Comparison of pneumococcal vaccination response in children with sickle cell disease: HbSS and HbSC

Introduction: Sickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. Objective: To compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. Methods: Patients with HbSS (n = 33) and HbSC (n = 11), aged 7-18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. Results: Absolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p = 0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥ 1.3 mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p = 0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p = 0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p = 0.003), pneumonia (p = 0.036) or both (p = 0.011), compared to good vaccine responders. Conclusion: HbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary

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Comparison of pneumococcal vaccination response in children with sickle cell disease: HbSS and HbSC.

INTRODUCTION: Sickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. OBJECTIVE: To compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. METHODS: Patients with HbSS (n=33) and HbSC (n=11), aged 7-18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. RESULTS: Absolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p=0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥1.3mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p=0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p=0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p=0.003), pneumonia (p=0.036) or both (p=0.011), compared to good vaccine responders. CONCLUSION: HbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary.

Fluid pressurization and tractional forces during TMJ disc loading: A biphasic finite element analysis.

OBJECTIVES: To investigate the ploughing mechanism associated with tractional force formation on the temporomandibular joint (TMJ) disc surface. SETTING AND SAMPLE POPULATION: Ten left TMJ discs were harvested from 6- to 8-month-old male Yorkshire pigs. MATERIALS AND METHODS: Confined compression tests characterized mechanical TMJ disc properties, which were incorporated into a biphasic finite element model (FEM). The FEM was established to investigate load carriage within the extracellular matrix (ECM) and the ploughing mechanism during tractional force formation by simulating previous in vitro plough experiments. RESULTS: Biphasic mechanical properties were determined in five TMJ disc regions (average±standard deviation for aggregate modulus: 0.077±0.040 MPa; hydraulic permeability: 0.88±0.37×10-3 mm4 /Ns). FE simulation results demonstrated that interstitial fluid pressurization is a dominant loading support mechanism in the TMJ disc. Increased contact load and duration led to increased solid ECM strain and stress within, and increased ploughing force on the surface of the disc. CONCLUSION: Sustained mechanical loading may play a role in load carriage within the ECM and ploughing force formation during stress-field translation at the condyle-disc interface. This study further elucidated the mechanism of ploughing on tractional force formation and provided a baseline for future analysis of TMJ mechanics, cartilage fatigue and early TMJ degeneration.

A pilot study of nocturnal temporalis muscle activity in TMD diagnostic groups of women.

Temporomandibular disorder (TMD) incidences are believed to be related to parafunctional behaviours like teeth clenching. This pilot study aimed to (i) develop an automated clench-detection algorithm, and (ii) apply the algorithm to test for differences in nocturnal clenching in women with and without TMD. Subjects gave informed consent to participate. Adult women were categorised using Diagnostic Criteria for TMD according to presence/absence (+/-) of both TM joint disc placement (DD) and chronic pain (P) into two groups (+DD+P, -DD-P) with 12 subjects each. Surface temporalis electromyography was recorded during oral tasks performed by subjects at two laboratory sessions. The data were used to characterise muscle activity per N of bite force (µV/N) for each subject, develop the clench-detection algorithm and test its accuracy. Ambulatory surface temporalis electromyography was self-recorded by each subject over three nights and analysed using the algorithm and bite force (N) versus muscle activity µV/N calibrations. Bonferroni-adjusted homoscedastic t-tests assessed for significant between-group differences in clenching (P < 0·05). Sensitivity, specificity and accuracy of algorithm-detected laboratory clenches were all ≥96%. During self-recordings 95% of clenches had durations of <4 s and peak forces of <10 N in both groups. Mean clench durations were significantly longer (P = 0·042) in +DD+P (1·9 ± 0·8 s) than -DD-P subjects (1·4 ± 0·4 s). Mean temporalis duty factors (%clench time/total recording time) were significantly larger (P = 0·041) in +DD+P (0·47 ± 0·34%) than -DD-P (0·26 ±0·22%) subjects. Nocturnal temporalis muscle activities detected by a validated algorithm were longer per clench and recording time in +DD+P compared to -DD-P women.

A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis.

SETTING: Randomised Phase IIB clinical trial. OBJECTIVES: To assess whether increasing the dose of rifampicin (RMP) from 10 mg/kg to 15 or 20 mg/kg results in an increase in grade 3 or 4 hepatic adverse events and/or serious adverse events (SAE). METHODS: Three hundred human immunodeficiency virus negative patients with newly diagnosed microscopy-positive pulmonary tuberculosis (TB) were randomly assigned to one of three regimens: 1) the control regimen (R10), comprising daily ethambutol (EMB), isoniazid (INH), RMP and pyrazinamide for 8 weeks, followed by INH and RMP daily for 18 weeks; 2) Study Regimen 1 (R15), as above, with the RMP dose increased to 15 mg/kg body weight daily for the first 16 weeks; and 3) Study Regimen 2 (R20), as above, with RMP increased to 20 mg/kg. Serum alanine transferase (ALT) levels were measured at regular intervals. RESULTS: There were seven grade 3 increases in ALT levels, 1/100 (1%) among R10 arm patients, 2/100 (2%) in the R15 arm and 4/100 (4%) in the R20 arm (trend test P = 0.15). One (R15) patient developed jaundice, requiring treatment modification. There were no grade 4 ALT increases. There was a non-significant increase in culture negativity at 8 weeks with increasing RMP dosage: 75% (69/92) in R10, 82.5% (66/80) in R15 and 83.1% (76/91) R20 patients (P = 0.16). CONCLUSIONS: No significant increase in adverse events occurred when the RMP dose was increased from 10 mg/kg to 15 mg/kg or 20 mg/kg.

Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome.

Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed.

Proprioceptively guided reaching movements in 3D space: effects of age, task complexity and handedness.

Aging is associated with impaired upper limb proprioceptive acuity, as reflected by decreased position matching accuracy with increasing task complexity and movement extent. Most studies have primarily used single-joint or planar paradigms to examine age-related changes in proprioception. It is unclear whether these changes can be generalized to more complex multi-joint movements, where additional sensory feedback may affect performance. Since age-related declines in cognitive function may impair the ability to integrate multiple sources of sensory feedback, deficits in position matching ability in older adults may persist when tasks are performed in three-dimensional space. The accuracy with which young and older participants reproduced remembered reference hand positions was assessed under different experimental conditions. Participants matched target locations located directly to the front or 45° to the side relative to the midline using the preferred and non-preferred arms. Either the same (i.e., ipsilateral matching) or the opposite (i.e., contralateral matching) arm was used to reproduce the target location. No differences in matching accuracy were found between young and older participants when matching ipsilaterally. When matching contralaterally, accuracy was worse in older participants for target locations located to the side, which may reflect age-related changes in the perception of peripersonal space. In contrast to previous studies, accuracy did not differ between the preferred and non-preferred arms in either group. These results extend previous findings demonstrating age-related impairments in proprioceptively guided arm movements when interhemispheric transfer is required.

Transmission of Escherichia coli O157:H7 in cattle is influenced by the level of environmental contamination.

A pen infection-transmission experiment was conducted to elucidate the role of pathogen strain and environmental contamination in transmission of Escherichia coli O157:H7 (ECO157) in cattle. Five steers were inoculated with a three-strain mixture of ECO157 and joined with five susceptible steers in each of two experimental replicates. Faecal and environmental samples were monitored for ECO157 presence over 30 days. One ECO157 strain did not spread. Transmission rates for the other two strains were estimated using a generalized linear model developed based on a modified 'Susceptible-Infectious-Susceptible' mathematical model. Transmission rates estimated for the two strains (0·11 and 0·14) were similar. However, the rates significantly (P = 0·0006) increased 1·5 times for every 1-unit increase in the level of environmental contamination measured as log10 c.f.u. Depending on the level of environmental contamination, the estimated basic reproduction numbers varied from <1 to 8. The findings indicate the importance of on-farm measures to reduce environmental contamination for ECO157 control in cattle that should be validated under field conditions.

The strain-specific dynamics of Escherichia coli O157:H7 faecal shedding in cattle post inoculation.

This study reports analysis of faecal shedding dynamics in cattle for three Escherichia coli O157:H7 (ECO157) strains (S1, S2 and S3) of different genotype and ecological history, using experimental inoculation data. The three strains were compared for their shedding frequency and level of ECO157 in faeces. A multistate Markov chain model was used to compare shedding patterns of S1 and S2. Strains S1 and S2 were detected seven to eight times more often and at 10(4) larger levels than strain S3. Strains S1 and S2 had similar frequencies and levels of shedding. However, the total time spent in the shedding state during colonization was on average four times longer for S1 (15 days) compared to S2 (4 days). These results indicate that an ECO157 strain effect on the frequency, level, pattern and the duration of faecal shedding may need to be considered in control of ECO157 in the cattle reservoir.

[HLA-B27 polymorphism and spondyloarthropathies]. / Polimorfismo do alelo HLA-B27 no desenvolvimento das espondilartropatias.

The association of HLA-B27 with ankylosing spondylitis (AS), and other spondyloarthropathies (SpA), remains as one of the strongest between HLA molecules and human disease. Since it was reported, in 1973, it has been extensively studied in order to understand the underlying pathogenic mechanism. The objective of this article is to review the current knowledge on the structure and polymorphism of HLA-B27 molecule, as well as describe the main pathogenic hypotheses trying to explain its association with AS.

[In vitro nystatin sensitivity of vaginal isolates of Candida spp]. / Sensibilidad in vitro a la nistatina de aislamientos vaginales de Candida spp.

The minimum inhibitory concentration (MIC) of nistatine, one of the most used antifungal agents for this micosis, was determined in 68 Candida strains isolated from vaginal smears. Candida albicans represented 75% of the total strains whereas C. parapsilosis, C. krusei and C. glabrata were much less frequently found. The predisposing factors were pregnancy and antibacterial treatment whereas leukorrhea and itching were the prevailing symptoms in most of the cases. MIC values from the use of a broth dilution method ranged from 0,5-8mg/mL and the geometric mean was 1.36mg/ mL. For C. albicans, MIC was 4mg/mL due to two strains that showed the highest MIC values (8 mg/mL). Similarly, the strains showed low MIC values, this means that therapeutic failures are not inherent to the emergence of resistant strains.

Periodontal manifestations of collagen vascular disorders.

Chronic degeneration of connective tissue components can be produced by a variety of autoimmune mechanisms. The designations connective tissue disease and collagen-vascular disease are commonly used to describe such conditions when a patient exhibits chronic, immune-mediated deterioration of connective tissue structures in a systemic distribution. Recognized conditions that fit this definition include rheumatoid arthritis, lupus erythematosus, progressive systemic sclerosis, CREST syndrome, and mixed connective tissue disease. Several characteristic oral manifestations of these conditions are recognized. Xerostomia associated with any of these conditions in addition to dryness of the eyes is the definition of secondary Sjögren's syndrome. Fibrosis of facial skin and the resulting limited jaw opening are diagnostic features of progressive systemic sclerosis. Several periodontal manifestations are associated with these connective tissue disorders. Dramatic periodontal ligament space widening that is associated with some cases of progressive systemic sclerosis has been appreciated for more than five decades. However, it has been more recently reported that the majority of progressive systemic sclerosis patients exhibit at least subtle generalized periodontal ligament widening when intraoral radiographs are carefully evaluated. This finding is, however, of limited periodontal significance because the teeth are typically not mobile. Comparisons of periodontitis indices such as pocket depth between healthy subjects and patients with progressive systemic sclerosis do not reveal significant differences (21). In addition, recent evidence suggests a tendency for more severe or progressive manifestations of periodontitis as a consequence of xerostomia that may result from these diseases.

Intraocular pressure control after contact transscleral diode cyclophotocoagulation in eyes with intractable glaucoma.

PURPOSE: The effect of contact transscleral diode cyclophotocoagulation (TDC) on intraocular pressure (IOP) and its safety was determined in eyes with intractable glaucoma. METHODS: The charts of 41 consecutive patients (43 eyes) who underwent the laser procedure were reviewed. After surgery, data were collected from chart entries at I hour, 1 day, 4 to 6 weeks, 4 to 6 months, and at the final visit (6-24 months). Mean differences in IOP before and after treatment were compared using the paired Student t test. Associated complications also were assessed. RESULTS: The mean +/- standard deviation follow-up period was 11.9+/-5.3 months (range, 6-24 months). One patient who died after 1 month of follow-up and another patient with neovascular glaucoma who underwent an anterior chamber washout 1 week after laser to treat an uncontrolled IOP spike were excluded from the study. Repeat treatment was done in 12 (28%) eyes. At each follow-up visit postoperatively, a significant reduction from preoperative IOP was obtained (mean reduction of 50% at the final visit). At the final visit, 64% of patients achieved an IOP of <22 mmHg and a reduction of > or =20%. An IOP spike occurred in three (7%) eyes. Long-term complications included loss of vision (> or =2 lines) in eight (22%) patients, corneal decompensation in one (2%), phthisis bulbi in one (2%), and corneal graft rejection in one (2%). CONCLUSION: Although effective IOP reduction was demonstrated in eyes with intractable glaucoma after TDC, a significant proportion (26%) of eyes had severe long-term complications.

Bad news and good news: what the dentist needs to know about transmissible spongiform encephalopathies.

Since reports of the "mad cow disease" epidemic in Great Britain erupted in the international press, sensational and intimidating articles about the risk that bovine spongiform encephalopathy and related diseases may pose to humans have appeared. The bad news is that compelling scientific evidence suggests so-called prion disease can and has infected humans, although the overall risk appears to be low. Furthermore, at present, there is no reliable antemortem diagnosis, specific treatment, or vaccine to prevent the disease. The agent thought to be responsible for this unusual class of disease is a rogue protein (called a prion) that, unlike all other agents known to cause infectious disease, contains neither DNA nor RNA. According to a popular hypothesis, normal membrane-associated prion proteins undergo conformational changes that can cause disease. The "bad" prion forms cause holes or a spongy appearance in the brain in all disease variants, hence the generic designation of spongiform encephalopathy. The good news is that risk for exposure to prion disease is exceedingly remote in the dental practice and that current universal infection control procedures are probably sufficient.

An empirical study of economies of scope in home healthcare.

OBJECTIVE: To apply the economic theory of economies of scope to the home healthcare industry. DATA SOURCES: Data on 488 observations obtained from the Cost Report (HCFA Form 1728-86) of all Connecticut state-licensed, Medicare-certified home health agencies. STUDY DESIGN: The Cost Report was the primary source of data for this study. Information on total cost, scope, and other related factors was collected. Logarithmic and nonlinear regression analyses were used to identify factors related to scope and also to test for economies of scope. DATA COLLECTION METHOD: Data collected were both cross-sectional and time series (from 1988-1992). Data accuracy was verified using description of frequencies, measures of central tendency and variation, and a calculation package so that a computer calculation on the data could be compared with the agency's calculation. PRINCIPAL FINDINGS: It was determined that initially as scope increases, costs go down, thus proving economies of scope. For larger values of scope, it was determined that costs go up, proving diseconomies of scope. CONCLUSIONS: Many of the home health agencies included in this study provide more services than is cost effective given the economic theory of economies of scope.

Bacterial aminopeptidases: properties and functions.

Aminopeptidases are exopeptidases that selectively release N-terminal amino acid residues from polypeptides and proteins. Bacteria display several aminopeptidasic activities which may be localised in the cytoplasm, on membranes, associated with the cell envelope or secreted into the extracellular media. Studies on the bacterial aminopeptide system have been carried out over the past three decades and are significant in fundamental and biotechnological domains. At present, about one hundred bacterial aminopeptidases have been purified and biochemically studied. About forty genes encoding aminopeptidases have also been cloned and characterised. Recently, the three-dimensional structure of two aminopeptidases, the methionine aminopeptidase from Escherichia coli and the leucine aminopeptidase from Aeromonas proteolytica, have been elucidated by crystallographic studies. Most of the quoted studies demonstrate that bacterial aminopeptidases generally show Michaelis-Menten kinetics and can be placed into either of two categories based on their substrate specificity: broad or narrow. These enzymes can also be classified by another criterium based on their catalytic mechanism: metallo-, cysteine- and serine-aminopeptidases, the former type being predominant in bacteria. Aminopeptidases play a role in several important physiological processes. It is noteworthy that some of them take part in the catabolism of exogenously supplied peptides and are necessary for the final steps of protein turnover. In addition, they are involved in some specific functions, such as the cleavage of N-terminal methionine from newly synthesised peptide chains (methionine aminopeptidases), the stabilisation of multicopy ColE1 based plasmids (aminopeptidase A) and the pyroglutamyl aminopeptidase (Pcp) present in many bacteria and responsible for the cleavage of the N-terminal pyroglutamate.

Mutational analysis of the active site of Pseudomonas fluorescens pyrrolidone carboxyl peptidase.

On the basis of chemical inhibition studies and a multiple alignment of four pyrrolidone carboxyl peptidase (Pcp) amino acid sequences, seven conserved residues of the Pseudomonas fluorescens Pcp, which might be important for enzyme activity, have been modified by site-directed mutagenesis experiments. Wild-type and mutant Pcps were expressed in Escherichia coli, purified, and characterized by the ability to cleave the synthetic chromogenic substrate pyroglutamyl-beta-naphthylamide and the dipeptide pyroglutamyl-alanine. Substitution of Glu-10 and Glu-22 by Gln led to enzymes which displayed catalytic properties and sensitivities to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide similar to those of the wild-type Pcp. These residues are not essential for the catalytic activity. Replacement of Asp-89 by Asn and Ala resulted in enzymes which retained nearly 25% of activity and which had no activity, respectively. Substitution of the Cys-144 and His-166 residues by Ala and Ser, respectively, resulted in inactive enzymes. Proteins with changes of Glu-81 to Gln and Asp-94 to Asn were not detectable in crude extract and were probably unstable in bacteria. Our results are consistent with the proposal that Cys-144 and His-166 constitute the nucleophilic and imidazole residues of the Pcp active site, while residue Glu-81, Asp-89, or Asp-94 might constitute the third part of the active site. These results lead us to propose Pcps as a new class of thiol aminopeptidases.

Pyrrolidone carboxyl peptidase (Pcp): an enzyme that removes pyroglutamic acid (pGlu) from pGlu-peptides and pGlu-proteins.

Pyrrolidone carboxyl peptidase (EC 3.4.11.8) is an exopeptidase commonly called PYRase, which hydrolytically removes the pGlu-proteins. pGlu also known as pyrrolidone carboxylic acid may occur naturally by an enzymatic procedure or may occur as an artifact in proteins or peptides. The enzymatic synthesis of pGlu suggests that this residue may have important biological and physiological functions. Several studies are consistent with this supposition. PYRase has been found in a variety of bacteria, and in plant, animal, and human tissues. For over two decades, biochemical and enzymatic properties of PYRase have been investigated. At least two classes of PYRase have been characterized. The first one includes the bacterial and animal type I PYRases and the second one the animal type II and serum PYRases. Enzymes from these two classes present differences in their molecular weight and in their enzymatic properties. Recently, the genes of PYRases from four bacteria have been cloned and characterized, allowing the study of the primary structure of these enzymes, and their over-expression in heterelogous organisms. Comparison of the primary structure of these enzymes revealed striking homologies. Type I PYRases and bacterial PYRases are generally soluble enzymes, whereas type II PYRases are membrane-bound enzymes. PYRase II appears to play as important a physiological role as other neuropeptide degrading enzymes. However, the role of type I and bacterial PYRases remains unclear. The primary application of PYRase has been its utilization for some protein or peptide sequencing. Development of chromogenic substrates for this enzyme has allowed its use in bacterial diagnosis.