Post-streptococcal scleredema an unusual rare mimicker of scleroderma: a case report.

cleredema of Buschke is a rare pathological disorder of connective tissue, which is characterized by a woody, diffuse induration of the skin, most often in the upper extremities. We report an extremely rare complication of post-streptococcal infection in a six-year-old male complaining of gradually progressing, painless skin thickening and tightness which was preceded by a one-month history of fever, cough, and tonsillitis. By reporting this case, we hope to contribute to the creation of a database for future research aimed at better understanding the incidence, pathophysiology, and management of this extremely rare complication.

Aquaporin-4 IgG antibody-related disorders in patients with juvenile systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to: (a) screen a large group of unselected patients with juvenile systemic lupus erythematosus for anti-aquaporin 4 antibodies (AQP4-Ab); (b) identify clinical and laboratory predictors of the presence of AQP4-Ab positivity in juvenile systemic lupus erythematosus. METHODS: Sera from 90 patients with juvenile systemic lupus erythematosus were tested for the presence of AQP4-Ab using a cell-based assay. Demographics, clinical and immunological features, treatment received were summarized. Fisher's exact test was used to identify clinical predictors of positivity for AQP4-Ab. RESULTS: Five of 90 (5.5%) patients tested positive for AQP4-Ab, all of which had neurological involvement, mainly transverse myelitis and optic neuritis. AQP4-Ab-positive patients were more likely to have neurological symptoms (P = 0.002), less likely to experience dermatological manifestations (P = 0.045), and less likely to have detectable anti-dsDNA antibodies (P = 0.022). These patients were also more likely to have received anti-epileptic (P = 0.023) and anti-coagulant (P = 0.007) drugs. CONCLUSIONS: The findings of this study indicate that some patients with juvenile systemic lupus erythematosus develop antibodies against aquaporin-4 and may be at risk of developing a neurological clinical phenotype. We suggest that all juvenile systemic lupus erythematosus patients should be systematically screened for the presence of AQP4-Ab and this may help identify a high risk for neurological involvement in juvenile systemic lupus erythematosus.

Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system.

The blood brain barrier consisting of astrocytes, pericytes and brain microvascular endothelial cells plays a vital role in the pathogenesis of neurotropic viruses by controlling the access of circulating molecules, immune cells or viruses into the central nervous system (CNS). However, this barrier is not impenetrable and neuroviruses have evolved to disrupt and evade it. This review aims to describe the underlying entry mechanisms of several neuroviruses such as (Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), Nipah virus (NiV), Rabies virus (RABV), Herpes simplex virus (HSV) and Human immunodeficiency virus (HIV)) into the CNS through BBB disruption. The mechanisms, through which neurotropic viruses enter the BBB, are being studied and are becoming clearer, however, some aspects still remain unknown. Some of these viruses are able to invade the brain parenchyma by a 'Trojan horse' mechanism, through diapedesis of infected immune cells that either cross the BBB paracellularly or transcellularly. Important mechanisms of BBB disruption associated with paracellular entry of viruses include alterations in expression or phosphorylation of tight junction proteins, disruption of the basal lamina and disruption of the actin cytoskeleton. In the absence of such mechanisms, indirect effects of viruses on the immune system are likely causes of barrier disruption.

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005-2021).

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required.

Efficacy of modified Leeming-Notman media in a resazurin microtiter assay in the evaluation of in-vitro activity of fluconazole against Malassezia furfur ATCC 14521.

BACKGROUND: Malassezia furfur is lipodependent yeast like fungus that causes superficial mycoses such as pityriasis versicolor and dandruff. Nevertheless, there are no standard reference methods to perform susceptibility test of Malassezia species yet. AIMS: Therefore, in this study, we evaluated the optimized culture medium for growth of this lipophilic yeast using modified leeming-Notman agar and colorimetric resazurin microtiter assay to assess antimycotic activity of fluconazole against M. furfur. RESULTS: The result showed that these assays were more adjustable for M. furfur with reliable and reproducible MIC end-point, by confirming antimycotic activity of fluconazole with MIC of 2µg/ml. CONCLUSION: We conclude that this method is considered as the rapid and effective susceptibility testing of M. furfur with fluconazole antifungal activity.

Evaluation of magnetic resonance imaging abnormalities in juvenile onset neuropsychiatric systemic lupus erythematosus.

The aim of this study was to describe the abnormalities identified with conventional MRI in children with neuropsychiatric systemic lupus erythematosus (NPSLE). This was single-centre (Great Ormond Street Hospital, London) retrospective case series of patients with juvenile NPSLE seen in 2003-2013. Brain MR images of the first episode of active NPSLE were reviewed. All patients fulfilled the 1999 ACR case definitions for NPSLE syndromes. Presenting neuropsychiatric manifestations, immunological findings and treatment are reported. Results are expressed as median and ranges or percentages. Fisher's exact test was used to identify clinical predictors of abnormal MRI. A total of 27 patients (22 females), median age 11 years (4-15), were identified. Presenting clinical symptoms included the following: headaches (85.1 %), mood disorder/depression (62.9 %), seizures (22.2 %), acute psychosis (18.5 %), cognitive dysfunction (14.8 %), movement disorder (14.8 %), acute confusional state (14.8 %), aseptic meningitis (7.4 %), demyelinating syndrome (3.7 %), myelopathy (3.7 %), dysautonomia (3.7 %) and cranial neuropathy (3.7 %). The principal MR findings were as follows: (1) absence of MRI abnormalities despite signs and symptoms of active NPSLE (59 %); (2) basilar artery territory infarction (3 %); (3) focal white matter hyperintensities on T2-weighted imaging (33 %); (4) cortical grey matter lesions (3 %); and (5) brain atrophy (18.5 %). The presence of an anxiety disorder strongly associated with abnormal MRI findings (p = 0.008). In over half the children with NPSLE, no conventional MRI abnormalities were observed; white matter hyperintensities were the most commonly described abnormalities. Improved MR techniques coupled with other alternative diagnostic imaging modalities may improve the detection rate of brain involvement in juvenile NPSLE.

Effect of plasma homocysteine concentration on early and late events in patients with acute coronary syndromes.

BACKGROUND: Although a raised plasma homocysteine is a risk factor for vascular disease, it is not known whether it is associated with an adverse cardiac outcome in patients admitted with acute coronary syndromes. We evaluated the relationship between plasma homocysteine and short-term (28 days) and long-term (median 2.5 years) prognosis in acute coronary syndromes. METHODS AND RESULTS: We evaluated the relationship of quintiles of homocysteine to fatal and nonfatal coronary disease early (28 days) and late (29 days to a median of 2. 5 years) after admission to a single unit of patients with unstable angina (n=204) and myocardial infarction (n=236). The end points studied were cardiac death (n=67) and/or myocardial (re)infarction (n=30). Cox regression and logistic regression were used to estimate the relationship of homocysteine to coronary events. The event rate within the first 28 days (22 cardiac deaths and 5 nonfatal infarctions) was not related to the admission homocysteine level. In the 203 unstable angina and 214 myocardial infarction survivors, an apparent threshold effect was seen on long-term follow-up, with a significant step-up in the frequency of events between the lowest 3 quintiles (14 cardiac deaths and 11 nonfatal infarctions) and the upper 2 quintiles (31 fatal and 12 nonfatal events). Patients in the upper 2 quintiles (>12.2 micromol/L) had a 2.6-fold increase in the risk of a cardiac event (95% CI, 1.5 to 4.3, P<0.001). CONCLUSIONS: Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.

Relationships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes.

BACKGROUND: It has been suggested by clinical, epidemiological, and experimental in vitro studies that homocysteine potentiates thrombin generation. This prothrombotic effect however has not previously been demonstrated in patients presenting with acute coronary syndromes (ACS). METHODS AND RESULTS: Patients with ACS (n =117) presenting with confirmed acute myocardial infarction (MI) (n =57) or unstable angina pectoris (UAP) (n =60) were consecutively recruited together with patients (n =18) in whom the presenting chest pain was not of cardiac origin (NCP), included as controls. Plasma samples were collected on admission and before clinical intervention. Homocysteine was assayed by high performance liquid chromatography, and both Factor VIIa and prothrombin fragment F1+2 were analyzed by ELISA. There were significant elevations in F1+2 in MI (P<0.001) and UAP (P=0.003), and modest elevations in Factor VIIa in UAP (P<0.05) compared with NCP but no differences in homocysteine levels among those groups. On dividing patients with ACS into quartiles of homocysteine, there was a stepwise increase in F1+2 (P<0.0001) and of Factor VIIa (P<0.05). There were significant correlations in ACS between homocysteine and F1+2 (r=0.46, P<0.0001), homocysteine and Factor VIIa (r=0.24, P<0.01), and F1+2 and Factor VIIa (r=0.41, P<0.0001). There was no correlation between homocysteine and either F1+2 (r=-0.15, P=0.57) or Factor VIIa (r=0. 22, P=0.37) in the NCP patients. CONCLUSIONS: Elevated plasma homocysteine is associated with and may cause elevated Factor VIIa and thrombin generation in patients presenting with ACS. These findings suggest an explanation for the prothrombotic effect of homocysteine in ACS.

Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes.

OBJECTIVES: This study was conducted to determine whether the amount of myocardial damage during acute coronary syndromes (ACS) is related to the admission plasma homocysteine concentration. BACKGROUND: Elevated homocysteine levels are associated with increased thrombosis in patients presenting with ACS. It is not known whether this association is reflected in the degree of myocardial injury in those patients. METHODS: We studied consecutive patients presenting with acute myocardial infarction (MI) (n = 205) and unstable angina pectoris (UAP) (n = 185). Plasma samples were collected on admission and prior to clinical intervention and were assayed for homocysteine by high performance liquid chromatography (HPLC). Myocardial necrosis was assessed by measurements of cardiac troponin T (cTnT) on admission and 12 h after admission (peak cTnT). The patients were studied by quintiles of homocysteine concentration. RESULTS: There was a significant increase in peak cTnT in the 5th homocysteine quintile in MI (analysis of variance [ANOVA], p = 0.005), the levels being 4.10, 3.86, 4.13, 6.20 and 7.85 microg/liter for quintiles 1 to 5, respectively (p < 0.0001, for top vs. bottom quintile). Similarly, there was a step-up in peak cTnT levels in the top homocysteine quintile in UAP (ANOVA, p < 0.0001), the levels being 0.03, 0.03, 0.02, 0.04 and 0.15 microg/liter, (p < 0.0001 for top vs. bottom quintile). In a multivariate regression model, the association between peak cTnT and the top homocysteine quintile remained strong after adjustment of other confounders including age, gender, final diagnosis and thrombolysis treatment (odds ratio [OR]: 2.92 (1.75-4.87) p < 0.0001). The patients with UAP were further examined according to peak cTnT levels below (cTnT negative) or above (cTnT positive) 0.1 microg/liter. Homocysteine levels were significantly higher in cTnT positive than cTnT negative patients; 13.8 (11.7-15.3) vs. 10.3 (9.4-11.3) micromol/liter, respectively, p = 0.002. CONCLUSIONS: Elevated homocysteine levels are associated with a higher risk of ischemic myocardial injury in patients presenting with ACS.

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases.

This study identifies multiple copies of the AML1 gene on a duplicated chromosome 21, dup(21), as a recurrent abnormality in acute lymphoblastic leukemia (ALL). Clusters of AML1 signals were visible at interphase by fluorescence in situ hybridization (FISH). In metaphase, they appeared tandemly duplicated on marker chromosomes of five distinct morphological types: large or small acrocentrics, metacentrics, submetacentrics or rings. The markers comprised only chromosome 21 material. Karyotypes were near-diploid and, besides dup(21), no other established chromosomal changes were observed. A total of 20 patients, 1.5 and <0.5% among consecutive series of childhood and adult ALL respectively, showed this phenomenon. Their median age was 9 years, white cell counts were low and all had a pre-B/common immunophenotype. Although this series is not the first report of this abnormality, it is the largest, permitting a detailed description of the variety of morphological forms that duplicated chromosome 21 can assume.

ETV6/AML1 fusion by FISH in adult acute lymphoblastic leukemia.

Dual-color interphase fluorescence in situ hybridization (FISH) with ETV6 and AML1 probes was used for the first time on a series of 159 adult patients with acute lymphoblastic leukemia (ALL), for detection of the t(12;21)(p13;q22) translocation. Seven patients (4.4%) were found, with 50-100% of positive cells, of whom one of two tested, proved negative for the fusion product by RT-PCR. Two of them, aged 43 and 50 years, are the oldest patients so far confirmed to have the translocation. Three who relapsed at 10, 11 and 24 months, suggest that adults may not enjoy the good short-term prognosis reported for t(12;21)-positive children. Thirty-one-negative cases had signal numbers differing from the two expected for each gene. In 15 cases these results were consistent with the karyotype. In nine cases with uninformative cytogenetics, the numbers were consistent with those for centromeres and indicated a hidden aneuploidy. Loss of ETV6 genes in two cases and AML1 amplification in three others were not suspected from the cytogenetics. In conclusion, FISH proved to be reliable in defining ETV6/AML1 positivity in this group of patients as well as providing valuable insights into negative cases.

Plasma insulin-like growth factor-1 elevated in mild-to-moderate but not severe heart failure.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) promotes favorable cardiac remodeling in heart failure. However, the relation of plasma IGF-1 in patients with various degrees of heart failure is not known. METHODS: Venous plasma samples were collected from patients with clinically documented heart failure (n = 24) and from control subjects (n = 21) for measurements of IGF-1 levels. In the heart failure group, functional assessment of the physical capacity was determined by means of the New York Heart Association (NYHA) score. Objective determination of ventricular performance was made by transthoracic echocardiographic measurement of left ventricular fractional shortening (FS). RESULTS: IGF-1 levels were higher in patients with heart failure (mean age, 67 +/- 2 years; 17 men) than in control subjects (age, 71 +/- 2 years; 9 men) (20.2 +/- 2 mU/L, 14.1 +/- 2 mU/L, respectively, P <.05). However, the elevated IGF-1 levels were demonstrated only in patients with mild-to-moderate symptoms (NYHA classes I and II) of heart failure (24.7 +/- 3.3 mU/L, n = 12, P =.005 vs control subjects) but not in patients with severe symptoms (NYHA classes III and IV) (15.7 +/- 2.3 mU/L, n = 12). There was a strong positive correlation between IGF-1 levels and left ventricular FS (%) (r = 0.58, P =.003, n = 24). Adjustments for other potential confounders including age, sex, treatment received, and underlying cause of heart failure did not alter the relation between IGF-1 and left ventricular FS (odds ratio, 2.01; 95% confidence interval, 1.26 to 6.24; P =.01). CONCLUSIONS: Plasma levels of IGF-1 show distinct variations with the severity of heart failure and may play a vital role in compensated heart failure.

MR imaging of endomyocardial fibrosis (EMF).

We present a case of endomyocardial fibrosis and discuss the use of cardiac magnetic resonance imaging (CMR) as a tool in aiding the diagnosis.

Intravenous anti-D immunoglobulin in the treatment of resistant immune thrombocytopenic purpura in pregnancy.

A 35-week pregnant 38-year-old woman presented with isolated thrombocytopenia (platelet count 4 x 10(9)/l). Investigations confirmed immune thrombocytopenic purpura, and she received treatment with prednisolone and intravenous immunoglobulins with no increment in the platelet count. At 37 and 38 weeks of the pregnancy, she received two doses of WinRho (anti-D immunoglobulin) at 50 microg/kg. Five days later, with a platelet count of 46 x 10(9)/l, she had an uncomplicated normal vaginal delivery. WinRho is a useful adjunct to other first-line treatment modalities for immune thrombocytopenia in pregnancy.

Effects of left atrial receptor stimulation on carotid chemoreceptor-induced renal responses in dogs.

1. Dogs were anaesthetized with thiopentone sodium and alpha-chloralose and artificially ventilated. The carotid sinus regions were vascularly isolated and perfused with arterial or venous blood to stimulate the chemoreceptors. Left atrial receptors were stimulated by distending four balloons, three in the left pulmonary vein-atrial junctions and one in the left atrial appendage. Mean aortic pressure was held constant by means of a pressure control device. Atenolol and atropine (2.0 and 0.5 mg kg-1, respectively), and gallamine triethiodide (3.0 mg kg-1 h-1) were given I.V. Renal blood flow was measured by an electromagnetic flowmeter, glomerular filtration rate by creatinine clearance, urinary sodium by flame photometry and solute excretion by osmometry. 2. In fifteen tests in eight dogs (in one dog responses of both left and right kidneys were determined), at a constant aortic pressure (AoP) of 92.0 +/- 3.2 mmHg, and carotid sinus pressure (CSP) of 95.0 +/- 2.0 mmHg, stimulation of left atrial receptors with balloon inflation resulted in significant increases in renal blood flow (RBF) by 8.3 +/- 0.9 from 255.0 +/- 14.6 ml min-1 (100 g kidney weight)-1 (n = 9), in glomerular filtration rate (GFR) by 4.1 +/- 0.6 from 21.2 +/- 1.9 ml min-1 (100 g)-1, in filtration fraction (FF) by 0.04 +/- 0.003 from 0.20 +/- 0.01, in urine flow rate (V) by 0.08 +/- 0.02 from 0.33 +/- 0.05 ml min-1 (100 g)-1, in sodium excretion (UNaV) by 4.4 +/- 0.9 from 27.7 +/- 4.2 mumol min-1 (100 g)-1, in osmolar excretion (UosmV) by 62.0 +/- 5.6 from 303.0 +/- 28.3 mu osmol min-1 (100 g)-1, and in a decrease in free water clearance (CH2O) by 0.13 +/- 0.03 from -0.63 +/- 0.04 ml min-1 (100 g)-1. Left atrial pressure (LAP) and heart rate (HR) did not change significantly from 6.9 +/- 0.3 cmH2O, and 133.0 +/- 3.4 beats min-1 respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary effects of carotid chemoreceptor stimulation on gracilis muscle and renal blood flow and renal function in dogs.

1. In chloralose-anaesthetized and artificially ventilated dogs, the carotid sinus regions were vascularly isolated and perfused either with arterial or mixed (arterial and venous) blood (partial pressure of O2 (PO2) 43.8 +/- 2.4 mmHg, mean +/- S.E.M. n = 14) to stimulate the carotid chemoreceptors. The carotid sinus pressure was held constant at 142.0 +/- 2.8 mmHg. Measurements were made of renal and gracilis muscle blood flow by wrap-round electromagnetic flow probes placed around the renal and gracilis arteries, glomerular filtration rate by creatine clearance, urinary sodium excretion by flame photometry and solute excretion by osmometry. 2. In ten dogs, with intact cervical vagosympathetic trunks, carotid chemoreceptor stimulation produced significant increases in aortic pressure (AoP) of 12.7 +/- 1.1% (n = 10, P < 0.001), in glomerular filtration rate (GFR) of 14.7 +/- 4.1% (P < 0.001), urine flow rate (V) of 16.5 +/- 3.5% (P < 0.002), in urinary sodium excretion (UNaV) of 17.5 +/- 2.5% (P < 0.005) and in urinary osmolar excretion (UosmV) of 13.2 +/- 2.2% (P < 0.001), but a significant decrease in renal blood flow (RBF) of 5.8 +/- 1.8% (P < 0.02). In six of these dogs in which gracilis muscle blood flow (MBF) was also recorded, carotid chemoreceptor stimulation caused significant increases in AoP of 12.8 +/- 1.4% (n = 6, P < 0.001) and in MBF of 10.0 +/- 1.6% (P < 0.002), and a small but significant decrease in RBF of 3.6 +/- 1.5% (P < 0.02). 3. In fourteen dogs, with sectioned cervical vagosympathetic trunks, carotid chemoreceptor stimulation produced increases in AoP of 22.0 +/- 2.6% (n = 14, P < 0.001), in GFR of 36.9 +/- 4.2% (P < 0.001), in V of 30.1 +/- 4.4% (P < 0.001), in UNaV of 31.4 +/- 5.3% (P < 0.001), and in UosmV of 25.7 +/- 5.8% (P < 0.001). However, it produced a greater decrease in RBF of 10.5 +/- 1.9% (P < 0.001). In ten of these dogs, where MBF was recorded, carotid chemoreceptor stimulation caused greater increase in AoP of 22.4 +/- 3.0% (n = 10, P < 0.001) and in MBF of 32.8 +/- 3.7% (P < 0.001), and a greater decrease in RBF of 9.8 +/- 1.9% (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Modification of carotid chemoreceptor-induced changes in renal haemodynamics and function by carotid baroreflex in dogs.

1. Mongrel dogs were anaesthetized with thiopental sodium and chloralose and artificially ventilated. The carotid sinus regions were vascularly isolated and perfused either with arterial or mixed (arterial and venous) blood (PO2, 44.2 +/- 3.3 mmHg, mean +/- S.E.M.) to stimulate the chemoreceptors. Cervical vagosympathetic trunks were ligated and atenolol (2 mg kg-1, I.V.) was given in all dogs and gallamine triethiodide (3 mg kg-1 h-1, I.V.) was given in two dogs. Renal blood flow was measured by an electromagnetic flowmeter, glomerular filtration rate by creatinine clearance, sodium excretion by flame photometry and solute excretion by osmometry. The viability of the preparations was tested by recording total vascular capacitance responses to stimulation of carotid baro- and chemoreceptors. 2. In eleven tests in seven dogs at a constant aortic pressure of 88.9 +/- 2.6 mmHg stimulation of carotid chemoreceptors at a high carotid sinus pressure (194.0 +/- 3.6 mmHg) resulted in significant increases in urine flow of 22.8 +/- 3.0%, urinary sodium excretion of 30.7 +/- 5.2%, fractional sodium excretion of 35.3 +/- 18.6%, osmolar excretion of 17.5 +/- 4.1% and a decrease in free water clearance of 30.8 +/- 3.1% without significant changes in urinary sodium concentration, renal blood flow, glomerular filtration rate, and filtration fraction. 3. In seventeen tests in these seven dogs at a constant aortic pressure of 94.0 +/- 2.2 mmHg, stimulation of carotid chemoreceptor at a low carotid sinus pressure (72.0 +/- 1.3 mmHg) resulted in significant decreases in renal blood flow of 10.6 +/- 2.5%, glomerular filtration rate of 19.6 +/- 6.8%, filtration fraction of 13.2 +/- 5.5%, urine flow of 23.4 +/- 4.1%, urinary sodium concentration of 20.3 +/- 4.1%, urinary sodium excretion of 38.5 +/- 4.6%, fractional sodium excretion of 20.2 +/- 7.7%, osmolar excretion of 23.9 +/- 4.0% and an increase in free water clearance of 23.1 +/- 2.5%. 4. The results show that moderate stimulation of carotid chemoreceptors at a low carotid sinus pressure, when the activity in renal nerves is high and blood volume is low, can produce significant reflex decreases in renal haemodynamic and functional variables. However, at a high carotid sinus pressure when the renal sympathetic activity is low and blood volume is high, carotid chemoreceptor stimulation produces diuresis and natriuresis but no change in renal haemodynamics.

Nitric oxide formation contributes to beta-adrenergic dilation of resistance coronary vessels in conscious dogs.

The contribution of the L-arginine/nitric oxide pathway to beta-adrenergic dilation of resistance coronary vessels was examined in conscious dogs instrumented for measuring coronary blood flow (CBF), left ventricular (LV) wall thickening, and LV and aortic pressures and for intracoronary injections of acetylcholine (0.003 micrograms/kg), nitroglycerin (0.175 micrograms/kg), and graded doses of isoproterenol (0.0005 to 0.004 micrograms/kg). Peak increases in CBF with intracoronary isoproterenol (0.001 micrograms/kg) averaged 105 +/- 10% from baseline. With acetylcholine, CBF increased by 158 +/- 11%, and with nitroglycerin, CBF increased by 139 +/- 10%. After the administration of intracoronary N omega-nitro-L-arginine methyl ester (L-NAME, 10 micrograms/kg per minute for 12 minutes) to block nitric oxide synthesis from L-arginine, baseline CBF was not altered, and CBF increased by 49 +/- 7% with isoproterenol and by 94 +/- 6% with acetylcholine; both values were smaller (P < .01) than those before the arginine analogue. With nitroglycerin, CBF was increased by 145 +/- 11%, not significantly different from the value before L-NAME. Intracoronary L-arginine (1.0 mg/kg per minute for 12 minutes), the precursor of nitric oxide synthesis, partially reversed the inhibition of L-NAME on CBF responses to acetylcholine and isoproterenol. After beta 1-adrenergic blockade, CBF responses to isoproterenol and acetylcholine were also reduced (P < .05) by the arginine analogue. When increases in CBF were prevented, peak changes in coronary vascular conductance with intracoronary bolus doses of acetylcholine and isoproterenol were attenuated (P < .01) by L-NAME. Thus, nitric oxide formation is an important intermediate in beta-adrenergic dilation of resistance coronary vessels in conscious dogs.