In vivo bone response and mechanical evaluation of electrosprayed CaP nanoparticle coatings using the iliac crest of goats as an implantation model

Recent trends in clinical implantology include the use of endosseous dental implant surfaces embellished with nano-sized modifications. The current study was initiated to evaluate the mechanical properties, as well as the potential beneficial effects, of electrosprayed CaP nanoparticle-coated (nano-CaP) implants on the in vivo osteogenic response, compared with grit-blasted, acid-etched (GAE) implant surfaces as controls. For this purpose nano-CaP coatings were deposited on cylindrical screw-type (St) implants and implanted bilaterally into the iliac crest of goats for 6 weeks. In addition to histological and histomorphometrical analyses, insertion torque and removal torque values were measured on implant placement and retrieval, respectively. The present study showed similar insertion and removal torque values for nano-CaP-coated and GAE control implants, with no statistically significant increase in torque value during the implant period for either group. With regard to bone–implant contact and peri-implant bone volume, no significant differences were found between nano-CaP-coated and GAE implants after 6 weeks implantation. In conclusion, this study has demonstrated that in situations in which implants are placed in a non-compromised situation using a standard press fit implantation strategy the performance of electrosprayed nano-CaP coatings is comparable with GAE implants, both with respect to implant fixation and bone healing response.     

Site-specific manifestations of invasive group a streptococcal disease: type distribution and corresponding patterns of virulence determinants

As part of a national surveillance program on invasive group A streptococci (GAS), isolates that caused specific manifestations of invasive GAS disease in The Netherlands were collected between 1992 and 1996. These site-specific GAS infections involved meningitis, arthritis, necrotizing fasciitis, and puerperal sepsis. An evaluation was performed to determine whether GAS virulence factors correlate with these different disease manifestations. PCRs were developed to detect 9 genes encoding exotoxins and 12 genes encoding fibronectin binding proteins. The genetic backgrounds of all isolates were determined by M genotyping and pulsed-field gel electrophoresis (PFGE) analysis. The predominant M types included M1, M2, M3, M4, M6, M9, M12, and M28. Most M types were associated with all manifestations of GAS disease. However, M2 was found exclusively in patients with puerperal sepsis, M6 predominated in patients with meningitis, and M12 predominated in patients with GAS arthritis. While characteristic gene profiles were detected in most M types, the resolution of detection of different gene profiles within M genotypes was enhanced by PFGE analysis, which clearly demonstrated the existence of some clonal lineages among invasive GAS isolates in The Netherlands. M1 isolates comprised a single clone carrying highly mitogenic toxin genes (speA, smeZ) and were associated with toxic shock-like syndrome. Toxin profiles were highly conserved among the most virulent strains, such as M1 and M3.     

High prevalence of eating disorders in narcolepsy with cataplexy: a case-control study

STUDY OBJECTIVES: To study the prevalence of and symptoms of eating disorders in patients with narcolepsy. DESIGN: We performed a case-control study comparing symptoms of eating disorders in patients with narcolepsy versus healthy population controls, using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1). To study whether an increased body mass index (BMI) could be responsible for symptoms of an eating disorder, we also compared patients with BMI-matched controls, using the SCAN as well as the Eating Disorder Examination-Questionnaire. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Patients with narcolepsy/cataplexy (n = 60) were recruited from specialized sleep centers. Healthy controls (n = 120) were drawn from a population study previously performed in the Netherlands. Separately, 32 BMI-matched controls were recruited. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In total, 23.3% of the patients fulfilled the criteria for a clinical eating disorder, as opposed to none of the control subjects. Most of these were classified as Eating Disorder-Not Otherwise Specified, with an incomplete form of binge eating disorder. On the symptom level, half of the patients reported a persistent craving for food, as well as binge eating. Twenty-five percent of patients even reported binging twice a week or more often. When compared with BMI-matched controls, the significant increases persisted in symptoms of eating disorders among patients with narcolepsy. Except for a higher level of interference in daily activities due to eating problems in patients using antidepressants, medication use did not influence our findings. CONCLUSIONS: The majority of patients with narcolepsy experience a number of symptoms of eating disorders, with an irresistible craving for food and binge eating as the most prominent features. Eating disorder symptomatology interfered with daily activities. These findings justify more attention for eating disorders in the treatment of patients with narcolepsy.     

Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles

In this study, the mechanical properties of an implanted calcium phosphate (CaP) cement incorporated with 20wt% poly (dl-lactic-co-glycolic acid) (PLGA) microparticles were investigated in a rat cranial defect. After 2, 4 and 8 weeks of implantation, implants were evaluated mechanically (push-out test) and morphologically (Scanning Electron Microscopy (SEM) and histology). The results of the push-out test showed that after 2 weeks the shear strength of the implants was 0.44+/-0.44MPa (average+/-sd), which increased to 1.34+/-1.05MPa at 4 weeks and finally resulted in 2.60+/-2.78MPa at 8 weeks. SEM examination showed a fracture plane at the bone-cement interface at 2 weeks, while the 4- and 8-week specimens created a fracture plane into the CaP/PLGA composites, indicating an increased strength of the bone-cement interface. Histological evaluation revealed that the two weeks implantation period resulted in minimal bone ingrowth, while at 4 weeks of implantation the peripheral PLGA microparticles were degraded and replaced by deposition of newly formed bone. Finally, after 8 weeks of implantation the degradation of the PLGA microparticles was almost completed, which was observed by the bone ingrowth throughout the CaP/PLGA composites. On basis of our results, we conclude that the shear strength of the bone-cement interface increased over time due to bone ingrowth into the CaP/PLGA composites. Although the bone-cement contact could be optimized with an injectable CaP cement to enhance bone ingrowth, still the mechanical properties of the composites after 8 weeks of implantation are insufficient for load-bearing purposes.     

Retrospective attenuation correction of PET data for radiotherapy planning using a free breathing CT.

PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction.     

Uniform procedure of (1)H NMR analysis of rat urine and toxicometabonomics Part II: comparison of NMR profiles for classification of hepatotoxicity.

A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition is proposed for early detection of toxicity of investigational compounds in rats. The method is applied to detect toxicity upon administration of 13 toxic reference compounds and one nontoxic control compound (mianserine) in rats. The toxic compounds are expected to induce necrosis (bromobenzene, paracetamol, carbon tetrachloride, iproniazid, isoniazid, thioacetamide), cholestasis (alpha-naphthylisothiocyanate (ANIT), chlorpromazine, ethinylestradiol, methyltestosterone, ibuprofen), or steatosis (phenobarbital, tetracycline). Animals were treated daily for 2 or 4 days except for paracetamol and bromobenzene (1 and 2 days) and carbon tetrachloride (1 day only). Urine was collected 24 h after the first and second treatment. The animals were sacrificed 24 h after the last treatment, and NMR data were compared with liver histopathology as well as blood and urine biochemistry. Pathology and biochemistry showed marked toxicity in the liver at high doses of bromobenzene, paracetamol, carbon tetrachloride, ANIT, and ibuprofen. Thioacetamide and chlorpromazine showed less extensive changes, while the influences of iproniazid, isoniazid, phenobarbital, ethinylestradiol, and tetracycline on the toxic parameters were marginal or for methyltestosterone and mianserine negligible. NMR spectroscopy revealed significant changes upon dosing in 88 NMR biomarker signals preselected with the Procrustus Rotation method on principal component discriminant analysis (PCDA) plots. Further evaluation of the specific changes led to the identification of biomarker patterns for the specific types of liver toxicity. Comparison of our rat NMR PCDA data with histopathological changes reported in humans and/or rats suggests that rat NMR urinalysis can be used to predict hepatotoxicity.     

Stress susceptibility as a determinant of the response to adrenergic stimuli in mesenteric resistance arteries of the rat

Characterized by the behavioral response to apomorphine, two outbred lines of Wistar rats can be recognized with constitutionally determined high (apomorphine susceptible, APO-SUS) or low (apomorphine unsusceptible, APO-UNSUS) adrenal responses to similar environmental stress. Within the accumbens nucleus, the APO-SUS and APO-UNSUS rats differ in alpha -adrenergic receptor responsiveness. This study explored whether these differences in adrenergic receptor sensitivity also exist in mesenteric resistance arteries. A Mulvany myograph was used to study the vasomotor responses of isolated mesenteric resistance arteries to adrenergic receptor stimulation. Phenylephrine (alpha1-agonist)-induced vasoconstriction did not differ between the two lines (pEC : 5.8 +/- 0.05 microM versus 5.8 +/- 0.04 microM and Emax: 36 +/- 2 kPa versus 33 +/- 1 kPa for APO-SUS, n = 9, and APO-UNSUS, n = 11, respectively, p > 0.1). After precontraction with phenylephrine, salbutamol (beta -agonist)-induced relaxation was less in APO-SUS rats (pEC50 4.9 +/- 0.06 versus 5.3 +/- 0.06M for APO-SUS, n = 9, and APO-UNSUS, n = 7, respectively, p < 0.001). Likewise, clonidine (alpha2-agonist)-induced relaxation was reduced in APO-SUS rats (pEC50: 6.7 +/- 0.07 versus 7.0 +/- 0.04, for APO-SUS, n = 9, and APO-UNSUS, n = 8, respectively; p < 0.01). In conclusion, constitutionally determined high susceptibility to stress is accompanied by an impaired vasorelaxation to adrenergic stimuli whereas vasoconstriction is unaffected. An unopposed vasoconstrictor action of norepinephrine may place the APO-SUS rats at increased risk for the development of hypertension, insulin resistance, and atherosclerosis.     

Chromogenic endotoxin determination in blood — clinical relevance

Summary In a pilot study in 400 patients LPS-quantification in blood using chromogenic substrates, bacterial cultures and bacterial quantification were performed. Decreased plasma levels of antithrombin III and plasminogen were early predictors of gram-negative septicemia, which already were apparant 3 days prior to the first positive LPS-test. It is concluded that daily determinations of LPS may reduce the delay in proper antibiotic therapy.