Immunological changes in patients with primary osteoarthritis of the hip after total joint replacement

We aimed to assess whether the immunological abnormalities which have been observed in patients with loose total hip replacements (THRs) are present in patients with a well-fixed prosthesis. We examined blood samples from 39 healthy donors, 22 patients before THR and 41 with well-fixed THRs of different types (15 metal-on-metal, 13 metal-on-polyethylene, 13 ceramic-on-ceramic). Before THR, the patients showed a decrease in leukocytes and myeloid cells in comparison with healthy donors, and a prevalence of type-1 T lymphocytes, which was confirmed by the increase in ratio of interferon-gamma to interleukin 4. Moreover, patients with metal-on-metal or metal-on-polyethylene implants showed a significant decrease in the number of T lymphocytes and a significant increase in the serum level of chromium and cobalt, although no significant correlation was observed with the immunological changes. In the ceramic-on-ceramic group, leukocytes and lymphocyte subsets were not significantly changed, but a significant increase in type-2 cytokines restored the ratio of interferon-gamma to interleukin 4 to normal values. We conclude that abnormalities of the cell-mediated immune response may be present in patients with a well-fixed THR, and that the immunological changes are more evident in those who have at least one metal component in the articular coupling.     

Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development

We have previously identified polymorphisms in the serotonin transporter gene promoter region and in intron 2 that were more common among sudden infant death syndrome (SIDS) cases compared with control subjects. To elucidate further the genetic profile that might increase an infant's vulnerability to SIDS, we focused on the recognized relationship between autonomic nervous system (ANS) dysregulation and SIDS. We therefore studied genes pertinent to early embryologic development of the ANS, including MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1, TLX3, and EN1 in 92 probands with SIDS and 92 gender- and ethnicity-matched control subjects. Eleven protein-changing rare mutations were identified in 14 of 92 SIDS cases among the PHOX2a, RET, ECE1, TLX3, and EN1 genes. Only 1 of these mutations (TLX3) was identified in 2 of 92 control subjects. Black infants accounted for 10 of these mutations in SIDS cases and 2 control subjects. Four protein-changing common polymorphisms were identified in BMP2, RET, ECE1, and EDN1, but the allele frequency did not differ between SIDS cases and control subjects. However, among SIDS cases, the allele frequency for the BMP2 common polymorphism demonstrated ethnic differences; among control subjects, the allele frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic differences. These data represent further refinement of the genetic profile that might place an infant at risk for SIDS.     

Selectively preventing development of third molars in rats using electrosurgical energy

BACKGROUND: Third molars are teeth with questionable value. People who never develop third molars avoid confronting the disease and pain these teeth often cause. Since third molars do not begin to develop until children are approximately five years of age, a window of opportunity exists to therapeutically prevent this tooth's development. The dentition of neonate rats possess developmental stages of molars similar to that of five-year-old children. This pilot study tests the hypothesis that third molars can be selectively prevented from developing. METHODS: Thirty-three neonate rats received a momentary pulse of electrosurgical energy to one of their maxillary tuberosities. The tuberosities on the contralateral sides received no treatment. Intraoral and radiographic examinations of sacrificed animals occurred when they were between 47 and 52 days old. Several tuberosity areas from sacrificed animals underwent histologic examination. RESULTS: Ten rats showed no intraoral or radiographic evidence of third molar development, and six developed smaller-than-normal third molars. Development of the maxilla also was affected frequently. One treated tuberosity area that was missing a third molar showed no histologic evidence of tooth-forming tissues, cyst formation or other significant abnormal tissue changes. CONCLUSIONS: Maxillary third molars can be selectively prevented from developing in rat pups at or near the time of tooth bud initiation; however, electrosurgical energy is too powerful and uncontrollable to reliably confine its damage to only the tooth-forming tissues. CLINICAL IMPLICATIONS: Third molars may be able to be selectively prevented from developing in growing children near the time of tooth bud initiation if less-differentiated precursor tooth-forming tissues can be selectively targeted.     

Acquisition of i(8q) as an early event in malignant triton tumors

Malignant triton tumors (MTT) are rare soft-tissue tumors characterized by a mixture of cells with nerve sheath and skeletal muscle differentiation. MTT is a histological variant of malignant peripheral nerve sheath tumors (MPNST). No characteristic cytogenetic anomaly has been detected in MPNST or MTT. In this paper, we report on the cytogenetic findings of an MTT from a 20-year old male with neurofibromatosis (NF1). The tumoral karyotype showed the modal number to be near-diploid and an abnormal karyotype with a Robertsonian translocation and 4 markers: 49,XY,der(14;15)(q10;q10),+4mar. Spectral karyotyping revealed the karyotype: 49,XY, der(14;15)(q10;q10),+i(8)(q10)x4. Fluorescence in situ hybridization analysis of the tissue confirmed the presence of the additional i(8)(q10) in all tumoral cells. The sequence analysis of p53 revealed a polymorphism in exon 9, codon 329. The two alleles, TTC and TCC, codify for phenylalanine and serine, respectively. Our results indicate that all neoplastic cells have the same cytogenetic pattern, suggesting that both cell lines, which show nerve sheath and skeletal muscle differentiation, are derived from a unique stem cell. The acquired Robertsonian chromosomal recombinants might represent an event in the tumorigenesis of MTT, and the present data suggest that genes located on 8q can be involved in the development of MTT.     

The ultrastructure of nasal mucosa in children with asthma

Nasal brushing has sometimes been used to characterize some affections of the respiratory tract, but seldom employed in chronic diseases such as asthma, for the possible presence of cellular inflammation in the small specimens used for electron microscopy. The present study evaluated the ultrastructure of epithelial cells obtained by nasal brushing in 11 allergic children with asthma, before and after staying in an environment free of allergens, usually implicated in the genesis of inflammatory events. The ultrastructural alterations of the nasal mucosa have been graded on the basis of their severity. Grade I lesions were characterized by well-differentiated mucous and ciliated cells. The ciliated cells appeared usually well preserved but decreased in number. In grade II lesions, most of the epithelial surface was covered by mucous cells. A further phenotype composed of poorly differentiated ciliated or mucous cells was detected. Grade III lesions showed aspects of depletion of the ciliated and mucous cells. The epithelium was largely composed of undifferentiated cells. Furthermore, the comparison of specimens at 2 different times of sampling did not differ. The data demonstrate that in allergic children with asthma, the nasal mucosa showed ultrastructural changes, which appeared to be unmodifiable during a prolonged stay in an environment free of allergens. Moreover, the nasal epithelium may provide a convenient sampling site, allowing grade of mucosal damage, with the benefit that the brush method is minimally invasive and avoids complications related to bronchoscopic examination.     

Control of imported and acquired methicillin-resistant Staphylococcus aureus (MRSA) in mechanically ventilated patients: a dose-response study of enteral vancomycin to reduce absolute carriage and infection

This study aimed to quantify the animate source provided by the patients using the concept of "absolute carriage" by multiplying the carrier rate by the level of carriage; and to compare the impact of a low and high dose of an oropharyngeal vancomycin gel on the absolute MRSA carriage and infection. In all, 265 patients were included, 126 were MRSA positive. Fifty-five patients received 2% vancomycin gel during the first year whilst 4% vancomycin gel was given to 50 patients during the second year. Surveillance swabs of throat and rectum were obtained from all eligible patients on admission and then twice weekly. The vancomycin protocol was started as soon as the surveillance cultures were positive for MRSA. Those patients received one gram of enteral vancomycin daily, divided into four doses. During the first year 2% vancomycin gel 4 ml (80 mg) was applied in the oropharynx in four doses in addition to the enteral solution (Group A). During the second year 4% vancomycin gel 4 ml (160 mg) was used (Group B). The absolute carriage was high during both periods: 3.6 for Group A, and 3.2 for Group B. The 4% vancomycin protocol significantly reduced the absolute carriage, compared to the 2% vancomycin protocol: 2.6 versus 1.5 (P < 0.01). Significant reduction in secondary endogenous infections was found in the second year: seven versus 15 patients (P < 0.05). A total of 3,588 microbiological samples were processed. Neither Staphylococcus aureus with intermediate sensitivity to vancomycin (VISA) nor vancomycin-resistant enterococci (VRE) were detected.     

Preoperative percutaneous portal vein embolization: evaluation of adverse events in 188 patients

PURPOSE: To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE). MATERIALS AND METHODS: Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16-78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the chi(2) test. RESULTS: Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1). CONCLUSION: PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.     

Synthesis and antimalarial activities of some furoxan sulfones and related furazans

Furoxan derivatives bearing a sulfone moiety at position 3 or 4 were synthesized and tested for their antimalarial action on the chloroquine-sensitive D10 and the chloroquine-resistant W2 strains of Plasmodium falciparum. The furazan analogues were considered for comparison. The most active compounds were the products in which the -SO2R groups are at the 3-position of the furoxan system. These latter substances displayed an antimalarial activity in the microM range, possibly related in part to their ability to release NO.