5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

Bias resulting from missing information: some epidemiological findings.

The biases resulting from missing information were examined in three psychiatric epidemiological studies. In each study, cases with missing information could be compared with the main sample because data were available from several sources or at several points in time through a longitudinal study. In almost all instances, cases with missing data differed systematically in terms of variables crucial to the questions being studied. In general, they tended to include a higher proportion with problems of various kinds--such as, behavioural deviance, reading backwardness, child or adult psychiatric disorder, and marital discord. The characteristics or circumstances of those giving information were generally more strongly associated with co-operation in testing or interviewing than the characteristics of those about whom information was sought. In some situations, the nature and degree of distortion resulting from missing information could lead to biased results.     

Mine Blast Injuries - Our Experience

Background

The sudden increase in incidence and magnitude of mine blast injuries prompted us to highlight the problem and its management.

Methods

The cases of mine blast injuries occurring during mining and demining in a particular geographical area were analysed. Total 27 cases of mine blast injuries occurred during mining or demining operations in a period of 13 months.

Results

Various body regions were involved in the mine blast injuries but the main brunt was borne by feet and legs followed by multiple body regions due to splinters. 14 patients underwent below knee (BK) amputation while 4 patients required through knee (TK) amputations. The effect of blast was so severe that most of the cases required 2 to 5 times wound debridements. The initial aggressive debridement / open stump amputation saved the limb and life of all patients.

Conclusion

A mine blast causes extensive injuries and psychological trauma. Management is needed urgently, surgery is difficult, and amputation is often inevitable. Maximum lives and limbs can be saved with aggressive debridement, repeated inspections and dressings under anaesthesia and definitive closure at optimum time.Key Words: Amputation, Antipersonnel mine, Crush syndrome, Debridements, Mine blast injury, Secondary missiles, Shrapenels     

The Portex 'Soft Seal' single use laryngeal mask -- a preliminary study in pediatric anesthesia

BACKGROUND: Portex have developed a single use pediatric laryngeal mask (LM), which is available in all sizes. METHODS: We prospectively evaluated its use in 40 infants and children undergoing a variety of surgical procedures. RESULTS: The LM provided a satisfactory airway in all patients. Insertion was quick and easy and achieved at the first attempt in 38 patients. Repositioning was required during anesthesia in four cases. CONCLUSIONS: The Portex 'Soft Seal' LM performs satisfactorily in elective pediatric anesthesia.     

Acute stress disorder and posttraumatic stress disorder in children and adolescents involved in assaults or motor vehicle accidents

OBJECTIVE: The authors investigated acute stress disorder and later posttraumatic stress disorder (PTSD) in children and adolescents who had been involved in assaults or motor vehicle accidents. METHOD: They interviewed 93 patients 10-16 years old who were seen in an emergency department for having been assaulted or involved in a motor vehicle accident within 4 weeks after the assault or accident to assess acute stress disorder. At 6 months, they reinterviewed 64 (68.8%) of the patients to assess PTSD. RESULTS: At initial interview, 18 (19.4%) of the 93 patients had acute stress disorder and 23 (24.7%) met all acute stress disorder criteria except dissociation. At 6 months, eight of the 64 patients (12.5%) had PTSD. Acute stress disorder and PTSD did not differ in prevalence between patients who had been assaulted and those who had been in accidents. Sensitivity and specificity statistics and regression modeling revealed that the diagnosis of acute stress disorder was a good predictor of later PTSD but that dissociation did not play a significant role. CONCLUSIONS: Acute stress disorder has merit as a predictor of later PTSD in children and adolescents, but dissociation has questionable utility.     

Does narrow‐band ultraviolet B phototherapy work in atopic dermatitis through a local or a systemic effect?

The likely mechanisms of action of narrow-band ultraviolet B (NB-UVB) in atopic dermatitis are several. We attempted, in a 12 patient prospective intraindividually controlled study, to determine whether the effect of NB-UVB in atopic dermatitis is primarily through systemic or local effects. Change in observer-assessed severity of patches of dermatitis covered during each whole-body NB-UVB treatment was compared with change in uncovered neighbouring patches. We found great variation between patients in responses. Only in two (of 12) patients was there a large difference between directly exposed and covered patch dermatitis severity. We suspect that the balance of local and systemic effects important in determining response to NB-UVB in atopic dermatitis varies from patient to patient. This study did not conclusively answer our original question, but did show that in some patients localized effects of NB-UVB are important.     

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.     

Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion

PURPOSE: The pharmacokinetics and metabolism of cyclophosphamide (CPA) when given as a 1-h and a 24-h infusion to children were compared. METHODS: Thirteen children with a variety of different malignancies received an identical dose of cyclophosphamide as a 1- and 24-h infusion. In each case the concentration of CPA and its principal metabolites were measured by a thin-layer-chromatography-photographic-densitometry technique. RESULTS: Cyclophosphamide clearance was greater during the 24-h infusion, following time-dependent increases in the metabolism of the drug (autoinduction) (median 5.1 vs 3.1 l/h/m2: P = 0.037). Autoinduction was seen in five children (38%), producing a median end of infusion concentration of 49% (range 28-89%) of the maximum and was not accompanied by an increase in the production of the principal inactive metabolites carboxyphosphamide and dechloroethylcyclophosphamide. CONCLUSIONS: These results suggest potential benefits of prolonging the infusion of CPA in clinical practice.     

Consolidation therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of cytosine arabinoside, epipodophyllotoxins and cyclophosphamide

The intensification of post-remission induction therapy has been shown to improve the relapse-free survival for childhood acute lymphoblastic leukaemia (ALL), and is now a standard component of the treatment of childhood acute lymphoblastic leukaemia. For cytosine arabinoside (ara-C), methotrexate, vincristine and corticosteroids, in-vitro studies indicate that the extracellular drug concentration and exposure time are important determinants of cytotoxicity for human leukaemia cell lines. For L-asparaginase, epipodopyllotoxins and cyclophosphamide, there have been few studies of the relationship between cellular pharmacology and cytotoxicity in relation to ALL. The clinical and cellular pharmacology of methotrexate and cytosine arabinoside have been studied in relation to childhood ALL in vivo. For these drugs, there is evidence to suggest that maintenance of plasma concentrations that are biochemically optimal is necessary to maximize anti-leukaemic effects. For cytosine arabinoside in particular, optimal extracellular fluid concentrations are not likely to be achieved or maintained by bolus or short-duration i.v. infusions. A potentially important example of this may be served by the success of antimetabolite-based intrathecal chemotherapy for CNS-directed treatment of childhood ALL. Intrathecal administration of both methotrexate and cytosine arabinoside results in prolonged leukaemic cell exposure to cytotoxic concentrations of the drug. For vincristine, anthracyclines and asparaginase, the actual dose intensity received by children during consolidation therapy may be important, and there is considerable interpatient variation in the pharmacokinetics of cyclophosphamide and teniposide in the therapy of childhood cancers. The importance of this relationship to childhood ALL is not known. The pharmacological and cellular pharmacological studies performed at St Jude Children's Research Hospital (Memphis, TN, USA) have allowed investigation of the relationships between the clinical and cellular pharmacology of methotrexate and prognosis, and have supported the individualization of consolidation therapy with this drug. Cytosine arabinoside has been less well studied in relation to childhood ALL, although evidence exists to suggest that the administration of conventional-dose bolus or infusion schedules may not be optimal in terms of the antileukaemic efficacy of this antimetabolite. For L-asparaginase, ongoing studies may allow the relationship between dose and schedule of administration to be related to pharmacodynamic measures such as asparagine depletion and prognosis. Therefore, through knowledge of clinical and cellular pharmacological properties, it may be possible to optimize the consolidation phase of therapy for childhood ALL, without disrupting the fundamental principles by which the overall treatment is administered. This may be particularly important for children with disease that has inherent or acquired resistance to therapy.