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Biomedical subjects

R Kearney

Publications and source records attributed to R Kearney.

At least 19 recordsLinked to original sources

Confirmation of caudal needle placement using nerve stimulation.

BACKGROUND: The study was designed to examine a new method of confirming proper caudal needle placement using nerve stimulation. METHODS: Thirty-two pediatric patients were studied. A 22-gauge insulated needle was inserted into the caudal canal via the sacral notch until a "pop" was felt. The needle placement was classified as correct or incorrect depending upon the presence or absence of anal sphincter contraction (S2-S4) to electrical simulation (1 to 10 mA). RESULTS: Three patients were excluded, two because they inadvertently received neuromuscular blockers and one because the patient's anatomy precluded any attempt at a caudal block. The sensitivity and specificity of the test were both 100% in predicting clinical outcomes of the caudal block. Six patients had a negative stimulation test after the first attempt to place the needle. Four of these went on to receive a second attempt of needle insertion after a subcutaneous bulge or resistance to local anesthetic injection were observed. Following needle reinsertion, positive stimulation tests were elicited. These patients received the local anesthetic injection with ease and had good analgesia postoperatively. No attempt was made to reinsert the needle in the remaining two patients with a negative stimulation test, as they did not show subcutaneous bulge or resistance upon injection. These patients had poor analgesia postoperatively. The positive predictive value of the test was greater than the presence of a "pop" alone (P < 0.05) but not significantly different (P = 0.492) over the presence of "pop" and easy injection. CONCLUSION: This test may be used as a teaching and adjuvant tool in performing caudal block.

Anesthesia, Caudal

A rapid precurarization technique using rocuronium.

PURPOSE: To evaluate a rapid and time-saving precurarization technique using rocuronium to prevent succinylcholine-induced myalgia. METHOD: In a prospective, double blind randomized study, 42 ASA 1-2 patients were assigned to one of three pretreatment groups: 0.01 ml.kg-1 normal saline, 0.1 mg.kg-1 atracurium, and 0.1 mg.kg-1 rocuronium. Anaesthesia commenced with 1.5 micrograms.kg-1 fentanyl and 0.5 mg.kg-1 lidocaine at time zero. Pretreatment was administered 60 sec later, followed by 2.5 mg.kg-1 propofol. At 90 sec, 1.5 mg.kg-1 succinylcholine was injected and 30 sec later, the trachea was intubated and the ease of intubation was graded. The patient was observed for the presence and severity of fasciculations. Myalgias were recorded on postoperative days 1, 2 and 7. RESULTS: The incidence of fasciculations in the rocuronium group (21.4%) was lower (P < 0.001) than atracurium (78.5%) or placebo (92.8%) groups. On postoperative day 1, the incidence of postoperative myalgia in the rocuronium group (14.2%) was less than the placebo group (78.2%; P < 0.002) and atracurium group (85.7%; P < 0.001). The incidence of myalgia in the rocuronium group (7.1%) was lower than in the placebo group (78.5%; P < 0.001) but not different from the atracurium group (42.8%; P = 0.077) on postoperative day 2. On postoperative day 7, there was no difference among the three groups. Fasciculations were related to postoperative myalgia. There was no difference in intubating conditions among the three groups. CONCLUSION: Rocuronium pretreatment given just before induction of anaesthesia with propofol reduces fasciculations and succinylcholine-induced myalgia.

Adult

Withholding oral fluids from children undergoing day surgery reduces vomiting.

The effect of withholding oral fluids on the incidence of postoperative vomiting was evaluated in 317 children undergoing day surgery. Children were randomized by cohort into one of two groups either drinking oral fluids or having oral fluids withhold for 4-6 h postoperatively. All patients received replacement intravenous fluids sufficient to cover the anticipated fasting period. Vomiting was assessed in hospital through to the first postoperative day. Compliance to the protocol was excellent. The incidence of vomiting in the group with fluids withheld was significantly less than (P < 0.004) that of the group which drank (38% vs 56%). This difference was seen whether or not patients thought to be at high risk for postoperative vomiting (strabismus or adenoidectomy +/- tonsillectomy) were included in the analysis. The greatest effect of withholding oral fluids was seen in patients receiving opioids (P < 0.001) where vomiting was reduced from 73% to 36%. Withholding oral fluids postoperatively from children undergoing day surgery reduces the incidence of vomiting.

Ambulatory Surgical Procedures

Extra-abdominal closure of enterocutaneous fistula.

Enterocutaneous fistula is a dread complication of gastrointestinal disease and gastrointestinal operation. These patients typically have undergone numerous abdominal operations, often with peritoneal contamination, carcinoma, and/or a history of radiation, making operation for repair daunting, if not impossible. We describe a method for closure of enterocutaneous fistula, which we have used successfully in four such patients. After failure of nonsurgical management, each patient's fistula was closed with a combination of skin, muscle, and fascial flaps after intubation of the fistula with a Malecot catheter. No intra-abdominal dissection was necessary. All fistulas healed completely. We recommend this closure in any patient who has failed surgical or nonsurgical therapy or in whom celiotomy is contraindicated or is to be avoided.

Cutaneous Fistula

Blepharoplasty in the patient with exophthalmos.

The plastic surgeon performing blepharoplasty should maintain a high degree of surveillance for the presence of exophthalmos. Exophthalmos may be masked by the presence of eyelid compensations and substantial amounts of eyelid fat. The surgeon should know how to detect the condition and measure its extent.

Exophthalmos

Postural disturbances in paroxysmal positional vertigo.

Postural sway was computed in 14 patients suffering from paroxysmal positional vertigo, before and after the paroxysm. In all patients, the nystagmus elicited during the paroxysm was compatible with excitation of the posterior semicircular canal. Patients stood on a force plate for 20 s while the anteroposterior and mediolateral projections of the center of force were recorded and standard deviations computed. Recordings were made after placing the patient's head in the opposite (healthy) and the provocative position. Vertigo was elicited and the nystagmus was observed in 10 of 14 patients. Analysis of the sway data in these patients (N = 10), using the Wilcoxon matched pairs test, showed that the mediolateral sway remained unchanged, while the anteroposterior sway increased, following the provocative maneuver (p less than 0.01). It is concluded that paroxysmal positional vertigo, in which the elicited nystagmus is compatible with excitation of the posterior semicircular canal, increases the anteroposterior rather than the mediolateral sway immediately following the paroxysm.

Adult

Immunity in Pekin ducks experimentally and naturally infected with duck hepatitis B virus.

The immune response to duck hepatitis B virus (DHBV) had not been elucidated. An assay was therefore established to detect the presence of antibody to DHB surface antigen (anti-DHBs) in serum of experimentally inoculated and naturally infected ducks. Anti-DHBs in serum was detected by indirect RIA from the percentage inhibition of binding of rabbit anti-DHBs to purified DHBsAg. Specificity was confirmed by positive and negative controls, infected and noninfected sera, and a mouse monoclonal antibody to DHB core antigen (anti-DHBc). Serum and liver samples were tested for DHBV DNA by dot-blot hybridization assay. Adult ducks repeatedly inoculated with DHBV remained non-viraemic but developed anti-DHBs. This antibody activity neutralized the infectivity of DHBV, which was experimentally inoculated into 1-day-old ducklings. In naturally infected flocks anti-DHBs was detected in a proportion of noninfected adult ducks as well as 1-day-old hatchlings. Anti-DHBs activity in hatchlings neutralized the infectivity of experimentally inoculated DHBV. Pekin ducks can therefore mount a neutralizing antibody response to DHBV, and immunity may be transferred in ovo from dam to off-spring.

Aging

The role of a functionally distinct IgM anti-type III pneumococcal polysaccharide (SIII) in low-dose paralysis to SIII in mice.

Prior treatment (priming) with a weakly immunogenic dose of Type III pneumococcal polysaccharide (SIII) results in the development of an antigen-specific state of unresponsiveness termed low-dose paralysis which is believed to be mediated by suppressor T cells. The present findings show that the passive administration of functionally distinct non-complement-fixing (NCF) IgM anti-SIII antibodies either in monoclonal form or from protein-A absorbed immune serum could significantly suppress the direct plaque-forming cell (PFC) response to an immunogenic dose of SIII administered concurrently. The degree of suppression was comparable with that induced by low-dose paralysis. Low-dose paralysis was consistently induced in athymic (nude) mice 4 days, but not 3 days, after priming with a low dose of SIII, and was associated with the delayed appearance of NCF-IgM anti-SIII in the serum of athymic mice. In contrast, low-dose paralysis was readily induced in normal BALB/c mice 3 days after priming when NCF-IgM anti-SIII antibodies were present. Comparable inhibiton of the direct anti-SIII PFC response was observed when Concanavalin A (Con A) or NCF-IgM anti-SIII serum was administered with SIII antigen. That Con A and NCF-IgM anti-SIII together did not produce additive suppression was attributed to the adsorption of NCF-IgM anti-SIII antibodies to Con A. Complement-dependent single radial haemolysis mediated by CF hybrid IgM/A or CF-IgM anti-SIII serum was blocked by monoclonal NCF-IgM or IgA anti-SIII antibodies and indicated that each of the antibodies was specific for the same SIII-determinant. Evidence is presented to show that low-dose paralysis in the CF-IgM response to SIII is not mediated by suppressor T cells but can be attributed to highly avid NCF-IgM anti-SIII antibodies, formed preferentially to low doses of SIII, being able to reduce the immunogenicity of SIII administered subsequently. We propose that low-dose paralysis to SIII is the result of an immunobiological function of highly avid NCF-IgM anti-SIII antibodies which not only confer resistance against capsulated pneumococci but preferentially bind soluble SIII-antigen to reduce its immunogenicity and thereby protect specific CF-IgM positive B cells from being rendered tolerant by direct contact with higher doses of SIII antigen.

Animals

Blocking of IgM-mediated single radial haemolysis by IgA and non-complement-fixing IgM anti-type-III pneumococcal antibodies.

The results reported here provide information on the effects of mouse non-complement-fixing (NCF) IgM anti-type-III pneumococcal polysaccharide (SIII) in blocking single radial haemolysis (SRH) mediated by complement-fixing (CF) IgM or CF hybrid IgM/A anti-SIII antibodies. The results consistently showed that highly avid NCF IgM or IgA anti-SIII antibodies could prevent the detection of CF IgM or CF IgM/A anti-SIII antibodies by SRH. The altered haemolysis produced by NCF IgM and IgA antibodies in the primary response is similar to that reported when the SRH test was used to screen for primary rubella infection. The findings indicate that false-negative results can be due to the early production of NCF IgM antibodies which can block the detection of CF IgM antibodies particularly if the erythrocytes are coated suboptimally with antigen.

Animals

Modulation of anti-tumour immunity and the effect of bacterial endotoxin on the growth of different syngeneic tumours from small inocula in mice.

Studies were undertaken to determine the influence of E. coli lipopolysaccharide (LPS) on the growth of various doses of two antigenically-distinct syngeneic murine fibrosarcomas designated H1 and H7. The 'weakly' antigenic H1 tumour injected subcutaneously (s.c.) along the abdominal wall was profoundly susceptible to the growth-potentiating effects of a single intraperitoneal (i.p.) injection of 2 micrograms LPS, administered concurrently. 'Sneaking through' effects in control mice were observed with doses of 10 and 100 H1 tumour cells. Rejection of medium-sized inocula 25 or 500 H1 tumour cells were abolished by the administration of LPS. In contrast, the 'strongly' antigenic H7 tumour did not exhibit the 'sneaking through' phenomenon and its growth was only temporarily affected by LPS. Studies were also performed to determine the effect of LPS on the kinetics of delayed-type hypersensitivity (DTH) induced by mitomycin C-treated (MCT) H1 or H7 tumour cells inoculated s.c. into the footpads of mice. The 'strongly' antigenic MCT H7 tumour cells induced consecutive waves of footpad swelling of diminishing intensity and corresponded to periods of anti-tumour resistance. The specific phase of MCT H7-induced footpad swelling, maximal at day 6, was delayed in its induction if LPS was administered concurrently with MCT H7 tumour cells. In contrast, the 'weakly' antigenic MCT H1 tumour cells induced only one specific phase of footpad swelling which was rapidly down-regulated. The induction of immunity by MCT H1 tumour cells was also delayed by the concomitant administration of LPS. Because the 'weakly' antigenic H1 tumour was unable to sustain consecutive waves of anti-tumour immunity, the delay in the expression of such immunity by LPS allowed the H1 tumour cells to multiply to eventually overwhelm a rapidly down-regulated immune response. In contrast, the incidence of tumours arising from the 'strongly' antigenic H7 tumour cells was not significantly affected in LPS-treated mice because the tumour cells which escaped the first encounter with delayed anti-tumour immunity, succumbed to subsequent waves of resistance in both normal and LPS-treated mice injected with fewer than 1 X 10(5) H7 tumour cells.

Animals

Regulation of immunity and tolerance to type III pneumococcal polysaccharide (SIII) by functionally distinct IgM anti-SIII antibodies.

When BALB/c mice and athymic (nude) mice are injected intraperitoneally (i.p.) with pneumococcal type III polysaccharide (SIII), their antibodies as measured by passive haemagglutination (HA) are inhibited more easily by high doses of SIII than antibody measured by passive haemolysis (HL). The HA activity, due mainly to a highly avid non-complement-fixing (NCF) type of IgM, was further distinguished from the HL activity (CF-IgM, or CF-IgM plus CF hybrid IgM/A anti-SIII antibodies) by the failure of the NCF-IgM anti-SIII to bind to protein-A of Staphylococcus aureus (Sa). High-dose tolerance in the HL anti-SIII antibody response of BALB/c and athymic mice was induced only in the absence of circulating NCF-IgM anti-SIII antibodies. The presence of NCF-IgM anti-SIII antibodies formed to multiple daily increasing amounts of SIII, commencing with 0.01 micrograms SIII, decreased the magnitude of the HL anti-SIII response to subsequent daily increments of SIII antigen injected into BALB/c and athymic (nude) mice. Thus, the effect on the HL anti-SIII response was independent of T-cells. The concomitant administration of NCF-IgM anti-SIII rendered SIII less tolerogenic in primed mice. In contrast to the HL activity, the NCF-IgM anti-SIII antibodies were induced to low doses of SIII, conferred protection against viable pneumococci, but did not precipitate the soluble antigen in agar. It is proposed that immune paralysis (as defined by the failure of SIII-injected mice to resist pneumococcal challenge) is not necessarily a condition of total unresponsiveness but is due to an absence of protective NCF-IgM anti-SIII antibodies. Thus, immune paralysis can co-exist with either the presence or absence of non-protective CF-IgM or CF-IgM/A anti-SIII antibodies.

Animals

Modulation of anti-tumour immunity induced by syngeneic mitomycin C-treated murine tumour cells.

Experiments were performed to examine the kinetics of delayed-type hypersensitivity (DTH) to mitomycin-C-treated syngeneic murine fibrosarcomas inoculated into the footpads of mice. Evidence is presented to show that a "strongly" antigenic tumour, designated H7, elicits consecutive waves of footpad swelling in both primary and secondary responses. Periods of anti-tumour resistance coincided with the expression of each successive wave of footpad swelling in normal and immune mice. The down-regulation of the response, between the successive peaks of footpad swelling, was accompanied by active tumour growth. In contrast, the non-cross-reacting "weakly" antigenic tumour, designated H1, induced footpad swelling which was expressed only once after either primary or secondary sensitization. Unlike that induced by the "strongly" antigenic H7 tumour, the anti-tumour immunity to the H1 tumour was not sustained beyond its initial specific phase. Consequently, H1 tumour cells which survived the initial phase of anti-tumour immunity appeared to encounter no further resistance. Thus the distinctive feature of the "weakly" antigenic H1 tumour was its inability to sustain consecutive waves of tumour resistance as exhibited by the "strongly" antigenic H7 tumour. It is proposed that "weakly" and "strongly" antigenic tumours are distinguished by their different abilities to down-regulate the anti-tumour immune response. The "weakly" antigenic tumour induces specific immunity which is rapidly down-regulated while that induced by the "strongly" antigenic tumour is sustained by successive waves of anti-tumour activity of diminishing intensity. Suppression of some but not all waves of footpad swelling occurred in mice with growing H7 tumours.

Animals

Serum IgM/A, IgA and functionally distinct IgM anti-type III pneumococcal polysaccharide (SIII) antibodies in BALB/c and athymic (nude) mice.

The influence of hereditary absence of thymus upon the synthesis of IgA, complement-fixing (CF) hybrid IgM/A, CF-IgM and non-CF-IgM antibodies to pneumococcal type III polysaccharide (SIII) injected into BALB/c and athymic nude mice was studied. Techniques involved the differential absorption of the serum antibodies by protein-A of Staphylococcus aureus (Sa), coprecipitation in gels with 125I-SIII and autoradiography. IgM/A anti-SIII activity was not demonstrable in nude mice but was produced in significant amounts, by day 5, in BALB/c mice injected with SIII. By day 8, nude mice produced more IgA anti-SIII antibodies than BALB/c mice injected with the same antigen. IgA anti-SIII antibodies were not detected in either strain 5 days after SIII administration. The absence of hybrid IgM/A anti-SIII antibodies in athymic mice, prior to the appearance of monotypic IgA anti-SIII antibodies at day 8, suggests that IgM/A and not IgA synthesis is largely T cell-dependent. The evidence also implies that hybrid IgM/A antibody production, maximal on day 5 in BALB/c mice, and absent from nude mice, is not an essential product in the switching from IgM to IgA synthesis. Both strains of mice produced comparable amounts of complement-fixing (CF)-IgM and NCF-IgM anti-SIII antibodies, with the production of non-complement-fixing (NCF)-IgM anti-SIII in athymic mice being delayed. Results indicate that attempts to quantitate the levels of IgA by assays incorporating anti-IgA anti-sera may be complicated by the presence of IgM/A hybrid antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Binding of murine IgM and monoclonal IgM/A (k) hybrid anti-type III pneumococcal polysaccharide (SIII) antibodies to staphylococcal protein A.

Evidence is produced to show that two specific subclasses of IgM antibodies are formed during the primary immune response to Type III pneumococcal polysaccharide (SIII) in mice. The IgM proteins can be divided into two groups based on different reactivities with protein-A. As with human IgM subclasses, it is proposed to call the two IgM subclasses IgM1 and IgM2, where the latter is defined by the ability to react with protein-A of Staphylococcus aureus. Only the IgM molecule which reacted with protein-A produced passive haemolysis in the presence of guinea-pig complement. Results also show that the IgA anti-SII activity in serum of SIII-immune mice on day 5 of the primary response is due to hybrid IgM/A(k) antibody which is undetected by conventional methods for enumerating antibody-forming cells because cells producing IgM/A antibody develop direct plaques with guinea-pig complement. A monoclonal IgM/A(k) anti-SIII produced from spleen cells 5 days after injection of 10 micrograms SIII plus pertussis vaccine exhibited similar properties to molecules with mu and a-determinants in serum. The IgM/A hybrid antibody reacted strongly with protein-A and produced passive haemolysis of SIII-coated erythrocytes in the presence of guinea-pig, but not mouse, complement. Despite its specificity for the capsular antigen of Type III pneumococci, the IgM/A hybrid antibody conferred only temporary immunity in mice challenged with viable pneumococci. The nature and properties of IgM/A antibodies as well as those of the subclasses of IgM may give important clues to the genetic regulation and expression of antibody production. These findings may provide an explantation for some of the anomalies in various areas of immunological research.

Animals

Potentiation of tumour growth by endotoxin in serum from syngeneic tumour-bearing mice.

The subcutaneous growth of 2 antigenically distinct syngeneic methylcholanthrene-induced murine fibrosarcomas, designated H1 and H7, were significantly augmented by the concomitant administration of E. coli endotoxin (LPS). Amounts as little as 0.2 micrograms i.p. potentiated tumour growth. The weakly antigenic tumour, H1, was more susceptible to provocation by LPS than the more strongly antigenic H7. Maximum provocation of H1 tumour growth occurred when LPS was injected 1 day before the administration of 5000 tumour cells. In contrast, significant anti-tumour resistance resulted if LPS was administered 6 days before the inoculation of tumour cells. Preliminary evidence indicates that low doses of LPS can facilitate the "sneaking through" phenomenon. Enhancement of tumour growth could not be demonstrated with sera or plasma from tumour-bearing mice, unless the samples were contaminated with endotoxin. The results illustrate the importance of excluding endotoxin from solutions used in studies of experimental tumours.

Animals

Specific tumor immunity induced with mitomycin C-treated syngeneic tumor cells (MCT). Effects of carrageenan and trypan blue on MCT-induced immunity in mice.

Mitomycin C treatment of 3-methylcholanthrene-induced syngeneic tumor cells in male mice of the highly inbred strain CBA/WEHI was a convenient and effective method for producing viable but nondividing tumor cells. A single sc injection of 1 x 10(6) mitomycin C-treated syngeneic tumor cells (MCT) induced a specific antitumor immune response that could mediate rejection of small subcutaneous tumor grafts and substantially inhibit growth of larger grafts in normal mice. The response was evident between 3 and 7 days after immunization and persisted for at least 120 days. Adoptive transfer experiments with peritoneal exudate cells from MCT-immunized mice indicated that a cellular basis for resistance was likely in the absence of a detectable humoral component. Administration of MCT to mice with established tumor grafts did not, however, affect tumor growth. Experiments with carrageenan and trypan blue showed that neither induction nor expression of cytotoxic effector cells in MCT-immunized mice was inhibited by these substances, though carrageenan and trypan blue augmented tumor growth in normal mice.

Animals

A method for the induction of a prolonged elevated IgM response without the formation of IgG antibody, by injecting carrageenan-treated mice with multiple doses of sheep erythrocytes.

Carrageenan, a known macrophage toxin and immunosuppressive agent, has been studied for its effect on antibody responses following single doses or multiple daily increasing doses of sheep red blood cells (SRBC) injected intraperitoneally (i.p.) in male CBA strain mice. Results showed that lambda carrageenan administered prior to a single i.p. injection of SRBC markedly suppressed both the IgM and IgG responses. However, when carrageenan-treated mice were injected with multiple daily increasing amounts of SRCB antigen, high titers of specific antibody activities were produced in serum while only IgM plaque-forming cells (PFC) were detected in the spleens up to 8 weeks later. Higher serum titers were obtained if Bordetella pertussis vaccine was administered i.p. shortly before the first antigen dose was injected in the carrageenan-treated mice. Direct PFC (IgM) but not indirect PFC (IgG) were detected in suspensions of spleen cells late in the response of these mice. Such treatment may provide a useful method for raising high titers of cytotoxic IgM antibody to other T-dependent antigens. Evidence is presented to show that pertussis vaccine--a known potentiator of the IgG response--does not reverse the inhibitory effects of carrageenan. Results also provide evidence for the requirement of functional macrophages in the induction of helper-cell activity for the thymus dependent IgG response in vivo.

Animals