Can intravenous beta blockade predict long-term haemodynamic benefit in chronic congestive heart failure secondary to ischaemic heart disease? A comparison between intravenous and oral carvedilol

Several studies in the past have shown the long-term beneficial effects of -blockers in congestive heart failure. Despite the interest in this mode of therapy, their clinical application has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show any improvements with standard -blocker therapy. Carvedilol, a new, non-selective -blocking agent with concurrent -blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischaemic heart disease. All had resting left ventricular ejection fraction 45% and were maintained on diuretic therapy. Acute haemodynamic measurements were made after intravenous carvedilol (2.5–7.5 mg) and also after chronic therapy for 8 weeks (carvedilol 12.5–50 mg b.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated in 11 of the 12 patients after 8 weeks of therapy. Mean±standard error systolic intraarterial blood pressure (133 ± 6 to 114 ± 5 mmHg, P <0.005), heart=" rate=" (81=" ±=" 3=" to=" 61=" ±=" 1=" beats/min,=">P <0.0001), pulmonary=" artery=" wedge=" pressure=" (19=" ±=" 2=" to=" 12=" ±=" 1=" mmhg,=">P <0.001) and=" systemic=" vascular=" resistance=" (1748=" ±=" 115=" to=" 1497=" ±=" 89=" dynes/=">⁵/m², P < 0.02)=" were=" reduced=" with=" an=" increase=" in=" mean=" ±=" se=" of=" stroke=" volume=" index=" (31=" ±=" 1.8=" to=" 40=" ±=" 1.6=">²/beat, P < 0.0005)=" and=" left=" ventricular=" ejection=" fraction=" (25=" ±=" 3=" %=" to=" 32=" ±=" 3=" %,=">P < 0.01)=" after=" 8=" weeks=" of=" therapy=" with=" carvedilol.=" this=" is=" in=" contrast=" to=" the=" acute=" haemodynamic=" effects=" of=" carvedilol,=" which=" only=" showed=" a=" reduction=" in=" heart=" rate=" (81=" ±=" 3=" to=" 74=" ±=" 3=" beats/min,=">P < 0.0001),=" systolic=" intra-arterial=" blood=" pressure=" (133=" ±=" 6=" to=" 117=" ±6=" mmhg,=">P < 0.0005)=" and=" pulmonary=" artery=" wedge=" pressure=" (19=" ±=" 2=" to=" 14=" ±=" 2=" mmhg,=">P < 0.002)=" at=" 10=" min=" post-injection.=" the=" systemic=" vascular=" resistance,=" left=" ventricular=" ejection=" fraction=" and=" stroke=" volume=" index=" failed=" to=" show=" any=" significant=" improvement.=" thus=" intravenous=" carvedilol=" produces=" a=" reduction=" in=" filling=" pressure,=" which=" is=" maintained=" after=" chronic=" treatment.=" this=" property=" is=" clearly=" beneficial=" for=" chronic=" heart=" failure=" patients=" and=" differs=" from=" standard=">-blockers. The discrepancy of the haemodynamic changes between the acute and chronic long-term response to carvedilol lends further support to the concept of upregulation of -adrenoceptors in cognestive heart failure.     

Einfluß von Cisaprid auf die Oesophagusmotilität bei Gesunden und Patienten mit progressiver systemischer Sklerodermie

Summary Prokinetic agents might be useful in patients with progressive systemic sclerosis (PSS) who have disturbed function of the lower esophageal sphincter and impaired acid-clearance of the tubular esophagus. We therefore compared, by means of esophageal manometry, the effect of 20 mg cisapride orally vs. placebo in 12 patients with progressive systemic sclerosis and proven esophageal dysfunction as well as in 10 healthy volunteers in a double-blind, prospective trial. An increase of the lower esophageal resting pressure from 18.1±2.4 mm Hg to 23.9±8.1 mm Hg* after cisapride administration was observed in healthy volunteers, and from 10.9±3.2 mm Hg to 13.6+4.0 mm Hg^* in the PSS patients. The amplitudes of peristaltic waves in the distal part of the esophagus were increased by cisapride from 83.8±10.6 mm Hg to 95.6±15.5mm Hg^* in volunteers and from 28.9+12.8 mm Hg to 36.8±16.2 mm Hg in patients (^*:P<0.05). These results indicate that cisapride has a therapeutic rationale in the treatment of esophageal dysfunction in PSS; further clinical investigations are justified.

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Abkürzungsverzeichnis PSS progressiv systemische Sklerodermie - UÖS unterer Oesophagussphinkter - OÖS oberer Oesophagussphinkter - ¯x Mittelwert - SD Standardabweichung - n.s. nicht signifikant - p.o. per os - vs. versus - i.v. intravenös - pH Wasserstoffionenkonzentration - H₂ Histamin-Rezeptoren Typ 2 Die Untersuchung erfolgte mit finanzieller Unterstützung der Janssen GmbH, Neuss.     

Increased numbers of circulating basophils with decreased releasability after administration of rhG-CSF to allergic patients

Preliminary studies in hematological patients have indicated that treatment with rhG-CSF reduces basophil releasabilityex vivo. We examined this phenomenon further, in allergic patients. Ten patients with grass pollen rhinoconjunctivitis were given rhG-CSF (5 g/kg/day s.c.) for 5 days, and examined before and after treatment. Basophil counts increased from 5 to 19×10⁹/l (P<0.01). total=" blood=" histamine=" increased=" from=" 80=" to=" 160=">g/l (P<0.01), corresponding=" to=" a=" decrease=" in=" average=" basophil=" histamine=" content=" from=" 1.5=" to=" 0.81=" pg/cell=">P<0.01). isolated=" mononuclear=" cells=" showed=" a=" significantly=" decreased=" histamine=" release=" (hr)=" when=" stimulated=" with=" a23187=" and=" grass.=" whole=" blood=" experiments=" showed=" a=" similar=" decreased=" hr=" to=" grass=" and=" anti-ige=">P<0.01). however,=" we=" found=" an=" increase=" in=" total=" blood=" histamine.=" we=" conclude=" that=" treatment=" with=" rhg-csf=" (1)=" increases=" the=" number=" of=" circulating=" blood=" basophils,=" (2)=" reduces=" the=" average=" histamine=" content=" per=" basophil,=" and=" (3)=" reduces=" the=" basophil=" releasability.=" these=" findings=" could=" be=" due=" to=" the=" mobilization=" of=" immature=" basophils=" from=" the=" bone=">     

Interdigestive gastroduodenal manometry in humans. Indication of duodenal phase III as a retroperistaltic pump

To elucidate the specific function of the three phases (I-III) of the migrating motor complex (MMC) by manometry, detailed analysis of individual pressure waves in the proximal duodenum was performed. Twenty healthy subjects (10 men and 10 women of whom 11 were tube-naive) underwent computerized manometry for 5 h during fasting followed by 45 min after a meal using an 8-channel water perfused catheter. Three recording points were in the antrum, three in the proximal duodenum (2 cm apart), one in the distal duodenum and one in the proximal jejunum. In all subjects at least one phase III (median 2) was observed during the 5-h fasting recording. In the proximal duodenum the mean proportion of retrograde pressure waves, out of all propagating waves, was significantly increased in the last part of phase III (85 ± 9%, mean, SE), compared with early phase III (6 ± 5%), late phase II (5 ± 4%) and the feeding phase (10 ± 5%), irrespective of gender or previous tube-experience. The median length of the MMCs was 108.5 min. There was no statistically significant difference between men and women or between tube-naive and tube-experienced subjects for the duodeno-jejunal motility indices of phase II and phase III, nor for duration or migration of phase III. The postprandial motility index of the small intestine was increased compared with the interdigestive late phase II, particularly in the jejunum (P < 0.02). The last part of the duodenal interdigestive phase III in healthy subjects shows the feature of a retroperistaltic pump. This cyclic sequence of retropropagation coincides with the reported rapid alkalinization of the duodenal bulb and the gastric antrum occurring in early antral phase I.     

A double-blind,randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute,extended guttate psoriasis

Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10–90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA+DHA<0.1 g/100=" ml).=" the=" severity=" of=" disease=" was=" evaluated=" by=" scoring=" daily=" erythema,=" infiltration,=" and=" desquamation=" and=" by=" a=" subjective=" scoring=" of=" clinical=" manifestations=" offered=" by=" the=" patients.=" leukotriene=" (lt)=" and=" platelet-activating=" factor=" (paf)=" generation=" were=" investigated=" in=" ionophore-stimulated=" neutrophils=" obtained=" on=" days=" 0,=" 1,=" 3,=" 5,=" 10,=" and=" 40.=" moderate=" improvement=" in=" clinical=" manifestations=" was=" noted=" in=" the=" n-6=" group=" (changes=" in=" score=" systems=" between=" 16–25%=" from=" baseline=" within=" 10=" days).=" in=" contrast,=" the=" severity=" of=" disease=" markedly=" decreased=" in=" all=" patients=" of=" the=" n-3=" group,=" with=" improvements=" in=" all=" score=" systems=" ranging=" between=" 45%=" and=" 76%=" within=" 10=" days=">P<0.05 for=" each=" variable).=" the=" difference=" in=" response=" to=" the=" two=" regimens=" was=" evident=" within=" 4–7=" days=" after=" onset=" of=" lipid=" infusion.=" a=" more=" than=" ten=" fold=" increase=" in=" neutrophil=" epa-derived=" 5-1ipoxygenase=" product=" formation=">₅, its omega-oxidation products, non-enzymatic degradation products of LTA₅ and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis.The study was supported by the Deutsche Forschungsgemeinschaft (DFG La 73/20-1)     

Histamine release in the course of elective conventional cholecystectomy in aged patients: Problems in defining release in relation to specific intraoperative events

The effectiveness of an H₁ ^–+H₂-prophylaxis against perioperative acute pseudoallergic reactions in which histamine is involved, and against postoperative complications the incidence of which may be increased by these reactions, was the central problem of a randomized trial in 162 aged patients during elective conventional cholecystectomy. As main endpoint it was planned to use the systemic histamine release reaction, as it already had been defined for the conscious and anaesthetized human subject. However, it had to be reassessed and redefined for the intraoperative period after improvement of the plasma histamine assay and new findings about stress-induced histamine release and the kinetics of histamine release during certain phases of operation.Intraoperative release is, at present, defined solely as an increase of plasma histamine values after a particular action (phase of operation). It includes criteria concerning plasma histamine changes either in comparison to the base value before surgery or to the preceding value before the last surgical action. Histamine elevations must exceed the last value by more than 3 standard deviations of the analytical error (i.e. 200% if value <0.25 ng/ml=" and=" 40%=" above).=" basic=" requirements=" for=" the=" histamine=" assay=" (quality=" control),=" correct=" sample=" taking=" and=" appropriate=" preparation=" have=" to=" be=" fulfilled=" over=" the=" whole=" trial=" period.=" when=" these=" criteria=" were=" applied=" to=" the=" 162=" patients=" an=" overall=" incidence=" of=" histamine=" release=" during=" cholecystectomy=" of=" 55.6%=" was=" found=" with=" 9.7–20%=" during=" an=" individual=" phase=" of=" operation.=" the=" data=" of=" this=" study,=" performed=" under=" routine=" conditions,=" with=" a=" sufficient=" number=" of=" patients=" with=" elevated=" risk=" and=" event=" controlled=" plasma=" histamine=" values,=" lead=" to=" a=" better=" understanding=" of=" intraoperative=" histamine=" release,=" its=" incidence=" and=">     

Effect of the novel radical scavenger AD0261 on lymphocyte activation

A recent investigation has indicated that reactive oxygen species (ROS) may play an important role in the activation of lymphocytes. The main aim of the present study is to find out what effect on lymphocyte activation is attributable to radical scavengers (RSs). AD0261 (AD) is a novel RS which displays strong inhibitory action on the generation of lipid peroxides and superoxide anions. This compound has been shown to be effective in inhibiting tritiated thymidine ([3H]TdR) incorporation into, IL-2 release from and IL-2 receptor (Rc) expression on Con A-stimulated mouse spleen cells and PHA-P-stimulated lymphocytes of human peripheral blood, IC50 values being in the range 1–10 M. It also inhibited erythema formation elicited by transferring PHA-P-stimulated lymphocytes into guinea pigs (30–40% inhibition at 10 M,p<0.05). further=" study=" showed=" that=" the=" activity=" of=" ornithine=" decarboxylase=" (odc),=" which=" is=" a=" critical=" enzyme=" for=" cell=" proliferation,=" was=" inhibited=" by=" ad=" in=" a=" dose-dependent=" manner=" (ic50="1.0">M). In summary, AD would seem to affect the lymphocyte activation by inhibiting ODC activity, probably through the action of ROS trapping.     

Esophageal dysfunction in diabetes mellitus: is there a relation to clinical manifestation of neuropathy?

Summary In a prospective study, we evaluated 33 diabetic patients [type I (n = 8) and type II (n = 25)]. Esophageal motor functions were examined by registering clinical symptoms and by performing esophageal manometry. We also investigated peripheral and autonomic neuropathy. In diabetics, the lower and upper esophageal sphincter pressure and amplitudes of peristaltic waves were reduced. Compared with controls (n = 30), in diabetics the esophageal peristaltic velocity was reduced significantly, and the duration of contractions were decreased as well. Multipeaked waves were uncommon in diabetics, while non-propulsive contractions were seen more often. No correlation was found between esophageal dysfunction and peripheral or autonomic neuropathy. Some 60% of diabetics reported esophageal symptoms; however, no relationship between these symptoms and the extent of dysfunction in esophageal motility was found.Abbreviations PNP peripheral sensorimotor polyneuropathy - ACN autonomic cardiac neuropathy - LES lower esophageal sphincter - UES upper esophageal sphincter - EMG electromyography - ECG electrocardiography     

The effects of sodium oxybate on core body and skin temperature regulation in narcolepsy

Patients suffering from narcolepsy type 1 show altered skin temperatures, resembling the profile that is related to sleep onset in healthy controls. The aim of the present study is to investigate the effects of sodium oxybate, a widely used drug to treat narcolepsy, on the 24‐h profiles of temperature and sleep‐wakefulness in patients with narcolepsy and controls. Eight hypocretin‐deficient male narcolepsy type 1 patients and eight healthy matched controls underwent temperature measurement of core body and proximal and distal skin twice, and the sleep–wake state for 24 h. After the baseline assessment, 2 × 3 g of sodium oxybate was administered for 5 nights, immediately followed by the second assessment. At baseline, daytime core body temperature and proximal skin temperature were significantly lower in patients with narcolepsy (core: 36.8 ± 0.05 °C versus 37.0 ± 0.05 °C, F = 8.31, P = 0.01; proximal: 33.4 ± 0.26 °C versus 34.3 ± 0.26 °C, F = 5.66, P = 0.03). In patients, sodium oxybate administration increased proximal skin temperature during the day (F = 6.46, P = 0.04) to a level similar as in controls, but did not affect core body temperature, distal temperature or distal–proximal temperature gradient. Sodium oxybate administration normalised the predictive value of distal skin temperature and distal–proximal temperature gradient for the onset of daytime naps (P < 0.01). In conclusion, sodium oxybate administration resulted in a partial normalisation of the skin temperature profile, by increasing daytime proximal skin temperature, and by strengthening the known relationship between skin temperature and daytime sleep propensity. These changes seem to be related to the clinical improvement induced by sodium oxybate treatment. A causal relationship is not proven.     

Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma)

Patients with progressive systemic sclerosis (PSS; scleroderma) were typed for the HLA-A, -B, and -DR antigens. No significant differences in the frequencies of any HLA-A or -B antigen were found. In the subgroup of patients with PSS and diffuse scleroderma (PSS-DS), the frequency of Bw35 was increased (0.30 vs 0.17 in controls;P<0.005, correctedP>0.2). Although patients with PSS-DS also had an increased frequency of DR1 antigen (0.27 vs 0.12 in local controls;P<0.005, correctedP<0.05), no association between Bw35 and DR1 antigens could be detected. We found no increase in the frequencies of the DR3 or DR5 antigens in patients with PSS. However, in a subset of PSS patients with pulmonary fibrosis, an increase in DR3 and a decrease in DR4 antigens (P<0.005) were observed. Serum antibodies to centromere occurred more frequently in DR1-positive than DR1-negative patients (0.46 vs 0.18;P<0.005). This study of a large number of patients with PSS failed to confirm previously reported associations of PSS with the HLA-B8/DR3 haplotype or HLA-DR5 antigen.     

Change in Electromyographic Activity of Wrist Extensor by Cylindrical Brace

Purpose

To verify the effect of a newly-developed cylindrical type forearm brace, which was designed to give focal counterforce perpendicularly on the muscle belly of the wrist extensor.

Materials and Methods

The dominant hands of 24 (12 males, 12 females) healthy subjects were tested. Two types of forearm braces (focal cylindrical type and broad pneumatic type) were examined. The braces were applied at the extensor carpi radialis brevis, 5 to 7 cm distal to the lateral epicondyle. Two surface electrodes were attached to the proximal and distal parts of the brace. By quantitative electromyography, the mean amplitudes of voluntary extensor carpi radialis brevis contraction before and after applying each brace were recorded and analyzed.

Results

The mean amplitudes of the focal cylindrical brace and broad pneumatic brace were reduced significantly compared to no brace (p<0.05), with a larger reduction for the cylindrical brace than the pneumatic brace (p<0.05). There was no significant difference between the proximal and distal mean amplitudes with each brace.

Conclusion

A cylindrical type brace decreased electromyographic activity in the wrist extensor more effectively than did the pneumatic type brace.     

Obésité, hypertension artérielle,hypercholestérolémie et diabète non traités chez les adultes infectés ou pas par le VIH à Mbuji-Mayi (République démocratique du Congo)

Little is known about the major cardiovascular risk factors in HIV-infected as compared to the HIV-uninfected patients in the Democratic Republic of Congo (DR Congo). We determined the prevalence of hypertension, obesity (BMI ≥ 30 kg/m²), total cholesterol > 200 mg/dl, HDLcholesterol &≤ 40 mg/dl, and glycemia > 126 mg/dl. We also calculated the average and/or median of total cholesterol, HDL-cholesterol, and glycemia among HIV-infected and HIV-uninfected patients.We conducted a cross-sectional study that enrolled 592 HIV-uninfected and 445 HIV-infected patients of whom 425 (95.5%) were on first-line antiretroviral therapy based on stavudine–lamivudine–nevirapine. Clinical and laboratory data of the patients were collected. The results were analyzed by chi-square, t-student, and Wilcoxon rank sum tests. 11.5% of HIV-infected patients had an average blood pressure suggesting hypertension versus 10.6% of HIV-uninfected (P = 0.751). But in absolute value, HIVinfected patients had a median of diastolic blood pressure of 90 mmHg versus 85 mmHg of HIV-uninfected (P < 0.001). 4.04% of HIV-infected patients had a BMI suggesting obesity versus 6.08% of HIV-uninfected patients (P = 0.187). For fasting glucose: 2.50% of HIV-infected patients versus 4.20% of HIV-uninfected patients had a serum fasting glucose suggesting diabetes (P<0.176). 11.9% of HIV-infected patients had a total cholesterol greater than 200 mg/dl versus 7.4% of HIVuninfected patients (P=0.019). For HDL-cholesterol: 36.40% of HIV-infected patients had a serum fasting ≤ 40 mg/dl versus 15.70% of HIV-uninfected patients (P < 0.001). HIV-infected patients had a median fasting total cholesterol higher (140 mg/ dl) thanHIV-uninfected patients (133mg/dl) [P=0.015].HIVuninfected patients had a median fasting HDL-cholesterol higher (58.5 mg/dl) than HIV-infected patients (49 mg/dl) [P < 0.001]. HIV-infected women were more likely to have a higher mean of total cholesterol: 147.70 #x00B1; 52.09 mg/dl versus 135.72 &#x00B1; 48.23 mg/dl for the HIV-infected men (P = 0.014) and of HDL-cholesterol: 55.80 ± 30.77 mg/dl versus 48.24 ± 28.57mg/dl for the HIV-infected men (P = 0.008). In this study population, prevalence of hypertension was elevated in HIVinfected versus HIV-uninfected patients. Being HIV positive on first-line antiretroviral therapy based on stavudine–lamivudine–nevirapine was associated with high prevalence of total cholesterol > 200 mg/dl and HDL-cholesterol ≤ 40 mg/dl. Proactive screening and prompt management of dyslipidemia and hypertension in this population should be a priority.     

Tubuloglomerular feedback and autoregulation of glomerular filtration rate in Wistar-Kyoto spontaneously hypertensive rats

Experiments were done in Wistar-Kyoto spontaneously hypertensive rats (SHR) to examine the efficiency of autoregulatory adjustments of kidney and nephron filtration rate (GFR) to acute changes in blood pressure (BP) over a broad blood pressure range. When BP of the SHR was reduced from 158±7 to 118 ±3 mm Hg by aortic clamping, kidney-GFR remained unchanged from 1.19±0.11 to 1.17±013 ml·min^–1·g^–1 kidney weight (KW), respectively. Single nephron GFR (SNGFR) measured at early distal tubule sites was similarly unchanged with the same BP change, 27.9±1.5 vs. 24.9±2.1 nl·min^–1·g^–1 KW (P>0.10). Proximal and distal estimates of SNGFR were significantly different from each other at high BP (7 nl·min^–1·g^–1,P<0.025), but were not different at low BP (2.0 nl·ml^–1·g^–1,P>0.10). Studies assessing tubuloglomerular feedback activity were done with orthograde perfusion of the loop of Henle using recollections of early proximal flow rate (EPFR) as an index of change of glomerular filtration rate. A change in perfusion rate from 0 to 45 nl·min^–1 induced a reduction in early proximal flow rate of 40.5 ±4.5%. Juxtaglomerular renin activity of superficial nephrons was 36.2±4.3 in the SHR, a value insignificantly different from 23.7±4.4 ng Angiotensin II amide·0.1 ml^–1·h^–1. 5 glomeruli^–1 in normal controls (P>0.05). The SHR appears to behave as a normal animal with respect to tubologlomerular feedback and autoregulatory renal vascular adjustments. Like normal rat models, the SHR demonstrated dependence on maintenance of distal filtrate delivery to achieve single nephron GFR autoregulation.Financial support for these studies and for Dr. Ploth were made available by funds from the Deutsche Forschungsgemeinschaft     

Subclinical hypothyroidism: neurobehavioral features and beneficial effect of l-thyroxine treatment

Summary Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of l-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month l-thyroxine course (0.1–0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ)=89.1 ± 2.9; P=0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P=0.03), anxiety (P=0.05), somatic complaints (P=0.0005), and depressive features (P=0.002) scales; the total score was also significantly higher (42.0±3.8; P=0.005). After l-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9±4.0; P=0.002 (treated versus untreated)]; somatic complaints (P=0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P=0.04) significantly decreased with respect to untreated patients. The remarkable effects of l-thyroxine treatment observed in the present study indicate that patients with subclinical hypothyroidism may require early therapy to provide specific treatment for their neuropsychological alterations and to avoid progression toward frank hypothyroidism.Abbreviations TSH thyrotropin - TRH thyrotropin-releasing hormone - l-T₄ levothyroxine - TT₄ total thyroxine - FT₄ free thyroxine - TT₃ total 3,5,3-triiodothyronine - FT₃ free 3,5,3-triiodothyronine - WMS Wechsler Memory Scale - CCEI Crown and Crisp Experiential Index     

Segmental heterogeneity of basal and aldosterone-induced electrogenic Na transport in human colon

Recent in vitro studies in human colon have demonstrated marked segmental differences in electrogenic Na transport. In the present study, the Na channel blocker amiloride was used further to characterise basal and aldosterone-induced electrogenic Na transport in isolated human distal and proximal colon. Bathed in NaCl Ringer solution, distal and proximal colon exhibited similar basal electrical properties, but the amiloride-sensitive short-circuit current (I _sc) was 200% greater in the distal than in the proximal segment. Bathed in choline-Cl Ringer solution, totalI _sc decreased by 97% in distal colon and by 88% in proximal colon, indicating that Na dependent transport process(es) account almost entirely for theI _sc in both segments. Substituting Na₂SO₄ for NaCl Ringer solution (i) increased amiloride-sensitiveI _sc by 56% (p<0.01) in distal colon but had no effect on amiloride-sensitiveI _sc in proximal colon, and (ii) decreased amiloride-insensitiveI _sc in distal and proximal colon by 52% (p<0.05) and 81% (p<0.001) respectively. After the addition of nystatin to the apical membrane, the relationship between totalI _sc and mucosal Na concentration indicated that the activity of the basolateral membrane Na pump was similar in both colonic segments. In a further series of experiments, exposure of distal colon to 1 mol/l aldosterone for 5 h increased totalI _sc by 52% (p<0.05), which reflected stimulation of its amiloride-sensitive component; in contrast, aldosterone had no effect on proximal colon. These results indicate that Na-dependent electrogenic processes (with electrogenic Na transport predominant) are present throughout human colon, but there is marked segmental variability in the Na conductive properties of the apical membrane. Apical Na entry in distal colon occurs mainly through classical amiloride and aldosterone-sensitive Na channels. In contrast, the predominant apical Na entry mechanism in proximal colon is an amiloride and aldosterone-insensitive path-way.     

Dietary supplementation of fish oil rich in eicosapentaenoic acid enhances bovine serum albumin induced immune complex nephritis in NZB/W F1 mice

In order to evaluate the effects ofw-3 polyunsaturated fatty acid on BSA nephritis in female NZB/W F1 mice, animals were fed a diet containing fish oil (FO), safflower oil (SO) or beef tallow (BT) as a lipid source. After preimmunization 4 times with BSA, 50 mg/kg of BSA was given intraperitoneally every day for 4 weeks. Proteinuria was demonstrated in 50% of FO (n=18), in 33% of BT (n=21), but only in 5% of SO (n=19,p<0.005 vs.=">p<0.05 vs.=" bt)=" animals.=" anti-bsa=" antibodies=" did=" not=" differ=" among=" the=" three=" groups.=" circulating=" bsa-anti=" bsa=" immune=" complexes=">₂ of the ratio to pooled standard sera) were –1.3±0.3 in FO, –2.2±0.4 in SO and –2.7±0.5 in BT (p<0.05 vs.=" fo)=" at=" sacrifice=" at=" 18=" weeks=" of=" age.=" prostaglandin=">₂ and thromboxane B₂ production by mashed renal cortex was markedly suppressed in FO (p<0.001, vs.=" so=" and=" bt).=" by=" light=" microscopy,=" fo=" showed=" more=" glomerular=" hypercellularity=" and=" mesangial=" increase=" than=" so=">p<0.001). by=" immunofluorescence=" and=" electron=" microscopy,=" heavier=" mesangial=" and=" loop=" or=" subepithelial=" deposits=" were=" seen=" in=" fo=" than=" in=" so=">p<0.005). fish=" oil=" may=" be=" involved=" in=" immune=" complex=" formation=" and=" its=" clearance=" by=" suppressed=" prostanoid=" production,=" resulting=" in=" enhanced=" bsa=">     

High perceived social standing is associated with better health in HIV-infected Ugandan adults on highly active antiretroviral therapy

Perceived social standing (PSS) was evaluated as a determinant of differences in health outcomes among Ugandan HIV-infected adults from Kampala using cross-sectional study design. PSS was defined using the MacArthur scale of subjective social status translated and adapted for the study setting. Socio-demographic and psychosocial correlates of PSS ranking at enrollment were determined using linear regression models. High versus low PSS was defined based on the median PSS score and evaluated as a determinant of body mass index, hemoglobin, quality of life (QOL) and frailty-related phenotype via linear regression. A log-binomial regression model estimated the relative-risk of good, very good or excellent versus fair or poor self-rated health (SRH) in relation to PSS. Older age, increasing social support and material wealth were correlated with high PSS ranking, whereas female sex, experience of multiple stigmas and multiple depressive symptoms were correlated with low PSS ranking. High PSS participants were on average 1.1 kg/m² heavier, had 4.7 % lower frailty scores and 3.6 % higher QOL scores compared to low PSS patients (all p < 0.05); they were also more likely to self-classify as high SRH (RR 1.4, 95 % confidence interval 1.1, 1.7) but had comparable hemoglobin levels (p = 0.634). Low PSS correlated with poor physical and psychosocial wellbeing in HIV-positive Ugandan adults. The assessment of PSS as part of clinical management, combined with efforts to reduce stigma and improve social support, may identify and possibly reduce PSS-associated health inequality in Ugandan adults with HIV.     

An introduction to wave intensity analysis

Wave intensity analysis applies methods first used to study gas dynamics to cardiovascular haemodynamics. It is based on the method of characteristics solution of the 1-D equations derived from the conservation of mass and momentum in elastic vessels. The measured waveforms of pressure P and velocity U are described as the summation of successive wavefronts that propagate forward and backward through the vessels with magnitudes dP _± and dU _±. The net wave intensity dPdU is the flux of energy per unit area carried by the wavefronts. It is positive for forward waves and negative for backward waves, providing a convenient tool for quantifying the timing, direction and magnitude of waves. Two methods, the PU-loop and the sum of squares, are given for calculating the wave speed c from simultaneous measurements of P and U at a single location. Given c, it is possible to separate the waveforms into their forward and backward components. Finally, the reservoir-wave hypothesis that the arterial and venous pressure can be conveniently thought of as the sum of a reservoir pressure arising from the total compliance of the vessels (the Windkessel effect) and the pressure associated with the waves is discussed.

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Red blood cell flow cessation and diameter reductions in skeletal muscle capillaries in vivo — the role of oxygen

When perfusion pressure is reduced, red blood cell flow in the capillaries of skeletal muscle ceases at a positive pressure difference across the vascular bed, while arterioles dilate and venules are not constricted. This flow cessation (i.e., cessation of red blood cell flow) and luminal diameter changes in capillaries following femoral arterial pressure reduction were investigated in the rabbit tenuissimus muscle in situ (n=42) using intravital video microscopy. Arterial pressure was reduced by occlusion of the aorta distal to the renal arteries. During the experiments, leg and muscle were placed in a sealed box. The muscle was exposed to low PO₂ by leading a gas mixture deprived of O₂ through the box. Locally at the muscle surface, i.e., under the microscope objective, PO₂ was varied by varying the PO₂ in the superfusion solution. In all experiments, the remainder of the muscle was kept at low (< 20 mm Hg) PO₂. The incidence of flow cessation was virtually zero at low local (< 20 mm Hg) PO₂ and became almost 100% at local values above 70 mm Hg. Initial equivalent capillary diameters were 3.1–5.8 m (median 4.0 m) and did not correlate with local O₂ tension. During aorta occlusion, capillary diameters significantly (P < 0.0001) decreased by a median value of 8% at all local PO₂ values; in 14 out of 54 capillaries local diameter became less than 2.8 m. The extent of diameter reduction did not correlate with PO₂. In the 14 capillaries in which the diameter became less than 2.8 m flow cessation occurred in only four cases. The minimal diameter reached was always at the site of an endothelial nucleus. The capillary diameter reductions are probably due to passive recoil. In the 48 capillaries in which flow ceased, only in four cases did a red blood cell stop at the site of the nucleus. We conclude that capillary diameter reductions (local and generalized) lead to a considerable increase in capillary resistance which contributes to the occurrence of flow cessation but cannot solely explain it.