Sustained release metoclopramide for prophylaxis of post-operative nausea and vomiting.

Oral metoclopramide may be given as a premedicant to reduce post-operative nausea and vomiting, but there is little evidence that it is effective. We studied the anti-emetic action of a sustained release formulation of metoclopramide (Gastromax 30 mg) in 39 fit women undergoing inpatient laparoscopy under general anaesthesia with a standardized anaesthetic technique in a double-blind placebo-controlled trial. No benefit was demonstrated. (Incidences: nausea: 13 of 20 patients [placebo] and 13 of 19 [metoclopramide]; vomiting: 13 of 20 and 12 of 19.)

Peripartum changes in gastric emptying.

Applied potential tomography was used to measure changes in gastric emptying during the peripartum period. Gastric emptying was measured sequentially in each of 10 healthy patients at 37-40 weeks gestation, 2-3 days postpartum and after the 6-week postnatal assessment (control). Mean (SD) times to 50% emptying were 15 (6.05), 11 (5.9) and 15 (5.5) min, respectively. There was no statistically significant change in gastric emptying as a result of pregnancy in this group of women. Retrospective power analysis (assuming alpha = 0.05 and beta = 0.20) shows the study design was adequate to detect a difference of 8 min.

Gastric fluid volume and pH in elective surgical patients: triple prophylaxis is not superior to ranitidine alone.

The effect of oral ranitidine alone was compared with sequentially administered ranitidine, metoclopramide, and sodium citrate on gastric fluid volume and pH in 196 healthy, elective surgical inpatients, each of whom was randomly assigned to one of four groups. Patients in all groups received oral ranitidine 150 mg 2-3 hr before the scheduled time of surgery. Those in Group 1 also received oral metoclopramide 10 mg one hour before surgery, and sodium citrate 0.3 M 30 ml on call to the operating room; Group 2 received sodium citrate but no metoclopramide; Group 3 received metoclopramide but no sodium citrate; Group 4 received ranitidine alone. Following induction of anaesthesia a #18 Salem sump tube was passed into the stomach and all available gastric fluid was aspirated. Volumes were recorded and pH measured. In all groups mean pH was greater than 5.8, although at least one patient in each group had pH less than 2.5. Mean volumes were significantly greater in patients who received citrate (Groups 1 and 2: 22 and 19 ml) than in those in those who did not (Groups 3 and 4: 10 and 8 ml). One patient in Group 2 and one in Group 3 had pH less than 2.5 with volume greater than 25 ml. Our results do not demonstrate any advantage of double or triple prophylaxis over ranitidine alone. The practical difficulty of correctly administering two or even three medications, each at different but exact preoperative intervals, is emphasized.

Amphetamine ingestion presenting as eclampsia.

A case of amphetamine abuse in late pregnancy is reported. The presenting features of convulsions, confusion, agitation with hypertension and proteinuria led to a diagnosis of eclampsia for which a caesarean section was performed. Investigations and differential diagnosis of convulsions in late pregnancy are reviewed. A general urinary drug screen gives results after 24 hr whereas, if amphetamine abuse is suspected, this can be confirmed within three hr if a specific test for urinary amphetamines is performed. The sympathomimetic effects of a single dose of amphetamine are contrasted with the depression of the sympathetic nervous system which occurs after long-term use. Implications for anaesthesia are discussed.

Field bioassay to evaluate contact and residual toxicities of insecticides to carabid beetles (Coleoptera: Carabidae).

A 2-yr field study evaluated the effects of selected insecticides on Bembidion obscurellum Motschulsky and Bembidion quadrimaculatum L., carabid predators of the wheat midge, Sitodiplosis mosellana (Géhin). A bioassay method using caged beetles indicated that insecticides differed significantly in their contact and residual toxicities when applied at maximum recommended field rates. Deltamethrin, the least toxic insecticide, caused approximately 30% mortality in both beetle species, but its residual toxicity on the soil remained constant for 1 wk. Dimethoate was initially more toxic (73% mortality) than deltamethrin but less toxic after 1 wk (12% mortality). Carbofuran and chlorpyrifos, the most toxic contact sprays, caused 83 to 100% mortality. After 1 wk, the residual toxicity of carbofuran had declined markedly (5% mortality) whereas the toxicity of chlorpyrifos remained high (82% mortality). Pitfall trapping was an inconclusive method of evaluating the toxicity of insecticidal sprays to carabid adults. In plots treated with carbofuran, pitfall catches of Bembidion species were not significantly different from those in control plots during a 6-wk period after spraying. In plots treated with chlorpyrifos, catches of Bembidion species were significantly lower than those in control plots 3-16 d after spraying, but not thereafter. Results suggested that adult immigration and residual toxicity influence pitfall catches and recovery of carabid populations after spraying.

Effect of cyclosporine A on the corneal inflammatory response in herpes simplex virus keratitis.

The effects of cyclosporine A (CyA), a selective inhibitor of T-lymphocyte function, on the corneal inflammatory response in herpes simplex virus (HSV) stromal keratitis was followed during the course of experimental HSV keratitis in the rabbit. The corneal response, characterized by polymorphonuclear leukocytes (PMN) and mononuclear cells, is an immunologically specific event that is dependent on the presence of viral antigens and immune cells. CyA treatment during the course of HSV keratitis resulted in a more severe and persistent stromal disease and more anterior chamber involvement than that seen in the solvent control-treated HSV-infected animals. Clinical observations correlated well with histological studies which confirmed a greater incidence of mononuclear and PMN infiltrates throughout the anterior chamber and stroma in the CyA-treated animals. HSV antigens were present in the corneas from both infected groups as observed by immunofluorescence staining, but endothelial localization of HSV antigens was seen primarily in the CyA-treated animals, often accompanied by cells in the anterior chamber. No significant differences in IgG and IgM staining in the diseased corneas and anterior chamber were noted between the CyA-treated and solvent control groups which suggests that there was no local B-cell immunosuppression.

Effects of cyclosporine A on clinical and immunological parameters in herpes simplex keratitis.

The immunosuppressive effects of cyclosporine A (CyA) on the clinical and antiviral immune responses were examined in experimental herpes simplex virus (HSV) keratitis in the rabbit in order to clarify the role that immune lymphocytes play in herpetic stromal disease. Cyclosporine A was administered intramuscularly to rabbits daily starting from the time of corneal infection with HSV until day 14 postinfection. Control HSV-infected rabbits received daily injections of the solvent vehicle alone. HSV-infected rabbits receiving CyA treatment showed more severe and persistent stromal keratitis, and a greater incidence and duration of virus recovery from the cornea. Suppression of cellular immune responses to T cell mitogens, B cell mitogens (anti-rabbit immunoglobulins), and HSV antigens were observed in the CyA treatment group. These results show that in CyA-treated HSV-infected rabbits the antiviral immune responses are inhibited. Acute viral infections with cytopathic viruses such as HSV may therefore be more dramatic, suggesting that CyA may facilitate the potentiation of HSV infections ordinarily suppressed by immune cells.

Routes of viral spread in the von Szily model of herpes simplex virus retinopathy.

Intraocular inoculation of herpes simplex virus type 1 (HSV-1) in one eye of rabbits results in encephalitis and contralateral necrotizing viral retinopathy. The effects of viral inoculation site and optic nerve (ON) transection on the spread of virus to the brain and contralateral eye in this model were investigated. A surgical technique was developed for transection of the retrobulbar optic nerve posterior to the entrance of the central retinal vessels. HSV-1 was inoculated into the AC or vitreous of one eye in normal rabbits and in rabbits with one ON transected, either ipsilateral or contralateral to the side of inoculation. Animals were followed clinically for signs of disease. Encephalitis and contralateral retinopathy (CR) occurred following both AC and vitreous inoculation of virus, although CR developed later in AC-inoculated rabbits. Ipsilateral retinopathy (IR) developed in 83% of vitreous-inoculated rabbits, but in only 5% of AC-inoculated animals. IR developed 8 days after the onset of CR in the AC-inoculated group. ON transection on the side of virus inoculation prevented development of CR only in vitreous-inoculated rabbits. ON transection on the side opposite virus inoculation prevented CR regardless of the site of inoculation. These findings suggest that HSV-1 can leave the inoculated eye by multiple routes depending on the site of virus inoculation, but that virus reaches the retina of the contralateral eye via the optic nerve.

Autoimmunity in hereditary retinal degenerations. II. Clinical studies: antiretinal antibodies and fluorescein angiogram findings.

Testing by indirect immunofluorescence for the detection of antiretinal antibodies and lymphocyte stimulation for cell-mediated immunity to retinal antigens was performed on blood obtained from 59 patients with retinitis pigmentosa (RP) and 29 without RP who had other types of retinal disease. The results from the patients' immunological studies were correlated in a masked fashion with six parameters of the fluorescein angiogram: disc staining, peripapillary oedema, vascular arcade oedema, macular oedema, and focal vascular staining (late phases), and disc telangiectasia (early phases). Significant correlations for both groups together were found for IgG antiretinal antibody reactivity and macular oedema (p less than 0.038) and disc staining (p less than 0.033). The non-RP retinal disease group had more significant correlations, including IgG antiretinal antibody reactivity with vascular arcade oedema (p less than 0.018), disc staining (p less than 0.018), and peripapillary oedema (p less than 0.023); the RP patients had significant correlation with IgG reactivity and arcade oedema (p less than 0.045). With combinations of IgG, IgM, and lymphocyte reactivity various significant correlations were found with the fluorescein angiogram.

Autoimmunity in hereditary retinal degeneration. I. Basic studies.

One hundred and sixteen patients with retinitis pigmentosa (RP), 64 patients with other eye diseases, and 36 control subjects with no known eye disease were examined for antiretinal autoimmune activity. Sera were screened by indirect immunofluorescence on normal donor human eye sections to detect antibodies to human retinal antigens. Forty three of 116 RP patients (37%), 21 out of 64 non-RP patients with other eye diseases (33%), and 1 out of 42 controls (2%) had antibodies reacting with donor eye retinal antigens. Lymphocytes were tested by an in vitro transformation assay to detect cell mediated immunity to retinal antigens. Sixteen RP patients (19%), 11 non-RP patients (18%), and four controls (10%) showed lymphocyte sensitisation. Autoimmune responses were detected in many degenerative ocular disorders, but it is not known if they play a contributory pathogenic role.

Experimental retinal autoimmunity (ERA) in strain 13 guinea pigs: induction of ERA-retinopathy with rhodopsin.

Strain 13 guinea pigs injected with either homologous or bovine rhodopsin, the visual pigment of the retinal outer segments, in complete Freund's adjuvant (CFA) developed experimental retinal autoimmunity (ERA). Initial clinical signs of disease were seen within 21 days after immunization. Pathologic examination of the eyes revealed the presence of inflammatory cells in the choroid and the destruction of the retinal rod outer segments. The unique feature of this disease is that despite the destruction of the inner and outer segments of the retina, at no time is there a substantial inflammatory cell infiltrate. Even as late as 45 days after immunization, when destruction of the retinal ganglion cell layer was noted, no inflammatory cells were detected in the retina. These findings suggest that the retinal inner and outer segments are the target of the autoimmune reaction subsequent to sensitization with purified rhodopsin-CFA.

Localization of specific autoantibodies in the retinal photoreceptor cell layer in experimental retinal autoimmunity.

The presence and localization of autoantibodies was determined in strain 13 guinea pigs with experimental retinal autoimmunity (ERA) induced by immunization with rhodopsin and rod outer segments (ROS). Sera were obtained from rhodopsin-immunized and from ROS-immunized guinea pigs before, during, and after onset of clinical uveitis. Autoantibodies were detected by indirect immunofluorescent staining of autogenic retinas as well as normal guinea pig retinas. Sera from animals with clinical disease showed specific labeling of the photoreceptor cell layer of the retina. The rhodopsin autoantibody showed a more defined specificity than the ROS autoantibody staining, only the retinal photoreceptors and retinal pigment epithelium. Specific fluorescence was localized only in the retina, and not in any other ocular or nonocular tissues. Neither the rhodopsin nor the ROS antibodies stained the uvea. Sera from animals taken before the onset of clinical disease did not demonstrate the presence of retinal-binding autoantibodies. These findings suggest that photoreceptor-binding autoantibodies appear in the sera of animals immunized with rhodopsin and with ROS, but only in animals with clinical disease. However, these antibodies probably are not the primary cause of pathology, since previous passive transfer experiments (data not shown here) could not be achieved with anti-ROS or with anti-rhodopsin antibodies. These autoantibodies could occur secondarily as a response to the bovine antigens which cross-reacted with the autologous guinea pig antigens. Subsequently these antibodies could be of primary importance in further tissue alteration and destruction.

Experimental herpesvirus keratitis in the rabbit: topical versus intrastromal infection routes.

Intrastromal and topical routes of infection of rabbit corneas with the HF strain of herpes simplex virus type 1 were compared clinically to determine which route of infection would present the best model of disciform edema and of deep stromal keratitis for our further studies on how the immune response of the infected animals may influence the expression of clinical disease. In addition, virus clearing and persistence of viral antigens as immunologic stimuli were monitored by virologic and electron microscopic immunocytochemical studies. We found topical infection to be preferable to the intrastromal infection route for presenting stromal disease in that it resulted in a higher incidence of epithelial disease with less anterior chamber involvement. The topical infection route model should be valuable in studies of cell-mediated immune response against HSV-infected cells.

Experimental Klebsiella-induced endophthalmitis in the rabbit.

Klebsiella organisms have been reported in postoperative endophthalmitis. We describe an experimental model of endophthalmitis with anterior segment inflammation over the injection of Klebsiella oxytoca into the rabbit vitreous. Within 24 hours, polymorphonuclear leukocytes were found at the corneal limbus, adjacent to the endothelium, in the iris and ciliary body, throughout the vitreous, and in the optic nerve. Retinal photoreceptor degeneration was widespread within 48 hours. Mononuclear cells appeared in the vitreous within 72 hours. Increased pathologic manifestations concomitant with decreased numbers of recoverable, viable organisms implicate the endotoxins of K oxytoca in the observed pathologic condition. Our model may be useful in further studies on antibiotic therapy in Klebsiella ocular infections and in continuing work on the cross-reaction between Klebsiella and HLA-B27.

Immunopathogenesis of corneal inflammation in herpes simplex virus stromal keratitis: role of the polymorphonuclear leukocyte.

The present studies suggest that polymorphonuclear leukocytes (PMNs) play an essential role in the development of corneal infiltrates in stromal herpes virus (HSV) keratitis. Corneal infiltration was seen rarely in herpes-infected animals treated with anti-PMN serum or with chemotherapy to reduce the numbers of circulating PMNs. By contrast, at least two thirds of the control animals with intact PMNs and infected with herpes virus developed stromal infiltrates. Host complement was localized with HSV antigen and rabbit gamma globulin along with inflammatory cells in the corneas of animals with stromal infiltrates. In the absence of PMN infiltrates, neither complement nor a significant amount of gamma globulin was localized in the corneal stroma. In the PMN-depleted animals, only viral antigen was detected in the stromal keratocytes.