Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine

BACKGROUND: Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalational anesthetic currently under investigation for use in humans. Recently, the authors showed that desflurane is a trigger of malignant hyperthermia (MH) in susceptible swine. To date, there has been no in vivo comparison of the relative ability of inhalational anesthetics to trigger MH. The effects of desflurane, isoflurane, and halothane on six MH-susceptible purebred and six MH-susceptible mixed-bred Pietrain swine were examined. METHODS: The animals were exposed to 1 MAC and 2 MAC (if MH was not triggered after 1 MAC hour) doses of each of the three volatile anesthetics in random sequence at 7-10-day intervals and changes in end-tidal CO2, arterial blood gases, serum lactate, core and muscle temperature, blood pressure, and heart rate were measured. RESULTS: There was a statistical difference between anesthetics in the time required to trigger MH; halothane exposure resulted in the fastest onset of an MH episode (20 +/- 5 min), compared with isoflurane (48 +/- 24 min) and desflurane (65 +/- 28 min), both of which required significantly longer exposures. There was no statistical difference between the MH purebred and mixed-bred swine in the time required to trigger MH (defined as a PaCO2 of 70 mmHg) with a given agent, and time to triggering was also independent of the order of exposure to the three anesthetics. Malignant hyperthermia susceptibility was confirmed in ten surviving animals, by both in vivo succinylcholine challenge and in vitro contracture testing. CONCLUSIONS: Although all three volatile anesthetics triggered MH, exposure to halothane resulted in significantly shorter times to MH triggering when compared with desflurane and isoflurane.     

Lessons learned from the DIASTAT vascular access graft

In male Syrian hamsters, short days induce regression of the reproductive system, but eventually spontaneous recrudescence occurs ensuing from refractoriness to the inhibitory photoperiod. Although the photoperiod of 12 L:12 D (12 h light:12 h dark) may act like a short day by inducing the testicular cycle outlined above, it may fail to evoke the increase of circulating concentrations of prolactin that accompanies testicular recrudescence. This photoperiod may fail to induce photorefractoriness, as indicated by the prolonged low concentrations of prolactin in the blood. Herein, hamsters were exposed to either 8 L:16 D or 12 L:12 D from weaning and by 28 weeks exposure to either photoperiod, the hamsters had large testes following recrudescence from a photoperiod induced-regression). Transfer to 8 L:16 D from 12 L:12 D at 28 weeks resulted in a second testicular regression and recrudescence. In a second experiment, the testes of hamsters moved to 8 L:16 D from 12 L:12 D after 29 weeks exposure to the latter photoperiod similarly regressed and then regrew. Serum concentrations of prolactin decreased in these males after transfer to the shorter daylength but also decreased in hamsters kept under 12 L:12 D both groups were usually below those of hamsters moved to 14 L:10 D. These results show that exposure for 28 or 29 weeks to 12 L:12 D was insufficient to induce photorefractoriness, despite the recrudescence of the testes following involution.     

Meeting a person with AIDS in the classroom: an evaluation

Meeting a person with AIDS in the classroom was evaluated to determine if it had an impact on students' perceived susceptibility to HIV infection and attitudes toward persons with AIDS. The meeting was incorporated into the Grade 9 AIDS education program of a school district in Nova Scotia. Four schools participated in this study. Two schools were randomly assigned to the treatment group, which met the person with AIDS, and the remaining two schools formed the comparison group. Measures of the two attitudinal variables were collected using a self-report questionnaire that was administered both prior to and two weeks after the educational intervention. Meeting a person with AIDS in the classroom had no measurable impact on students perceived susceptibility to HIV infection nor on their attitudes toward persons with AIDS. Suggestions for using the educational intervention more effectively and for further research are made.     

Ceftiofur hydrochloride: plasma and tissue distribution in swine following intramuscular administration at various doses

Coccidioides immitis, the primary pathogenic fungus that causes coccidioidomycosis, is most commonly found in the deserts of the southwestern United States and Central and South America. During the early 1990s, the incidence of coccidioidomycosis in California increased dramatically. Even though most infections are subclinical or self-limited, the outbreak is estimated to have cost more than $66 million in direct medical expenses and time lost from work in Kern County, California, alone. In addition to the financial loss, this pathogen causes serious and life-threatening disseminated infections, especially among the immunosuppressed, including AIDS patients. This article discusses factors that may be responsible for the increased incidence of coccidioidomycosis (e.g., climatic and demographic changes and the clinical problems of coccidioidomycosis in the immunocompromised) and new approaches to therapy and prevention.     

The branch site adenosine is recognized differently for the two steps of pre-mRNA splicing

The functional groups responsible for branch site identity in the two steps of pre-mRNA splicing as well as for spliceosome assembly were tested by incorporation of site-specific modifications at the branch site of a pre-mRNA. These results show that recognition of the adenosine occurs early in complex formation and that the branch site adenosine is recognized differently before the first step and for the second step. Further, direct UV cross-linking with these modified RNAs was used to identify a factor whose interaction was dependent upon the identity of the branch site nucleotide.     

Culture and characterization of sinusoidal endothelial cells isolated from human liver

BACKGROUND: Epidemiologic data concerning skin diseases in many rural areas in sub-Saharan Africa are not available. Little is known about the effect of regular treatment schedules by paramedical staff (especially community health workers) in the primary healthcare system on the severity and prevalence of dermatoses. METHODS: 5780 school and pre-school children from 13 primary schools in four sublocations in rural western Kenya (Kisumu District) were examined for dermatoses by the author, together with community health workers in 1993. On-the-spot training and weekend seminars about important and common dermatoses were also given. In 1994 a dermatology program was started within the primary healthcare system. Twelve trained community health workers carried out regular school visits once a week and diagnosed and treated pupils with dermatoses. Treatment was performed with gentian violet 1% solution for bacterial skin infections, Whitfield's ointment for dermatophytoses, benzylbenzoate emulsion 25% for scabies, and hydrocortisone acetate 1% cream for eczemas. All schools were visited again in 1995 to evaluate the long-term effects of the program. RESULTS: In 1993, the prevalence rate for dermatoses was 32.4%. Most of the skin diseases found were of infective origin (27.1% were caused by bacteria, 21.6% by fungi, and 17.6% by arthropods, mainly scabies mites). Dermatitis accounted for 3.5%. In 1995, the prevalence of dermatoses declined to 29.6% (p<0.05), and this reduction was most strongly observed for tropical ulcers and tinea capitis. Additionally, there was an improvement in the extent and severity of skin diseases. CONCLUSIONS: This study defines, for the first time, the number and extent of skin diseases in children in rural Kisumu District; most dermatoses were of infective origin. The study demonstrates that community health workers in the primary healthcare system are capable of dealing successfully with the most common dermatoses in children following a short training period.     

Expression of protein kinase C gene family members is temporally and spatially regulated during neural development in vitro

The dog mastocytoma BR cell line provides us with a permanent source of canine mast cells, allowing a characterization of secretory mediators that exert important effects in canine allergic and nonallergic diseases and in physiological processes. We studied the ultrastructural characteristics and histamine releasing activity after immunological and non-immunological stimuli of the dog mastocytoma BR cell line, and compared the cell line to normal skin mast cells enzymatically isolated from healthy dogs. The histamine content of BR cells was 0.04 +/- 0.002 pg/cell, approximately 100-fold less than that found in canine skin mast cells. Non-immunologic stimuli induced similar concentration-dependent histamine release from skin mast cells and BR cells: 29.3 +/- 0.9% vs. 12.7 +/- 0.7% (calcium ionophore A23187), 23.3 +/- 0.7% vs. 18.8 +/- 0.7% (substance P) and 12.5 +/- 0.3% vs. 12.1 +/- 0.9% (compound 48/80), respectively. Immunologic stimulation, however, was only effective on canine skin mast cells, causing 30.9 +/- 1.7%, 27.7 +/- 0.6% and 12.2 +/- 0.9% histamine release in response to anti-canine IgE, concanavalin A, and antigen Asc S 1, respectively. The absence of functional IgE receptors in BR cells was confirmed by the lack of response to anti-IgE and antigen Asc S 1 following passive sensitization with dog atopic serum and dog antigen sensitized serum. We conclude that BR cells are able to release histamine after non-immunologic stimulation in a similar manner to canine skin mast cells, but that there are morphological and functional differences possibly due to different states of maturity or differentiation. For this reason the study of the highly homogeneous BR cells could offer insights into dog mast cell biology in contexts where freshly isolated cells cannot be used because of low purity and recovery.     

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q

The degree and nature of patient involvement in consultations with health professionals influences problem and needs recognition and management, and public accountability. This paper suggests a framework for understanding the scope for patient involvement in such consultations. Patients are defined as co-producers of formal health services, whose potential for involvement in consultations depends on their personal rights, responsibilities and preferences. Patients' rights in consultations are poorly defined and, in the National Health Service (NHS), not legally enforceable. The responsibilities of patients are also undefined. I suggest that these are not to deny, of their own volition, the rights of others, which in consultations necessitate mutuality of involvement through information-exchange and shared decision-making. Preferences should be met insofar as they do not militate against responsibilities and rights.     

Long-term evaluation of the ventricular defibrillation energy requirement

INTRODUCTION: Defibrillation energy requirements in patients with nonthoracotomy defibrillators may increase within several months after implantation. However, the stability of the defibrillation energy requirement beyond 1 year has not been reported. The purpose of this study was to characterize the defibrillation energy requirement during 2 years of clinical follow-up. METHODS AND RESULTS: Thirty-one consecutive patients with a biphasic nonthoracotomy defibrillation system underwent defibrillation energy requirement testing using a step-down technique (20, 15, 12, 10, 8, 6, 5, 4, 3, 2, and 1 J) during defibrillator implantation, and then 24 hours, 2 months, 1 year, and 2 years after implantation. The mean defibrillation energy requirement during these evaluations was 10.9+/-5.5 J, 12.3+/-7.3 J, 11.7+/-5.6 J, 10.2+/-4.0 J, and 11.7+/-7.4 J, respectively (P = 0.4). The defibrillation energy requirement was noted to have increased by 10 J or more after 2 years of follow-up in five patients. In one of these patients, the defibrillation energy requirement was no longer associated with an adequate safety margin, necessitating revision of the defibrillation system. There were no identifiable clinical characteristics that distinguished patients who did and did not develop a 10-J or more increase in the defibrillation energy requirement. CONCLUSION: The mean defibrillation energy requirement does not change significantly after 2 years of biphasic nonthoracotomy defibrillator system implantation. However, approximately 15% of patients develop a 10-J or greater elevation in the defibrillation energy requirement, and 3% may require a defibrillation system revision. Therefore, a yearly evaluation of the defibrillation energy requirement may be appropriate.     

Sanger DNA-sequencing reactions performed in a solid-phase nanoreactor directly coupled to capillary gel electrophoresis

A miniaturized, solid-phase nanoreactor was developed to prepare Sanger DNA-sequencing ladders which was directly interfaced to a capillary gel electrophoresis system. A biotinylated fragment of the rat brain actin gene (1 kbp) was amplified by PCR and attached to the interior wall of an (aminoalkyl)silane-derivatized fused-silica capillary tube via a biotin/streptavidin/biotin linkage. Coverage of the capillary wall with the biotinylated DNA averaged 77 +/- 10%. Stability of the anchored template under pressure (33 nL/s) and electroosmotic flows (11.3 nL/s) were favorable, requiring rinsing for > 150 h to reduce the surface coverage by only 50%. In addition, the immobilized template was stable toward temperatures required for preparing sequencing ladders, even under cycling conditions. Standard Sanger dideoxynucleotide termination performed in a large-volume (approximately 8 microL) solid-phase reactor using the thermally stable polymerase enzymes Taq and Vent and the polymerases T7 and Bst with off-line slab gel electrophoresis and autoradiographic detection indicated that acceptable fragment generation was achieved only in the case of the thermally stable polymerases. Banding was not apparent for T7 and Bst since all reagents were inserted into the column in a single plug at the beginning of the reaction. A small volume reactor (volume approximately 62 nL) was then used to perform DNA polymerase reactions and was coupled directly to a capillary gel column for separation. The capillary reactor was placed inside a thermocycler to control the temperature during chain extension and was directly connected to the gel column via zero dead volume fused-silica connectors. The complementary DNA fragments generated (C-track only) in the reactor were denatured using heat and directly injected onto the gel-filled capillary for size separation with detection accomplished using near-IR laser-induced fluorescence. Extension and single-base separation resolution of the C-track, which was directly injected onto the gel column, was estimated to be > 450 bases from the primer annealing site with plate numbers ranging from 1 x 10(6) to 2 x 10(6)/m.