Muscarinic suppression of the M-current in the rat sympathetic ganglion is mediated by receptors of the M1-subtype.

1. Under voltage-clamp dissociated adult and foetal rat superior cervical ganglion (s.c.g.) cells exhibited a non-inactivating voltage- and time-dependent component of K+ current termed the M-current (IM). IM was detected and measured from the current decay during hyperpolarizing voltage steps applied from potentials where IM was pre-activated. 2. Neither the resting membrane current nor the amplitude of these current decay relaxations were reduced by omitting Ca from the bathing fluid, showing that the M-current was not a 'Ca-activated' K-current dependent on a primary Ca-influx. Concentrations of (+)-tubocurarine sufficient to block the slow Ca-activated K-current IAHP did not inhibit IM or antagonize the effect of muscarinic agonists on IM, showing that IM was not contaminated by IAHP. Tetraethylammonium (1 mM), which blocks the fast Ca-activated K-current IC, produced a small inhibition of IM. This was not due to contamination of IM by IC since muscarinic agonists did not consistently block IC. 3. The muscarinic agonists muscarine, oxotremorine, McN-A-343 and methacholine reversibly suppressed IM, resulting in an inward (depolarizing) current. The rank order of potency was: oxotremorine greater than or equal to muscarine greater than McN-A-343 greater than methacholine. 4. The suppression of IM by muscarine was similar in cultured cells derived from adult and foetal tissue to that seen in the intact ganglia. 5. IM-suppression by muscarine was inhibited by pirenzepine (Pz) and AF-DX 116 with mean pKB values of 7.53 +/- 0.13 (n = 3) and 6.02 +/- 0.13 (n = 4) respectively. 6. The suppression of IM by muscarinic agonists was not affected by gallamine (10-30 microM). 4-Diphenylacetoxy-N-methylpiperidine methiodide inhibited the response at 300 nM. 7. Pirenzepine inhibited the contractions of the guinea-pig isolated ileum produced by muscarine with a mean pKB of 6.37 +/- 0.03 (n = 8). 8. These results suggest that the receptors mediating suppression of the M-current accord with those designated pharmacologically as M1 and that these receptors reach maturity at a very early stage in the development of the rat s.c.g.     

Lack of concordance of growth rates of primary and recurrent breast cancer

The degree of concordance of growth rates of primary tumors with corresponding recurrences was investigated by using data from 184 patients with breast cancer with measurable recurrences. For conduction of this examination, the detection processes of both the primary tumor and the recurrence were explored. The probability of detection of a recurrence per unit time was found to be nearly proportional to the tumor's diameter. Approximately 60,000 cells initiated the recurrence, and the distribution of doubling times of the recurrences was exponential, with a mean of 2.1 months. The probability of detection of the primary tumor per unit time was approximately proportional to its volume. The distribution of doubling times of primary tumors was nearly exponential; from other evidence, we inferred that the mean doubling time was also close to 2.1 months. Several techniques to measure growth rate agreement between the primary and recurrent tumors within individuals were developed, and all of them yielded the result that the growth rates are nearly unrelated.     

Social and psychological factors associated with adolescents'' self-acceptance of occlusal condition

Studies using plaster models of teeth and photographs simulating the full range of occlusal conditions have found high agreement between measures of adolescent social acceptability of these conditions and perceived need for orthodontic treatment. This study examined the association between adolescents' acceptability of their own occlusal condition, severity of malocclusion, and likelihood of undergoing orthodontic treatment. The factors predicting the acceptability of occlusal condition of 13-yr-olds, as assessed by the SASOC scale, were measurements of acceptability of general physical appearance, and the severity of occlusal condition. Variability in SASOC scores appeared to be independent of gender, socioeconomic status, and ethnicity. Gender, and severity of occlusal condition were important differences between subjects who had received, planned, or were undergoing orthodontic treatment, and those who had not. Neither SASOC scores nor perceived need for treatment accounted for a significant proportion of the variance between these groups. Although adolescents seeking orthodontic treatment had a greater severity of malocclusion than those not, little difference was observed between these groups in acceptance of occlusal condition.     

Changes to osteoporosis prevalence according to method of risk assessment.

The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. INTRODUCTION: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. MATERIALS AND METHODS: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. RESULTS: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. CONCLUSIONS: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.     

Satisfaction with Team Midwifery Care for Low‐ and High‐Risk Women: A Randomized Controlled Trial

ABSTRACT:Background: In 1996 a new model of maternity care characterized by continuity of midwifery care from early pregnancy through the postpartum period was implemented for women attending Monash Medical Centre, a tertiary level obstetric service, in Melbourne, Australia. This study's purpose was to assess the impact of this model on women's views and experiences of care during the antenatal, intrapartum, and postpartum periods compared with views of women receiving standard maternity care. Methods: One thousand low‐ and high‐risk women who booked at the antenatal clinic and met the eligibility criteria were randomly allocated to continuity of midwifery care from a group of seven midwives in collaboration with medical staff, or to standard care from a variety of midwives and medical staff. Women's views of care were measured by means of a postal questionnaire at four months after the birth. Results: Team midwifery care was associated with increased satisfaction with antenatal, intrapartum, and some aspects of postpartum care. The differences were most obvious for antenatal care. Conclusions: Continuity of midwifery care is realistically achievable in a tertiary obstetric referral service and is associated with increased satisfaction. (BIRTH 30:1 March 2003)     

Comparison of novel computer detectors and human performance for spike detection in intracranial EEG.

OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate automated spike detectors are necessary for understanding the role of spikes in epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three automated iEEG spike detectors were compared against two human EEG readers using iEEG segments from eight patients. A consensus set of detections was generated for detector calibration. Spike verification was calculated after both human EEG readers independently reviewed all detections. RESULTS: Humans and two of the three automated detectors demonstrated comparable accuracy. In four patients, automated spike detection sensitivity was >70% and accuracy was >50%. In the remaining four patients, EEG background morphology resulted in poorer performance. Blinded human verification accuracy was 76.7+/-6.6% for computer-detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS: Automated iEEG spike detectors perform comparably to humans, but sensitivity and accuracy are patient dependent. Humans verified the majority of computer-detected spikes. SIGNIFICANCE: In some patients automated detectors may be used for mapping spike occurrences in epileptic networks. This may reveal associations between spike distribution, seizure onset, and pathology.     

Geriatric trauma: resource use and patient outcomes.

INTRODUCTION: Elderly patients who suffer trauma have a higher mortality and use disproportionately more trauma resources than younger patients. To compare these 2 groups and determine the outcomes and characteristics of elderly patients, we reviewed patients in these 2 groups admitted and treated in our tertiary care provincial trauma centre. METHODS: From the provincial trauma registry we selected a cohort of 40 geriatric patients (group 1) (> or = 65 yr of age) with an ISS of 16 or more who were admitted to and spent time in our trauma service for more than 48 hours and compared them with a similar randomly selected cohort of 44 patients (group 2) aged 20-30 years. Family physicians were contacted for follow-up of these patients 2 years after discharge. We considered length of hospital stay, complications, disposition of the patients and use of consultation services. RESULTS: Patients in group 1 had a mean age of 72.1 years (range from 65-98 yr) and a mean ISS of 27.3 (range from 17-50). Patients in group 2 had a mean age of 26.3 years (range from 22-29 yr) and a mean ISS of 26.3 (range from 17-54). Hospital stay was significantly longer in the group 1: 34.5 days (95% confidence interval [CI]: 24-44 d) versus 21.6 days (95% CI: 15-28 d). More elderly patients experienced complications (35 v. 13, p < 0.001) and required medical consultations (35 v. 26, p < 0.001). In-hospital death rates were 8% (3 of 40) and 4% (2 of 44) respectively (p = 0.3). Fewer geriatric patients could be discharged home (35% [14 of 40] v. 27% [22 of 44], p = 0.056) or to rehabilitation facilities (28% [11 of 40] v. 34% [15 of 44], p = 0.3). Five geriatric patients were discharged to nursing homes (p = 0.007). Of the geriatric patients discharged to rehabilitation facilities or home, 75% were independent 2 years after discharge. CONCLUSIONS: Aggressive care for geriatric trauma patients is warranted, and resources should be directed toward rehabilitation. Based on our findings, we expect that creating a directed care pathway for these patients, targetting complications and earlier discharge, will further improve their outcomes.     

Cutaneous postural vasoconstriction is modified by exogenous but not endogenous female hormones in young women

Previously reported attenuation of skin postural vasoconstriction in women during the luteal menstrual cycle phase may be due to a progesterone-mediated decrease in myogenic or veno-arteriolar (VAR) mechanisms. Skin perfusion was measured in the shin and foot dorsum by Laser Doppler Fluxometry during leg dependency that increased vascular transmural pressure below (myogenic constriction only) and above (myogenic and VAR) the 25 mmHg threshold for activation of the VAR, and during venous distension to activate the VAR alone (cuff inflation to 50 mmHg). In six young women with normal menstrual cycles, vasoconstrictor responses to all interventions did not differ between days 7–13 (follicular) and 18–23 (luteal) of the normal menstrual cycle when progesterone levels were low and at their peak respectively. In eight women taking combined oral contraceptives (OC) and tested during pill consumption days, reductions in foot skin perfusion were smaller (P = 0.05) than in the luteal phase of the normal cycle for leg dependency below (−36.9 ± 5.2% OC vs. −52.5 ± 7.8% luteal, mean ± S.E.M.) and above (−43.7 ± 3.4% OC vs. −55.1 ± 4.8% luteal) the VAR threshold, and for venous distension (−53.1 ± 2.6% OC vs. 66.4 ± 5.5% luteal). In women with normal menstrual cycles, impaired postural vasoconstriction may be confined to those who experience pre-menstrual symptoms rather than a direct effect of endogenous hormones. Reduced vasoconstriction in the dependent foot during OC use is consistent with the known vasodilator action of exogenous hormones and its long-term effects