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Biomedical subjects

L Calder

Publications and source records attributed to L Calder.

At least 19 recordsLinked to original sources

A Canadian survey of transfusion practices in critically ill patients. Transfusion Requirements in Critical Care Investigators and the Canadian Critical Care Trials Group.

OBJECTIVES: To characterize the contemporary red cell transfusion practice in the critically ill and to define clinical factors that influence these practices. DESIGN: Scenario-based national survey. STUDY POPULATION: Canadian critical care practitioners. MEASUREMENTS AND MAIN RESULTS: We evaluated transfusion thresholds before transfusion and the number of red cell units ordered, under the given conditions. Of 254 Canadian critical care physicians, 193 (76%) responded to the survey. The primary specialty of most respondents was internal medicine (56%). Internal medicine respondents were in practice for an average of 8.4 +/- 5.7 (SD) yrs, and worked most often in combined medical/surgical intensive care units. Baseline hemoglobin transfusion thresholds averaged from 8.3 +/- 1.0 g/dL in a scenario involving a young stable trauma victim to 9.5 +/- 1.0 g/dL for an older patient after gastrointestinal bleeding. Transfusion thresholds differed significantly (p< .0001) between all four separate scenarios. With the exception of congestive heart failure (p> .05), all clinical factors (including age, Acute Physiology and Chronic Health Evaluation II score, preoperative status, hypoxemia, shock, lactic acidosis, coronary ischemia, and chronic anemia) significantly (p< .0001) modified the transfusion thresholds. A statistically significant (p< .01) difference in baseline transfusion thresholds was noted across four major regions (with a maximum of five academic centers per region) of the country. Low physician numbers in two of the regions did not allow for further investigation of regional variations. CONCLUSIONS: There is significant variation in critical care transfusion practice, with many intensivists adhering to a 10.0-g/dL threshold, while other physicians described a much more restrictive approach to red cell transfusion. Also, many physicians opted to administer multiple units, despite published guidelines to the contrary. Additionally, the administration of red cells was strongly influenced by a number of clinical factors, many unique to intensive care unit patients. There is a need for prospective studies to define optimal practice in the critically ill.

Adult

One year of tuberculosis in Auckland.

AIM: To describe the recent epidemiology of tuberculosis in Auckland and the outcome of contact investigations. METHOD: Routine public health data were used to review the experience of tuberculosis (TB) in the Auckland region during a twelve month period in 1992-3. RESULTS: There were 152 cases, an age-standardised rate of 2.7 per 100,000 for Europeans, 37.8 for Maori, 70.9 for Pacific Island Polynesians and 131.3 for other ethnic groups. Fifty-two (35%) were born in New Zealand; 46 (31%) in Asia; 44 (30%) in the Pacific Islands. Forty-seven percent of foreign-born cases (28% of all cases) arrived in New Zealand in the 4 years preceding their notification. Forty-one per cent of cases appear not to have been diagnosed until 3 months or longer after the onset of their symptoms. Fifteen cases (including three sputum smear-positive cases) took 4 weeks or longer from diagnosis to be notified to the public health office. 12.5% of isolates were not notified. Two per cent of the 1079 contacts examined had tuberculosis. CONCLUSION: This review highlights the need for tuberculosis and the importance of timely comprehensive screening of immigrants from high incidence countries; reducing the interval between onset of symptoms and diagnosis; improving the notification rate of tuberculosis; and focusing contact investigation on those at highest risk.

Adolescent

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol.

BACKGROUND: Medical termination of pregnancy can be successfully performed with a combination of mifepristone (RU 486) and a prostaglandin analogue. We conducted a prospective, randomized trial to compare oral with vaginal administration of the prostaglandin E1 analogue misoprostol for first-trimester abortion in women treated initially with mifepristone. METHODS: The study population consisted of 270 women seeking abortion within 63 days after the onset of amenorrhea. The dose of mifepristone was 600 mg, and the dose of misoprostol was 800 micrograms. The study had two primary end points: expulsion of the conceptus without the need for a surgical procedure, and abortion within four hours after the administration of misoprostol. RESULTS: Expulsion of the conceptus without the need for a surgical procedure occurred in 95 percent of the women who received misoprostol vaginally and in 87 percent of those who received it orally (P = 0.03). The rate of continued pregnancy was 7 percent with the oral regimen and 1 percent with the vaginal regimen (P = 0.01). Ninety-three percent of the women receiving misoprostol vaginally had abortions within four hours, as compared with only 78 percent of the women receiving the drug orally (P < 0.001). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: After the administration of mifepristone, vaginal administration of misoprostol is more effective and better tolerated than oral administration for the induction of first-trimester abortion.

Abortion, Induced

Self-aggregation of purified and membrane-bound erythrocyte CD38 induces extensive decrease of its ADP-ribosyl cyclase activity.

The transmembrane glycoprotein CD38 is a bifunctional enzyme that catalyzes at its ectocellular domain both the synthesis and the hydrolysis of cyclic ADP-ribose (cADPR). The complete reaction, converting NAD+ to nicotinamide and ADP-ribose, reproduces an NAD+glycohydrolase (NADase) reaction. CD38 purified from human erythrocyte membranes has been recently shown to undergo stable oligomerization induced by either NAD+ or beta-mercaptoethanol. We demonstrate that oligomerization is also triggered by reduced glutathione (GSH) and that the GSH-induced self-aggregation of purified CD38 is accompanied by extensive and comparable decrease of its ADP-ribosyl cyclase and NADase activities. GSH-induced oligomerization of CD38 and strong enzyme inactivation take place also in situ on erythrocyte membranes.

ADP-ribosyl Cyclase

Self-aggregation of the transmembrane glycoprotein CD38 purified from human erythrocytes.

The 46 kDa human transmembrane glycoprotein CD38 is a multicatalytic enzyme exhibiting ADPribosyl cyclase, cyclic ADPribose hydrolase and NAD(+)-glycohydrolase activities at its extracellular domain. When CD38, purified to homogeneity from human erythrocyte membranes, was incubated with NAD+ or beta-mercaptoethanol, extensive aggregation took place. Addition of both compounds to CD38 led to the formation of still larger aggregates (over 300 nm), which were resistant to TCA precipitation. Extensive and stable CD38 self-aggregation was shown by, i) SDS-PAGE and autoradiography of the [32P]NAD(+)-incubated CD38, ii) SDS-PAGE followed by immunochemical detection of CD38 on the transblots, iii) direct electron microscopy on negatively stained CD38 samples. Self-aggregation of CD38 might be correlated with its putative function as a transducer of activation and proliferation signals in a number of hematopoietic cells.

ADP-ribosyl Cyclase

Cervical priming with prostaglandin E1 analogues, misoprostol and gemeprost.

Although it is well established that cervical priming before surgically induced abortion reduces the incidence of complications, its use is infrequent and confined to groups perceived to be at high risk. We compared the effect of prostaglandin E1 analogues, gemeprost and misoprostol, on the cervix. Both induced clinical and histochemical changes that were significantly different from controls and were likely to have therapeutic value. Misoprostol, however, is cheap, easily stored, and associated with few side-effects. Cervical pre-dilation with misoprostol may be considered in all women having surgically induced abortions.

Abortifacient Agents, Nonsteroidal

Drug resistant tuberculosis in Auckland 1988-92.

AIM: To report the prevalence of drug-resistant Mycobacterium tuberculosis in Auckland. METHOD: Review of all M tuberculosis culture positive cases from January 1988 to December 1992. Ethnicity was recorded from the national Paxus medical information data base and drug sensitivity results from the Green Lane Hospital tuberculosis reference laboratory. The clinical details of all patients with drug resistant tuberculosis were extracted from hospital case records. RESULTS: Of the 417 patients with positive cultures, 43 (10%) had isolates resistant to one or more antituberculous drugs. Only 4 patients had multidrug-resistant organisms (defined as resistance to at least isoniazid and rifampicin) and there is no evidence that this is an increasing problem. Resistance rates were highest in those previously treated for M tuberculosis, and those born in, or likely to have acquired their organism from, Samoa, all other Pacific Islands, or South East Asia. CONCLUSIONS: Drug resistant M tuberculosis is a problem in Auckland but rates and patterns are little different from 1980-1982. Multidrug-resistance is not yet a problem in Auckland, as it is in the United States of America. Ways of maintaining this situation are discussed.

Antitubercular Agents

Japanese Aedes albopictus among four mosquito species reaching New Zealand in used tires.

Since a 1988-89 survey of northern New Zealand revealed no additions to the known mosquito fauna, this country's used tire importations have much increased. Relevant entomological quarantine was thus monitored in a November 1992-January 1993 Auckland project, during which almost 1/3 of 8,549 casings from Japan proved wet on inspection. In this study and at 2 South Island ports afterwards, 5 vessels from Japan and one from Australia were found to have brought in mosquito-infested used tires. Live Aedes albopictus (all larval instars, pupae, and adults) and Aedes japonicus, and dead Tripteroides bambusa were discovered in shipments from Japan (3 interceptions each in the first 2 cases, and one in the 3rd). Live Tripteroides tasmaniensis were recorded from the Australian cargo. One of the Ae. albopictus arrivals was followed by an apprehended introduction at an Auckland importer's premises.

Aedes

Effects of L-type calcium channel antagonists on the serotonin-depleting actions of MDMA in rats.

The calcium channel antagonists verapamil nifedipine and flunarizine all increased the threshold for convulsions induced by N-methyl-D-aspartate in rats. By contrast, only flunarizine blocked the long-term serotonin-depleting effects of 3,4-methylenedioxymethamphetamine. Flunarizine was also the only drug that antagonized methamphetamine-induced stereotypy. These findings suggest that calcium influx through L-type channels does not participate in the neurotoxic mechanism of MDMA, and that the neuroprotective actions of flunarizine are probably related to its anti-dopaminergic activity.

3,4-Methylenedioxyamphetamine

Tactics for the control of wildlife rabies in Ontario (Canada).

Two different tactics are currently being utilized to control rabies in foxes, skunks and raccoons in Ontario, Canada. The first tactic, which involves live-capturing with cage-traps and vaccinating by intramuscular injection, was successful in immunizing 54%-72% of the skunk and raccoon populations in a 60 km2 area of Toronto, Ontario. This area has been free of rabies for two-and-a-half years. The second tactic, involving the distribution of baits containing modified live-virus (ERA) rabies vaccine, was implemented to control rabies in foxes in both urban and rural areas of Ontario. In Toronto, 50% and 63% of the foxes were vaccinated during 1989 and 1990, respectively. Over the same period, 45% and 61% of the foxes in a 30,000 km2 area of south-eastern Ontario were immunized. Rabies is declining in both of these areas. A contingency plan has been devised to control an epizootic of raccoon rabies which is threatening to invade Ontario from the United States of America.

Administration, Oral

The hospital transfusion committee: a step towards improved quality assurance.

Quality assurance has an important contribution to make in the judicious use of scarce resources. Auckland Hospital has established a transfusion committee because there was an escalating usage of blood and blood products which are expensive prescription medicines. A pilot audit of red cell transfusions indicated that 29% of red cell transfusions may have been unnecessary. A wide range of initiatives at Auckland Hospital has reduced blood product usage. Inappropriate use of blood carries an opportunity cost and may subject patients to unnecessary risk of reactions, including potential disease transmission. Strategies which need to be employed by transfusion committees include the introduction of clinical audit, physician education, restrictions on availability, and clinical budgeting. It is recommended that transfusion committees be set up in all major hospitals.

Blood Transfusion

Proconvulsant and anticonvulsant effects in mice of acute and chronic treatment with cocaine.

The proconvulsant and anticonvulsant effects of acute and chronic exposure to cocaine were investigated in adult, male, CF-1 mice. The proconvulsant effects of cocaine in mice only manifested themselves after daily exposure to motor-stimulant doses. Although daily treatment decreased electroshock convulsion threshold, no motor convulsions were observed. Animals in the proconvulsant state, however, kindled to electrically-induced convulsions more rapidly than did controls. Furthermore, daily treatment with cocaine and electroshock also enhanced the development of electrical kindling. These results illustrate that the excitatory properties of cocaine in the CNS can enhance phenomena which cause a persistent increase in excitability of the CNS. In contrast to the proconvulsant activity after chronic exposure, cocaine, administered acutely, in motor-stimulant doses, was anticonvulsant in a variety of tests using electroshock and chemically-induced convulsions. The drug elevated electroshock thresholds for both minimal and maximal convulsions and these responses were not blocked by haloperidol. In tests for minimal chemically-induced convulsions, cocaine elevated the threshold to N-methyl-DL-aspartate, but not to bicuculline; against maximal convulsions, the drug was anticonvulsant against both N-methyl-DL-aspartate and bicuculline. Cocaine did not affect convulsion thresholds for strychnine, arecoline or aminophylline; these data suggest that the anticonvulsant action of cocaine is relatively selective for the gamma-aminobutyric acid (GABA) and glutamate systems.

Amphetamine

Telescopic scanning and age-related maculopathy.

We report the management of various aspects of the care provided over a span of 12 years for a patient with age-related maculopathy (ARM). The use of a low-power telescope proved to be particularly helpful because, with it, she learned eccentric viewing and made best use of her remaining vision.

Aged

Anti-acetylcholine receptor antibodies induced in mice by syngeneic receptor without adjuvants.

Acetylcholine receptor (AChR)-bearing membranes from the BC3H-1 cell lines were injected, without adjuvant, either intrathymically (i.t.) followed by intraperitoneal (i.p.) booster doses, or i.p. alone, into (C57BL X BALB/c)F1 mice. Over 75% of the animals developed serum anti-AChRs which reacted with the cell-line AChR and with normal mouse endplate AChR. The titres were within the lower range of those of myasthenia gravis patients, and some mice showed reduced miniature endplate potential (m.e.p.p) amplitudes. these results indicate that loss of tolerance to acetylcholine receptors can result from immunization against syngeneic AChR without adjuvant. This approach may provide a useful model for studying mechanisms of autoimmunity against acetylcholine receptor.

Action Potentials

Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes.

We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 19 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responders' thymic cells, irradiated to abrogate antibody production and suppression (P less than 0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P less than 0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases.

Adolescent