A menopause-specific quality of life questionnaire: development and psychometric properties

Objective:

to develop a condition-specific quality of life questionnaire for the menopause with documented psychometric properties, based on women's experience. Methods: Subjects: Women 2–7 years post-menopause with a uterus and not currently on hormone replacement therapy. Questionnaire development: A list of 106 menopause symptoms was reduced using the importance score method. Replies to the item-reduction questionnaire from 88 women resulted in a 30-item questionnaire with four domains, vasomotor, physical, psychosocial and sexual, and a global quality of life question. Psychometric properties: A separate sample of 20 women was used to determine face validity, and a panel of experts was used to confirm content validity. Reliability, responsiveness and construct validity were determined within the context of a randomized controlled trial.Construct validation involved comparison with the Neugarten and Kraines' Somatic, Psychosomatic and Psychologic subscales, the reported intensity of hot flushes, the General Well-Being Schedule, Channon and Ballinger's Vaginal Symptoms Score and Libido Index, and the Life Satisfaction Index.

Results:

The face validity score was 4.7 out of a possible 5. Content validity was confirmed. Test-retest reliability measures, using intraclass correlation coefficients were 0.81, 0.79, 0.70 and 0.55 for the physical, psychosocial, sexual domains and the quality of life question. The intraclass correlation coefficient for the vasomotor domain was 0.37 but there is evidence of systematic change. Discriminative construct validity showed correlation coefficients of 0.69 for the physical domain, 0.66 and 0.40 for the vasomotor domain, 0.65 and −0.71 for the psychosocial domain, 0.48 and 0.38 for the sexual domain, and 0.57 for the quality of life question. Evaluative construct validity showed correlation coefficients of 0.60 for the physical domain, 0.28 for the vasomotor domain, 0.55 and −0.54 for the psychosocial domain, 0.54 and 0.32 for the sexual domain, and 0.12 for the quality of life question. Responsiveness scores ranged from 0.78 to 1.34.

Conclusions:

The MENQOL (Menopause-Specific Quality of Life) questionnaire is a self-administered instrument which functions well in differentiating between women according to their quality of life and in measuring changes in their quality of life.     

Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias: management and treatment import

Retrogenesis is the process by which degenerative mechanisms reverse the order of acquisition in normal development. Alzheimer's disease (AD) and related conditions in the senium have long been noted to resemble "a return to childhood" Previously, we noted that the functional stages of AD precisely and remarkably recapitulated the acquisition of the same functional landmarks in normal human development. Subsequent work indicated that this developmental recapitulation also applied to the cognitive and related symptoms in AD. Remarkably, further investigations revealed that the same neurologic "infantile" reflexes, which mark the emergence from infancy in normal development, are equally robust indicators of corresponding stages in AD. Neuropathologic and biomolecular mechanisms for these retrogenic processes are now evident. For example, the pattern of myelin loss in AD appears to mirror the pattern of myelin acquisition in normal development. Also, recent findings indicate that mitogenic factors become reactivated in AD, and, consequently, the most actively "growing" brain regions are the most vulnerable. Because of this robust retrogenic process, the stages of AD can be translated into corresponding developmental ages (DAs). These DAs can account for the overall management and care needs of AD patients. A science of AD management can be formulated on the basis of the DA of the Alzheimer's patient, taking into consideration differences of AD from normal development as well as homologies.     

Interhemispheric reorganization of motor hand function to the primary motor cortex predicted with functional magnetic resonance imaging and transcranial magnetic stimulation

The objective of this study was presurgical assessment of reorganization of motor hand function in an 11-year-old girl with intractable epilepsy and a right-sided hemiplegia resulting from an extensive perinatal left hemispheric stroke. Prior to a left functional hemispherectomy, functional magnetic resonance imaging (MRI) showed that both nonparetic and paretic motor hand function predominantly activated the right primary motor cortex, whereas no activation was found in the left hemisphere. Transcranial magnetic stimulation of the right central area yielded responses in both the nonparetic and the paretic hand, whereas no responses were obtained after stimulation of the affected hemisphere. Both techniques indicated that motor function was mediated by corticospinal fibers originating from the undamaged (primary) motor cortex and predicted no further loss of motor hand function after surgery. Indeed, subsequent functional hemispherectomy induced no new sensorimotor deficits. Functional MRI was repeated 22 months after surgery and matched preoperative sensorimotor functional MRI findings, confirming reorganization of the primary motor cortex. No additional reorganization was introduced by surgery.     

The development of marked elevation in white blood cell count does not predict inferior outcome in chronic lymphocytic leukemia

Although elevation of the white blood cell (WBC) count at diagnosis of chronic lymphocytic leukemia (CLL) appears to predict shortened survival, its significance later in the course of the disease remains unclear. We reviewed all cases of CLL seen in our center between 1980 and 1999 to evaluate the frequency and clinical significance of WBC elevation > 100 x 10(9)/L. CLL was confirmed according to standard diagnostic criteria and data was collected from diagnosis, occurrence of WBC > 100 x 10(9)/L, and last follow-up. 235 consecutive patients with CLL were identified; 94 were excluded. 141 included patients had a median age of 61 years and median WBC 19.7 x 10(9)/L at diagnosis. Median follow-up for all patients was 56 months, and median survival was 104 months. 41 patients (29%) had > or = 1 episode of WBC > 100 x 10(9)1/L, occurring at a median of 38 months from diagnosis. Compared to controls matched for modified Rai stage, development of a WBC > 100 x 10(9)/L did not predict inferior survival (median 107 vs. 101 months, p = 0.72). We conclude that the occurrence of a WBC count > 100 x 10(9)/L in patients with CLL does not shorten the survival, and patients require therapy only if other indications for treatment are present.     

Risk-adapted therapy for clinical stage I-II Hodgkin's disease: 7-years results of radiotherapy alone for low-risk disease, and ABVD and radiotherapy for high-risk disease

Treatment outcomes were documented for 204 adult patients with clinical Stage I-II Hodgkin's disease who were treated with risk-adapted ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and radiotherapy (RT) at the Toronto-Sunnybrook Regional Cancer Centre between 1984 and 1994. Forty-nine patients with clinical Stage I disease (excluding bulky mediastinal presentations) and 50 patients with a combination of clinical Stage IIA disease, age 50 years or less, and favourable pathology (lymphocyte predominant or nodular sclerosing histology) were identified as low risk and treated with RT alone to 35 Gy. One hundred and five high-risk patients were treated with chemotherapy (86 with ABVD) followed by RT to 25 Gy. The 7-year cause-specific, overall and disease-free survivals were 95%, 90% and 75% respectively for the low-risk cohort, and 91%, 90% and 88% respectively for the high-risk cohort. In-field relapses accounted for 50% of the failures in both groups. Sixteen of 24 (67%) patients with RT failure and 6/14 (43%) with combined modality therapy (CMT) failure were salvaged. Twenty-eight per cent of the patients treated with RT and 21% of those treated with CMT developed hypothyroidism by 7 years. Fatal complications were recorded in 6% of the low-risk patients managed with RT and 8% of high-risk patients managed with CMT. Septic death and second malignancy accounted for the majority of treatment-related fatalities. Risk-adapted therapy emphasizing RT alone for selected patients with favourable prognostic factors and CMT based on ABVD provides excellent long-term disease control. Further treatment refinements, including the wider application of CMT with lower doses of chemotherapy and RT, will be required to reduce the rate of fatal complications to more acceptable levels.     

Comparison between alprazolam and hydroxyzine for oral premedication

The safety and efficacy of alprazolam and hydroxyzine administered orally as surgical premedicants were compared in a double-blind controlled study. Sixty-five patients were given either alprazolam 1 mg or hydroxyzine 75 mg, one to two hours before surgery. Anxiety was assessed by both the patient and the anaesthetist, the patient using a visual analogue scale, the anaesthetist employing both analogue and ordinal ratings. Sedation was assessed by the anaesthetist only, using the same two methods. Amnesia was appraised with a simple memory test. Safety was assessed by recording adverse effects and measuring haemodynamic variables. Premedication with alprazolam produced a modest reduction in anxiety (28%) (P < 0.01) while hydroxyzine had no detectable effect. The comparison of the sedation level and of the memory test revealed no difference between the two premedicants. Minor side effects were only observed in the hydroxyzine group. Changes in blood pressure were more pronounced in the hydroxyzine group. This study shows that alprazolam and hydroxyzine are safe and efficient oral premedicants. However, alprazolam is preferable to hydroxyzine in terms of anxiolytic and adverse effects.     

Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier: kinetics and metabolism in the rat

There is evidence that P-glycoprotein (P-gp) in the blood-brain barrier (BBB) may be involved in the aetiology of neurological disorders. For quantification of P-gp function in vivo, (R)-[11C]verapamil can be used as a positron emission tomography (PET) tracer, provided that a mathematical model describing kinetics of uptake and clearance of verapamil is available. To develop and validate such a model, the kinetic profile and metabolism of (R)-[11C]verapamil have to be known. The aim of this study was to investigate the presence of labeled metabolites of [11C]verapamil in the plasma and (brain) tissue of Wistar rats. For this purpose, extraction and high-performance liquid chromatography (HPLC) methods were developed. The radioactive metabolites of (R)-[11C]verapamil in the liver were N-dealkylated compounds, O-demethylated compounds and a polar fraction formed from N-demethylation products of (R)-[11C]verapamil. Apart from this [11C] polar fraction, other radioactive metabolites of [11C]verapamil were not detected in the brain tissue. Thirty minutes after injection, unmetabolized (R)-[11C]verapamil accounted for 47% of radioactivity in the plasma and 69% in the brain. Sixty minutes after injection, unmetabolized (R)-[11C] verapamil was 27% and 48% in the plasma and the brain, respectively.     

Primary lateral sclerosis as a phenotypic manifestation of familial ALS

Primary lateral sclerosis (PLS) is a diagnosis of exclusion in patients with progressive spinobulbar spasticity and could be part of the clinical spectrum of ALS. Unlike ALS, which is familial in 5 to 10% of the cases, PLS has been described as a sporadic disorder in adults. The authors report two patients with PLS from unrelated SOD1-negative familial ALS families. These observations provide further evidence that PLS can be linked pathophysiologically to ALS.