Pharmacokinetics and physiological effects of intravenous hydromorphone in conscious dogs.

This study evaluated the pharmacokinetics, the sedative and anti-nociceptive effects of intravenous hydromorphone in dogs. Five adult dogs were administered hydromorphone (0.1 mg/kg and 0.2 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) at weekly intervals. Blood samples were drawn before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma hydromorphone only was measured by high pressure liquid chromatography (HPLC) with electrochemical detection and pharmacokinetic parameters calculated. Anti-nociceptive and sedation scores were submitted to Kruskal-Wallis one-way anova on ranks and post-hoc Bonferroni test with 5% significance level. The data fitted a two-compartment model with a fast distribution (<1 min for both doses) and slower elimination rate. Mean elimination half-life was 80 +/- 52.7 and 57.7 +/- 30.4 min for the high and low dose, respectively. The apparent mean volumes of distribution at steady-state were 7.2 +/- 3 and 4.5 +/- 2.4 L/kg, while the clearance was 74.7 +/- 19 and 68.1 +/- 20 mL/kg/min for the high and low doses, respectively. Compared to saline, hydromorphone and morphine produced significant anti-nociception and sedation of similar magnitude for 120 min. In conclusion, intravenous hydromorphone has a large volume of distribution, and high clearance rate that exceeds hepatic blood flow. In dogs, it produced mechanical anti-nociception and sedation of a magnitude similar to morphine.

Modulation of retinal transducin and phosphodiesterase activities by synthetic peptides of the phosphodiesterase gamma-subunit.

Synthetic peptides corresponding to various regions of the light-activated guanosine 3',5'-cyclic monophosphate phosphodiesterase (PDE) gamma-subunit (PDE gamma) from bovine retinal rod outer segments were synthesized and tested for their ability to inhibit PDE activity, and GTPase activity of transducin. One of these peptides, corresponding to PDE gamma residues 31-45, inhibited PDE activity and GTPase activity in a dose-dependent manner. The GTPase activity was inhibited by PDE gamma-3 non-competitively. This region of the PDE gamma subunit may be involved in the direct interaction of transducin and PDE alpha beta with PDE gamma.

Synthesis and biological activity of a series of diaryl-substituted alpha-cyano-beta-hydroxypropenamides, a new class of anthelmintic agents.

A series of alpha-cyano-beta-hydroxypropenamides was prepared and tested for anthelmintic activity. alpha-Cyano-beta-hydroxy-N-[4- (trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana. In sheep trials, 1 caused 100% reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta. Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated. Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.

Iatrogenic haematoma causing airway obstruction in a burned patient.

Haematoma is a rare complication of central venous cannulation. This report describes such a haematoma causing significant airway obstruction in a burned patient, and illustrates the need to be aware of unusual complications of attempted therapy.

Infectious bovine keratoconjunctivitis: a review.

The economic impact of infectious bovine keratoconjunctivitis (IBK) warrants continued investigation of the mechanisms by which Moraxella bovis survives on and colonizes the corneal surface. Virulent strains of M bovis produce hemolysin and exhibit different plasmid profiles than nonvirulent strains. Interactions among host, environment, vector, season, and concurrent infection influence the prevalence of IBK. Mycoplasma sp. or infectious bovine rhinotracheitis virus may enhance or hasten the disease process. The manifestations of IBK may range from mild conjunctivitis to severe ulceration, corneal perforation, and blindness. Treatment of IBK is dictated by economic considerations, intended animal use, and feasibility of administration. Antibiotic therapy is aimed at achieving drug concentrations in tears to meet or exceed the minimum inhibitory concentration for prolonged periods. At present, IBK is not a preventable disease. Affected animals must be separated from the herd and vector control vigorously instituted. Carrier animals must be identified and removed from the herd. Vaccination trials have been unsuccessful because of pili antigen cross-reactivity, variable strains, and uncontrolled environmental factors. Recent investigations have determined that M bovis may utilize host iron sources via iron-repressible outer membrane proteins and siderophores for growth. Elucidation of normal defense mechanisms of the bovine eye may lead to new strategies to enhance the immune response against M bovis.

Identification of lactoferrin in bovine tears.

OBJECTIVE: To determine whether bovine tear film contains the iron-binding glycoprotein, lactoferrin. ANIMALS: 40 Adult Hereford, Angus, and Simmental cattle. PROCEDURE: Protein analysis: pooled bovine tears were used for protein analysis (size exclusion high-performance liquid chromatography [HPLC] fractionation). HPLC was used for tear analysis. A diode array detector was used (215 and 280 microns) for chromatogram analysis and comparisons. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): protein electrophoresis was performed, using 7.5% running gels with 4% stacking gels. Molecular weight of proteins in the unknown samples was determined as recommended by the manufacturer of the standards. Protein sequencing: amino acid sequencing, using automated Edman degradation of HPLC purified protein, was performed. The sequence obtained was compared with the known protein sequence of bovine lactoferrin. RESULTS: HPLC analysis of whole bovine tears resulted in a consistent chromatogram. Peak collection was performed to recover a protein from the bovine tear film with chromatogram characteristics nearly identical to purified bovine lactoferrin. Silver-stained SDS-PAGE of this peak revealed a band with molecular mass consistent with bovine lactoferrin (estimated mass of 78 kd). The first 13 amino acid residues of this protein were identical to the amino acid sequence of bovine lactoferrin. CONCLUSION: Analysis of whole bovine tears, using size exclusion HPLC, SDS-PAGE, and amino acid sequencing, provided evidence that bovine tears contain lactoferrin. CLINICAL RELEVANCE: Lactoferrin probably exerts a bacteriostatic effect in bovine tear film. Locally produced lactoferrin may bathe the ocular surface and sequester iron from potential pathogens.

Congenital palmar nail syndrome.

Two patients are described who have a congenital ectopic nail on the little finger associated with absent flexion in this finger. One patient was treated by surgical excision of the nail.

The V-Y Palmar flap.

We describe a V-Y palmar flap that allows both skin advancement and scar lengthening, and which has proved useful in the treatment of Dupuytren's disease.

An experience of the Snow-Littler procedure.

This paper reviews the results of the Snow-Littler procedure performed in twelve hands with classical central longitudinal deficiency and in one hand with symbrachydactyly, cleft type. There were no instances of major flap necrosis although two flaps showed tip ischaemia. The width of the first web was, in the main, satisfactory but four webspace revisions were performed. Supplementary skin grafting at the time of surgery was necessary in complete and/or complex thumb index syndactylies and in the patient with symbrachydactyly. In eight cases, a transverse metacarpal ligament was reconstructed. In the five other cases, no clinical instability or radiological divergence of the index and ring fingers occurred, in spite of no transverse metacarpal ligament reconstruction. Three de-rotational osteotomies of transposed index fingers were performed in patients who had a transverse metacarpal ligament reconstruction. These results indicated significantly improved appearance and improved function following the Snow-Littler procedure.

Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs.

This study examined the pharmacokinetics and physiologic effects of two infusions rates of morphine in conscious dogs. Five adult dogs were randomly studied at weekly intervals. An initial dose of either 0.3 or 0.6 mg/kg were each followed by infusions of 0.17 and 0.34 mg/kg/h. Plasma morphine concentrations, physiological parameters, sedation and mechanical antinociception were evaluated during each infusion. Morphine was assayed by high pressure liquid chromatography (HPLC) with electrochemical coulometric detection and pharmacokinetic parameters were calculated. Data were fitted to a bi-compartment model with a rapid distribution (<1 min for both doses) and slower termination rate. For the high and low doses, respectively, mean+/-SD terminal half-life was 38+/-5 and 27+/-14 min, apparent volumes of distribution at steady-state were 1.9+/-0.5 and 1.3+/-0.8 L/kg, with clearances of 50+/-15 and 67+/-20 mL/kg/min. Steady-state plasma concentrations ranged from 93 to 180 ng/mL and 45 to 80 ng/mL in the high and low doses, respectively. Respiratory rate increased significantly, pulse oximetry remained>95% and body temperature decreased significantly during both infusions. No vomition or neuroexcitation occurred. Sedation and mechanical antinociception were both mild during the lower infusion rate, and mild to moderate during the higher infusion rate. In conclusion, morphine pharmacokinetics was not altered by increasing infusion rates, producing stable, long-lasting plasma concentrations.

Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs.

This study compared plasma histamine concentrations, behavioral and cardiovascular parameters following intravenous administration of hydromorphone and morphine in conscious dogs. Five adult female dogs received a 15-sec bolus injection of saline, hydromorphone (0.1 and 0.2 mg/kg) or morphine (0.5 and 1.0 mg/kg) randomly at weekly intervals. Blood samples were collected from the jugular vein before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma histamine concentration, noninvasive oscillometric blood pressure, heart rate and rhythm were evaluated. Data were analyzed with repeated measures anova and Tukey-Kramer post hoc test with a 5% significance level. Median plasma histamine increased significantly only after the higher dose of morphine. Maximum plasma histamine measured was 0.8 ng/mL after saline and, after the lower and higher doses, respectively, 10.2 and 9.7 ng/mL for hydromorphone, and 440 and 589 ng/mL for morphine. One dog became hypotensive immediately after receiving the highest dose of morphine. Occasional ventricular premature contractions occurred in one dog after both opioids and dosages. No dogs vomited or defecated, but all salivated profusely with both opioids. Neuroexcitation occurred in four dogs following each opioid. In conclusion, intravenous hydromorphone induced minimal histamine release and was well tolerated by these conscious healthy dogs.

The use of a proximally based posterior interosseous adipofascial flap to prevent recurrence of synostosis of the elbow joint and forearm.

We report on four children in whom a proximally based, posterior interosseous artery adipofascial flap was used as an adjunct to surgical resection of synostoses of the forearm and elbow. Three traumatic radio-ulnar and one congenital humero-radial synostoses were treated. The postoperative pronation to supination arc of motion was excellent in all of the traumatic cases and fair in the congenital case.

Group G streptococcus--an emerging cause of graft loss?

Following anecdotal reports of skin graft loss due to non-group A streptococcal infection, a retrospective study was performed to compare the effect of streptococcal infections on our recent practice (1987-1990) and on a similar period 15 years earlier. Graft loss was estimated following streptococcal infection of any kind for the two periods, and compared to Staph. aureus controls. In the recent period, graft take was significantly decreased for streptococcus G compared to other non A groups and Staph. aureus controls. No differences were found for the early period. It is suggested that group G streptococcus may now be associated with decreased graft survival and that this is a recently observed effect, possibly due to altered bacterial pathogenicity.

Outcome analysis of a modified Tajima procedure.

Secondary nasal correction of cleft patients is acknowledged to be a difficult problem. There are many different operations but few objective assessments of their results. We have evaluated the results of a modified Tajima operation by use of the Bristol computer technique. Eighteen patients were followed up for a mean of 33 months (range 10-56). Measures of asymmetry were obtained for different photographic views, preoperatively and at later postoperative visits. In all views there was a significant improvement in shape in the early postoperative photos. This same improvement was also seen when comparing preoperative to late postoperative results i.e. this initial improvement is maintained over time. There was no significant difference between the early and late postoperative views. In this small series the modified Tajima technique has given statistically significant lasting improvement. However, few other operations have been objectively assessed and hence comparison is difficult. We advocate the use of the computer technique for other procedures to allow meaningful comparisons between them.

Joint replacement and patient education.

To improve patient service and in an attempt to enhance the outcome of joint replacement an information booklet has been produced and supplied to all patients admitted for this procedure at Harlow Wood hospital. A postal questionnaire was sent to groups of patients before and after the introduction of the booklets, three months after operation. The level of patient satisfaction with the information given improved from 54% to 82%. A significant improvement was noted in the patient's understanding of the procedure and management of their joint replacement. However, only 53% of patients fully understood the possible complications of the procedure.

When to return to work following a routine inguinal hernia repair: are doctors giving the correct advice?

Recurrence of an inguinal hernia following routine repair is not influenced by the convalescent time off work. Advice on this interval off work should not be influenced by the type of hernia, or the physical content of the patient's occupation. To determine if this is the case a questionnaire was sent to the 32 consultant surgeons and 487 general practitioners in the Nottingham district. They were asked when they advised males between 18 and 65 years of age to return to work following a routine hernia repair and what factors influenced this time interval. The median advised time off work (4-6 weeks) was longer than that proposed by earlier studies (3-4 weeks). The advice of only 4% of doctors was not influenced by other factors. The physical content of the patient's job and whether he was self-employed had most influence on the advice doctors gave on when to return to work. In conclusion most doctors are wrongly advising patients on when to return to work following an inguinal hernia repair.

ADP-ribosylation of bovine S-antigen by cholera toxin.

The S-antigen (alias 48K protein or arrestin) of bovine rod photoreceptors contains two stretches of amino acid sequence homologous to the ADP-ribosylation sites of the alpha subunit of transducin (Ta). We have found that cholera toxin transfers the ADP-ribosyl group from NAD to purified bovine S-antigen as well as to S-antigen in rod outer segment membranes, while Bordetella pertussis toxin is unable to catalyze the transfer reaction efficiently. Under the same conditions, both toxins catalyzed ADP-ribosylation of Ta in rod outer segments. The ADP-ribosylation of S-antigen by cholera toxin indicates that S-antigen not only exhibits sequence homology with the ADP-ribosylation sites of Ta, but it must also resemble Ta in the tertiary structure of the domain which determines the susceptibility of S-antigen to the catalytic action of cholera toxin. These results suggest that S-antigen may function as a competitor of Ta in some stage of the cGMP cascade of visual transduction.