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Depression is the most frequent psychiatric disorder in the aged and a major cause of dependence. Its prognosis is poor on account of its consequences on physical health, the risk of suicide and of chronic evolution. It severely impairs the quality of life of the patients and makes a major contribution to the cost of public health since depressed subjects are hospitalized and use medical care more frequently than non depressed patients. However, they do not receive proper treatment for their depression. There is a large agreement on the necessity to improve the diagnosis of depression in the aged and to provide its adequate management. The difficulty of its diagnosis is not related to some specificity of depression but to the attitude of physicians toward aging. The recent guidelines for the diagnosis of depression insist on the indepency of the criteria regarding to age. The specificity of depression in the aged is only related to some clinical aspects and factors related to aging which interfere with its recognition, especially significant somatic complaints, cognitive disturbances and anxiety. Depression is no part of normal aging, but many risk factors are associated with aging, especially bereavement. A close clinical approach is required to distinguish depression from bereavement.

Objective: First, to validate an ultrasonographic measure of the acromio-humeral distance (AHD); second, to compare the AHD variation during active abduction in patients with shoulder impingement syndrome (SIS) and healthy subjects; and third, to evaluate the relationship between functional status and AHD variations before and after rehabilitation in SIS subjects., Design: This study has 3 components: (1) a reliability study, (2) a case-control study, and (3) a preliminary pretreatment/posttreatment clinical trial., Setting: Primary care hospital setting., Participants: Seven SIS patients and 13 healthy subjects., Interventions: For the clinical trial, the SIS subjects participated in 12 sessions of a rehabilitation program over 4 weeks., Main Outcome Measures: First, intraclass correlation coefficient for interobserver reliability; second, AHD measured at 0 degrees, 45 degrees, and 60 degrees of active abduction; and third, Western Ontario Rotator Cuff Index., Results: Intraclass correlation coefficient for interobserver reliability ranged from 0.86 to 0.92 for the 3 shoulder positions. A significant reduction of the AHD was found within groups between rest and active abduction (P < 0.05). Comparison of AHD between groups was not statistically different (P = 0.06; beta < 0.80). In pre-post rehabilitation analysis, improvement of the Western Ontario Rotator Cuff Index score was positively correlated to the reduction of the AHD narrowing as the arm was abducted (r = 0.86; P = 0.01)., Conclusions: The ultrasound measure of AHD is reliable and sensitive. Although a distinct pattern of AHD variation in SIS patients could not be confirmed, a strong positive relationship was found between the reduction of AHD narrowing and functional improvement following rehabilitation. Ultrasound measurement of AHD might help identify SIS patients who will benefit from rehabilitation.

Objective: To review randomized controlled trials evaluating the effectiveness of therapeutic exercise and orthopedic manual therapy for the treatment of impingement syndrome., Data Source: Reports up to October 2002 were located from MEDLINE, the Cochrane Database of Systematic Reviews, the Physiotherapy Evidence Database (PEDro), the TRIP database, and the Cumulative Index to Nursing & Allied Health Literature (CINAHL) using "shoulder" and "clinical trial"/"randomized controlled trial" as search terms., Study Selection: Studies were included if (1) they were a randomized controlled trial; (2) they were related to impingement syndrome, rotator cuff tendinitis, or bursitis; (3) one of the treatments included therapeutic exercise or manual therapy., Data Extraction: Two independent observers reviewed the methodological quality of the studies using an assessment tool developed by the Cochrane Musculoskeletal Injuries Group. Differences were resolved by consensus., Data Synthesis: Seven trials met our inclusion criteria. After consensus, the mean methodological score for all studies was 13.9 +/- 2.4 (of 24). Four studies of 7, including the 3 trials with the best methodological score (67%), suggested some benefit of therapeutic exercise or manual therapy compared with other treatments such as acromioplasty, placebo, or no intervention., Conclusions: There is limited evidence to support the efficacy of therapeutic exercise and manual therapy to treat impingement syndrome. More methodologically sound studies are needed to further evaluate these interventions.

Objective: To determine if duration and time of onset of treatment with diclofenac sodium influence force recovery after exercise-induced muscle damage in rats., Design: Randomized placebo-controlled trial., Setting: Animal laboratory., Animals: A total of 217 female adult Wistar rats., Intervention: Rats were submitted to a protocol consisting of 450 eccentric contractions of the ankle dorsiflexors. Treatment by gavage with diclofenac sodium (1 mg/kg, twice daily) was started at different times pre- and postprotocol or for various treatment durations., Main Outcome Measures: In vitro contractile properties., Results: When treatment was initiated shortly postprotocol, force recovery was roughly proportional to treatment duration during the first 3 days but not at 7 and 28 days postprotocol. A 7-day treatment was no more effective than 1- or 2-day treatments when force was measured at 7 and 28 days; however, such prolonged treatment had no deleterious effect on muscle force at either time. A single-dose prophylactic treatment was as effective as a 2-day treatment initiated soon after the protocol when force was assessed 2 days postprotocol; on the other end, a treatment delayed for 3 days had no effect when force was measured at 7 days., Conclusions: Treatment with diclofenac sodium extending past the acute inflammatory phase was no more effective than short and timely treatment in this model of skeletal muscle damage.

Lengthening contractions trigger an adaptive response decreasing the susceptibility to exercise-induced muscle damage (EIMD). We hypothesized that 1) this adaptation can be observed when voluntary muscle recruitment is bypassed and 2) inflammation repression lessens the adaptive response. Rat ankle dorsiflexors were submitted to two bouts of elicited lengthening contractions 14 days apart; in vitro force production and macrophage concentrations were obtained before and 2 days after each bout in rats treated or not for 2 or 7 days with diclofenac. The first bout caused a 45% force deficit in the placebo group vs. 25% in the diclofenac group, whereas the ED1+ macrophage concentration increased by 10- and 5-fold, respectively. After the second bout, only diclofenac-treated rats (2 or 7 days) presented significant force deficits and increases in ED1+ and ED2+ macrophage concentrations, but this was more pronounced in the 7-day group. We conclude that adaptation to lengthening contractions does not depend on neural components but is likely mediated by strengthening of muscle structural/cellular elements and that inflammation is important for this process.

Objective: To develop and test the reliability of a tool for rating websites that provide information on evidence-based medicine., Design: For each site, 60% of the score was given for content (eight criteria) and 40% was given for organization and presentation (nine criteria). Five of 10 randomly selected sites met the inclusion criteria and were used by three observers to test the accuracy of the tool. Each site was rated twice by each observer, with a 3-week interval between ratings., Setting: Laval University, Quebec city., Participants: Three observers., Main Outcome Measures: The intraclass correlation coefficient (ICC) was used to rate the reliability of the tool., Results: Average overall scores for the five sites were 40%, 79%, 83%, 88%, and 89%. All three observers rated the same two sites in fourth and fifth place and gave the top three ratings to the other three sites. The overall rating of the five sites by the three observers yielded an ICC of 0.93 to 0.97. An ICC of 0.87 was obtained for the two overall ratings conducted 3 weeks apart., Conclusion: This new tool offers excellent intraobserver and interobserver measurement reliability and is an excellent means of distinguishing between medical websites of varying quality. For best results, we recommend that the tool be used simultaneously by two observers and that differences be resolved by consensus.

POORLY DEFINED USE: The first of three leading problems in the use of psychotropic drugs in elderly subjects is related to the overall situation of their use, often tainted by an ìideologicalî point of view. Prescribers are ìforî or ìagainstî psychotropic and justify their prescription by the need to take into account the general situation rather than strictly clinical arguments. Some prescriptions are written for the family or institutions. Even the definition of the elderly subject is extremely vague and is generally taken to include subjects over 65, a very heterogeneous group. Too few studies have been devoted to subjects over 80. NEED FOR GOOD CLINICAL ANALYSIS: The second type of problem is raised by the clinical expression of psychotic disorders in the elderly, too often considered to be limited to the classical signs of depression, dementia, and confusion. A careful clinical analysis is essential before prescription, with an adapted therapeutic response to each pathological situation. In addition, good clinical analysis would allow better diagnosis of depression, a condition largely underestimated and undertreated. BY THERAPEUTIC CLASS: It is now classical to denounce inappropriate use of neuroleptics and question their efficacy in controlling behavioral disorders in dementia. This attitude results from the impact of the adverse effects. Several authors have emphasized the contribution of new antipsychotic drugs but very few controlled studies have been reported. For antidepressors, the current consensus would suggest that prescription doses are generally insufficient and treatment durations too short. Finally, though it is widely accepted that use of benzodiazepines should be limited in dose and duration, data on drug use however show the contrary, emphasizing the difficulty in changing habits. New compounds including thymoregulators are increasingly used for elderly subjects but here again, like for antipsychotic drugs, too few studies have been published and many points remain to be elucidated.

Family medicine programmes at Canadian universities have expanded dramatically over the past several years. The development of effective means of faculty evaluation is a real concern for these departments as they strive to maintain the high quality of their teaching programmes in the face of rapid change. The literature on faculty evaluation, including reviews and articles discussing the application of faculty evaluations, is reviewed. The current state of faculty evaluation at three Canadian family medicine department has also been surveyed. Student evaluations were found to be valid, accurate and well studied. They are not perfect, however, and require the use of additional methods such as peer review or video review in conjunction in order to provide a comprehensive evaluation of all areas of faculty activity. Faculty evaluation in family medicine teaching units and community-based settings has not been well studied. Our survey of faculty evaluation at three Canadian universities shows much room for improvement, particularly in community-based settings where evaluation is almost non-existent. Expanding the use of faculty evaluations for formative means and linking evaluation to faculty development opportunities are essential if improvements to the currently used systems are to be successful and accepted by faculty. Special consideration must be given to community-based settings where systems designed for use in larger university settings will need to be modified substantially before they can be used effectively. Further research is required in this area.

Carbonic anhydrase III (EC 4.2.1.1) is the most abundant cytosolic protein in type I skeletal muscle fibers. Investigations of its physiological role have mostly been conducted with rat muscles, which sometimes are unsuitable for in vitro studies. The objective of the present study was to characterize the carbonic anhydrase in the mouse soleus muscle to verify if this muscle can be used as a model to further study the enzyme's function. Total carbonic anhydrase specific activity in the mouse soleus was comparable to the value for rat. However, 60% of the total carbonic anhydrase activity in the mouse was of the sulfonamide-sensitive type and, therefore, not related to carbonic anhydrase III. Electrophoretic analysis revealed the presence of a 29-kDa protein in total and cytosolic extracts of the mouse soleus. Immunoblotting with an antibody developed against rat carbonic anhydrase III showed that it was also specific for this 29-kDa peptide, which presumably is the mouse carbonic anhydrase III. Inhibition of the sulfonamide-sensitive activity had no effect on contractile and fatigue characteristics, whereas inhibition of the sulfonamide-resistant carbonic anhydrase III activity led to a significant increase in resistance to fatigue. We conclude that the mouse soleus may represent an excellent model to understand the contribution of different carbonic anhydrase isoforms to muscle physiology.

Carbonic anhydrase III (CA III; EC 4.2.1.1) is the most abundant cytosolic enzyme in type I skeletal muscle fibers. We have previously shown that inhibiting the CA III activity of type I muscle can influence fatigability. Our goal was to test the hypothesis that the influence on fatigability of CA III inhibition is linked to an increased utilization of carbohydrates. Rat soleus muscles were incubated in vitro in a physiological solution with or without CA inhibitor (methazolamide, 1 mM) and submitted to a fatigue protocol. When the bathing solution contained glucose, the muscles incubated with methazolamide maintained a higher level of tension production than control muscles for the first 55-60 min of the test compared with 35-40 min when glucose was not added. Measurement of muscle glycogen content revealed that muscles incubated with CA inhibitor were utilizing their glycogen at a higher rate than control muscles over the first 45 min of the fatigue protocol. When glycolysis was inhibited with sodium iodoacetate, fatigability was not influenced by the addition of a CA inhibitor. These results further support the existence of a link between CA III activity and energy metabolism in type I skeletal muscle fibers.

Myoblasts from rudiments of slow and fast muscle, anterior latissimus dorsi (ALD) and posterior latissimus dorsi (PLD) respectively, of 9-day-old quail embryos were cultured in vitro for a period of up to 60 days in order to give rise to well-differentiated muscle fibres. These fibres were innervated by neurons from either quail or mouse embryo spinal cord and their innervation pattern was examined by the visualization of acetylcholine receptors (ACh-R) and of acetylcholinesterase (ACh-E) activity at the neuromuscular contacts. In the culture system used, quail neurons always innervated muscle fibres at several sites and only when a fast-type activity was imposed on these neurons did a reduction in the number of the previously established neuromuscular contacts take place. In contrast, in the muscle fibres innervated by mouse neurons, a spontaneous reduction in the number of the previously established neuromuscular contacts occurred but this spontaneous reduction depended upon the level of differentiation reached by the muscle fibres in vitro. In the cultures of muscle fibres previously innervated by mouse neurons, the addition of quail neurons did not provoke any modification in the initial innervation pattern, and no quail ACh-R cluster was observed. In contrast, in the muscle fibres previously innervated by quail neurons, the mouse neurons contacted these fibres, resulting in a decrease in the number of quail ACh-R clusters. These results emphasize the part played by neurons in the establishment of the innervation pattern when muscle fibres have reached a high level of differentiation. In vitro, the slow and fast characteristics of the muscle fibres do not influence this pattern.

Carbonic anhydrase III (CA III) is influenced by neuronal factors in skeletal muscles of the rat. CA III protein and its mRNA levels were assessed in slow- and fast-twitch muscles after short-term denervation by ligature of the sciatic nerve and reinnervation following removal of the sheath tightly fixed around the nerve. Significant elevations in the CA III mRNA content of fast-twitch muscles were recorded after denervation, but they were cancelled following spontaneous muscle reinnervation. No such variations were observed in the slow-twitch soleus muscle. CA III specific activity or cytosolic CA III protein content increased in both types of muscles after denervation, while a decrease was solely observed in the soleus after reinnervation. These results suggest that neuronal mediators may be responsible for up and down variations in CA III gene expression and (or) mRNA stability in slow- and fast-twitch muscles exposed to identical stimuli. Variations of the mRNA and the protein probably reflect, in a time-related manner, the well-programmed changes in fiber type of the muscles in the context of the denervation-reinnervation model.

Carbonic anhydrase III (CA III; EC 4.2.1.1) is the most abundant cytosolic enzyme in type I skeletal muscle fibers. Methazolamide, a specific CA inhibitor, was used to characterize the effects of inhibiting CA III on the resistance to fatigue and recovery of the rat soleus muscle using a 60-min fatigue protocol performed in vitro at 25 degrees C. Incubation with 10(-3) M methazolamide resulted in a smaller decrease in tension production during the fatigue protocol, thereby increasing the total tension-time integral for the fatigue test. However, the rate and extent of recovery after the test were lower in the experimental group compared with the control group. A similar effect was observed at physiological temperature (35 degrees C). The results indicate that inhibition of CA III significantly influences tension production as early as 30 s into the stimulation protocol. Inhibition of CA III only during the recovery period did not influence the recovery profile, thereby indicating that the impaired recovery was related to the presence of methazolamide during the stimulation period.

The epithelial rudiment of 4 day-old quail embryo adenohypophysis, cultivated in vitro under conditions allowing glandular differentiation, displays peripheral cells that progressively acquire follicular cell features. They elongate, develop numerous microvilli, junctional complexes, interlocking membranes and bundles of microfilaments. These follicular-like cells derive from peripheral epithelial cells that, in situ, become glandular. These results show that follicular cells can develop from undifferentiated cells. They undergo this pathway of development, in all likelihood, as a result of perturbations in their microenvironment.

This laboratory previously reported that a major 30 kilodalton (kDa) protein of the soluble cytoplasmic fraction of the rat slow-twitch soleus muscle is modulated by thyroid hormone. This protein has been purified and a portion of the primary structure has been determined. The sequence analysis suggested that the 30-kDa protein is carbonic anhydrase III (CA III; EC 4.2.1.1). The reaction of the protein with a CA III specific antibody and the similar modulation of CA III by thyroid hormone also support this conclusion. Immunochemical quantification of CA III and measurement of CA activity were performed in skeletal muscles of defined fiber-type composition from rats that were rendered hyperthyroid by treatment with 3,3',5-triiodo-L-thyronine. These experiments revealed that CA activity and CA III content are deinduced in the soleus muscle (primarily type I fibers) and induced in the superficial vastus lateralis muscle (primarily type IIb), whereas no changes were detected in the tibialis anterior muscle (primary type IIa). These results show that the modulation of CA III by thyroid hormone in rat skeletal muscle is not limited to the slow-twitch soleus muscle and that the amplitude and direction of this modulation are directly related to the initial fiber-type composition of the skeletal muscle.

1. Acetazolamide (ACET)-resistant and -sensitive carbonic anhydrase (CA) activity was measured in post-mitochondrial supernatants from the soleus (SOL), deep vastus lateralis (DVL) and superficial vastus lateralis (SVL) muscles of rats and rabbits. 2. The relative total CA activity in the three muscles of both species can be summarized as SOL greater than DVL greater than SVL. 3. ACET-resistant CA activity was found in the SOL and DVL muscles of both species whereas a low level of ACET-sensitive CA activity was detected in the SVL muscle. 4. ACET-sensitive CA activity was also found in sarcoplasmic reticulum preparations from rat and rabbit SOL muscles.

Adenohypophyseal region of quail embryo has been examined by electron microscopy from stage 12 to stage 21 of Zacchei (1961). The Seessel's pouch develops prior to the early stages of adenohypophysis formation, then regresses while Rathke's pouch proliferates and differentiates. From Rathke's pouch formation by stage 12 (48 h of incubation) until appearance of the first secretory granules by stage 21 (6 days of incubation), there are no major ultrastructural modifications in adenohypophyseal cells. Mitochondria, Golgi vesicles, polysomic ribosomes, pinocytotic vesicles, and mitotic figures become more numerous while nucleocytoplasmic ratio and the number of ribosomes and lipid droplets decreases. The major change is the appearance of secretory granules by day 6 of incubation. This phenomenon occurs at the same time as in chick embryo, despite an incubation period shorter for quail than for chick. Mitotic figures are mainly distributed near the pouch lumen, while secretory granules are first located in the peripheral cells of the cephalic part of pars distalis primordium. The hypothetical role of mesenchyme and vascularization is discussed.

Isolated epithelial rudiments of 3--4 days quail embryo adenohypophysis were cultivated in vitro. Differentiation of glandular cells occurred when culture conditions allowed the formation of explants characterized by the presence of a fibroblastic sheet and of an epithelial roof surrounding a central cavity. Differentiation did not occur when culture conditions did not allow the fibroblastic sheet to be established or resulted in the absence of a cavity. The importance of the explant structure in differentiation is also indicated by the location of glandular cells. In vitro they differentiate near the cavity derived from Rathke's pouch lumen while in situ they first appear at the periphery of the rudiment, near the basement membrane. The results of this study show that the adenohypophyseal primordium can differentiate without any mesenchymal influence. The observed differentiation seems to be correlated with fibroblast-secreted material, and this hypothesis is discussed.

A general method for isolating biologically active messenger RNA (mRNA) from agarose gels is reported. Purified cellular RNA is resolved by preparative agarose gel electrophoresis and recovered in high yields (80%) by passive diffusion. Polyadenylated mRNA isolated from the eluted RNA is functionally intact based on the ability of the RNA to serve as a template in cell-free translation systems and complementary DNA synthesis reactions. The entire procedure is simple and rapid. A substantial purification of the mRNAs coding for skeletal muscle myosin heavy chain, light chain subunits and carbonic anhydrase III has been achieved employing this method.

Slow anterior latissimus dorsi (ALD) and fast posterior latissimus dorsi (PLD) muscles of 9-day-old quail embryos were cultured in vitro without neurons for 1 to 12 weeks. Several differences could be observed between ALD- and PLD-derived cells. PLD cultures proliferated less rapidly than ALD cultures. ALD-derived muscle fibres exhibited wide Z lines, numerous mitochondria, and a poorly developed sarcotubular system, while PLD-derived muscle fibres exhibited narrow Z lines, few mitochondria, and an abundant sarcotubular system. Staining for myofibrillar ATPase revealed that all well-differentiated ALD-derived muscle fibres were of the beta' type, while PLD-derived fibres were of beta and beta R types. These results show that myoblasts from slow and fast muscle rudiments can express in vitro some of the characteristic features of slow and fast muscle fibres, independently of motor innervation.