Cysteamine revisited: repair of arginine to cysteine mutations.

Cysteamine is a small aminothiol endogenously derived from coenzyme A degradation. For some decades, synthetic cysteamine has been employed for the treatment of cystinosis, and new uses of the drug continue to emerge. In this review, we discuss the role of cysteamine in cellular and extracellular homeostasis and focus on the potential use of aminothiols to reconstitute the function of proteins harboring arginine (Arg) to cysteine (Cys) mutations, via repair of the Cys residue into a moiety that introduces an amino group, as seen in basic amino acid residues Lys and Arg. Cysteamine has been utilized in vitro and ex vivo in four different genetic disorders, and thus provides "proof of principle" that aminothiols can modify Cys residues. Other aminothiols such as mercaptoethylguanidine (MEG) with closer structural resemblance to the guanidinium moiety of Arg are under examination for their predicted enhanced capacity to reconstitute loss of function. Although the use of aminothiols holds clinical potential, more studies are required to refine specificity and treatment design. The efficacy of aminothiols to target proteins may vary substantially depending on their specific extracellular and intracellular locations. Redox potential, pH, and specific aminothiol abundance in each physiological compartment are expected to influence the reactivity and turnover of cysteamine and analogous drugs. Upcoming research will require the use of suitable cell and animal models featuring Arg to Cys mutations. Since, in general, Arg to Cys changes comprise about 8% of missense mutations, repair of this specific mutation may provide promising avenues for many genetic diseases.

Detection of adenovirus infection in children in Jordan.

Between November 1997 and May 1998, 350 nasopharyngeal aspirates (NPA) were obtained from children admitted to the Respiratory Disease Unit at Princess Rahma Hospital, northern Jordan who were clinically diagnosed as suffering from respiratory tract infections. NPA were investigated for the presence of adenovirus using shell vial (SV) culture assay, conventional culture (CC) assay, and direct immunofluorescence assay (DFA). Of the 350 NPA, adenoviruses were detected in 54 (15.4%) by the combined techniques used. SV identified 34 (63%), CC 48 (89%) and DFA 30 (56%). Most virus isolations were in children aged 1-< 5 years old and were associated with pneumonia in 39% and bronchopneumonia in 32%. SV assay showed a sensitivity and specificity of 68.8% and 99.7%, respectively, for detecting adenovirus from NPA. These results emphasize that CC assay is still important for the diagnosis of adenovirus, although SV and DFA are superior diagnostic assays.

Enhanced detection of respiratory syncytial virus by shell vial in children hospitalised with respiratory illnesses in northern Jordan.

During the period between November 1997 and May 1998, a total of 350 nasopharyngeal aspirates were obtained from children admitted to the Respiratory Disease Unit at Princess Rahma Hospital, northern Jordan, and diagnosed clinically as suffering from respiratory tract infections. Nasopharyngeal aspirates were investigated for the presence of respiratory syncycial virus (RSV) by using shell vial (SV) culture assay, conventional culture assay, and direct immunofluorescence assay. Out of 350 nasopharyngeal aspirates, 101(28.9%) were found positive by any of SV, conventional culture, and immunofluorescence; 91 (90.1%) by SV, 87(86.1%) by culture, and 83(82.2%) by immunofluorescence. The maximum number of virus isolations was noted in children below the age of 1 year and was associated with bronchiolitis. SV assay showed the highest sensitivity (94.3%) and specificity (96.9%) for detecting RSV from nasopharyngeal aspirates. These results emphasise the importance of SV culture assay for diagnosis of RSV, although immunofluorescence is a valuable, rapid diagnostic assay.

Prevalence of parainfluenza and influenza viruses amongst children with upper respiratory tract infection.

OBJECTIVE: The objective of this study was to determine the prevalence of Parainfluenza and Influenza causing upper respiratory tract infections and to evaluate shell vial culture assay and direct immunofluorescence assay. METHODS: A retrospective study during the period between November 1997 and May 1998. A total of 350 nasopharyngeal aspirates were obtained from children suffering from respiratory tract infections. Nasopharyngeal aspirates were investigated for the presence of Parainfluenza 1, 2 and 3, Influenza A and B using shell vial culture assay, conventional culture assay and direct immunofluorescence assay. RESULTS: Parainfluenza 1 were identified in 3%, Parainfluenza 2 in 5% and Parainfluenza 3 in 6%. Influenza A were identified in 4% and Influenza B in 2%. Parainfluenza 1, 2 and 3 were isolated in children less than 5 years old. Most of Parainfluenza cases were associated with other upper respiratory infections. Shell vial assay showed a sensitivity of 90-93% and specificity of 99-100% for detecting Parainfluenza 1, 2 and 3. CONCLUSION: These results emphasize that shell vial assay is important for the diagnosis of Parainfluenza and Influenza, although direct immunofluorescence assay is the superior diagnostic assay.

Visual evaluation of residual curarization in anesthetized patients using one hundred-hertz, five-second tetanic stimulation at the adductor pollicis muscle.

UNLABELLED: We were looking for a clinical test to indicate a train-of-four (TOF) ratio of approximately 0.9. We compared the adductor pollicis muscle (AP) visually evaluated response to ulnar nerve 100-Hz, 5-s tetanus (RF100 Hz) with the measured AP TOF ratio in 30 ASA physical status I or II adult anesthetized (propofol, sufentanil, N2O/O2) patients. After the induction of anesthesia, the left ulnar nerve was stimulated at the wrist (single twitch and TOF) and the resultant isometric force was measured. When TOF was assessed, the independent investigators, unaware of the left AP-measured TOF ratios, visually evaluated the presence or absence of AP fading elicited by right ulnar nerve 100-Hz, 5-s tetanus. The 30 patients were randomly allocated to receive either 0.5 mg/kg atracurium (n = 15) or 0.1 mg/kg vecuronium (n = 15). The neuromuscular blockade was allowed to resolve spontaneously. A multiple logistic regression analysis was performed by computing the 771 visual observations. The probabilities of success of 100-Hz, 5-s tetanus to detect TOF ratios of 0.8, 0.85, and 0.9 were 99%, 96%, and 67%, respectively. The sensitivity and specificity of 100-Hz, 5-s tetanus as an indicator of TOF ratios of 0.85 and 0.9 are 100% and 75%, 54% and 67%, respectively. We conclude that RF100 Hz visual assessment seems to be highly sensitive in evaluating residual paralysis, as the absence of RF100 Hz visual fading at the AP is compatible with a TOF ratio > 0.85. IMPLICATIONS: After the administration of muscle relaxants, the absence of visual fading at the adductor pollicis, elicited in anesthetized patients by 100-Hz, 5-s tetanus, is compatible with a train-of four ratio > 0.85. Therefore, clinical observation of fading after 100-Hz, 5-s tetanus seems to be a highly sensitive test in evaluating residual paralysis.