Overview of management of atrial fibrillation in symptomatic elderly patients: pharmacologic therapy versus AV node ablation.

Atrial fibrillation is an abnormal heart rhythm affecting the upper chambers of the heart in which uncoordinated electrical depolarizations lead to ineffective contractions. Approximately five million patients in the US have atrial fibrillation, and this number is expected to double to 10 million over the next 30 years. Advancing age is a major risk factor for the development of atrial fibrillation; new cases of atrial fibrillation are diagnosed in men over age 80 at the rate of 2% per year. Although several drugs are available for management of atrial fibrillation, the efficacy of these drugs may be limited in elderly patients. In this review, we provide an overview of management of atrial fibrillation, with special emphasis on pharmacologic therapy versus arteriovenous (AV) node ablation in symptomatic elderly patients.

The clinical course of multifocal atrial tachycardia in infants and children.

OBJECTIVES: This study outlines the clinical course, treatment and the late outcome of infants and children with multifocal atrial tachycardia (MAT). BACKGROUND: Multifocal atrial tachycardia is defined by three distinct P-waveforms, irregular P-P intervals, isoelectric baseline between P-waves and rapid rate on an electrocardiogram. Several smaller prior reports have described pediatric patients with MAT, but their long-term outcome has not been fully assessed. METHODS: The clinical records, echocardiograms and long-term follow-up of patients with MAT were reviewed and compared to previous reports of MAT. RESULTS: Fourteen boys and seven girls (median age 1.8 months) presented with MAT. At diagnosis, six patients had respiratory illness, of whom two were critical. Ten were asymptomatic. Seven patients had structural heart disease (SHD), one of whom died. Four of 15 patients (27%) with echocardiograms had diminished ventricular function. Ventricular rates were 111 to 253 beats/min (mean 181 beats/min). Median duration of the arrhythmia was 4.9 months (mean 6.7 months). Electrical cardioversion was attempted in 4 patients without success and 15 patients received antiarrhythmic medication. Seventeen patients were followed for a mean of 60 months. Four patients were lost to follow-up. There were no late arrhythmias. CONCLUSIONS: The majority of children with MAT are healthy infants under one year of age; a few may exhibit mild to life-threatening cardiorespiratory disease. Less often, MAT accompanies SHD. Mild ventricular dysfunction may be observed in the presence of MAT, but symptoms are few and resolution is generally complete. Response to antiarrhythmic agents is mixed, and cardioversion is of no avail. Finally, long-term cardiovascular and developmental outcome depends principally on underlying condition; for otherwise healthy children, it is excellent.

An adenoviral vector system for functional identification of nuclear receptor ligands.

A recombinant adenovirus system has been designed that confers glucocorticoid responsiveness upon infected cells in culture. Two mutually dependent viruses are required: a trans-activator virus containing the human glucocorticoid receptor transcription unit and a second receptor virus harboring a glucocorticoid response element linked to the firefly luciferase gene. Another reciprocal pair of viruses has been generated; one member expresses the rat thyroid hormone receptor alpha, while the other contains the luciferase gene regulated by a thyroid hormone-responsive DNA element. Corticosteroid- or thyroid hormone-induced transcription can be efficiently and accurately quantitated from cells coinfected with the appropriate complementary virus pair 20 h after infection in 96-well microtiter plates. This coinfection assay offers a convenient way to measure transcriptional activation by nuclear receptors and has certain key advantages over the commonly used cotransfection method. Its sensitivity and precision make it a practical approach to rapidly identify substances extracted from complex biological samples activating candidate "orphan" nuclear receptor molecules.

Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in rat liver, kidney, pituitary and brain.

The hepatic, vascular-type (V1aR) and the renal, antidiuretic-type (V2R) vasopressin receptor cDNAs were recently cloned from rat liver and kidney libraries, respectively. DNA fragments containing the region encoding the putative 5/6 transmembrane loops of these receptors were subcloned, separately, into RNA polymerase promoter-containing vectors from which 35S-labeled sense and antisense riboprobes were synthesized. In situ hybridization histochemistry showed high levels of V1aR transcripts in the liver and the renal medulla among the vascular bundles. Sparser labeling was found in the renal cortex, but there were no grains over the glomeruli. V1aR mRNA was detected in many brain areas, including the hippocampal formation, central amygdala, dorsolateral septum, lateral hypothalamus, suprachiasmatic, ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus, nucleus of the solitary tract, cerebellum, spinal nucleus of the trigeminal tract, reticular formation, inferior olivary nucleus, and choroid plexus. Rare labeled cells were seen along the periphery of the posterior pituitary. V2R transcripts were not detected in the liver or brain, but were present in high amounts in the inner and outer renal medulla, primarily associated with collecting ducts. Sparser labeling was found in the renal cortex, and no grains were seen over the glomeruli. These data confirm the expression of the V1a vasopressin receptor in liver and brain and demonstrate that kidney expresses mRNAs encoding V1a and V2 vasopressin receptors.

Temperature-dependence of the action of nerve blocking agents and its relationship to membrane-buffer partition coefficients: thermodynamic implications for the site of action of local anaesthetics.

The local anaesthetic action of a series of nerve blocking agents was examined at temperatures between 4 degrees C and 20 degrees C in isolated sciatic nerves from cold-adapted frogs. Cooling alone had little effect on the amplitude of the action potential but the conduction velocity was decreased and the duration increased. Cooling had little effect on the local anaesthetic action of the short chain alkanols but that of the long chain alkanols, benzyl alcohol, benzocaine and pentobarbitone was markedly enhanced. The partition of both short and long chain alkanols and of pentobarbitone into a liposome suspension of similar composition to axonal membrane lipids was reduced by cooling from 40 degrees C to 4 degrees C. The results are not compatible with the lipid hypotheses of anaesthetic action. The implications for the nature of the site of action are discussed.

Cerebrospinal fluid profile in patients with acute Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood for which there is currently no diagnostic test. The clinical presentation of KD may initially resemble other infectious diseases, including bacterial or viral meningitis. For this reason lumbar puncture (LP) is sometimes performed during the evaluation of these patients. To understand the range of cerebrospinal fluid (CSF) changes that may be associated with acute KD, a retrospective review of unselected KD patients from three pediatric centers was performed. METHODS: Retrospective chart review was performed on KD patients evaluated during the first 10 days of illness who had an LP performed before the administration of intravenous gamma-globulin. RESULTS: During the 6.5-year study period, 46 KD patients underwent LP as part of their clinical evaluation. Of these patients 18 (39.1%) had CSF pleocytosis, 1 (2.2%) had a CSF glucose <45 mg/dl and 8 (17.4%) had an elevated CSF protein. Of the patients with CSF pleocytosis, the median white blood cell count was 22.5 cells (range, 7 to 320 cells), with a median of 6.0% neutrophils (range, 0 to 79%) and 91.5% mononuclear cells (range, 11 to 100%). CONCLUSIONS: In the present series approximately one-third of KD patients who underwent an LP had CSF pleocytosis with a mononuclear cell predominance. No patient had significant hypoglycorrhachia, and elevation of the CSF protein was uncommon. CSF abnormalities were similar between US and Japanese KD patients. The basis for the CSF pleocytosis in acute KD patients remains unknown.

Survival of Schistosoma mansoni in the human host: estimates from a community-based prospective study in Puerto Rico.

Changes over time in the prevalence and intensity of Schistosoma mansoni infection were measured by serial quantitative stool examinations using the modified Ritchie concentration technique in a 9-year prospective study of an endemic Puerto Rican community with a population of about 1,000 persons. The complete interruption of transmission was achieved by snail control during the 2nd year of the study, in February 1973. Annual stool specimens were obtained from all willing community residents. In addition, from 27 of these residents 10 consecutive stools were collected in each of 3 years: 1973, 1976, 1977. After a chemotherapy campaign with oxamniquine in 1980, only eight of these 27 persons remained untreated. Ten consecutive stools were collected from seven of these untreated individuals in 1981. We calculated the rate of decline (beta) in geometric mean egg count in the cohort of 27 over 5 years and in the subcohort of seven over 9 years. Similarly, beta was calculated from the change in the single annual stool counts in 528 persons providing data for all of the first 6 years of the study. Estimates of the average life-span (-1/beta, in a model assuming constant rate of death) of the adult S. mansoni with 95% confidence intervals are for the cohort of 27, 5.5 years (4.0 to 9.1), for the cohort of seven, 37 years (8.0 to infinity), and and for the cohort of 528, 35 years (16 to infinity).(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone.

A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while in combination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria.

The public health significance of urinary schistosomiasis as a cause of morbidity in two districts in Mali.

Schistosoma haematobium-related morbidity was studied in the perennial irrigation area of Office du Niger and the small reservoirs area of Plateau Dogon in Mali. Questionnaire, clinical, parasitologic, and ultrasound examination data were collected from 1,041 individuals at the baseline survey in 1991; 705 were re-examined one year after treatment. At baseline, the overall prevalence of S. haematobium infection was 55.2%; half of those infected had no clinical symptoms and 30% had pathologic lesions. Both infection and morbidity were more frequent in children than in adults, with a peak prevalence at 7-14 years of age. The rates of lesions were more than twice as high in those heavily infected as in lightly infected individuals. Reagent strip testing for microhematuria was more sensitive in detecting individuals with pathologic lesions than in detecting individuals with infection. One year after treatment with praziquantel, more than 80% of the urinary tract lesions had cleared. It is concluded that S. haematobium-related morbidity is frequent in Mali, but passive case detection for treatment would not cover a great deal of early stages of the disease; active intervention using reagent strip testing for microhematuria at the most peripheral levels would be an efficient system for morbidity control and monitoring of control operations.

The role of the posterior cerebellar vermis in cardiovascular control.

The effects of electrical stimulation of the posterior cerebellar vermis in anaesthetized, decerebrate and conscious animals are described, and include marked changes in blood pressure and heart rate and an inhibition of the baroreceptor reflex. These effects appear to be restricted to lobule IX, and can be duplicated by chemical stimulation, indicating that they are a genuine cerebellar phenomenon. The results of both neuroanatomical and neurophysiological experiments to investigate the pathways responsible for the effects are described, and these show there to be a direct projection of Purkinje cell axons to the parabrachial nucleus. Experiments designed to test a possible involvement of lobule IX in the alerting response have proved negative, and while lobule IX itself appears to have no role in conditioned cardiovascular responses, lesions of lobules VI and VII do result in a significant impairment of the acquisition of conditioned bradycardia in the rabbit.

Validation of malaria surveillance case reports: implications for studies of malaria risk.

STUDY OBJECTIVE: The aim of the study was to investigate the quality of national malaria surveillance reports in the United Kingdom. DESIGN: Persons with malaria reported to the Malaria Reference Laboratory (MRL) in 1987 were contacted by post to verify existing records with respect to key variables. The MRL data set was then analysed for inaccuracies. SETTING: The study was confined to UK residents. PARTICIPANTS: 602 persons with malaria in 1987 responded (53%). MEASUREMENTS AND MAIN RESULTS: Review of case reports showed few missing data except for duration of residence in the UK, detailed chemoprophylactic regimens, and compliance. There were more missing surveillance data in reports of ethnic minority groups, principally in dates of travel (p = 0.008) and chemoprophylaxis use (p less than 0.0001). Patient recall in the survey was at variance with the surveillance reports in dates of travel and onset of infection, chemoprophylaxis use, and in compliance. Surveillance reports overestimated the number of days between leaving a malarious area and onset of symptoms (by 9 d for P falciparum and by 24 d for P vivax), and underestimated the delay between onset and diagnosis of P falciparum by 3 d. Over 50% of patients who had recalled the use of chloroquine, proguanil, pyrimethamine/dapsone, and pyrimethamine had not been recorded as having taken these drugs on the surveillance reports. Reported compliance also differed between the two data sets. CONCLUSIONS: It is recommended that research units test the quality of their surveillance data before embarking on analytical studies used to generate health policy guidelines.

Correlated nerve conduction, somatosensory evoked potential and neuropathological studies in clioquinol and 2,5-hexanedione neurotoxicity in the baboon.

Observations have been made on 10 baboons receiving a high-dose regimen of clioquinol administered orally, 6 receiving a low-dose regimen and 6 treated with 2,5-hexanedione. The results were compared with those obtained from 10 control animals. Motor and sensory nerve conduction velocity was markedly reduced in the hexanedione-treated animals but only very minor abnormalities were detected in the clioquinol-treated baboons. Cervical and Rolandic somatosensory evoked potentials to lower and upper limb stimulation were delayed in both the high-dose clioquinol-treated and the hexanedione-treated animals, particularly in the latter. Histopathological studies in the low-dose clioquinol-treated group showed no abnormalities. In the high-dose group; axonal degeneration was confined to the spinal cord, cerebellar vermis and optic tract. It was most marked in the rostral portions of the dorsal spinal columns and the caudal parts of the direct and crossed corticospinal tracts. Occasional dorsal column fibres had degenerated back to the root entry zone in the cord. The distribution was that of a selective central distal axonopathy. There appeared to be no correlation with estimated blood levels of unaltered clioquinol. In hexanedione-treated animals there was also degeneration in the distal optic tracts and peripheral nerves in a pattern of central-peripheral distal axonopathy.

Consequences of helminth aggregation for the dynamics of schistosomiasis.

The distribution of schistosome worms among their human hosts is not random but aggregated. The consequences of introducing aggregation into models of schistosomiasis transmission, especially that of Macdonald, are explored. There are two possibilities for aggregation, with the sexes distributed either independently or together. Both have profound though differing effects on the breakpoint concept, which is largely destroyed when the sexes are aggregated together, and Macdonald's epidemiological conclusions are not robust to variations from the Poisson distribution. The conclusion from his model that if schistosome densities in man are reduced appropriately the infection will spontaneously proceed to extinction even in the presence of conditions suitable for transmission, is also not therefore robust.

The interpretation of intensity and aggregation data for infections of Schistosoma haematobium.

The relationships between mean intensities of infection, the aggregation of infection among hosts, and host age are analysed using data from 2 large (> 3000 individuals) field studies of Schistosoma haematobium infection. The data show a convex relationship between mean intensity and age, a convex relationship between an inverse index of aggregation and age, and an age-dependent relationship between the mean and aggregation of infection intensity when levels of infection are high. These patterns are qualitatively compared with the output of mathematical models based on an immigration-death process (model I), and incorporating age-dependent changes in the distribution of exposure to infection as suggested by field data (model II), or reductions in the rate of infection as a function of either current (model III) or cumulative (model IV) parasite burdens, that is, density-dependent processes without or with memory, respectively. Models II and III were able to reproduce observed patterns, but model IV, which is a possible representation of acquired immunity, was not. These results are consistent with the following assumptions: (i) age-related patterns of aggregation can be generated without recourse to density-dependent processes; (ii) the epidemiological impact of density-dependent processes depends on whether these act with or without memory; and (iii) any acquired immunity to human S. haematobium infection may be significantly less than life-long.

Survival of toxigenic Vibrio cholerae O1 with a common duckweed, Lemna minor, in artificial aquatic ecosystems.

Cholera epidemics occur twice a year in Bangladesh. During epidemics, Vibrio cholerae O1 are isolated from patients, as well as from the surface water, but the bacteria disappear during inter-epidemic periods. Their reservoirs or sites of survival and multiplication during inter-epidemic period are still unknown. The present survival study in the laboratory explored the role of an aquatic plant, Lemna minor (duckweed), as a possible reservoir. L. minor was added to sea-salt solution at pH 8.5, containing V. cholerae. Survival of V. cholerae on L. minor, in water on which L. minor was floating, and in control water (without L. minor) was monitored at regular intervals. Survival of both environmental and clinical strains of V. cholerae was assessed by viable counts on thiosulphate-citrate-bile salt-sucrose agar. It was observed that both strains survived better on L. minor than in water on which L. minor was floating or in control water. It is suggested that plants may serve as an effective environmental reservoir for V. cholerae either through a non-specific association or by interaction with V. cholerae in commensal relationship.

Infecting dose and severity of falciparum malaria.

The causes of the wide spectrum of severity in malaria have only partly been elucidated. There are theoretical reasons for thinking that the infecting dose may influence the severity, but evidence is scare. We have analysed the records of 82 non-immune neurosyphilis patients bitten by a known number of mosquitoes infected with one of 3 strains of Plasmodium falciparum, whose treatment was delayed. After controlling for strain, the number of mosquitoes was not associated with the prepatent period nor with any of the outcome measures. For one of the main strains, patients with shorter prepatent periods were more likely to receive treatment during the acute phase of the infection, but no other association with measures of severity was found. This study suggest that infecting dose is unlikely to be an important determinant of severity.

Regulation of Leishmania populations within the host. IV. Parasite and host cell kinetics studied by radioisotope labelling.

Tritiated thymidine pulse labelling followed by autoradiography has been used to analyse the kinetics of Leishmania donovani infections within the mouse host. Resistant strains of mice show much lower parasite proliferation rates than do susceptible strains. In chronic infections the rate is also reduced. Parasitised mononuclear phagocytes may undergo mitosis. No evidence for selective destruction of parasitised cells in chronic infections was found by labelling methods. It is possible to get parasite labelling in vitro immediately after biopsy to levels comparable to those seen in vivo.

Inoculum size and severity of malaria induced with Plasmodium ovale.

Although it might be expected that the size of the infecting inoculum would influence the severity of the consequent malaria, evidence that it does so is scarce. Using records from 80 non-immune neurosyphilis patients who received malaria therapy with a single strain of Plasmodium ovale by blood inoculation, the relationships between the number of trophozoites inoculated, the prepatent period, and measures of severity of the resulting malaria were examined. The number of trophozoites was not related to any of the outcome measures, but patients with shorter prepatent periods had higher and more peaks of fever and longer lasting infections.

Intensity dependent time-resolution and dynamic range of Photochron picosecond streak-cameras.

The dynamic range of operation of Photochron I and Photochron II picosecond streak cameras is shown to depend upon the time-resolution employed. For events approximately 2 ps a useful dynamic range of 30 is obtainable, and this increases to a value of 180 for 30-ps events. No accumulative saturation effects occur at a time resolution as short as 2 ps.

Repetitive vacuum ultraviolet xenon excimer laser.

A repetitive, tunable, high-power vacuum ultraviolet laser operating on the 172-nm bound-free transition in xenon has been developed for use in photochemistry, selective excitation spectroscopy, and in the generation of coherent radiation in the XUV spectral region. A compact high-voltage generator is employed in conjunction with a coaxial cold-cathode diode to pump high-pressure xenon at a repetition rate of up to 10 Hz, though at present gas heating limits the operation of the laser to 0.5 Hz. The apparatus has been designed for compatibility with fluorine, and is consequently a suitable pumping source for the rare gas halide exciplex lasers. The gas handling techniques which enabled reliable, reproducible laser action to be achieved in xenon for several hundred pulses are described.