Anaesthesia for primary repair of cleft lip and cleft palate: a review of 244 procedures

The peri-operative course of 194 patients undergoing 244 procedures for primary repair of cleft lip and palate over an 8-year-period was studied. A marked increase in the extent of intra-operative monitoring was noted during this period. The Pierre Robin syndrome was the most common associated abnormality and was found in 17% of patients in this series. There were no deaths. A total of 101 procedures were undertaken in infants with cleft lip of whom 10% received an intra-operative blood transfusion. Post-operative opiate analgesics were administered following 97% of these procedures and profound respiratory depression was observed in three children. The use of lignocaine and noradrenaline did not significantly reduce the operative blood loss. A post-operative pyrexial illness was significantly associated with the presence of a positive pre-operative nasal and throat swab and this could be significantly reduced by pre-operative antibiotic treatment. A total of 143 children underwent repair of cleft palate and of these 16.8% received an operative blood transfusion. An elective tracheostomy was required in one patient because of unsuccessful attempts at endotracheal intubation. One patient developed a respiratory arrest after two doses of diamorphine peri-operatively. The use of lignocaine and noradrenaline significantly reduced the operative blood loss. The presence of a positive bacteriological nose or throat swab did not influence the development of a post-operative pyrexia which could however be significantly reduced by the use of pre-operative antibiotics.     

Site-specific biotinylation

We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the ε-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the ε-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle⁷]ET-1 analog containing ε-biotinylaminocaproyllysine at position-9. This peptide, with K_d= 0.08 nM, has 1000-fold higher affinity for the ET_A receptor than the commercially available N_α-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags.     

Modifying infant stress responses to major surgery: spinal vs extradural vs opioid analgesia

Twenty-six infants due to undergo major abdominal or thoracic surgery under general anaesthesia were randomized to receive additional analgesia with group A) spinal/epidural analgesia; B) epidural analgesia or C) opioid analgesia with fentanyl. We wished to determine if spinal analgesia followed by epidural analgesia might result in more complete control of cardiovascular or stress responses than the other two treatment groups. Heart rate and blood pressure were recorded at five min intervals throughout surgery. Blood samples were taken for measurement of catecholamines and whole blood sugar on induction, 45 min after skin incision and at the end of surgery. Heart rate rose significantly at the start of surgery in groups B and C but not group A. Systolic blood pressures were higher in group C compared to A and B. The rise in plasma glucose concentrations was significantly different between the groups in the order C>B>A (P<0·05). A similar trend was seen in the plasma adrenaline and noradrenaline concentrations but this failed to achieve significance due to the limited sample size.     

Antihistamines Block Radiation-Induced Increased Intestinal Blood Flow in Canines

Antihistamines Block Radiation-Induced Increased IntestinalBlood Flow in Canines. COCK-ERHAM, L. G., DOYLE, T. F., DONLON,M. A., AND GOSSETT-HAGERMAN, C. J. (1985). Fundam. Appl. Toxicol.5, 597–604. Radiation-induced systemic hypotension isaccompanied by increased intestinal blood flow (IBF) and anincreased hematocrit (HCT) in dogs. Histamine infusion leadsto increased IBF and intestinal edema with consequent secretionof fluid into the intestinal lumen. This study was performedto determine whether these effects could be diminished by prioradministration of H₁ and H₂ histamine blockers. Dogs were givenan iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25mg/min) for 1 hr before and for 1 hr after radiation (H₁ andH₂ blockers, respectively). Mean systemic arterial blood pressure(MBP), IBF, and HCT were monitored for 2 hr. Systemic plasmahistamine levels were determined simultaneously. Data obtainedindicated that the H₁ and H₂ blockers, given simultaneously,were successful in blocking the increased IBF and the increasedHCT seen after 100 Gy, whole-body, radiation. However, thepostradiation hypotension was only somewhat affected, with theMBP falling to a level 28% below the preradiation level. Plasmahistamine levels reached a sharp peak, as much as 20% abovebaseline, at 4 min postradiation. These findings implicate histaminein the radiation-induced increase in IBF and HCT but not forthe gradual decrease in postradiation blood pressure     

ARE SLOW-ACTING ANTI-RHEUMATIC DRUGS MONITORED TOO OFTEN? AN AUDIT OF CURRENT CLINICAL PRATICE

Rheumatologists usually recommend monthly blood monitoring whenpatients with rheumatoid arthritis (RA) are treated with slow-actinganti-rheumatic drugs (SAARDs). Is monthly monitoring neededor could its frequency be reduced? We audited the opinions ofUK rheumatologists and reviewed clinical experience at threecentres. To ascertain the interval at which patients are monitoredand the determinants of monitoring policy we sent a questionnaireto 193 consultant rheumatologists; 143 (74%) replied. The majorityuse monthly monitoring for most SAARDs except sulphasalazine,chloroquine and hydroxychloroquine. There is extensive variation,which is not related to the type of rheumatology unit or whethera shared scheme with general practitioners is used. Reviewingexperience in 390 patients treated with SAARDs at three adjacentrheumatology units in London showed that haematological adversereactions were infrequent. During 1560 patient-years of treatmentinvolving 18 720 monthly monitoring visits there were 13 haematologicaladverse reactions (1 1 thrombocytopenias and two leucopenias).Five thrombocytopenias occurred in the first 6 months of therapy;two were gradual and three developed more rapidly over 1–2months. Six thrombocytopenias developed after 6 months of treatment;five occurred gradually over 5 months or more and one borderlinelow platelet count was seen once. The two leucopenias were borderlinelow white cell counts occurring gradually over 3–6 months.Such frequent monitoring is expensive. The total cost of monitoring390 patients for 1560 patient-years was $420 000. The cost ofdetecting each adverse reaction was $ 32 000. Three-monthlymonitoring when therapy is established after an initial stabilizingperiod would have identified seven out of eight late adversereactions. Monitoring policies are mainly based on clinicalconsensus with few prospective studies of their value; theyneed re-evaluation. KEY WORDS: Rheumatoid arthritis, Drug toxicity, Slow-acting anti-rheumatic drugs