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Biomedical subjects

L Kerr

Publications and source records attributed to L Kerr.

At least 19 recordsLinked to original sources
PubMed1992

Learning during general anaesthesia: implicit recall after methohexitone or propofol infusion.

Forty-four patients undergoing coronary artery surgery were allocated randomly to receive an infusion of propofol or methohexitone as a hypnotic supplement to a fentanyl-based anaesthetic technique. A taped message was played to the patients, consisting of 10 words associated with prompt sentences and a suggestion for a specific postoperative behavioural response. Twenty patients (10 propofol and 10 methohexitone) (perioperative group) were exposed to the taped message during surgery and in the immediate postoperative period and the other 24 patients (postoperative group) were exposed to the tape only in the postoperative period, after return to the intensive care unit (ICU). No patient had explicit recall of any events during the period when the tape was played. The patients in the propofol group who heard the tape during surgery had significant implicit recall of the word associations compared with the equivalent 10 methohexitone patients (P = 0.004), when tested 48 h after surgery. The patients who were played the tape whilst receiving identical infusion regimens for sedation in the ICU did not demonstrate implicit recall of the word associations in either the propofol or the methohexitone groups. There was no evidence of a response to the specific behavioural suggestion during the postoperative interview. The results confirm that auditory perception can occur during clinically adequate anaesthesia, and that suppression of auditory awareness or learning is a function of both the pharmacological degree of sedation and the degree of surgical stimulation.

Anesthesia, General↗
PubMed1992

Mefloquine prophylaxis: an overview of spontaneous reports of severe psychiatric reactions and convulsions.

Since the time of its introduction in 1985, mefloquine (Lariam) has been used extensively for malaria prophylaxis. The international Drug Safety Department of the manufacturer gathered all spontaneous adverse drug reactions reported in association with this drug from all available sources and monitored the literature on a world-wide basis. The serious neurologic and psychiatric adverse events reported in association with Lariam prophylaxis from the time of introduction until May 1991 were reviewed. During this time, 59 serious neurologic and psychiatric adverse reactions were reported as follows: 26 convulsions, 12 depressions, 20 psychotic episodes, and one toxic encephalopathy; none were fatal. While spontaneous reporting systems are biased by under-reporting, they provide useful instruments for analysis of clinical risks factors. The neurologic and psychiatric adverse events reported in association with mefloquine prophylaxis were of the same types as those reported with other quinine derivative antimalarials. The precise mechanism of serious neurologic and psychiatric reactions is unknown. The only patient population identified at this time as having an increased risk of developing these serious reactions to mefloquine are persons with a history of seizures or manic-depressive illness. Mefloquine prophylaxis should not be prescribed to such patients.

Adolescent↗
PubMed1991

Pulmonary hypertension in a group of dairy calves.

An episode of pulmonary arteritis and sclerosis in twenty 5- to 6-month-old dairy calves was investigated. Sixteen of the calves died acutely, without marked premonitory signs of disease. Four calves evaluated clinically had lethargy, pallor, weakness, tachycardia, tachypnea, and jugular venous distention. Cardiac catheterization performed in 3 of the calves revealed pulmonary hypertension; 1 of these calves survived. Necropsy findings in 19 calves included pale lungs and excess free fluid in the pleural and abdominal cavities. In addition, 13 of 19 calves had a dilated and thin-walled right ventricle; 4 of the calves had right-sided cardiac hypertrophy, and 2 had dilatation of the pulmonary artery. Microscopically, pulmonary arteritis and sclerosis of the small to medium-sized arteries were evident in all calves submitted for necropsy. A lung biopsy specimen from a surviving calf had similar lesions. Centrilobular hepatic necrosis was found in 17 of 19 calves. Investigation of the disease episode, including feed analysis for toxins and serologic and microbiological studies of clinically affected calves and clinically normal in-contact penmates, failed to reveal any associated risk factor. The pulmonary arterial changes in the calves were similar to lung lesions in rats fed monocrotaline.

Animals↗
PubMed1991

Immunosuppression elicited by stressors and stressor-related odors.

Exposure of footshock 72 h after administration of sheep red blood cells (SRBC) provoked a reduction of the splenic plaque-forming cell (PFC) response and plasma antibody titers in CD-1 mice. At this time following SRBC inoculation the antibody titers and PFC response were also modifiable by nonpainful stressors, such as the presentation of a weak light or odor cues of conspecifics that had been exposed to a stressor (light). Data are discussed in terms of the sensitivity of the immune response to environmental and psychological stressors, and the implications of this particular sensitivity to further analyses of stressor effects on immune activity.

Animals↗
PubMed1990

Heteroconjugate antibody-directed killing of autologous human renal carcinoma cells by in vitro-activated lymphocytes.

Tumor cell lysis can be enhanced significantly in vitro when heteroconjugate (HC) antibodies (anti-CD3 x anti-tumor mAb) are used to specifically direct lymphocyte effector cells to the tumor cell target. In order to effectively utilize HC antibodies in an immunotherapy protocol, methods must be identified for the optimum expansion, activation, and retargeting of lymphocyte-effector populations from cancer patients. In this study, we have compared the proliferative responses of different normal and renal cell carcinoma (RCC) patient lymphocyte preparations (PBL, tumor-infiltrating lymphocytes) stimulated in vitro for periods up to 12 days with a variety of growth factor combinations (anti-CD3, rIL-2, rIL-4). These activated lymphocyte preparations were then tested in vitro for their ability to kill RCC tumor cells and tumor cell lines in the presence of HC preparations (anti-CD3 mAb covalently linked to mAb reactive to different RCC tumor-associated Ag). RCC patient PBL cultured with anti-CD3 plus rIL-2 for 12 days resulted in a 3- to 160-fold expansion of effector cells. These cells, as well as tumor infiltrating lymphocytes, when retargeted with appropriate HC antibodies were capable of mediating high levels of killing of autologous tumor cells. No constitutive autologous anti-tumor cell response was detected in the absence of added HC antibodies. Of the five anti-RCC mAb tested (A6H, K29, K20, UR07, and URO 3), HC containing URO 3 x anti-CD3 and K20 x anti-CD3 elicited the highest level of tumor cell lysis by the activated lymphocyte effector cells. Together these results demonstrate that HC antibodies may be a useful imunotherapeutic reagent for directing the killing of RCC tumor cells by autologous lymphocytes.

Antibodies, Neoplasm↗
PubMed1990

Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction.

The globozoospermic condition has provided a unique opportunity to determine how the abnormal mitochondrial organization and acrosomal loss associated with this syndrome, influence sperm function. Despite the abnormal midpiece architecture, the movement characteristics of the spermatozoa, in terms of the curvilinear, path, and progressive velocities, amplitude of head displacement, and hyperactivation were all within the normal range. Similarly, the behavior of the spermatozoa on Percoll gradients was normal, although the capacity of the isolated fractions to generate reactive oxygen species was negligible. Of particular significance was the fact that the globozoospermic spermatozoa were incapable of sperm-oocyte fusion or binding the human zona pellucida, even after an intracellular calcium signal had been generated with the ionophore A23187. The sudden induction of sperm-zona interaction could, however, be achieved by the use of a ferrous ion promoter system to induce limited lipoperoxidation. This result demonstrates that the enhancing effect of peroxidation on sperm-zona adhesion involves a direct action on the properties of the sperm-plasma membrane, rather than an indirect consequence of acrosomal damage and acrosin leakage. Such findings emphasize the value of specific teratozoospermic conditions, such as globozoospermia, in dissecting the mechanisms that regulate human sperm function.

Adult↗
PubMed1987

Function of the Y optic nerve fibres in the cat: do they contribute to acuity and ability to discriminate fast motion?

1. A controlled pressure block has been applied to the optic nerve of the cat, sufficient to bring about degeneration of the axons of the large (Y) nerve fibres caudal to the block site. This degeneration has been monitored by means of implanted electrodes in optic nerve and tract which have shown a loss of the short-latency (t1) response 4-6 days after the block, and also by histological examination of the optic nerve. 2. Cats with one optic nerve blocked in this way have been used in behavioural experiments, one or other eye being covered during the tests. Tested via the blocked nerve, all cats with loss of only Y fibres could perform certain tests: the visual placing reaction, the blink reflex, the pupillary (light) reflex and simple manoeuvres such as walking a plank and jumping from table to floor. 3. When acuity was tested by means of the Mitchell jumping apparatus, cats with loss of only Y fibres showed the same acuity using either eye. This was true also of one cat in which many X fibres had also degenerated, as evidenced by a 55% loss of the medium-latency (t2) response, but in another cat with 90% loss of the t2 response acuity was reduced to about half-normal. 4. Ability to discriminate fast motion was tested by a modification of the Mitchell apparatus. All cats were able to discriminate the motion of an 11.5 deg spot up to a velocity of 6260 deg/s, whether using their normal eye or their affected eye. However, the loss of the Y fibres reduced the ability to discriminate fast motion, so that for any given level of contrast the velocity which could be discriminated was about two-thirds of the velocity discriminated using the normal eye. The ability of the cat to discriminate fast motion seems to be similar to that of the human. 5. These results suggest that there is no sharp restriction of function between the Y and X systems but instead considerable overlap. However, each system possesses specialized features giving it superiority in certain conditions.

Animals↗
PubMed1985

Conus geographus toxins that discriminate between neuronal and muscle sodium channels.

We describe the properties of a family of 22-amino acid peptides, the mu-conotoxins, which are useful probes for investigating voltage-dependent sodium channels of excitable tissues. The mu-conotoxins are present in the venom of the piscivorous marine snail, Conus geographus L. We have purified seven homologs of the mu-conotoxin set and determined their amino acid sequences, as follows, where Hyp = trans-4-hydroxyproline. GIIIA R.D.C.C.T.Hyp.Hyp.K.K.C.K.D.R.Q.C.K.Hyp.Q.R.C.C.A-NH2 [Pro6]GIIIA R.D.C.C. T.P.Hyp.K.K.C.K.D.R.Q.C.K.Hyp.Q.R.C.C.A-NH2 [Pro7]GIIIA R.D.C.C.T.Hyp.P.K.K.C.K.D.R.Q.C.R.Hyp.Q.R.C.C.A-NH2 GIIIB R.D.C.C.T.Hyp.Hyp.R.K.C.K.D.R.R.C.K.Hyp.M.K.C.C.A-NH2 [Pro6]GIIIB R.D.C.C.T.P.Hyp.R.K.C.K.D.R.R. C.K.Hyp.M.K.C.C.A-NH2 [Pro7]GIIIB R.D.C.C.T.Hyp.P.R.K.C.K.D.R.R.C.K.Hyp.M.K.C.C.A-NH2 GIIIC R.D.C.C.T.Hyp.Hyp.K.K.C.K.D.R.R.C.K.Hyp.L.K.C.C.A-NH2. Using the major peptide (GIIIA) in electrophysiological studies on nerve-muscle preparations and in single channel studies using planar lipid bilayers, we have established that the toxin blocks muscle sodium channels, while having no discernible effect on nerve or brain sodium channels. In bilayers the blocking kinetics of GIIIA were derived by statistical analysis of discrete transitions between blocked and unblocked states of batrachotoxin-activated sodium channels from rat muscle. The kinetics conform to a single-site, reversible binding equilibrium with a voltage-dependent binding constant. The measured value of the equilibrium KD for GIIIA is 100 nM at OmV, decreasing e-fold/34 mV of hyperpolarization. This voltage dependence of blocking is similar to that of tetrodotoxin and saxitoxin as measured by the same technique. The tissue specificity and kinetic characteristics suggest that the mu-conotoxins may serve as useful ligands to distinguish sodium channel subtypes in different tissues.

Amino Acid Sequence↗