Experience of the use of velaxin (venlafaxine) in anxious depression

Thirty patients (seven men and 23 women, mean age 35.3 ± 7.8 years) with anxious and anxious-apathic depression were studied. Of these, 24 patients were treated in hospital and six in out-patient clinics. Patients were treated for eight weeks with venlafaxine at doses of 225–375 mg/day. Mental state was assessed using a series of scales (CGI, HDRS, BDI, HADS-21). A total of 27 patients (90%) completed treatment. There were 25 (83.3%) responders on the CGI scale: “improvement” in mental state occurred in 16 (59.3%) of patients and “marked improvement” occurred in nine (33.3%). “Insignificant improvement” was seen in two cases (7.4%). Complete elimination of symptoms of depression occurred in 33.3% of cases. Velaxin was found to be safe at intermediate therapeutic doses and there were improvements in laboratory results characterizing patients' somatic status. Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 108, No. 3, pp. 24–28, March, 2008.     

Frequency-domain analysis of cerebral autoregulation from spontaneous fluctuations in arterial blood pressure

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in crebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n=23) or impaired (group B, n=21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables in demonstrated by mean values of squared coherence >0.50 for both groups in the frequency range 0.02–0.50 Hz. However, group A has significanlty smaller coherences than group B in the frequency ranges 0.02–0.10 Hz and 0.33–0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3±1.05 and 1.80±1.2 rad Hz⁻¹, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25–0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.     

The effects of performing isometric training at two exercise intensities in healthy young males

No previous studies have examined the effects of isometric training intensity upon resting blood pressure (BP). The aims of this study were (a) to compare the effects of leg isometric training, performed at two intensities, upon resting systolic-SBP, diastolic-DBP and mean arterial-MAP BP; and (b) to examine selected cardiovascular variables, in an attempt to explain any changes in resting BP following training. Thirty-three participants were randomly allocated to either control, high- (HI) or low-intensity (LI) training for 8 weeks. Participants performed 4 × 2 min exercise bouts 3× weekly. Resting BP was measured at baseline, 4-weeks and post-training. SBP, DBP and MAP fell significantly in both groups after training. Changes were –5.2 ± 4.0, –2.6 ± 2.9 and –2.5 ± 2.2 mmHg [HI]; –3.7 ± 3.7, –2.5 ± 4.8 and –2.6 ± 2.5 mmHg [LI] for SBP, DBP and MAP, respectively. There were no significant changes in BP at 4 weeks. No significant changes were observed in any of the other cardiovascular variables examined. These findings suggest that isometric training causes reductions in SBP, DBP and MAP at a range of exercise intensities, when it is performed over 8 weeks. Furthermore, it is possible to reduce resting BP using a much lower isometric exercise intensity than has previously been shown.     

<Emphasis Type="Italic">Stenotrophomonas maltophilia</Emphasis> pneumonia in cancer patients without traditional risk factors for infection, 1997–2004

In order to elucidate the spectrum of Stenotrophomonas maltophilia pneumonia in cancer patients without traditional risk factors, 44 cancer patients (cases) with S. maltophilia pneumonia in whom S. maltophilia pneumonia risk factors were not present were compared with two S. maltophilia pneumonia risk groups (controls) including 43 neutropenic non-intensive care unit (ICU) and 21 non-neutropenic ICU patients. The case and control patients had similar demographic and underlying clinical characteristics. Compared with case patients with S. maltophilia pneumonia, neutropenic patients had higher exposure to carbapenem antibiotics (58 vs. 41%; p < 0.03), more frequent hematologic malignancy (95 vs. 64%; p < 0.0003), and they presented with concurrent bacteremia more often (23 vs. 0%; p < 0.0005). Patients with S. maltophilia pneumonia in the ICU needed vasopressor therapy more frequently than cases (62 vs. 5%; p < 0.0001). Hospital-acquired S. maltophilia pneumonia was more common among controls than cases (98 vs. 61%; p < 0.000002). Among the cases, 15 (34%) received outpatient oral antimicrobial therapy, while 29 were hospitalized and eight (28%) were subsequently admitted to the ICU. The mean duration of ICU stay, even among these eight patients (19 ± 40 days), was comparable to that of patients with neutropenia (23 ± 26 days) and those who developed S. maltophilia pneumonia during their ICU stay (34 ± 22 days; p = 0.46). The overall infection-associated mortality in the 108 patients with S. maltophilia pneumonia was 25%. Twenty percent of patients without traditional risk factors for S. maltophilia pneumonia died due to progressive infection. In a multivariate logistic regression analysis, only admission to the ICU predicted death (odds ratio 33; 95% confidence interval, 4.51–241.2; p < 0.0006). The results of this study indicate S. maltophilia pneumonia is a serious infection even in non-neutropenic, non-ICU patients with cancer. This work was presented in part at the 15th European Congress of Clinical Microbiology and Infectious Diseases, Copenhagen, Denmark, April 2–5, 2005 (abstract no P1374) and at the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington D.C., December 16–19, 2005 (abstract no K-1535).     

Experience in the use of actovegin in the treatment of patients with cognitive disorders in the acute period of stroke

Forty-three patients with mild-moderate ischemic stroke were studied in the acute period and were divided into two groups. The experimental group consisted of 32 patients who were given Actovegin; the reference group consisted of 11 patients who were given piracetam. Patients were investigated before treatment and at 10 and 30 days; investigations included examination, points assessments of neurological disorders using the original Gusev-Skvortsova scale, neuropsychological tests using the MMSE scale, rheoencephalography, and electroencephalography. Analysis of changes in clinical features in patients treated with Actovegin during the acute period showed that Actovegin had clear positive effects both on general cerebral and on focal neurological symptoms. By the end of treatment, the extent of recovery of impaired functions, assessed in terms of total ischemic points and cognitive functions, was significantly greater in patients treated with Actovegin than in patients given piracetam. These data lead to the conclusion that Actovegin is effective in the treatment of patients with ischemic stroke. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Stroke Supplement, Vol. 20, pp. 55–57, 2007.     

Vestibular control of arterial blood pressure during head-down postural change in anesthetized rabbits

This study was undertaken to elucidate neural control of the arterial blood pressure (ABP) in head-down postural change which causes both stimulation to the vestibular system and head-ward fluid shift. Experiments were carried out with urethane-anesthetized rabbits. The animal was mounted on a tilting table, tilted to 45° head-down in 5 s, and kept at the position for 5 min. The head-down rotation (HDR) induced a transient decrease in ABP (10 ± 3 mmHg; mean ± SE), and then the pressure gradually recovered toward the pre-HDR level during the 5 min at the head-down position. Pretreatment with hexamethonium bromide, a ganglionic transmission blocker, suppressed the HDR-induced drop of ABP, suggesting that the ABP drop was induced by an inhibition of autonomic neural outflows. Renal sympathetic nerve activity (RSNA) decreased considerably after 1.6 ± 0.2 s from the onset of HDR, which was followed by the ABP drop. Aortic depressor nerve activity (ADNA), an afferent for baroreceptor reflex, increased significantly during the rotation, but the peak of ADNA increase was 3.2 ± 0.5 s after the initiation of the HDR. Therefore, the suppression of RSNA seems to be induced mainly by a quicker mechanism than baroreceptor reflex. In order to test the possibility, we examined changes in ABP and RSNA during HDR using vestibular-lesioned rabbits. In these rabbits, RSNA and ABP did not change significantly during HDR. These results suggest that vestibular organs play a role in the transient drop in ABP induced by HDR through the suppression of sympathetic nerve outflows.     

Human–Computer Interaction in Radiotherapy Target Volume Delineation: A Prospective,Multi-institutional Comparison of User Input Devices

The purpose of this study was the prospective comparison of objective and subjective effects of target volume region of interest (ROI) delineation using mouse–keyboard and pen–tablet user input devices (UIDs). The study was designed as a prospective test/retest sequence, with Wilcoxon signed rank test for matched-pair comparison. Twenty-one physician-observers contoured target volume ROIs on four standardized cases (representative of brain, prostate, lung, and head and neck malignancies) twice: once using QWERTY keyboard/scroll-wheel mouse UID and once with pen–tablet UID (DTX2100, Wacom Technology Corporation, Vancouver, WA, USA). Active task time, ROI manipulation task data, and subjective survey data were collected. One hundred twenty-nine target volume ROI sets were collected, with 62 paired pen–tablet/mouse–keyboard sessions. Active contouring time was reduced using the pen–tablet UID, with mean ± SD active contouring time of 26 ± 23 min, compared with 32 ± 25 with the mouse (p ≤ 0.01). Subjective estimation of time spent was also reduced from 31 ± 26 with mouse to 27 ± 22 min with the pen (p = 0.02). Task analysis showed ROI correction task reduction (p = 0.045) and decreased panning and scrolling tasks (p < 0.01) with the pen–tablet; drawing, window/level changes, and zoom commands were unchanged (p = n.s.) Volumetric analysis demonstrated no detectable differences in ROI volume nor intra- or inter-observer volumetric coverage. Fifty-two of 62 (84%) users preferred the tablet for each contouring task; 5 of 62 (8%) denoted no preference, and 5 of 62 (8%) chose the mouse interface. The pen–tablet UID reduced active contouring time and reduced correction of ROIs, without substantially altering ROI volume/coverage.     

Exhaled carbon monoxide concentration is not elevated in patients with inflammatory bowel disease

The present study was initiated to examine whether the concentration of CO in the breath is elevated in patients with inflammatory bowel disease (IBD). Twenty-three clinically stable patients with IBD in the outpatient clinic (11 with Crohn’s disease, 12 with ulcerative colitis), who are non-smokers and non-passive smokers, were selected and the concentration of CO in their breath was measured using a breath gas analyser (TRI lyser mBA-3000). The concentration of CO in the breath of 23 patients with IBD was 2.5±0.9 (1.1–4.3) ppm. This concentration comes within the range of standard values in our previous reports (2.5±2.2 ppm). Any significant difference was not observed between 2.4±0.9 (1.5–4.3) ppm for the 11 Crohn’s disease patients and the 2.6±1.0 (1.1–3.9) ppm for the 12 ulcerative colitis patients. The results suggest that clinically stable patients with IBD do not show high values for concentration of CO in the breath.     

Patient–prosthesis mismatch may be irrelevant after aortic valve replacement with the 19-mm Perimount pericardial bioprosthesis in patients aged 65 years or older

The prevalence of patient–prosthesis mismatch (PPM) and its influence on clinical midterm results were examined in elderly patients whose activity was supposed to be less than that of younger patients. We evaluated valve function and the effects of PPM on the midterm results of the 19-mm Carpentier–Edwards Perimount (CEP) pericardial aortic valve in patients aged 65 years or older. Between August 1996 and May 2005, 51 patients underwent aortic valve replacement with the 19-mm CEP valve. The mean follow-up was 2.4 ± 1.8 years, involving a total of 134.4 patient-years. The mean age and body surface area at operation were 74.0 ± 5.0 years and 1.41 ± 0.14 m². There were two (3.9%) operative deaths. Three patients (5.9%) underwent enlargement of their small aortic annuli. The actuarial survival rate at 8 years, including operative mortality, averaged 90.2% ± 4.7%. The freedom from thromboembolism, reoperation, and valve-related mortality averaged 75.0% ± 21.7%, 97.8% ± 2.2%, and 95.3% ± 3.2%, respectively, at 8 years. High preoperative peak and mean transvalvular pressure gradients were significantly improved after the operation (peak, 93 ± 35 versus 28 ± 12 mmHg; mean, 58 ± 19 versus 17 ± 7 mmHg, respectively; P < 0.01). The mean left ventricular mass index was reduced from 192 ± 44 to 142 ± 46 g/m² at late follow-up (P < 0.01). The prevalence of PPM was low (17.6%) when an indexed effective orifice area of less than 0.85 cm²/m² was taken as the definition of PPM. The clinical results, postoperative pressure gradients, and reduction in left ventricular mass index were not different between the PPM and no-PPM groups. The 19-mm CEP valve produced satisfactory midterm clinical outcomes in patients aged 65 years or older whose activity was supposed to be less than that of younger patients, regardless of the presence or absence of PPM. Moderate PPM was rare and it did not adversely impact on the midterm results. The application of annulus enlargement could be limited to the small number of patients for whom the 19-mm CEP valves are not able to be inserted.     

Effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum

Artemether and artesunate, derivatives of the antimalarial artemisinin, as well as their main metabolite, dihydroartemisinin, all exhibit antischistosomal activities. The purpose of the current study was to compare the effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum. We carried out experiments with mice, infected with 40 cercariae of S. japonicum, and treated with artemether, aretesunate and dihydroartemisinin (all at a single dose of 300 mg/kg, and the dose of the mixed three drugs is also 300 mg/kg) at multiple doses or combination therapy on days 6–8 or 34–36 post-infection. Administration with artemether, artesunate or dihydroartemisinin for 3 successive days reduced total worm burdens by 79.5−86% (30.86 ± 4.98 of mean total worm burden in control), female worm burdens by 79.4−86.7% (11.29 ± 2.63 of mean female worm burden in control) (all P values <0.01 vs. control), depending on different treatment protocols given on days 6–8 post-infection. However, no differences were seen between each treatment group (all P > 0.05). While the same treatment was given on days 34–36 post-infection, total worm burden reductions of 73.8−75.8% were achieved (29.44 ± 3.36 of mean total worm burden in control), which were significant when compared with the untreated control group (all P values <0.01). In all different treatment groups, female worm reductions (ranging from 88.7% to 93.1%, while the mean female worm burden in control is 10.33 ± 1.80) were consistently higher than the total worm reductions, resulting always in significantly lower female worm burdens when compared to the corresponding control (all P values < 0.01). However, there were no significant differences found between each treatment group (all P values >0.05). It is concluded that artemether, artesunate and dihydroartemisinin can be used to control schistosomiasis japonica, as a strategy to prevent S. japonicum infection. Administration with artemether, artesunate and dihydroartemisinin at multiple doses or in combined treatment damages both juvenile and adult S. japonicum, without statistically significant differences among the three drugs at the same dose.     

A new methodological approach to assess cardiac work by pressure–volume and stress–length relations in patients with aortic valve stenosis and dilated cardiomyopathy

In experimental animals, cardiac work is derived from pressure–volume area and analyzed further using stress–length relations. Lack of methods for determining accurately myocardial mass has until now prevented the use of stress–length relations in patients. We hypothesized, therefore, that not only pressure–volume loops but also stress–length diagrams can be derived from cardiac volume and cardiac mass as assessed by cardiac magnetic resonance imaging (CMR) and invasively measured pressure. Left ventricular (LV) volume and myocardial mass were assessed in seven patients with aortic valve stenosis (AS), eight with dilated cardiomyopathy (DCM), and eight controls using electrocardiogram (ECG)-gated CMR. LV pressure was measured invasively. Pressure–volume curves were calculated based on ECG triggering. Stroke work was assessed as area within the pressure–volume loop. LV wall stress was calculated using a thick-wall sphere model. Similarly, stress–length loops were calculated to quantify stress–length-based work. Taking the LV geometry into account, the normalization with regard to ventricular circumference resulted in “myocardial work.” Patients with AS (valve area 0.73 ± 0.18 cm²) exhibited an increased LV myocardial mass when compared with controls (P < 0.05). LV wall stress was increased in DCM but not in AS. Stroke work of AS was unchanged when compared with controls (0.539 ± 0.272 vs 0.621 ± 0.138 Nm, not significant), whereas DCM exhibited a significant depression (0.367 ± 0.157 Nm, P < 0.05). Myocardial work was significantly reduced in both AS and DCM when compared with controls (129.8 ± 69.6, 200.6 ± 80.1, 332.2 ± 89.6 Nm/m², P < 0.05), also after normalization (7.40 ± 5.07, 6.27 ± 3.20, 14.6 ± 4.07 Nm/m², P < 0.001). It is feasible to obtain LV pressure–volume and stress–length diagrams in patients based on the present novel methodological approach of using CMR and invasive pressure measurement. Myocardial work was reduced in patients with DCM and noteworthy also in AS, while stroke work was reduced in DCM only. Most likely, deterioration of myocardial work is crucial for the prognosis. It is suggested to include these basic physiological procedures in the clinical assessment of the pump function of the heart.     

In vivo evaluation of the improved MCMS-0102 pacemaker with a rapid pacing mode for induction of experimental heart failure in animals

The MCMS-0102 cardiac pacemaker for rapid ventricular pacing to induce heart failure in animals has been improved in terms of miniaturization and performance. To determine the performance of the new MCMS-0102, six devices were implanted in beagle dogs, and two of these devices were reimplanted for continued pacing in a total of eight beagle dogs. The hearts were paced at 260 beats per minute for 4 weeks (P group: n = 8). The hemodynamic status of the P group was examined and compared with nonpaced dogs (NP group: n = 8). The neurohumoral status of the P group was evaluated before and after rapid pacing. Stable operation of the six devices during rapid pacing was confirmed using the telemetry system. Postmortem examinations revealed features similar to clinical heart failure characterized by massive ascites, pleural effusion, cardiomegaly, and liver congestion in all the paced dogs. Cardiac output was 1.1 ± 0.2 l/min in the NP group and 0.5 ± 0.1 l/min in the P group (P < 0.0001). The left atrial pressure and the central venous pressure of the P group and the NP group were 23 ± 6 versus 6 ± 2 mmHg (P < 0.0001) and 10 ± 3 versus 4 ± 3 mmHg (P < 0.001), respectively. In the paced dogs, plasma renin activity increased from 0.5 ± 0.4 to 8.5 ± 7.4 ng/ml/h (P < 0.05) and atrial natriuretic peptide levels increased from 69 ± 41 to 229 ± 72 pg/ml (P < 0.001). The improved MCMS-0102 was successfully implanted in beagle dogs and it succeeded in inducing the congestive heart failure model.     

Anaemia associated with canine lymphoma

Dogs with previously untreated multicentric lymphoma were evaluated for the presence of the anaemia of chronic disease (ACD). Specimens were collected for histopathology, haematology, serum biochemistry, direct antiglobulin test (DAT), total serum iron concentration (TSI), total iron binding capacity (TIBC), bone marrow cytology, bone marrow iron determination and serum erythropoietin concentration (EPO). Thirty-five dogs were included in the study. The haematocrit of anaemic dogs (n = 15, mean ± standard error: 0.316 ± 0.00841/1, reference range 0.37–0.55l/l) was significantly (p<0.0001) less than non-anaemic dogs (n = 20, mean 0.446 ± 0.0128 1/l). Anaemic dogs had normal TSI (mean 23 ± 3.1μmol/l, reference range 6–26μmol/l, normal TIBC (mean 61 ± 2.70μmol/l, reference range 50–69μmol/l, increased serum ferritin concentration (mean 1104 ± 192μg/l, reference range 80–800μg/l, and normal serum EPO (mean 14.6 ±1.88 U/1, reference range 5–15 U/l). Non-anaemic dogs had slightly increased TSI (mean 30 ± 2.8μmol/l), normal TIBC (mean 60 ± 4.3μmol/l), increased serum ferritin concentration (mean 1543 ± 302μg/l, and normal serum EPO (mean 14.5 ± 1.64 U/l,n = 23). These values were not significantly different between groups (p>0.1). Bone marrow iron stores were normal to increased in all dogs. These results do not support ACD as the cause of anaemia in dogs with lymphoma.     

Anaemia associated with canine lymphoma

Dogs with previously untreated multicentric lymphoma were evaluated for the presence of the anaemia of chronic disease (ACD). Specimens were collected for histopathology, haematology, serum biochemistry, direct antiglobulin test (DAT), total serum iron concentration (TSI), total iron binding capacity (TIBC), bone marrow cytology, bone marrow iron determination and serum erythropoietin concentration (EPO). Thirty-five dogs were included in the study. The haematocrit of anaemic dogs (n = 15, mean ± standard error: 0.316 ± 0.00841/1, reference range 0.37–0.55l/l) was significantly (p<0.0001) less than non-anaemic dogs (n = 20, mean 0.446 ± 0.0128 1/l). Anaemic dogs had normal TSI (mean 23 ± 3.1μmol/l, reference range 6–26μmol/l, normal TIBC (mean 61 ± 2.70μmol/l, reference range 50–69μmol/l, increased serum ferritin concentration (mean 1104 ± 192μg/l, reference range 80–800μg/l, and normal serum EPO (mean 14.6 ±1.88 U/1, reference range 5–15 U/l). Non-anaemic dogs had slightly increased TSI (mean 30 ± 2.8μmol/l), normal TIBC (mean 60 ± 4.3μmol/l), increased serum ferritin concentration (mean 1543 ± 302μg/l, and normal serum EPO (mean 14.5 ± 1.64 U/l,n = 23). These values were not significantly different between groups (p>0.1). Bone marrow iron stores were normal to increased in all dogs. These results do not support ACD as the cause of anaemia in dogs with lymphoma.     

Wavelet-Based System Identification of Short-Term Dynamic Characteristics of Arterial Baroreflex

The assessment of arterial baroreflex function in cardiovascular diseases requires quantitative evaluation of dynamic and static baroreflex properties because of the frequent modulation of baroreflex properties with unstable hemodynamics. The purpose of this study was to identify the dynamic baroreflex properties from transient changes of step pressure inputs with background noise during a short-duration baroreflex test in anesthetized rabbits with isolated carotid sinuses, using a modified wavelet-based time-frequency analysis. The proposed analysis was able to identify the transfer function of baroreflex as well as static properties from the transient input-output responses under normal [gain at 0.04 Hz from carotid sinus pressure (CSP) to arterial pressure (n = 8); 0.29 ± 0.05 at low (40–60 mmHg), 1.28 ± 0.12 at middle (80–100 mmHg), and 0.38 ± 0.07 at high (120–140 mmHg) CSP changes] and pathophysiological [gain in control vs. phenylbiguanide (n = 8); 0.32 ± 0.07 vs. 0.39 ± 0.09 at low, 1.39 ± 0.15 vs. 0.59 ± 0.09 (p < 0.01) at middle, and 0.35 ± 0.04 vs. 0.15 ± 0.02 (p < 0.01) at high CSP changes] conditions. Subsequently, we tested the proposed wavelet-based method under closed-loop baroreflex responses; the simulation study indicates that it may be applicable to clinical situations for accurate assessment of dynamic baroreflex function. In conclusion, the dynamic baroreflex property to various pressure inputs could be simultaneously extracted from the step responses with background noise.     

Role of polymorphic variants of gene of inducible NO synthase <Emphasis Type="Italic">NOS2</Emphasis> in brain infarction in patients with acute ischemic stroke

Cerebrovascular diseases, including stroke, are an important problem in public health. Stroke development depends on external factors and the individual genetic specificity of the patient. Excessive NO production by inducible NO synthase (iNOS) damages brain tissue at various stages of the disease. The goal of this work was to study the role of four polymorphic variants of gene of inducible NO synthase iNOS (−2447C/G, −1659C/T, −0.7(TTTA)n I/D, S608L (150C/T)) in brain infarction in patients with acute ischemic stroke. A statistically significant correlation between S608L (150C/T) polymorphism and infarction dynamics was observed during days 1–3 and 7–21 after infarction. These parameters correlate to the neurological status, which is estimated using the Orgogozo scale during days 1–7 of disease development. It was demonstrated that the C150C genotype was associated with ischemic focus propagation, regardless of its volume and neurological status by Orgogozo scale in patients with acute stroke. In the case of low initial volume, it was observed that the C150C genotype had an effect on ischemic damage during days 1–3.     

Influences of a dietary supplement in combination with an exercise and diet regimen on adipocytokines and adiposity in women who are overweight

The influence of a proprietary blend of modified cellulose and cetylated fatty acids (Trisynex™, Imagenetix, Inc., San Diego, CA 92127, USA) on adipocytokine and regional body composition responses to a weight loss program was examined. Twenty-two women (Supplement group (S) (n = 11): age = 36.8 ± 7.2 years; weight = 87.1 ± 6.2 kg; % body fat = 43.4 ± 4.1; Placebo group (P) (n = 11): age = 38.3 ± 6.8 years; weight = 86.9 ± 4.7 kg; % body fat = 44.3 ± 2.0) completed an 8-week placebo-controlled, double-blind study consisting of a caloric restricted diet and cardiovascular exercise. Body composition and serum insulin, leptin, and adiponectin were assessed at pre-, mid-, and post-intervention. From pre- to post-intervention, significant decreases (P < 0.05) were observed for body weight (S: 87.1 ± 6.2–77.9 ± 5.1 kg; P: 86.9 ± 4.7–82.7 ± 3.8 kg) (P < 0.05 S vs. P), % body fat (S: 43.4 ± 4.1–36.1 ± 3.6; P: 44.3 ± 2.0–40.6 ± 1.2) (P < 0.05 S vs. P), leptin (S: 28.3 ± 3.5–16.2 ± 2.6 ng ml⁻¹; P: 29.4 ± 3.2–19.9 ± 1.1 ng ml⁻¹) (P < 0.05 S vs. P), and insulin (S: 7.3 ± 0.8–5.1 ± 0.2 mU l⁻¹; P: 7.7 ± 0.9–5.1 ± 0.3 mU l⁻¹). Serum adiponectin increased (P < 0.05) (S: 12.2 ± 2.4–26.3 ± 3.0 μg ml⁻¹: 12.6 ± 2.0–21.8 ± 3.1 μg ml⁻¹) (P < 0.05 for S vs. P). Supplementation with a proprietary blend of modified cellulose and cetylated fatty acids during an 8-week weight loss program exhibited favorable effects on adipocytokines and regional body composition.     

Biological activity of FGF-23 fragments

The phosphaturic activity of intact, full-length, fibroblast growth factor-23 (FGF-23) is well documented. FGF-23 circulates as the intact protein and as fragments generated as the result of proteolysis of the full-length protein. To assess whether short fragments of FGF-23 are phosphaturic, we compared the effect of acute, equimolar infusions of full-length FGF-23 and various FGF-23 fragments carboxyl-terminal to amino acid 176. In rats, intravenous infusions of full-length FGF-23 and FGF-23 176–251 significantly and equivalently increased fractional phosphate excretion (FE Pi) from 14 ± 3 to 32 ± 5% and 15 ± 2 to 33 ± 2% (p < 0.001), respectively. Chronic administration of FGF-23 176–251 reduced serum Pi and serum concentrations of 1α,25-dihydroxyvitamin D. Shorter forms of FGF-23 (FGF-23 180–251 and FGF-23 184–251) retained phosphaturic activity. Further shortening of the FGF-23 carboxyl-terminal domain, however, abolished phosphaturic activity, as infusion of FGF-23 206–251 did not increase urinary phosphate excretion. Infusion of a short fragment of the FGF-23 molecule, FGF-23 180–205, significantly increased FE Pi in rats and reduced serum Pi in hyperphosphatemic Fgf-23 ^−/− knockout mice. The activity of FGF-23 180–251 was confirmed in opossum kidney cells in which the peptide reduced Na⁺-dependent Pi uptake and enhanced internalization of the Na⁺-Pi IIa co-transporter. We conclude that carboxyl terminal fragments of FGF-23 are phosphaturic and that a short, 26-amino acid fragment of FGF-23 retains significant phosphaturic activity.     

Spherometer measurements of human hip-joint geometry

The accuracy of sphericity measurements on human hip joints was studied with two types of 3-legged micrometer gauges. Initial calibration work on metal cylinders (30–65 mm diameter) achieved an error range of 4–8%. Correction was then made for this degree of error on a nomogram which reduced the errors in subsequent measurements to 0·–1·5%. The problem was that the percentage error in the micrometer reading was directly reflected in the percentage error in diametrical calculation. To achieve an acceptable accuracy of ±1%, the micrometer readings had to be accurate to within ±(15–23) μm, i.e. 0·0006–0·0009 in. (average of five measurements). This was only achieved in the metal calibration studies ±(0–15) μm, but not for the hip joint or its replicas, ±(7–109) μm. It was concluded that 3-legged gauges were a very unreliable method of taking diametrical measurements from human joint surfaces.     

Dependence of smooth muscle tone upon pulsatility in the iliac artery of the anaesthetised pig

The aim of the study was to examine features of the myogenic response of a conduit artery to the presence and absence of pulsatile pressure. The iliac arteries of 16 anaesthetised pigs (10 in control conditions, 6 under sympathetic blockade) were instrumented with flowmeter, sonomicrometry crystals for diameter measurement, a micro-tip manometer for pressure measurement and snares placed proximally and distally to the crystals to isolate a test segment from the remainder of the arterial system. When the snares were tightened to occlude the test segment, systemic arterial pressure remained constant. There was a large shift in the pressure–diameter relationship, in that there was a rapid decline in test segment pressure for the same diameter. This indicated arterial wall smooth muscle relaxation in response to removal of pulsatility of arterial pressure. The difference in mean pressure between pulsatility present and absent was significant (p < 0.0001, paired t test, n = 10). Before proximal and distal occlusion, test segment pressure was (mean ± SD) 92.26 ± 12.39 mmHg, whereas after distal and proximal occlusion at the same diameter, it was 42.34 ± 10.87 mmHg. We conclude that in the presence of pulsatile pressure, there is a large proportion of arterial wall smooth muscle tone related to stretch of the arterial wall during the cardiac cycle, indicating that, under normal pulsatile pressure conditions, much of the normal tone can be attributed to the pulsatile component of the arterial myogenic response.