High-resolution fluorescent imaging does not reveal a distinct atrioventricular nodal anterior input channel (fast pathway) in the rabbit heart during sinus rhythm

INTRODUCTION: We sought to determine the precise pathways of engagement of the AV node during sinus rhythm. METHODS AND RESULTS: Langendorff-perfused rabbit hearts were stained with 20 microM of the voltage-sensitive dye di-4-ANEPPS. Preparations containing the right atrium, sinoatrial (SA) and AV nodes, and interatrial septum were subsequently dissected and mapped in vitro using a 16 X 16 photodiode array with an adjustable resolution of 150 to 750 microns per diode. Motion artifacts were eliminated by using 15 mM 2,3-butanedione monoxime (BDM). Activation time-points were defined as (-dF/dt)max' where F = fluorescence. Isochronal maps of activation were plotted using the triangulation method. In all preparations, spontaneous activation began at the SA node, rapidly spread along the crista terminalis (CrT), entered the AV nodal region via the posterior "slow" pathway, and retrogradely spread to the septal region with a smaller conduction velocity compared to that along the CrT. Collision of anterograde and retrograde wavefronts was frequently observed in the mid-septum. Notably, there was no evidence for the presence of a distinct anterior entrance into the AV node. CONCLUSIONS: Fast pathway conduction during sinus rhythm results from a broad posterior wavefront that envelops the AV node with subsequent retrograde atrial septal activation.     

Acid tolerance response and survival by oral bacteria

Using 21 species of oral bacteria, representing six acidogenic genera, we undertook to determine whether the pH-limiting exponential growth is related to the ability of the organisms to generate an acid-tolerance response that results in enhanced survival at low pH. The lower pH limit of exponential growth varied by more than two units with that of Neisseria A182 at pH 6.34; growth of Lactobacillus casei RB1014 stopped at pH 3.81, with species of Actinomyces, Enterococcus, Prevotella and Streptococcus falling between these limits. The working hypothesis was that the organisms with the higher pH limits for growth are unable to respond to acidic environments in order to survive, whereas the more aciduric organisms would possess or acquire acid tolerance. Adaptation to acid tolerance was tested by determining whether the prior exposure of exponential-phase cells to a low, sub-lethal pH would trigger the induction of a mechanism that would enhance survival at a pH killing pH 7.5 control cells. The killing pH varied from pH 4.5 for Prevotella intermedia ATCC 25611 to pH 2.3 for the three Lactobacillus casei strains in the study, with the three Streptococcus mutans strains killed at pH 3.0 for 3 h. The adaptation experiments revealed three groups of organisms: non-acid-responders, generally representing strains with the highest terminal pH values; weak acid-responders in the middle of the pH list, generating low numbers of survivors at one or two pH values, and the aciduric, strong responders generating a high number of survivors at pH values in the range 6.0 to 3.5, but not at pH 7.5. Predominant among the latter group were the S. mutans and Lactobacilli casei strains, with the most significant adaptive response exhibited by S. mutans LT11 and S. mutans Ingbritt, involving a process that required protein synthesis. Time course experiments with the latter organisms indicated that 90-120 min was required after exposure to the triggering pH before the acid response was fully functional. These results indicate that the sudden exposure of strains of oral streptococci and lactobacilli, as well as Enterococcus faecalis, to pH values between 6.0 and 3.5 results in the induction of an acid tolerance response that enhances the survival of these strains at or below pH 3.5.     

Hepatic Retransplantation--an analysis of risk factors associated with outcome

Hepatic retransplantation is controversial because the results are inferior to primary transplants and organs are so scarce. To determine the factors that are associated with poor outcome within the first year following retransplantation, we performed a multivariate analysis, using stepwise logistic regression, of 418 hepatic retransplantations performed at a single institution from November 1987 to December 1993. The minimum follow-up was 1 year. Seven variables were found to be independently associated with subsequent graft failure (defined as either patient death or retransplantation): donor age (odds ratio 2.2 for each 10-year increase over age 45, 95% CI 1.3 to 3.7), female donor sex (odds ratio 1.7, 95% CI 1.05 to 2.7), recipient age (odds ratio 1.6 for each 10-year increase over age 45,95% CI 1.2 to 2.8), need for preoperative mechanical ventilation (odds ratio 1.8, 95% CI 1.1 to 2.9), pretransplant serum creatinine (odds ratio 1.24 for each increase of 1 mg/dl, 95% CI 1.1 to 1.4), pretransplant total serum bilirubin (odds ratio 1.4 for each 10-mg/dl increase over 15 mg/dl, 95% CI 1.1 to 1.8), and the primary immunosuppressant, using tacrolimus as the reference category (odds ratio for cyclosporine-based immunosuppression 3.9, 95% CI 2.3 to 6.8). Although not part of the logistic regression model, the timing of retransplantation was also found to be important, with the overall probability of failure increasing from 0.58 on day 0 to a peak of 0.8 on day 38 and decreasing slowly after that. The implications of these results regarding the appropriateness of retransplantation are discussed.     

Complications of renal cyst puncture

One hundred nineteen renal cyst punctures have been reviewed. There have been four complications (3.4 per cent), three requiring surgery. This should be expected, as all invasive diagnostic procedures are accompanied by some morbidity. The relative benefit of nonoperative diagnostic procedures in differentiating benign renal cyst from adenocarcinoma is discussed.     

The PHANTASTICA gene encodes a MYB transcription factor involved in growth and dorsoventrality of lateral organs in Antirrhinum

To study the impact of yeast populations on wine flavour and to better understand yeast growth dynamics, wines were produced by the (i) indigenous microflora, (ii) vigorous yeast starter EC1118 and (iii) slowly fermenting yeast Assmannshausen. Sensory analysis revealed that wines differed depending on the fermentation type. However, these yeast-related differences did not exceed the varietal character. Both added starter cultures clearly dominated the Saccharomyces population from the middle of fermentation onwards. The starter cultures differed in their repression of indigenous non-Saccharomyces yeast. EC1118 limited growth of non-Saccharomyces yeasts more strongly than Assmannshausen. Sulphite addition further repressed growth of non-Saccharomyces yeasts. On completion, more than one Saccharomyces strain was present in each fermentation, with the largest variety in the non-inoculated and the smallest in the EC1118-inoculated fermentation. Results from the two genetic assays, karyotyping, and PCR using delta-primers were not fully equivalent, limiting the usefulness of delta-PCR in studies of native Saccharomyces yeasts.     

The use and overlap of AED and general practice services by patients registered at two inner London general practices

BACKGROUND: The improvement of general practitioner (GP) availability has been suggested as a factor influencing the rise in attendance rates at accident and emergency departments (AEDs) in the United Kingdom, particularly in innercity areas. However, previous studies suggest that only 3-6% of patients attempt to contact their GP before attending the AED, and measures of the availability of appointments in the surgery are not associated with AED self-referral rates. AIM: To examine the overlap of services between general practice and AEDs, and the characteristics of patients who attend at both sites. METHOD: A prospective observational study, set in east London, of all AED attendances from two group practices located within two kilometers of the Royal London Hospital, over a seven month period in 1994. RESULTS: Of 1785 attendances analysed, 80% were self referrals. Rates of hospital admission (18.1%) and outpatient referral (9.5%) reflect national figures. There was a significantly higher proportion of attendance from those of white ethnicity among children under 16. Using the Sheffield process-based classification, 43% of adult attendances were categorized as primary care attendances. Within this category the rate of attendance declined with age. Twenty-five point eight per cent of primary care attendances occurred between 10.00 pm and 8.00 am. Among self-referrals to the AED, 16% were seen by their GP in the previous two weeks for a similar problem. Frequent attendance at the AED was associated with a significantly higher consultation rate at the GP surgery (F = 19.6, df = 5, P < 0.0001). Less than 2% of attendances were recalled to the AED for follow-up. A minority (14%) of attendances resulted in a communication with the GP. The seven-month AED attendance rates for the two practices were significantly different (72 per 1000 (95% CI 67-78) and 111 per 1000 (95% CI 105-116), despite similar practice organization and markers of social deprivation. CONCLUSIONS: AED attendance rates were below the national average. GP referral and admission rates to AEDs from inner urban practices mirror national rates. High rates of primary care attendance occurred in younger age groups, with more than expected occurring out of hours. The reduction in case follow-up within the AED must be supported by improvements in communication with GPs, and an expansion of practice-based nursing. Practices that are geographically close, and with similar sociodemographic features, may have different AED attendance rates. This has important implications for resource allocation in primary care.     

Heparin modulates the interaction of VEGF165 with soluble and cell associated flk-1 receptors

The 165-amino acid form of vascular endothelial growth factor (VEGF165) is a mitogen for vascular endothelial cells and a potent angiogenic factor. Expression of a chimeric receptor containing the extracellular domain of the flk-1 receptor fused to the transmembrane and intracellular domains of the human c-fms receptor in NIH-3T3 cells, resulted in the appearance of high affinity binding sites for 125I-VEGF165 on transfected cells. The binding of 125I-VEGF165 to the flk-1/fms chimeric receptor of the transfected cells as well as the VEGF165-induced autophosphorylation of the chimeric receptors were inhibited in the presence of low concentrations of heparin (1-10 micrograms/ml). In contrast, similar concentrations of heparin potentiated the binding of 125I-VEGF165 to the endogenous VEGF receptors of the transfected cells, indicating that to some extent, the effect of heparin on 125I-VEGF165 binding is receptor type-dependent. A soluble fusion protein containing the extracellular domain of flk-1 fused to alkaline phosphatase (flk-1/SEAP) was used to study the effects of heparin on the binding of 125I-VEGF165 to flk-1 in a cell-free environment. The fusion protein specifically inhibited VEGF165-induced proliferation of vascular endothelial cells, but bound 125I-VEGF165 inefficiently in the absence of heparin. Addition of low concentrations of heparin or heparan sulfate (0.1-1 microgram/ml) resulted in a strong potentiation of 125I-VEGF165 binding, whereas higher heparin or heparan sulfate concentrations inhibited the binding. The effect of heparin on the binding of 125I-VEGF165 to flk-1/SEAP could not be mimicked by desulfated heparin or by chondroitin sulfate. Both bFGF and aFGF inhibited the binding when low concentrations of heparin were added to the binding reaction. However, higher concentrations of heparin abolished the inhibition, indicating that the inhibition is probably caused by competition for available heparin. Taken as a whole, these results indicate that heparin-like molecules regulate the binding of VEGF165 to its receptors in complex ways which depend on the heparin binding properties of VEGF165, on the specific VEGF receptor type involved, and on the amount and composition of heparin-like molecules that are present on the cell surface of VEGF receptor containing cells.     

Effect of casemix funding on outcomes in patients admitted to hospital with suspected unstable angina

This study was undertaken to assess the appropriate management of patients with diverticulitis complicated by fistula formation. A retrospective chart review was conducted on patients with symptoms of a fistula who presented between 1975 to 1995. There were 42 patients (32 women, 76%; 10 men, 24%) who ranged in age from 46 to 89 years (mean 69.8 +/- 9.8). Six patients had multiple fistulas. The types of fistulas included colovesical (48%), colovaginal (44%), colocutaneous (4%), colotubal (2%), and coloenteric (2%). Operative procedures consisted of resection and primary anastomosis in 38 patients and a Hartmann's operation in one. Three patients were managed conservatively with antibiotics (two due to poor performance status, the third due to resolution of symptoms). There were no operative deaths. The postoperative course was uncomplicated in 69%, while 12 patients (31%) experienced 19 complications (40%). These consisted of urinary tract infection (9.5%), atelectasis (7.1%), prolonged ileus (4.8%), arrhythmias (4.8%) and renal failure, myocardial infarction, pseudomembranous colitis, peroneal nerve palsy, unexplained fever, pulmonary edema (2.4% each). There were no anastomotic leaks and no deaths. Hospital stay ranged from 6 to 31 days (mean 12.3 +/- 7.6). Fistulas due to diverticulitis were safely managed by resection and primary anastomosis without mortality and with acceptable morbidity in this series. Patients deemed to be poor operative risks can be managed with a course of nonoperative treatment.