILE found the system to be beneficial. Ninety-seven per cent felt their ability to find their personal literature improved by using MEDFILE, and 65% felt MEDFILE improved their clinical preparation. Of all surveyed recipients of the system, 96.8% felt MEDFILE would be useful in their future studies.

Dental management considerations in children with attention-deficit hyperactivity disorder.

Children suffering from attention-deficit hyperactivity disorder frequently have numerous orofacial anomalies of concern to the dentist. Behavioral manifestations of the disorder frequently impair the patient's ability to perform home care adequately, make dental treatment arduous, and place the patient at risk of physical abuse from family and peers. Familiarity with the symptoms and treatment of the disorder will better prepare the dentist to meet the needs of this unique group of patients.

Dental management of child and adolescent patients with schizophrenia.

Schizophrenia is a psychiatric disorder in which thought disturbances and aberrant behavior lessen an individual's ability to care for him or herself and to effectively work and communicate with others. The disorder affects 1 percent of the United States population. Onset of the florid psychotic symptoms most commonly occurs during adolescence or young adulthood, but most of these youngsters exhibit unusual behavior and peculiar thinking during childhood. Medications used in managing the disorder have numerous systemic and orofacial adverse side effects that must be recognized by dentists. Dental treatment strategies for the identification and management of these side effects are described as is a method to improve compliance with oral hygiene techniques.

Dental management of the child with developmental dyslexia.

Dyslexia, a biologically determined reading disorder effects an estimated 3 percent to 10 percent of school-age children in the United States. Standard pediatric dental protocols frequently have to be modified because many of these children concurrently suffer attention-deficit-hyperactivity disorder (ADHD), asthma, thyroiditis and inflammatory bowel disease (ulcerative colitis and Crohn's disease). Youngsters suffering from dyslexia and ADHD should have their dental appointments scheduled in the morning when they are most attentive and best able to remain seated in the dental chair. An aspirating dental syringe must be used in order to avoid an intravascular injection and the possibility of an adverse interaction between the pressor agents used with local anesthesia and the medication used to treat ADHD. Aspirin, other nonsteroidal antiinflammatory agents (e.g., ibuprofen) and local anesthetic agents containing vasoconstrictor and preservative (antioxidants, i.e., sulfite) agents should be avoided in children with concurrent asthma because of their propensity to trigger an asthmatic attack. Children with uncontrolled hyperthyroidism should receive only emergency care and this care should be provided in a hospital. Children with hypothyroidism are hyperresponsive to even small dosages of analgesics and anesthetic agents; proper dosing and venue of dental procedures should be a joint decision between the child's dentist and pediatrician. Children with dyslexia and concurrent inflammatory bowel disease may require shorter appointments and nitrous oxide sedation to reduce stress. Those receiving corticosteroids or with a history of steroid therapy within the past year may need supplementation to avoid an adrenal crisis brought about by the stress of dental care.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Ca2+/Mg2+ removal on aiNa, aiK, and tension in cardiac Purkinje fibers.

Sheep cardiac Purkinje fibers were exposed to solutions free of divalent cations for hour-long periods, while intracellular Na+ and K+ activities were measured using ion-sensitive microelectrodes. Intracellular Na+ activity (aiNa) increased to 50.1 +/- 8.1 mM, and intracellular K+ activity (aiK) decreased to 76.7 +/- 3.5 mM. These ionic changes could be blocked by the presence of Mg2+ or the Ca2+ channel blocking agents D 600 and nifedipine. The rise in aiNa and the fall in aiK was accentuated by the inhibition of the Na+-K+ pump with acetylstrophanthidin or by removal of extracellular K+. These results demonstrate that in cardiac Purkinje fibers removal of divalent cations produces intracellular loading of Na+ by Na+ entry through the Ca2+ channel. On reexposure to Ca2+-containing solutions, the cells become loaded with Ca2+, and the fibers exhibit large contractures. These observations implicate Na+-Ca2+ exchange in the entry of Ca2+ into these cells during Ca2+ repletion and in the etiology of the calcium paradox.

Detection of radiation-induced, accelerated atherosclerosis in patients with osteoradionecrosis by panoramic radiography.

PURPOSE: Osteoradionecrosis (ORN) of the mandible has long been considered the most destructive complication of head and neck irradiation. Recently, therapeutic irradiation has been implicated as the cause of induced/accelerated atherosclerosis of the cervical carotid artery and subsequent stroke. Panoramic radiography, previously shown to be capable of identifying carotid artery atherosclerosis in nonirradiated individuals, was used to assess the carotid vasculature of patients being treated for ORN. PATIENTS AND METHODS: The panoramic radiographs of 61 men (mean age, 60.5 years; range, 41 to 77 years) who received therapeutic irradiation to the neck 36 months or more previously were assessed for the presence of carotid artery atherosclerotic lesions. Sixty-one control subjects who never received therapeutic irradiation, but who were similarly susceptible to atherosclerosis by virtue of age, were assessed in a like manner. RESULTS: The irradiated individuals sustained a dose of 40 to 72 Gy to the area of the carotid bifurcation. Seventeen individuals (27.9%) with an irradiation dosage to the carotid bifurcation that averaged 59.2 Gy had a panoramic radiograph with a carotid atheroma (11 with unilateral lesions and six with bilateral lesions). The radiographs of the control subjects showed that three individuals (4.9%) had calcified carotid lesions. The mean age of these subjects was 66.1 years; two had unilateral lesions, and one had bilateral lesions. The difference in the proportion of individuals with ORN who manifested carotid artery atherosclerosis on their panoramic radiographs was statistically significant (P = .001) when compared with the nonirradiated control subjects. The lesions seen in both populations had a similar morphologic appearance and were radiographically located within the soft tissues of the neck 1.5 to 4.0 cm inferior-posterior to the angle of the mandible. CONCLUSIONS: Individuals with radiation doses sufficient to cause osteoradionecrosis of the mandible are at significantly higher risk of developing carotid artery atherosclerotic lesions than age-matched, nonirradiated controls.

The prevalence of carotid atheromas seen on panoramic radiographs of patients with obstructive sleep apnea and their relation to risk factors for atherosclerosis.

PURPOSE: Persons with obstructive sleep apnea syndrome (OSAS) suffer inordinately high rates of stroke, but the cause remains in doubt. Atherosclerosis (atheroma formation) of the extracranial carotid artery has been suggested as a possible cause. Because atheromas can be recognized on panoramic radiographs, this study compared their prevalence in subjects with OSAS and normal controls and analyzed their relation to atherogenic risk factors. PATIENTS AND METHODS: Panoramic radiographs and medical records of 54 male subjects (mean age, 60.4 years) with OSAS (apnea/hypopnea index [AHI] of 15 or greater and a history of snoring and excessive daytime sleepiness) were assessed for atheromas and risk factors. Age-matched controls were likewise assessed. RESULTS: Twelve individuals (22%) with OSAS showed atheromas on their radiographs. The radiographs of the controls showed that 3.7% had atheromas. This finding was statistically significant (P = .0079). The prevalence of type 2 diabetes mellitus among individuals with OSAS and atheroma formation (7 of 12 persons, 58%) was far greater than the prevalence of diabetes (10 of 42 persons, 24%) experienced by individuals with OSAS but free of atheroma formation. This finding was also statistically significant (P = .035). The lesions seen in both the subject and control populations were similar and were located in the neck, 1.5 to 2.5 cm inferior-posterior to the angle of the mandible. CONCLUSIONS: Persons with OSAS are more likely to manifest calcified atheromas on their panoramic radiographs than age-matched controls. Type 2 diabetes is significantly more prevalent in individuals with both OSAS and calcified atheromas.

Dental management of the child and adolescent with major depression.

Major depression is a psychiatric disorder in which mood, thought content, and behavioral patterns are impaired, often for an extended period of time. This condition appears to have an increasing prevalence among young children and adolescents. It may be associated with a disinterest in performing appropriate preventive oral hygiene techniques, a cariogenic diet, rampant dental decay, and advanced periodontal disease. Appropriate dental management necessitates a vigorous preventive dental education program and special precautions when administering local anesthetics and prescribing sedative and analgesic medications.