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Biomedical subjects

G S Anderson

Publications and source records attributed to G S Anderson.

At least 37 records · Page 2Linked to original sources

Potentiation of merocyanine 540-mediated photodynamic therapy by salicylate and related drugs.

Simultaneous exposure to merocyanine 540 (MC540) and light of a suitable wavelength kills leukemia, lymphoma and neuroblastoma cells but is relatively well tolerated by normal pluripotent hematopoietic stem cells. This differential phototoxic effect has been exploited in preclinical models and a phase I clinical trial for the extracorporeal purging of autologous bone marrow grafts. Salicylate is known to potentiate the MC540-mediated photokilling of tumor cells. Assuming that salicylate induces a change in the plasma membrane of tumor cells (but not normal hematopoietic stem cells) that enhances the binding of dye molecules it has been suggested that salicylate may provide a simple and effective means of improving the therapeutic index of MC540-mediated photodynamic therapy. We report here on a direct test of this hypothesis in a murine model of bone marrow transplantation as well as in clonal cultures of normal murine hematopoietic progenitor cells. In both systems, salicylate enhanced the MC540-sensitized photoinactivation of leukemia cells and normal bone marrow cells to a similar extent and thus failed to improve the therapeutic index of MC540 significantly. On the basis of a series of dye-binding studies, we offer an alternative explanation for the potentiating effect of salicylate. Rather than invoking a salicylate-induced change in the plasma membrane of tumor cells, we propose that salicylate displaces dye molecules from serum albumin, thereby enhancing the concentration of free (active) dye available for binding to tumor as well as normal hematopoietic stem cells.

Animals↗

Calculated thermal conductivities and heat flux in man.

Using data compiled by the Brussels Cadaver Analysis Study on 13 unembalmed cadavers, this study examined the validity of assumptions often made concerning the role of the skin and adipose tissue layers in thermal insulation in vivo. Skin thickness was previously reported to vary from 0.35 to 2.55 mm, depending on the site of measurement and gender of the subject. Assuming a thermal conductivity of 0.70 x 10(-3) kcal/(cm.s-1.degree C-1) for the skin, heat flux across the skin would vary between site and gender in the order of 7.5 times, ranging from 0.16 to 1.20 kcal.min-1.degree C-1.m-2. Due to the negligible thermal gradient across the skin layer, however, this would be of little physiologic significance. Assumptions concerning the homogeneity of skin thickness across gender and measurement site when investigating thermal insulation of the peripheral tissues would not, therefore, influence the reported results significantly. However, it has recently been shown that the calculated lipid fraction of the adipose tissue layer varies according to a person's level of adiposity. Using a two-component model of adipose tissue, the predicted thermal conductivity (k) of the adipose tissue in the present sample was found to range from 0.50 to 0.97 x 10(-3) kcal/(cm.s-1.degree C-1), being significantly lower (P = 0.005) in the five most obese cadavers [6.66 +/- 0.45 x 10(-4) kcal/(cm.s-1.degree C-1)] than in the five most lean cadavers [8.22 +/- 0.93 x 10(-4) kcal/(cm.s-1.degree C-1)]. Adiposity level correlated significantly (r = 0.80; P < 0.01) with calculated k values, suggesting caution must be taken when assuming a single k for the adipose tissue layer when examining divergent populations (i.e., obese vs. thin).

Adipose Tissue↗

A DNA-based approach to the identification of insect species used for postmortem interval estimation.

Insect larvae found on a corpse can be used for estimating postmortem intervals. Here, we describe a molecular method for rapid identification of these insects. Specific insect DNA fragments were amplified using the polymerase chain reaction (PCR), followed by direct DNA sequencing of the amplification products. We sequenced 2300 base pairs of mitochondrial DNA from each of three blowfly species: Phormia regina, Phaenicia sericata and Lucilia illustris. All three species are important in forensic entomology. We found 118 nucleotide differences between the L. illustris and P. sericata sequences, 186 between L. illustris and P. regina, and 192 between P. sericata and P. regina. Based on these abundant DNA sequence differences, we can unambiguously identify the immature larval stages of these insects. These DNA sequence differences were also used to predict species-specific, diagnostic restriction sites in the amplified DNA, and these predictions were verified by digestion with nine restriction enzymes. The DNA sequences reported here encode the mitochondrial COI, COII and tRNA-leucine genes.

Animals↗

Hypersensitivity of horses in British Columbia to extracts of native and exotic species of Culicoides (Diptera: Ceratopogonidae).

Six horses from British Columbia severely affected by Culicoides hypersensitivity, a seasonal dermatitis caused by the bites of Culicoides spp., were inoculated intradermally with extracts of six species or forms of Culicoides from British Columbia, United States, and Israel. Two native and four exotic species were thought to cause the disease in their own geographical area. The horses developed large welts within 20 min after injection of any of the six extracts, indicating an immediate (type I) reaction. The skin reactions caused by each extract peaked at or after 24 h, indicating an additional delayed (type IV) reaction. These reactions confirm that the reactions to the extracts were allergic in nature. The horses were physically irritated by each extract and developed transverse ridges in the injection area similar to those seen in natural cases of the disease, again indicating an allergic reaction. Previous studies showed that control horses injected with Culicoides extract showed only a small, short-term reaction, with no delayed component, no irritation, and no transverse ridge development, further indicating that the observed reactions were allergic in nature. The affected horses reacted to all extracts of Culicoides, despite the fact that they had not been previously exposed to most of the species, indicating that the allergen(s) was present in all the extracts tested.

Animals↗

A comparison of predictive tests of aerobic capacity.

This study examined the relationship among three predictive tests of aerobic capacity when analyzed within and across gender. Sixty-three active college students (37 males, 26 females) performed the multistage 20-metre shuttle run (SR), the Canadian Aerobic Fitness Test (ST), and the 1.5-mile run (DR). Predicted VO2max (ml.kg-1 x min-1) scores were obtained for each subject. Significant correlations were found among the VO2max results on all possible pairings of tests analyzed as a group, and by gender (p < .001) except for the females' SR and ST pairing (p > .05). One-way analysis of variance was performed for each of the three subject pools with significant F values for the grouped (F = 5.8, p < .01) and male (F = 30.7, p < .01) samples. Tukey HSD post hoc comparison identified significant differences among the SR and ST, and ST and DR VO2 max scores for both samples. However, there were no significant differences between the cell means when females were analyzed separately.

Adult↗

Relationship between blood lactate and excess CO2 in elite cyclists.

This study examined the relationship between expired non-metabolic CO2 (exCO2) and the accumulation of blood lactate. Particular emphasis was placed on the ventilatory (exCO2 and VE/VO2) and lactate threshold relationship. A total of 21 elite cyclists (15 males, 6 females) performed a progressive intensity bicycle ergometer test during which ventilatory parameters were monitored on-line at 15-s intervals, and blood lactate sampling occurred at each minute. Transition threshold values were determined for each of the three indices: excess CO2 (TexCO2), VE/VO2 (Tvent) and blood lactate (Tlac). The three threshold values (TexCO2, Tvent, Tlac) all correlated significantly (P less than 0.001) when each was expressed as an absolute VO2 (l min-1). A significant ANOVA (F = 8.41, P less than 0.001) and post-hoc correlated t-tests demonstrated significant differences between the TexCO2 and Tlac (P less than 0.001) and the TexCO2 and Tvent values (P less than 0.025). The Tlac occurred at an average blood lactate concentration of 3.35 mM, while the mean expired excess CO2 volume at the TexCO2 was 14.04 ml kg-1 min-1. Over an 11-min range across the threshold values (TexCO2 and Tlac), which were used as relative points of reference, the expired excess CO2 volume (ml kg-1 min-1) and blood lactate concentration (mM) correlated significantly (r = 0.69, P less than 0.001). Higher individual correlations over the same period of time (r = 0.82-0.96, P less than 0.001) stress the individual nature of this relationship. These results indicate a strong relationship between the three threshold values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Culicoides obsoletus (Diptera: Ceratopogonidae) as a causal agent of Culicoides hypersensitivity (sweet itch) in British Columbia.

Six horses severely affected by a seasonal dermatitis similar in both histopathology and epidemiology to Culicoides hypersensitivity (CH) and six unaffected or normal horses were inoculated intradermally with an extract of Culicoides obsoletus (Meigen), the most common Culicoides in southwestern British Columbia. Affected horses developed large welts within 20 min after injection, representing an immediate (type I) reaction; welts were largest 24 h or more after challenge, indicating in addition a delayed (type IV) reaction. This reaction was discernible for greater than 3 wk in some of the affected horses. Normal horses developed small welts which peaked 2-4 h after challenge. Affected horses were irritated by the injections and developed characteristically ridged skin at the injection sites, similar to that seen in natural lesions, whereas the normal horses showed neither discomfort nor clinical signs. C. obsoletus is one of the most numerous Culicoides species biting horses, feeds on parts of the body where lesions are found, and is, we believe, responsible for dermatitis in the Pacific Northwest. The skin test was repeated 2 yr later in three of the affected horses. In two, the reactions were similar to those in the first test, but in the third horse, the reaction was greatly reduced after the second test. This paralleled a decrease in the severity of its natural clinical signs. Thus, a skin test may be useful in the diagnosis of Culicoides hypersensitivity.

Animals↗

Individualization and enamel histology: a case report in forensic anthropology.

The cranium of a native Indian child about six years old was found in 1979 near Taseko River, British Columbia, Canada. While the remains matched the report of a child missing for eight years in terms of race, age at death, locale, and elapsed time since death, the cranium and dentition were basically unidentifiable because of the claimed lack of medical or dental history. There was no dental work, and the parents were unknown or dead. We report the presence, in the dental enamel of the primary and secondary dentition, of stress markers, termed striae of Retzius, whose locations correspond well with anecdotal reports and recently discovered medical records which describe the timing of specific episodes of stress. The enhanced probability of personal identification from dental histological stress markers is evaluated.

British Columbia↗

A review of blood lactate and ventilatory methods of detecting transition thresholds.

As far back as the 1930s exercise physiologists recognised the existence of critical levels of work intensity above which lactate accumulation increased drastically and energy production was affected. Investigation of these transition points (thresholds) both invasively and non-invasively has led to much recent controversy. Respiratory exchange variables such as Ve, Ve/VO2, VCO2, excess CO2 and blood lactate have been monitored for simple, double and exponential breakaway points to elucidate these critical work intensities. A number of studies have produced high correlations between endurance performance and anaerobic threshold calculations, further demonstrating the potential existence of critical work intensities. Much of the controversy surrounding these phenomena has centered on mechanisms and nomenclature. The term 'anaerobic threshold' has been severely criticised because in addition to the tissues being oxygen insufficient, an imbalance in the energy systems may have resulted. The anaerobic condition or lactate accumulation may be due to changes in lactate production and removal. Muscle fibre type and the fibre type recruitment patterns may also be important factors in threshold transitions. Further examination is made in this review of non-invasive measures for determining transition thresholds and protocols for elucidating the critical points.

Anaerobic Threshold↗

Enteric tumours of the lower female genital tract: a report of three cases.

Three enteric-type neoplasms of the lower female genital tract are described; an enteric adenocarcinoma of the cervix, an enteric adenocarcinoma of the vagina and a tubulo-villous adenoma of the vagina. The two adenocarcinomas were characterized by the presence of columnar cells with a prominent brush border and an abundance of goblet cells. The tubulovillous adenoma was identical to similar lesions found in the large intestine. The criteria for diagnosis of an enteric adenocarcinoma of the female genital tract are discussed and it is concluded that the histochemical demonstration of o-acetylated sialomucin is the most specific marker of intestinal differentiation. It is suggested that enteric tumours of the cervix arise from foci of gastrointestinal metaplasia. Enteric tumours of the vagina are more likely to develop from cloacal remnants.

Adenocarcinoma↗

Asymptomatic myocardial ischemia.

In the vast majority of patients, angina pectoris is the cornerstone on which the diagnosis and treatment of coronary heart disease are formulated. There is evidence to suggest that transient myocardial ischemia may occur without angina pectoris; such episodes are generally detected during ECG or hemodynamic monitoring. The exact incidence, pathophysiologic nature, and importance of asymptomatic myocardial ischemia is not well known and needs further study.

Coronary Disease↗

Merits of stress thallium-201 myocardial perfusion imaging in patients with inconclusive exercise electrocardiograms: correlation with coronary arteriograms.

Stress thallium-201 myocardial perfusion images were obtained in 65 patients with an inconclusive exercise electrocardiogram. All 65 patients underwent coronary angiograpic studies. The exercise electrocardiogram was judged inconclusive in 35 patients (54 percent) because submaximal exercise had been performed and in 30 patients (46 percent) who manifested ST-T segment abnormalities at rest. Exercise thallium-201 myocardial perfusion images were abnormal in 20 patients and normal in 45. Nineteen (95 percent) of the 20 patients with abnormal exercise images had severe disease of one or more major coronary arteries. Thirty-seven (82 percent) of the 45 patients with normal exercise images had no significant coronary artery disease; the remaining 8 patients had coronary artery disease. Therefore, 19 of 27 patients with coronary artery disease had abnormal exercise images (sensitivity 70 percent), and 37 of 38 patients without coronary artery disease had normal exercise images (specificity 97 percent). Thallium-201 imaging predicted the correct diagnosis in 56 patients (86 percent). Thus, exercise myocardial imaging with thallium-201 appears to be a useful diagnostic aid in patients with an inconclusive exercise electrocardiogram.

Adult↗

An outbreak of diphtheria in a hospital for the mentally subnormal.

An account is given of two separate outbreaks of diphtheria amongst mentally subnormal patients and nursing staff. In a total hospital population of about 1000 the number of people involved as carriers or cases was 60 and there were five deaths. The 60 people comprised 56 patients, of whom four were involved in both outbreaks, and four nurses. The organisms isolated were C. diphtheriae mitis but five strains were non-toxigenic. It is postulated that the outbreak began following the conversion of a non-toxigenic organism to a toxigenic one by bacteriophage action. The fatal cases were examples of membranous pharyngo-laryngo-tracheo-bronchial diphtheria with well marked pseudo-casts of the upper air passages.

Adult↗