Adaptation to herbivory by the Tammar wallaby includes bacterial and glycoside hydrolase profiles different from other herbivores

Metagenomic and bioinformatic approaches were used to characterize plant biomass conversion within the foregut microbiome of Australia''s “model” marsupial, the Tammar wallaby (Macropus eugenii). Like the termite hindgut and bovine rumen, key enzymes and modular structures characteristic of the “free enzyme” and “cellulosome” paradigms of cellulose solubilization remain either poorly represented or elusive to capture by shotgun sequencing methods. Instead, multigene polysaccharide utilization loci-like systems coupled with genes encoding β-1,4-endoglucanases and β-1,4-endoxylanases—which have not been previously encountered in metagenomic datasets—were identified, as were a diverse set of glycoside hydrolases targeting noncellulosic polysaccharides. Furthermore, both rrs gene and other phylogenetic analyses confirmed that unique clades of the Lachnospiraceae, Bacteroidales, and Gammaproteobacteria are predominant in the Tammar foregut microbiome. Nucleotide composition-based sequence binning facilitated the assemblage of more than two megabase pairs of genomic sequence for one of the novel Lachnospiraceae clades (WG-2). These analyses show that WG-2 possesses numerous glycoside hydrolases targeting noncellulosic polysaccharides. These collective data demonstrate that Australian macropods not only harbor unique bacterial lineages underpinning plant biomass conversion, but their repertoire of glycoside hydrolases is distinct from those of the microbiomes of higher termites and the bovine rumen.     

Does the Modification of the Apical Geometry of a Dental Implant Affect Its Primary Stability? A Comparative Ex Vivo Study

(1) Background: Primary stability—one fundamental criterion for the success of dental implants—is influenced by implant geometry even if the effect of apical shape modifications on implant primary stability has not yet been examined. Therefore, the aim of the ex vivo study was to compare primary stability of implants differing in apically located screw threads (J-line) or a flat tip (K-line) only. (2) Methods: 28 implants of each group of the same diameter (4.3 mm) were randomly inserted into porcine bone blocks. The first group (9, 11 and 13 mm) was inserted into “hard”, the second (11 mm) into “soft” bone, here using a normal and an undersized drilling protocol. Insertion torque (Ncm), Periotest^® value, resonance frequency (implant stability coefficient, ISQ) and push-out force (N) were measured. (3) Results: In “hard” bone, primary stability increased with increasing length in both groups but it was significantly higher in J-line (p < 0.03). An undersized preparation of the implant bed in “soft” bone resulted in a significant increase in primary stability in both groups. Here, J-line also showed a significantly increased primary stability when compared to equally prepared K-line (insertion torque: 37 Ncm vs. 26 Ncm; Periotest^®: −6.5 vs. −4.3; push-out force: 365 N vs. 329 N; p < 0.05 each). (4) Conclusions: Primary stability is significantly higher with increasing implant length and apically located screw threads as well as with undersized drilling protocols. When preparing the implant site and subsequently selecting the implant system, modifying factors such as implant geometry (also at the tip) should be taken into account.     

The distal colon provides reserve storage capacity during colonic fluid overload

Background—In addition to its absorptive functionthe capacity of the colon to retain fluid might be relevant incompensating for increased fluid loads and prevention of diarrhoea. Thedistal colon is considered to be mainly a conduit without extensivestorage function.
Aims—To evaluate colonic volume capacity in amodel of pure osmotic diarrhoea.
Methods—A non-absorbable, iso-osmotic solution(OS) containing polyethylene glycol (500 ml) was infused into thecaecum of nine healthy volunteers; the control group (n=5) received anequal amount of an easily absorbable electrolyte solution (ES). Fluids were radiolabelled with technetium-99m and gamma camera images wereobtained for 48 hours. Counts in the proximal and distal colon weremeasured and regional and overall colonic transit and stool output were quantified.
Results—After OS, in contrast to ES, faecal outputwas increased significantly (p<0.05), but colonic transit after OS was not different from transit after ES (p>0.05). This indicates storage of OS in the colon: after OS infusion, counts in the proximal colondecreased linearly while the distal colon stored approximately 30% ofradioactivity for the whole 48 hour study period. After OS, stooloutput correlated with distal (p<0.01), but not with proximal(p>0.05), colonic transit. In constrast, after ES, stool output wasdetermined by proximal colonic transit (p<0.05) but not by transitthrough the distal colon (p>0.05).
Conclusion—The distal colon retainsnon-absorbable fluid volumes extensively. In our model transit throughthe distal colon—but not the proximal colon—determined the time atwhich diarrhoea occurred.

Keywords:osmotic diarrhoea; colonic transit; storagecapacity; colonic scintigraphy

     

Evaluation of Three Lancing Devices: What Do Blood Volume and Lancing Pain Depend On?

Background:Globally millions of people with diabetes still prick their fingers to measure blood glucose. The aim of this study was to comprehensively evaluate and to compare three lancing devices set at the minimum (“1”) and at the maximum (“5”) lancing depth with respect to blood volume (BV) and pain related to lancing.Methods:Lancing devices tested were A—Glucoject Dual PLUS, B—droplet (both: HTL-Strefa S.A., Poland), and C—Microlet Next (Ascensia Diabetes Care, Switzerland), all used with personal lancets of three sizes 28G, 30G, and 33G. BVs were measured with calibrated capillaries. Pain related to lancing was expressed as a derivative of pain rating with visual analog scale.Results:In 90 participants with diabetes, 360 lancing procedures were performed. Overall, BV and pain were higher for “maximum” compared to “minimum” lancing depth (for both P < .001). Pain differed between devices (P ≤ .001), overall was higher for device A compared to B or C; in paired comparisons differences were significant for the following settings: A > B for 28G/1 and 33G/1, B > C for 30G/1, and A > C for 28G/1, 30G/1, and 33G/1. In aggregated comparison we did not prove a significant effect of lancet size on either BV nor pain (P = .1109, P = .4966, respectively).Conclusions:BV depended mainly on lancing depth. Pain depended on lancing depth and to some degree on device type. The results may serve as a source of comparative data of lancing devices performance for studies in which other lancing devices and/or lancets would be tested.The study was registered at ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT03479619","term_id":"NCT03479619"}}NCT03479619     

Bovine immunoglobulin concentrate-Clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine

Background—Bovine immunoglobulinconcentrate (BIC)-Clostridium difficile isprepared from the colostrum of cows immunised against C difficile toxins and contains highconcentrations of neutralising IgG antitoxin.
Aims—To determine the proportion ofBIC-C difficile which survives passagethrough the human stomach and small intestine.
Methods—Six volunteers with an endileostomy took 5 g of BIC-C difficilecontaining 2.1 g of bovine IgG on four occasions: alone, with anantacid, during treatment with omeprazole, and within enteric coated capsules.
Results—WhenBIC-C difficile was taken alone, a mean (SEM) of 1033 (232) mg of bovine IgG was recovered in the ileal fluidrepresenting 49% of the total ingested dose. Bovine IgG recovery wasnot significantly increased by antacid (636 (129) mg) or omeprazole(1052 (268) mg). The enteric capsules frequently remained intact oronly partially opened in the ileal effluent and free bovine IgG levelswere low in this treatment group (89(101) mg). Bovine IgG recovery washigher in volunteers with shorter (less than two hours) mouth to ileumtransit times (68% versus 36%, p<0.05). Specific bovine IgG againstC difficile toxin A was detected in ilealfluid following oral BIC. Toxin neutralising activity was also presentand correlated closely with bovine IgG levels(r=0.95, p<0.001).
Conclusion—BIC-Cdifficile resists digestion in the human upper gastrointestinaltract and specific anti-C difficile toxin Abinding and neutralising activity was retained. Passive oral immunotherapy with anti-C difficile BIC maybe a useful non-antibiotic approach to the prevention and treatment ofC difficile antibiotic associated diarrhoeaand colitis.

Keywords:pseudomembranous colitis; toxin; diarrhoea; IgG; immunotherapy; antibiotic; Clostridiumdifficile

     

Parvovirus B19 infection, hepatitis C virus infection, and mixed cryoglobulinaemia

BACKGROUND—Infection with human parvovirus B19 (B19) has been reported in a few patients with various vasculitis syndromes. Mixed cryoglobulinaemia (MC), a model of small vessel size vasculitis, may result from numerous infectious diseases, particularly hepatitis C virus (HCV) infection.
AIM—To assess the prevalence of seric B19 infection markers in a large series of patients with MC, with or without HCV infection.
PATIENTS AND METHODS—Sixty four patients were studied: essential MC (EMC, n = 19), MC associated with non-infectious diseases (non-essential MC, n = 9), and patients with HCV infection with (HCV-MC, n = 18) or without MC (HCV-no-MC, n = 18). Patients were considered to have MC if two successive determinations of their serum cryoglobulin concentration were above 0.05 g/l. Serum samples were analysed for specific IgG and IgM antibodies to B19 by enzyme immunoassay. B19 DNA detection was performed by polymerase chain reaction using a set of primers located in the VP1 gene, separately in serum and in cryoprecipitates to investigate a possible capture of B19 DNA in cryoprecipitate. The study also looked for a possible enrichment for of IgG antibodies to B19 in MC.
RESULTS—The presence of specific IgG antibodies to B19 was found in 68% EMC, 56% non-essential MC, 78% HCV-MC, and 78% HCV-no-MC. No patient of either group had specific IgM antibodies to B19, or B19 DNA in serum or in cryoprecipitate. Overall, IgG antibodies to B19 were found in 46 of 64 (72%) serum samples, a prevalence quite similar to the prevalence in general adult population (> 60 %). A specific enrichment of IgG antibodies to B19 in the MC was not found.
CONCLUSION—These results suggest that B19 infection is neither an aetiological factor of EMC, nor a cofactor that may lead to MC production in patients with chronic HCV infection.

Keywords: mixed cryoglobulinaemia; parvovirus B19; hepatitis C virus     

Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis

OBJECTIVE—To investigate the thrombin inhibitory capacity of antithrombin III in the inflamed human joint.
METHODS—Thrombin inhibitory capacity was measured, using a kinetic spectophotometric method, in matched plasma and synovial fluid samples of patients with rheumatoid arthritis (n=22) and osteoarthritis (n=16), together with normal control plasma samples (n=13). In the same samples, the concentration of antithrombin III was also determined by the method of radial immunodiffusion. The combination of these measurements allowed the calculation of the specific thrombin inhibitory capacity of these samples.
RESULTS—An increased concentration of antithrombin III in rheumatoid compared with osteoarthritic synovial fluid was noted (p<0.05). However, there was a significant depression in the specific activity of antithrombin III in rheumatoid synovial fluid when compared with matched plasma samples (p<0.001) or with osteoarthritic synovial fluid (p<0.05).
CONCLUSION—In rheumatoid synovial fluid the thrombin inhibitory capacity of antithrombin III is disproportionately depressed relative to the concentration of antithrombin III, indicating the inactivation of antithrombin III in the rheumatoid joint.

Keywords: antithrombin III; thrombin; rheumatoid arthritis; synovial fluid     

Cytotoxicity Test of One-Step Self-Etching Bonding Agents by Standardized Dentin Barrier Test Using Polyurethane Discs

This study was performed to standardize a dentin barrier test with the substitute and evaluate the cytotoxicity of one-step self-etching bonding agents. Each of the natural bovine dentin and polyurethane discs were 500-μm thick and were tested using a perfusion device. Following the treatment with 0.05% phenol on the natural bovine disc or three kinds of polyurethane discs—30, 40, and 50 pcf (pounds per cubic foot)—cell viability of L-929 was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and expressed as percentages of non-treated group, respectively. A substitute showing permeability similar to that of bovine dentin was determined based on this result. Cytotoxicity test of bonding agents was performed by the selected substitute, the results of which were expressed as percentages of the control. In addition, SEM images were taken after the tests. The cell viability by 40-pcf polyurethane disc was not statistically different from that by bovine dentin disc (P > 0.05). Futurabond DC resulted in the highest cell viability and Bond force the lowest by the 40-pcf polyurethane disc (P < 0.05). The adhesives on the 40-pcf polyurethane disc changed cellular morphology with different degrees on the SEM images. This standardized test might be useful for assessing the cytotoxicity of dental materials applied to dentin before clinical applications.     

Physiological cardiac reserve: development of a non-invasive method and first estimates in man

Objective—To investigate whether physiological cardiac reserve can be measured in man without invasive procedures and whether it is a major determinant of exercise capacity.
Design—Development of method of measurement and an observational study.
Setting—A regional cardiothoracic centre.
Subjects—70 subjects with a wide range of cardiac function, from heart failure patients to athletes.
Methods—Subjects underwent treadmill, symptom limited cardiopulmonary exercise tests to measure aerobic exercise capacity (represented by O₂max) and cardiac reserve. Cardiac output was measured non-invasively using the CO₂ rebreathing technique.
Results—Cardiac power output (CPO_max) at peak exercise was found to be significantly related to aerobic capacity: CPO_max (W) = 0.35 + 1.5O₂max (l/min), r = 0.87, p < 0.001. It also correlated well with exercise duration (r = 0.62, p < 0.001), suggesting that cardiac reserve is a major determinant of exercise capacity. In the study, cardiac reserve ranged from 0.27 to 5.65 W, indicating a 20-fold difference between the most impaired cardiac function and that of the fittest subject.
Conclusions—A non-invasive method of estimating physiological cardiac reserve was developed. The reserve was found to be a major determinant of exercise capacity in a population of normal subjects and patients with heart disease. This method may thus be used to provide a clearer definition of the extent of cardiac impairment in patients with heart failure.

Keywords: cardiac reserve;  cardiac power output;  oxygen consumption;  congestive heart failure     

Differential contribution of HLA-DR,DQ, and TAP2 alleles to systemic lupus erythematosus susceptibility in Spanish patients: role of TAP2*01 alleles in Ro autoantibody production

OBJECTIVE—To study the influence MHC class II and TAP2 alleles exert on systemic lupus erythematosus (SLE) susceptibility and on the clinical and serological manifestations of the disease, in a cohort of Spanish patients.
METHODS—HLA-DR serological typing and HLA-DQA, DQB, and TAP2 DNA sequence specific oligotyping, were carried out in 85 unrelated Spanish SLE patients and 186 healthy controls. Autoantibodies detection was carried out by indirect immunofluorescence and counter immunoelectrophoresis.
RESULTS—Total SLE group: the frequency of HLA-DR3 and HLA-DQA1*0501 is significantly increased in this group (p_c<0.005, δ=0.34 and p_c<0.005, δ= 0.45, respectively) although the highest δ value (δ=0.87) is obtained when the TAP2*01 alleles are considered. No DQB allele shows significant deviation from the control group. Renal damage: it mainly occurs in HLA-DR3 patients (p_c<0.0005 and δ=0.72). HLA-DQA1*0501 (p_c<0.05, δ=0.57) and DQB1*0201 (p_c NS, δ=0.56) are weaker susceptibility factors. Ro+ (but not La) group: this autoantibody response is associated with TAP2*01 alleles in homozygosity (p<0.05, δ=0.81). Ro/La+ group: it has a different genetic background as HLA-DQA1*0501 (δ=1) and HLA-DQB1*0201 (δ=1) are the main susceptibility factors.
CONCLUSIONS—A differential association between HLA-DR, DQA1, and DQB1 alleles and SLE or its clinical and serological manifestations are found. Furthermore, the associations are different to the ones reported in other ethnic groups. Finally, TAP2*01 group of alleles are associated with the highest susceptibility to SLE (higher than HLA-DR3) and may influence Ro (but not La) autoantibodies production, whereas HLA-DQA1*0501 and DQB1*0201 mediates concomitant Ro and La production.

     

Subgroups of primary Sjögren's syndrome. Sjögren's syndrome in male and paediatric Greek patients

OBJECTIVES—To describe the clinical and serological findings in male and paediatric Sjögren's syndrome (SS) patients.
PATIENTS AND METHODS—Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.
RESULTS—The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p<0.01) and with female patients (p<0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p<0.05) and Raynaud's phenomenon (p<0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p<0.025) and antibodies to Ro(SSA) nuclear antigens (p<0.025) compared with women.
CONCLUSION—Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.

     

Elicitation of structure-specific antibodies by epitope scaffolds

Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant “2F5-epitope scaffolds” possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (p < 0.04), while antibody responses against the graft—as dissected residue-by-residue with alanine substitutions—resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation.     

Increased incidence of biliary sludge and normal gall bladder contractility in patients with high spinal cord injury

Background—Patients with spinal cordinjury (SCI) have an increased prevalence of gallstones.
Aims—To study prospectively theincidence of gallstones and gall bladder contractility inpatients with SCI.
Patients and methods—Thirty sixconsecutive patients with SCI were studied: 18 patients with SCI abovethoracic 10 neuronal segment (>T10) and 18 patients with SCI below T10(<T10). An equal number each of disease controls (multiple fractures)and healthy controls were also studied. All patients and controlsunderwent serial ultrasonography to detect development of gallstonesand ultrasonographic measurement of gall bladder contractility.
Results—A significantly higher number(9/18) of patients with SCI >T10 developed biliary sludge comparedwith patients with SCI <T10 (2/18), disease controls (2/18), andhealthy controls (1/18) (p<0.05). No patient developed gallstones. Thegall bladder fasting volume was significantly decreased in patientswith SCI >T10 (20.56 ml; 95% confidence intervals (CI) 19.74 to21.38) compared with that in patients with SCI <T10 (27.33 ml, 95%CI 26.17 to 28.49; p<0.05), disease controls (27.92 ml, 95% CI 26.69to 29.15; p<0.05), and healthy controls (28.35 ml, 95% CI 27.25to29.45; p<0.05). Gall bladder contractility was normal in patients withSCI as shown by normal gall bladder residual volume and emptying time.
Conclusions—Patients with SCI aboveT10 have an increased incidence of biliary sludge and a decreased gallbladder fasting volume. Gall bladder contractility is, however, normal.

Keywords:spinal cord injury; biliary sludge; gall bladder

     

HEPATITIS AND AUSTRALIA ANTIGEN: AUTOSOMAL RECESSIVE INHERITANCE OF SUSCEPTIBILITY TO INFECTION IN HUMANS

Examples of inherited susceptibility to infection controlled by genes segregating at one or a small number of loci have been identified in lower animals. In this study we report data on what appears to be a similar situation in humans. “Australia antigen” is an antigen found in the sera of patients with acute and chronic hepatitis, and it may actually be a form of virus. It is very common in many tropical areas, and people in these areas having the antigen appear to be hepatitis carriers. The antigen is detected by immuno-diffusion in agar gel (Ouchterlony method). Individuals with the antigen are designated Au(1) and those without it Au(0). Family studies involving 1797 different individuals residing on the island of Bougainville are consistent with the hypothesis that susceptibility to chronic infection with the “antigen” is controlled by an autosomal recessive gene (Au¹). This confirms the conclusions previously arrived at from similar (but less extensive) studies on the island of Cebu. Individuals with this inherited susceptibility do not ordinarily have overt manifestations of hepatitis.

The sign test was used to determine family clustering. Segregation analysis was performed by the method of C. A. B. Smith. In the 41 Au(0) × Au(0) matings, 53.8 recessives were expected in the offspring and 56 were seen (0.7 > p > 0.5). In the Au(1) × Au(0) matings, 40.1 recessives were expected and 42 were seen (0.7 > p > 0.5). The Au(0) × Au(0) matings were also analyzed by the method of Li and Mantel, in which the recessive ratio of 0.25 is expected by the genetic hypothesis. The values observed were 0.2527 for the Bougainville study and 0.2461 for the Cebu study.

     

ANTIBODIES TO A UNIQUE REGION IN LYSOZYME PROVOKED BY A SYNTHETIC ANTIGEN CONJUGATE

A synthetic conjugate, prepared by covalent binding of a lysozyme fragment (sequence 64-83, denoted „loop” peptide) to a synthetic branched polypeptide, elicited in rabbits the formation of antibodies with specificity directed against a unique region in native lysozyme. These anti-„loop” antibodies were isolated immunospecifically on a lysozyme-cellulose immunoadsorbent. Antibodies with a similar specificity were isolated from antilysozyme sera with an immunoadsorbent prepared from the same „loop” peptide. The capacity of the anti-„loop” antibodies to distinguish between the „loop” peptide, containing a disulfide bridge, and the open-chain peptide derived from it suggests that they are directed against a conformation-dependent determinant.     

Efficacy of flecainide,sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality

Objective—A comparison of the efficacy of verapamil, sotalol, and flecainide to suppress right ventricular tachycardia (VT) in patients with a clinically normal heart.Design—Patients underwent treatment serially with verapamil (360 mg daily), sotalol (240 or 320 mg daily), and flecainide (200 or 300 mg daily), (the larger dose was for patients heavier than 80 kg) to suppress tachycardia. Each drug was given orally for five half lives before testing.Patients—23 patients with right VT associated with a clinically normal heart were studied.Outcome measures—The effects of drug treatment were examined by the number of ventricular events on 24 hour Holter monitoring, and the ability of tachycardia to be induced by treadmill exercise testing (Bruce protocol) and programmed ventricular stimulation (Wellens protocol), compared with drug free baseline tests.Setting—Patients were studied in a tertiary referral centre.Results—All three drugs suppressed ventricular salvos (>3, <5 consecutive ventricular premature contractions) (p < 0·01) and VT (p < 0·05) on Holter monitoring and did not differ statistically in effect. Exercise induced VT was also suppressed by all three drugs (p < 0·01), and of these sotalol was the most effective although this was not statistically significant (14/23 inducible when drug free, 4/23 on flecainide, 2/23 on sotalol, 5/23 on verapamil). Sustained and nonsustained VT induced by programmed stimulation was also suppressed by the three drugs (p < 0·01) and again sotalol was the best of these though the differences did not achieve statistical significance (17/23 inducible when drug free, 4/17 on flecainide, 2/17 on sotalol, and 6/17 on verapamil). Proarrhythmic effects of drugs were found in a few patients. There was no difference in the efficacy of the drugs in patients with histological abnormalities of the myocardium when compared with those of normal histology.Conclusions—Ventricular tachycardia associated with a clinically normal heart can be suppressed by flecainide, sotalol, or verapamil. In individual patients sotalol was the most frequently effective drug (effective in >89% of patients) and is a suitable choice for first line treatment.     

Pancreatic dysfunction and its association with fat malabsorption in HIV infected children

Background—Nutrient malabsorption frequentlyoccurs in HIV infected children, but very few studies have investigatedexocrine pancreatic digestive capacity in these cases.
Aims—To investigate pancreatic function in HIVinfected children and to determine whether faecal fat loss, a prominentfeature of intestinal dysfunction, is associated with pancreatic dysfunction.
Patients—Forty seven children with HIV infectionwithout apparent pancreatic disease and 45 sex and age matched healthy controls.
Methods—Pancreatic function was evaluated bymeasuring elastase 1 concentration and chymotrypsin activity in stoolsby ELISA and colorimetric methods, respectively. Intestinal functionwas evaluated by measuring fat and protein loss by the steatocrit method and by faecal α₁ antitrypsin concentration.
Results—14 (30%) had abnormal pancreaticfunction tests: seven had isolated elastase activity deficiency, threeisolated chymotrypsin deficiency, and four pancreatic deficiencies inboth enzymes. Patient enzyme values were significantly lower than thoseof controls. Low faecal pancreatic enzymes were not associated withsymptoms. Twelve children had steatorrhoea and four had increasedα₁ antitrypsin. Steatorrhoea was significantlyassociated with reduced faecal pancreatic enzymes. There was asignificant negative correlation between elastase 1 concentration andsteatocrit. Children with pathological faecal elastase 1 orchymotrypsin values did not differ from the other HIV infected childrenwith respect to nutritional and immunological status, stage of HIVdisease, presence of opportunistic infections, or drug administration.
Conclusions—Abnormal pancreatic function testsare a frequent feature of paediatric HIV infection; this condition isassociated with steatorrhoea, which probably contributes to the disease.

Keywords:HIV; children; pancreas; steatorrhea; malnutrition; intestine

     

From the Cover: The skeleton of tropical intraseasonal oscillations

The Madden–Julian oscillation (MJO) is the dominant mode of variability in the tropical atmosphere on intraseasonal timescales and planetary spatial scales. Despite the primary importance of the MJO and the decades of research progress since its original discovery, a generally accepted theory for its essential mechanisms has remained elusive. Here, we present a minimal dynamical model for the MJO that recovers robustly its fundamental features (i.e., its “skeleton”) on intraseasonal/planetary scales: (i) the peculiar dispersion relation of dω/dk ≈ 0, (ii) the slow phase speed of ≈5 m/s, and (iii) the horizontal quadrupole vortex structure. This is accomplished here in a model that is neutrally stable on planetary scales; i.e., it is tacitly assumed that the primary instabilities occur on synoptic scales. The key premise of the model is that modulations of synoptic scale wave activity are induced by low-level moisture preconditioning on planetary scales, and they drive the “skeleton” of the MJO through modulated heating. The “muscle” of the MJO—including tilts, vertical structure, etc.—is contributed by other potential upscale transport effects from the synoptic scales.     

The clinical relevance of antibodies to ribosomal-P common epitope in two targeted systemic lupus erythematosus populations: a large cohort of consecutive patients and patients with active central nervous system disease

OBJECTIVES—To develop an enzyme linked immunosorbent assay (ELISA) using as substrate a synthetic 22-aminoacid peptide, corresponding to the ribosomal P0, P1 and P2 common epitope. To study the specificity and sensitivity of the method and evaluate the frequency and clinical associations of anti-P antibodies in two groups of systemic lupus erythematosus (SLE) patients: (a) unselected SLE patients and (b) SLE patients with central nervous system (CNS) involvement.
PATIENTS AND METHODS—The C-terminal 22 aminoacid peptide of the ribosomal P proteins (Lys-Lys-Glu-Glu-Lys-Lys-Glu-Glu-Lys-Ser-Glu-Glu-Glu-Asp-Glu-Asp-Met-Gly-Phe-Gly-Leu-Phe-Asp) was synthesised according to Merrifield's solid phase procedure. Purification of the peptide was performed by preparative high performance liquid chromatography and confirmed by amino acid analysis. Using this peptide, in a concentration 5 µg/ml, an ELISA was developed. The presence of anti-P antibodies was evaluated by western blot using purified ribosomal proteins from rat liver. Sera from 178 consecutive patients with SLE and 28 patients with SLE and CNS manifestations were tested. Sera from 58 patients with rheumatoid arthritis and 57 patients with primary Sjögren's syndrome were used as controls. The cut off point of the assay was defined using 124 normal sera.
RESULTS—The specificity of the assay was evaluated by homologous inhibition. Pretreatment of positive sera with soluble 22mer peptide of the ribosomal P proteins resulted in 88% inhibition. The concordance between the peptide assay and western blot was found to be 83%. Thirty three of 178 (18.6%) of the unselected SLE patients had antibodies to P-protein common epitope. Their presence was associated with more active disease (European Consensus Lupus Activity Measurement, ECLAM scoring system) (p<0.001), higher levels of anti-ds DNA antibodies (p<0.05) and lower levels of the C4 component of complement (p<0.01). Eleven of 28 (39.3%) patients with SLE and active CNS involvement had antibodies to P-protein. The overall prevalence of anti-P antibodies in active CNS disease patients was statistically significantly higher, as compared with unselected SLE patients (χ²=6.04, p<0.05). These antibodies were found in a high proportion of patients without anticardiolipin antibodies (52.4%) and they were associated with diffuse CNS involvement (psychiatric disorders (71%) and epilepsy (75%)).
CONCLUSIONS—A synthetic analogue of the common epitope of ribosomal P-proteins can be use as an antigen for the detection of anti-P antibodies. These antibodies are associated with active SLE and CNS involvement particularly in patients without anticardiolipin antibodies.

     

Nocturnal hypoxia and arrhythmias in patients with impaired left ventricular function

Objectives—To document the incidence of hypoxic episodes in a series of patients with impaired left ventricular function, and to correlate the occurrence of hypoxia with severity of arrhythmia.Patients—34 patients with breathlessness and clinical evidence of left ventricular dysfunction.Main outcome measures—Simultaneous overnight finger oximetry and electrocardiographic monitoring.Results—High grade arrhythmias (Lown grade >III) occurred in 20/34 (59%) of patients, and frequent dips in oxygen saturation were noticed (mean dip frequency 4·8/h, range 0·1–20·0). 20/34 (59%) of patients had episodic hypoxaemia, including 13/34 (38%) with a classical Cheyne Stokes pattern. There was a correlation between dip frequency and the presence of high grade arrhythmias (those with high grade arrhythmia had mean (SD) 6·7 (5·5) dips/h ν 2·2 (3·4) in those without, p < 0·01); there was also a correlation between the presence of arrhythmias and episodic hypoxaemia (episodic hypoxaemia in those with high grade arrhythmias occurred in 17/20 (85%) ν 3/14 (21%) of those without arrhythmias, p < 0·002). There was no correlation between the presence of high grade arrhythmias or dip frequency and the extent of left ventricular impairment, which was present in all patients (mean (SD) ejection fraction 26% (13%)).Conclusion—Noticeable abnormalities of nocturnal oxygen saturation occur in patients with impaired left ventricular function, and these are associated with high grade arrhythmias. Interventions that limit desaturation may have valuable anti-arrhythmic effects.