Biomedical subjects
Publications and source records attributed to J Mercer.
The quality of life of a Hurler-Scheie patient who experienced improvement in several organ functions and regained mobility after 144 weeks of laronidase enzyme replacement therapy is described.
We present a patient on enzyme replacement therapy who showed rapid deterioration when laronidase was discontinued owing to pregnancy.
We present a case of myoepithelial carcinoma of the breast together with illustrations of the imaging and pathological appearances as well as discussion on the management of this condition.
Sensitization of adenylate cyclase is a recently discovered phenomenon. Melatonin can induce a sensitized response of adenylate cyclase in ovine pars tuberalis cells where the receptor for melatonin is endogenously expressed. Although the mechanism is not fully understood, sensitization of adenylate cyclase may be an important part of the mechanism by which melatonin encodes daylength in the pars tuberalis of sheep and other animals. We used this as a hypothesis to search for a natural ligand that would activate adenylate cyclase in ovine pars tuberalis cells. The approach revealed pituitary adenylate cyclase activating polypeptide to be an indirect activator of adenylate cyclase in the ovine pars tuberalis. We discuss this in relation to the mechanism and importance of sensitization to the function to the pars tuberalis.
BACKGROUND: Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule < or = 3 cm in diameter on initial chest radiography. METHODS: Clinical, physiological, and outcome data on 114 patients with an SPN < or = 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later. RESULTS: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median kappa values 0.79-0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (kappa=0.33), rose with CT information (kappa=0.44), and increased further with the addition of the FNB data (kappa=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedman's test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31-70%). FNB data contributed most to the benefit (p<0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy. CONCLUSION: Both CT and FNB make cost effective contributions to the clinical management of SPN < or = 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.
STUDY OBJECTIVES: There is uncertainty concerning the relative contribution of arousal, chemoreceptor stimulation, and their potentially interactive effects, to the acute cardiovascular changes observed during sleep in patients with sleep-disordered breathing. The purpose of this study was to compare cardiovascular responses (heart rate, skin blood flow, and pulse transit time, a non-invasive measure of arterial wall stiffness) to auditory induced arousal from stage 2 sleep under conditions of normoxia and overnight mild hypoxia. DESIGN: Randomised crossover. SETTING: Sleep Disorders Unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven healthy male subjects. INTERVENTIONS: Subjects slept wearing a facemask and breathed room air (one night; SaO2 approximately 98%) or an hypoxic gas mixture (two nights; SaO2 approximately 92%). Once in stage 2 sleep, subjects were administered one of 10 auditory tones (500 Hz, range 54-90 dB, 5-sec duration) via earphones or a sham tone (recording with no tone). MEASUREMENTS AND RESULTS: Cardiovascular responses were examined beat-by-beat for 20 seconds before and 30 seconds after auditory tones associated with arousals (3-10 second EEG changes) and after sham tones. Sleep efficiency and the percentage of sleep spent in each stage were not different between hypoxia and normoxia nights. Baseline heart rate was elevated on hypoxia nights compared with normoxia nights (59.5+/-1.7 vs. 54.4+/-1.6 b x min(-1), p=0.007). Heart rate, pulse transit time, and skin blood flow showed significant changes after arousal consistent with rapid parasympathetic withdrawal and sympathetic nervous system activation. No changes were observed after sham tones. There were no differences in time course or magnitude of cardiovascular responses between hypoxia and normoxia nights. CONCLUSIONS: We conclude that while mild hypoxia stimulates autonomic activity it does not augment the cardiovascular response to arousal from stage 2 sleep in normal subjects.
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c-Myc and p53 are two proteins that have critical roles in the regulation of apoptosis and the cell cycle. The authors review how these two proteins are thought to control the opposing events of proliferation and apoptosis and examine whether their well-documented biological roles in tumorigenesis can be applied to the vascular system.
A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by standard methods for susceptibility to antibiotics used for treatment and prophylaxis. The proportion of isolates fully susceptible to penicillin decreased from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less sensitive to penicillin except for two meningococci with a penicillin MIC of 1 mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from 1994 to 1999. There was no significant difference in the geometric mean penicillin MICs of serogroup B and serogroup C meningococci. Penicillin susceptibility was significantly associated with a poorer outcome. Isolates from survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other than the decrease in susceptibility to penicillin observed were more relevant to outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin resistance was infrequent (eight isolates in 6 years) and sporadic. A single isolate had decreased quinolone susceptibility. Despite the significant shift in susceptibility to penicillin recorded, this group of antibiotics remains a suitable treatment for IMD in Australia.
PURPOSE: The purpose of this study was to assess the effect of joint position and movement speed on hip (HT) and knee (KT) extensor torque, HT/KT ratio (HKR), and anterior tibial shear (S) in presurgical-ACL deficient (PRE; N = 15), post-ACL reconstructed (POST; N = 15), and uninjured controls (CON; N = 15). METHODS: Measurements were recorded on a semirecumbent variable resistance, closed-chain dynamometer. Tests were conducted at 1 and 1.5 Hz and maximum speed at 33% and 50% 1RM. HT, KT, and S were recorded during the extension phase of the cycle (85 degrees -25 degrees of knee flexion). RESULTS: KT was greatest when the knee was more flexed, whereas HT dominated when it was more extended. This suggests that the hamstrings, as a component of the hip extensors, may generate considerable propulsive force during knee extension, which may help counter anterior tibial shear. S increased whereas KT decreased, suggesting that the quadriceps continue to generate shear force despite the decreasing mechanical advantage producing KT. Increasing knee extension speed significantly decreased S in the POST and CON groups. The correlations between KT and S changed from significantly negative to significantly positive as the knee extended from 85 degrees to 25 degrees in the POST and CON groups. This may be related to the orientation of the patellar tendon, relative to the tibial longitudinal axis that shifts from a posterior to anterior direction, as the knee extends. CONCLUSIONS: Joint position and movement speeds affect the magnitude of hip and knee torques and anterior tibial shear. Reducing the magnitude of S during heavy loads may be a normal phenomenon, and POST surgical subjects may retain or regain this function by 1 yr after surgery.
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It has been postulated that the adaptations of lower extremity function exhibited by anterior cruciate ligament (ACL) deficient and post-ACL surgical patients represent early accommodations to the loss of ACL function after injury so that excessive anterior displacement of the tibia is prevented. Prior studies have suggested that compensation patterns in ACL deficient and post-ACL surgical subjects may affect joint moments of the knee as well as the hip. However, the variance in knee and hip forces between ACL deficient, post-surgical ACL and uninjured groups has not been clearly elucidated. The purpose of this study was to assess hip:knee extensor torque ratios relative to anterior tibia shear in pre-surgical-ACL deficient, post-surgical and uninjured subjects. Measurements of hip and knee joint moments and anterior tibia shear were recorded from 45 injured and uninjured subjects (21 men, 24 women) during lower extremity, variable resistance exercise. Anterior tibia shear was computed by decomposing joint moments and reaction forces according to a model derived from cadaver knee dissections and radiography, in combination, to estimate the tibio-femoral compressive and shear forces generated by the patellar tendon at various angles throughout the knee joint range. Three groups of subjects were studied: recently injured ACL deficient pre-surgical subjects who were scheduled for immediate surgery (PRE; n = 15); postsurgical subjects who had undergone ACL reconstructive surgery at least 1 year prior to testing (POST; n = 15); and uninjured controls (CON; n = 15). All PRE and POST subjects had a normal contralateral limb. Tests were conducted under six conditions: 1 and 1.5 Hz cadence and maximal speed at 33% and 50% one repetition maximum resistance. The results revealed that the hip:knee ratios were significantly greater for the post-ACL surgical group than the PRE and CON groups (P<0.01; P<0.03). There were significant negative correlations between the hip extensor:knee extensor torque ratios and maximal anterior tibia shear across all groups. The hip:knee extensor torque ratio increased with decreased anterior tibia shear in all groups with significant correlations ranging from -0.55 to -0.88 (P<0.01) for the injured limbs of PRE and POST groups, and -0.64 to -0.78; (P<0.01) for the CON group. The highest overall correlations were found for the post-surgical subjects. The results revealed that anterior tibia shear declined significantly with speed (P<0.01) in all groups. However, the converse was true for the hip:knee extensor torque ratio across speeds. The ratio increased significantly with speed (P<0.001) for all groups at the 33% and 50% resistances. The results suggest (1) that post-ACL surgical subjects appear to accommodate to ACL substitution by using hip extensors to a significantly greater extent than the uninjured controls in closed-chain lower extremity exercise; (2) that the hip:knee extensor torque ratio is significantly related to the magnitude of anterior tibia shear; and (3) that the anterior tibia shear is significantly reduced as speed increases in closed-chain lower extremity exercise.
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OBJECTIVE: To determine the quality of spirometry performed in primary care practice and to assess the impact of formal training. DESIGN: Randomized, controlled prospective interventional study. SETTING: Primary care practice, Auckland City, New Zealand. PARTICIPANTS: Thirty randomly selected primary care practices randomized to "trained" or "usual" groups. One doctor and one practice nurse were nominated to participate from each practice. INTERVENTIONS: "Trained" was defined as participation in an "initial" spirometry workshop at week 0 and a "maintenance of standards" workshop at week 12. "Usual" was defined as no formal training until week 12, when participants they attended the same "initial" workshop provided for the trained group. The study duration was 16 weeks. Each practice was provided with a spirometer to be used at their clinical discretion. MEASUREMENTS AND RESULTS: Spirometry data were uploaded weekly and analyzed using American Thoracic Society (ATS) criteria for acceptability and reproducibility. The workshops were assessed objectively with practical and written assessments, confirming a significant training effect. However, analysis of spirometry performed in clinical practice by the trained practitioners revealed three acceptable blows in only 18.9% of patient tests. In comparison, 5.1% of patient tests performed by the usual practitioners had three acceptable blows (p<0.0001). Only 13.5% of patient tests in the trained group and 3.4% in the usual group (p<0.0001) satisfied full acceptability and reproducibility criteria. However, 33.1% and 12.5% of patient tests in the trained and usual groups, respectively (p<0.0001), achieved at least two acceptable blows, the minimum requirement. Nonacceptability was largely ascribable to failure to satisfy end-of-test criteria; a blow of at least 6 s. Visual inspection of the results of these blows as registered on the spirometer for the presence of a plateau on the volume-time curve suggests that < 15% were acceptable. CONCLUSIONS: Although a significant training effect was demonstrated, the quality of the spirometry performed in clinical practice did not generally satisfy full ATS criteria for acceptability and reproducibility. Further study would be required to determine the clinical impact. However, the ATS guidelines allow for the use of data from unacceptable or nonreproducible maneuvers at the discretion of the interpreter. Since most of the failures were end-of-test related, the FEV1 levels are likely to be valid. Our results serve to emphasize the importance of effective training and quality assurance programs to the provision of successful spirometry in primary care practice.
Preschool children with attention-deficit/hyperactivity disorder (ADHD) (27 boys, 5 girls, mean age 4 years 10 months) participated in a double-blind placebo-controlled crossover drug study to assess the side effects of methylphenidate. Children received twice daily, for at least 1 week each, placebo, 0.3 mg/kg methylphenidate, and 0.5 mg/kg methylphenidate. Side effects were monitored by a parent rating scale designed for medication studies. In general, methylphenidate was tolerated relatively well, with no children withdrawing because of adverse effects. Of 17 childhood behaviors usually associated with side effects, 8 behaviors showed significant changes, generally at the higher dose of methylphenidate. Interestingly, 3 of the side effects were associated with improved behavior. The number of side effects appeared higher than what is usually reported in a population of school-age children, but few parents reported them as being severe. Severe side effects were reported in less than 10% of the sample, with approximately as many reports of severe effects on placebo as on low and high doses of the medication. The results indicate that methylphenidate has a relatively low toxicity in preschool children (over the first 7-10 days), that some behavioral changes that might be viewed as side effects of methylphenidate are actually normal behaviors or ADHD behaviors in preschool children (e.g., sociability), that these "side-effect" behaviors are more common in preschool than school-age children, that some "side effects" of methylphenidate are associated with improvements in behavior, and that preschool and school-age children may have different side effects of methylphenidate (e.g., mood changes and anxiety).
OBJECTIVE: To report on implications for methylphenidate treatment of this very young age group and the need to examine factors related to achieving compliance. METHOD: Thirty-one children with attention-deficit hyperactivity disorder (ADHD), aged 4 to 6 years, participated in a double-blind, placebo-controlled study using placebo, 0.3 mg/kg, and 0.5 mg/kg of methylphenidate twice per day. RESULTS: Improvements related to medication were obtained on cognitive tests of attention and impulsivity as well as behaviors assessed by parent rating scales. In an interactive setting with their mothers, attentional abilities and the children's ability to work more productively also showed improvement. However, no changes were obtained with respect to the children's tendency to comply with parental requests. Side effects increased slightly with the high dosage of medication but remained mild. CONCLUSION: The results suggest that methylphenidate can be used to improve the functioning of preschool-age children with ADHD, in a manner similar to their school-age counterparts.
Antibiotics have been the treatment of choice for a broad range of bacterial infections for decades. In recent years, however, concern has been growing over the increasing incidence of infections that are resistant to known antibiotics. A 1995 outbreak of ampicillin- and vancomycin-resistant enterococci (VRE) at the 3Y site of the McMaster University Medical Centre brought this concern home to us and resulted in the development of outbreak-management guidelines for VRE.
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