Genetic lessons from high altitude.

What lessons can we learn from mountain sickness or wellness that may apply to our patients? Does hypoxia affect us similarly regardless of its cause? Millions of individuals are as hypoxic from congenital or acquired heart or lung disease as healthy individuals may be at altitude. Certain adjustments enable many of such patients to lead nearly normal lives. I will compare their adjustments to those seen in the acclimatization of healthy persons to altitude. Some living organisms use strategies which enable them to tolerate a degree of hypoxia lethal to man. Are there lessons we can learn from them? In my short talk I will raise a few provocative questions, and these will lead me to discuss the relevance of basic research to the resolution of vexing human ailments. When does commercialization of research become a form of intellectual prostitution?

The first smallpox epidemic on the Canadian Plains: In the fur-traders' words.

William Tomison, in charge of the Hudson's Bay Company's Cumberland House on the Saskatchewan River, described the devastating smallpox epidemic of 1781 and 1782. He understood contagion, practised isolation and disinfection, and provided mortality statistics during a 'virgin soil' epidemic. Above all, he showed remarkable compassion. He and his men took dying Indians into their already crowded quarters, and provided them with food, shelter and 24 h care. This article describes the epidemic and its aftermath.

Smallpox and its control in Canada.

Edward Jenner's first treatise in 1798 described how he used cowpox material to provide immunity to the related smallpox virus. He sent this treatise and some cowpox material to his classmate John Clinch in Trinity, Nfld., who gave the first smallpox vaccinations in North America. Dissemination of the new technique, despite violent criticism, was rapid throughout Europe and the United States. Within a few years of its discovery, vaccination was instrumental in controlling smallpox epidemics among aboriginal people at remote trading posts of the Hudson's Bay Company. Arm-to-arm transfer at 8-day intervals was common through most of the 19th century. Vaccination and quarantine eliminated endemic smallpox throughout Canada by 1946. The last case, in Toronto in 1962, came from Brazil.

Bone age and growth in fetal alcohol syndrome.

We have found delayed mean bone age in 63 children with fetal alcohol syndrome (FAS). The mean bone age Z-score for boys (n = 31) was -2.12 SDs and for girls (n = 32) was -1.62 SDs. This might suggest that they have potential for catch-up growth. However, experience with children with intrauterine growth retardation suggests that this will not be the case and that FAS children will be of reduced height at maturity. Further support for this assumption was gained from a sample of 26 patients who were followed until at least the age of 14 years for females and 16 years for males. There was no significant change in height Z-scores from early childhood to early adulthood, the mean score being -2.16 SDs and -2.11 SDs at mean ages of 4.83 years and 18.69 years, respectively. On the other hand, there were significant changes in weight and head circumference. The mean weight Z-score changed from -2.10 SDs to -1.14 SDs (p < 0.001). The head circumference mean Z-score in 16 patients was -3.13 SDs at a mean age of 2.79 years and -2.63 SDs at a mean age of 17.37 years (p = 0.013). Short stature can continue to be used as a diagnostic criterion for FAS beyond childhood.

Techniques for application of faecal DNA methods to field studies of Ursids.

We describe methods for the preservation, extraction and amplification of DNA from faeces that facilitate field applications of faecal DNA technology. Mitochondrial, protein encoding and microsatellite nuclear DNA extracted and amplified from faeces of Malayan sun bears and North American black bears is shown to be identical to that extracted and amplified from the same individual's tissue or blood. A simple drying agent, silica beads, is shown to be a particularly effective preservative, allowing easy and safe transport of samples from the field. Methods are also developed to eliminate the risk of faecal DNA contamination from hair present in faeces.

Aerobic bacterial flora of addled raptor eggs in Saskatchewan.

In south-central Saskatchewan, Canada, in 1986, 1987 and 1989, the aerobic bacterial flora was evaluated from 75 unhatched raptor eggs of three species: 42 of the Swainson's hawk (Buteo Swainsoni), 21 of the ferruginous hawk (Buteo regalis), and 12 of the great horned owl (Bubo virginianus). In addled Swainson's hawk eggs, the most common bacterial genera were Enterobacter (18 eggs), Escherichia (12), and Streptococcus (10). Seven great horned owl eggs and six ferruginous hawk eggs also contained Escherichia coli. Salmonella spp. were not isolated. These bacteria were interpreted as secondary contaminants and not the primary cause of reproductive failure.

Tracheobronchial foreign body aspiration in children.

In this retrospective study, we reviewed the demographic and radiographic findings of 155 children with bronchoscopy-proven tracheobronchial foreign body aspiration (FBA). Two thirds of the patients were male, and most were children between 1 and 2 years of age. An aspirated peanut accounted for one third of all cases. Foreign body location was distributed nearly evenly to the right and left primary bronchi; tracheal foreign body was noted in 16 patients. The most frequent symptoms of FBA were cough (85 patients) and wheezing (60 patients). Although most patients were seen within 1 day of aspiration, 30 patients had symptoms that lasted at least 1 week before diagnosis. The most common radiographic findings were unilateral or segmental hyperlucency (59) or atelectasis (38). The trachea was the site of the foreign body in one half of children with a normal chest radiograph and FBA.

Dynamics of periodic breathing and arousal during sleep at extreme altitude.

To determine whether nocturnal periodic breathing (PB) at altitude is due primarily to unstable control of ventilation or the inability to maintain stable sleep states, we performed visual and computer analyses of the electroencephalographic and respiratory records of healthy volunteers at simulated altitudes of 4572, 6100 and 7620 m. Transient arousals were associated with < 52% of the apneas identified; thus, the PB cycle was not always associated with transient arousal. Following the termination of oxygen breathing, the reinitiation of PB was not dependent on the occurrence of arousal as the primary event. The transition from apnea to breathing preceded the appearance of arousal by approximately 1 to 4 sec. Ventilatory drive in the breaths immediately following arousal was significantly larger than corresponding control breaths, matched for SaO2. Our findings suggest that altitude-induced PB is unlikely to result from primary fluctuations in state. Arousals promote the development of PB with apnea and help to sustain these episodes, but are not necessary for their initiation.

Menkes' kinky-hair disease: radiologic findings in a patient treated with copper histidinate.

A patient with Menkes' kinky-hair disease was treated from an early age with copper histidinate. This patient did not display the progressive mental deterioration and early death typical of patients with Menkes' disease; on the contrary, his intellectual capabilities were above average for his age. The magnetic resonance imaging findings were unique, showing some tortuosity and elongation of the arteries but no evidence of cerebral atrophy, demyelination or subdural hygromas.

Comparison of areal and estimated volumetric bone mineral density values between older men and women.

We compared areal bone mineral density (BMD) of the total body (TBMD), antero-posterior lumbar spine at L3 (APS), lateral spine at L3 (LS) and femoral neck (FN). In order to understand better the effect of gender-related size differences on BMD, we also compared the estimated volumetric BMD at L3 (VLS) and the femoral neck (VFN). Subjects were asymptomatic women (n = 22) and men (n = 44) with an age range of 58-79 years. BMD at each site was measured by dual-energy X-ray absorptiometry using a Hologic 2000 in array mode. Results of the statistical analyses (ANOVA) showed the men to have significantly greater BMD at all areal sites [APS, LS (p < 0.05); FN (p < 0.01); TBMD (p < 0.001)]. The two estimated volumetric comparisons, however, showed no gender differences. Results demonstrate how measures from areal BMD measures can be misleading when comparing groups of different size. In older men and women planar measures may overestimate gender differences in BMD.

How well do older persons tolerate moderate altitude?

We studied the physiologic and clinical responses to moderate altitude in 97 older men and women (aged 59 to 83 years) over 5 days in Vail, Colorado, at an elevation of 2,500 m (8,200 ft). The incidence of acute mountain sickness was 16%, which is slightly lower than that reported for younger persons. The occurrence of symptoms of acute mountain sickness did not parallel arterial oxygen saturation or spirometric or blood pressure measurements. Chronic diseases were present in percentages typical for ambulatory elderly persons: 19 (20%) had coronary artery disease, 33 (34%) had hypertension, and 9 (9%) had lung disease. Despite this, no adverse signs or symptoms occurred in our subjects during their stay at this altitude. Our findings suggest that persons with preexisting, generally asymptomatic, cardiovascular or pulmonary disease can safely visit moderate altitudes.

Familial comparison of bone mineral density at the proximal femur and lumbar spine.

Familial resemblance of bone mineral density (BMD) was studied in the lumbar spine and three regions of the proximal femur in 41 biological mother-daughter (M-D), 42 mother-son (M-S), 24 mother-grandmother (M-G) pairs and 18 mother-grandmother-daughter (M-G-D) triads. Children were placed into three maturity categories based on an assessment of secondary sex characteristics and growth velocities. Two sets of standardized BMD Z-scores were derived for the children based on either their chronological age or their maturational status. These scores were compared with maternal Z-scores derived from age-specific norms. Similar comparisons were made between the Z-scores of the mothers and grandmothers. For all three regions of the proximal femur and for the total AP lumbar spine the correlations between Z-score values were similar and significant (P < 0.05) between the M-G and M-D pairs ranging from 0.41 to 0.57. In general, the familial correlations improved when maturity-status based Z-scores were used for comparison. The absolute BMD values measured in the grandmothers and the three maturity groups of the children--expressed as a percentage of the BMD of the mothers--showed that at the neck and the trochanteric regions of the proximal femur the late-pubescent girls and boys had a significantly (P < 0.05) greater bone density than their mothers (115-123%), whereas at the AP spine these groups averaged only 88% of their mothers BMD. This site differential was not apparent when comparing the post-menopausal grandmothers with the pre-menopausal mothers (80% at both sites). Three generation comparisons demonstrated a strong familial resemblance in bone mineral density. The value of incorporating maturity-based versus chronological-based parameters for comparison with adult measures in studies that involve growing children at different stages of development was also demonstrated.

The cloning and sequencing of the genes encoding phytase (phy) and pH 2.5-optimum acid phosphatase (aph) from Aspergillus niger var. awamori.

The genes encoding phytase (EC 3.1.3.8) and pH 2.5-optimum acid phosphatase (EC 3.1.3.2) have been cloned and sequenced from Aspergillus niger var. awamori. The translated nucleotide sequences yielded polypeptides of 467 and 479 amino acids (aa) for phytase and acid phosphatase, respectively. The genes were isolated using oligodeoxyribonucleotide probes based on the aa sequences of the purified proteins. Recombinant A. niger var. awamori strains carrying additional copies of the gene sequences demonstrated elevated enzyme activities.