Prospective to a randomized double-blind controlled trial to assess efficacy of double caudal analgesia in hypospadias repair.

BACKGROUND/PURPOSE: A prospective, randomised, double-blind, controlled trial to evaluate efficacy of double-caudal versus single-caudal injection for postoperative analgesia in hypospadias repair was performed. METHODS: Between October 1998 and September 2000, 160 boys underwent distal hypospadias repair. The first 80 boys were analyzed prospectively for postoperative analgesia after double-caudal bupivacaine, which involves the administration of a second bupivacaine injection into the caudal extradural space at the end of surgery. Pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). The study groups were: group 1, unstented Thiersch-Duplay urethroplasty (50); and group 2, stented Mathieu type repair (30). Results of this cohort formed the basis for a prospective, randomised, double-blind control trial comparing double-caudal against a single injection before operation. The further 80 patients were allocated randomly: group 3, single caudal injection of 1 mL kg(-1) of 0.25% plain bupivacaine at the start of surgery with unstented Thiersh-Duplay repair (25); group 4, similar single caudal injection but stented Mattieu type operation (15); group 5, second caudal and at end of operation (0.5 mL kg(-1) on each occasion) with unstented Thiersh-Duplay repair (25); and group 6, similar to group 5 but with stented Mattieu type repair (15). RESULTS: Patient demographics (age and weight) and mean duration of operative time were similar for all groups. There was no significant difference in early pain scores at 0 to 2 hours with a good correlation coefficient (r = 0.88). At 4, 6, and 8 hours there was a significant difference in pain scores between double and single caudals (P <.05). There was a significant difference in mean duration of caudal analgesia and need for oral analgesia between single caudal 3.45 versus 7.85 hours for double caudal (P <.001). Mean duration of caudal analgesia and requirement for oral analgesia after single caudal in group 3 (unstented) was 3.5 versus 3.4 hours in group 4 (stented). In double caudals this lengthened to 9.4 hours in group 5 (unstented) versus 6.3 hours in group 6 (stented; P <.05). This also was significant when operation time was excluded. CONCLUSIONS: A prospective study of double caudal analgesia showed good postoperative pain control after hypospadias surgery. This was followed by a prospective, randomised, double-blind controlled trial that has confirmed that double caudal injection of bupivacaine prolonged the duration of pain relief after hypospadias repair. The second or top-up caudal did not increase the total dose but supplemented and prolonged postoperative analgesia.

The activity of an anti-allergic compound, proxicromil, on models of immunity and inflammation.

A tricyclic chromone, proxicromil (sodium 6,7,8,9-tetrahydro-5-hydroxy-4-oxo-10-propyl-naphtho (2,3-b) pyran-2-carboxylate), has been tested for activity against certain immunological and inflammatory reactions. When given parenterally it suppressed the development of delayed hypersensitivity reactions in sensitized mice and guinea-pigs but did not affect the rejection of skin allografts in mice. The compound had no activity against certain in vitro correlates of delayed hypersensitivity reactions (lymphocyte transformation and lymphokine activity), but did have an inhibitory effect on lymphokine (MIF) productions at 10(-4) M but not at 10(-5) M. Proxicromil was also found to be active in non-immunologically mediated models of inflammation and in models having an immunological component which are known to be sensitive to non-steroidal anti-inflammatory drugs (adjuvant arthritis, reversed passive Arthus reaction). The activity of this compound was enhanced when administered in arachis oil when compared to its activity in saline. Proxicromil has not direct activity on the development of immune responsiveness but appear to suppress the expression of delayed hypersensitivity and immune complex mediated hypersensitivity reactions by virtue and its anti-inflammatory properties. This activity is not associated with inhibition of cyclo-oxygenase.

Oxygen-binding and immunological properties of complexes between dextran and animal haemoglobins.

Complexes of dextran 20 000 with haemoglobins of sheep, rabbit, dog, bovine and human origin were prepared through alkylation of haemoglobin by N-bromoacetylaminoethylamino-dextran. The yields were uniformly high. Complex-formation in each case was accompanied by the disappearance of reactive thiol groups on the haemoglobin, and by an increase in the affinity of the haemoglobin for oxygen. The immunological properties of dog, rabbit and sheep dextran-haemoglobin were investigated in both homologous and heterologous species. The complexes were found to be non-immunogenic in the homologous species. In heterologous species the anti-haemoglobin response induced by each complex was generally of a similar level to that induced by the haemoglobin alone.

Clinical dextrans lack mitogenic activity for normal human lymphocytes in vitro.

In vitro studies on mitogenic stimulation of lymphocytes from a panel of normal volunteers revealed no transformation in response to the presence of dextran 40, 70, 110 or 150 at concentrations ranging from 0.8 to 8,000 microgram/ml. High molecular weight native dextran B512 was mitogenic in 1 individual only. In addition, neither Leuconostoc-derived nor fermentation medium-derived moieties, sometimes present in clinical dextrans, were implicated as lymphocyte mitogens. It is concluded on the basis of these findings that clinical dextrans of average molecular weight 40,000--150,000 are not B- or T-cell mitogens.

Naturally-occurring double-stranded RNA and immune responses. IV. Influence of molecular size on antigenicity and adjuvant activity.

The immunological properties of a naturally-occurring double-stranded ribonucleic acid (ds-RNA), obtained from a mycophage of Penicillium chrysogenum, have been studied in relation to molecular size. Materials of reduced size, as reflected by molecular weight measurements, produced by ultrasonication of native ds-RNA, exhibited progressively lowered ability to induce an anti-ds-RNA response in mice. Adjuvant and immunosuppressive activities were of similar magnitude in both high and low molecular weight fractions. Evidence was also obtained of increased toxicity in materials of reduced size.

Double-stranded RNA antibodies in systemic lupus erythematosus.

Antibodies to viral double-stranded RNA (ds RNA) have been found in 40% of patients with systemic lupus erythematosus (SLE) and 14-5% of patients with rheumatoid arthritis. These antibodies were diagnostically more specific SLE than those directed against artificial polynucleotides, poly I:C and poly A:U. Although not disease specific, high titres of antibody to ds viral RNA were found almost exclusively in SLE. Serial studies failed to show that RNA antibody levels correlated with disease activity. Although of considerable interest in experimental studies on the pathogenesis of SLE, ds viral RNA antibodies are of little clinical significance in the management of SLE.

Naturally occurring double-stranded RNA and immune responses. Effects on plaque-forming cells and antibody formation.

A highly purified preparation of double-stranded RNA, obtained from virus-like particles in Penicillium cultures, was found to affert humoral immune responses in mice differentially depending on its time of administration in realtion to antigen. Double-stranded RNA administered with antigen, or a few hours after antigen, produced a variable degree of enhancement of plaque-forming cell numbers or agglutinating antibody levels depending on the antigen involved. Administration of double-stranded RNA 24 hours before antigen invariably produced a suppressed response. In mice which were either specifically hyporesponsive (tolerant) or non-specifically hyporesponsive (due to age or immunosuppressive drugs) double-stranded RNA administered with antigen resulted in a nearly normal immune response.

Protection against gram-negative infections with antiserum to lipid A from Salmonella minnesota R595.

The ability of antisera to lipid A, induced in rabbits by immunization with lipid A complexed to various carriers, to protect mice against gram-negative infection and to inhibit the fluid loss caused by an enteropathogenic strain of Escherichia coli in the piglet ligated gut was investigated. No significant protection was obtained in either case, although passive hemolysis and quantitative precipitation tests showed the presence of antilipid A antibodies in the sera. Fluorescent antibody studies suggest that the lipid A is in a cryptic position on the surface of smooth strains of gram-negative bacteria.