The effect of music therapy compared with general recreational activities in reducing agitation in people with dementia: a randomised controlled trial.

OBJECTIVE: This study aimed to compare the effects of music therapy with general recreational day activities in reducing agitation in people with dementia, residing in nursing home facilities. METHODS: In a randomised controlled design, residents with dementia (n = 94) were allocated to either music therapy or recreational activities. Both music therapy and general activities were offered twice weekly for 4 months. Changes in agitation were measured with a modified Cohen-Mansfield Agitation Inventory (CMAI) at four intervals on each intervention day. A mixed model analysis was used to evaluate the effectiveness of music therapy, compared with general activities, on CMAI scores at 4 h after the intervention, controlled for CMAI scores at 1 h before the session and session number. RESULTS: Data were analysed for 77 residents (43 randomised to music therapy and 34 to general activities). In both groups, the intervention resulted in a decrease in agitated behaviours from 1 h before to 4 h after each session. This decrease was somewhat greater in the music therapy group than in the general activities group, but this difference was statistically not significant (F = 2.885, p = 0.090) and disappeared completely after adjustment for Global Deterioration Scale stage (F = 1.500; p = 0.222). CONCLUSIONS: Both music therapy and recreational activities lead to a short-term decrease in agitation, but there was no additional beneficial effect of music therapy over general activities. More research is required to provide insight in the effects of music therapy in reducing agitation in demented older people.

Music in the nursing home: hitting the right note! The provision of music to dementia patients with verbal and vocal agitation in Dutch nursing homes.

BACKGROUND: The study aims to provide insight into the type of music being offered in Dutch nursing homes to patients with both dementia and verbal and vocal agitation. It also investigates the degree to which the music offered corresponds to the musical preferences of the nursing home residents. METHOD: Using random sampling, 20 nursing homes were selected to participate in this study. Within these homes, semi-structured interviews were conducted with nursing home physicians (n = 17) and other nursing home care providers (n = 20). Each interview focused on up to three psychogeriatric residents with verbal and vocal agitation. In total, 51 residents were discussed in the interviews. RESULTS: For each resident, the frequency of music, the type of music being offered, and the degree of correspondence between the music being offered and the resident's preferences varied. In almost all cases, music was being offered in the communal living room during the mid-morning coffee and the afternoon tea, while music was only infrequently offered to residents during meals. However, this music was not tailored to the preferences of the residents. During patient-centered care activities in the early morning and before sleep, when offered, the music was generally tailored to the preferences of the resident(s). CONCLUSION: Music is frequently played in nursing homes to patients with dementia who have verbal and vocal agitation. When offered to a group of residents, the music tends not to be tailored to the preferences of the residents. However, when offered individually, musical preferences are generally taken into account.

Music therapy for people with dementia.

BACKGROUND: Dementia is a clinical syndrome with a number of different causes which is characterised by deterioration in cognitive functions. Research is pursuing a variety of promising findings for the treatment of dementia. Pharmacological interventions are available but have limited ability to treat many of the syndrome's features. Little research has been directed towards non-pharmacological treatments. In this review the evidence for music therapy as a treatment is examined. OBJECTIVES: To assess the effects of music therapy in the treatment of behavioural, social, cognitive and emotional problems of older people with dementia. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group (CDCIG) Specialised Register was searched on 30 June 2003 using the term "music*". This Register contains records from all major health care databases and many ongoing trial databases and is updated regularly. The principal reviewer conducted additional searches to retrieve randomised controlled trials (RCTs) concerning the effect of music therapy on older people with dementia. SELECTION CRITERIA: Randomised controlled trials that reported clinically relevant outcomes associated with music therapy in treatment of behavioural, social, cognitive and emotional problems of older people with dementia. DATA COLLECTION AND ANALYSIS: Two reviewers screened retrieved studies independently for methodological quality using a checklist. Data from accepted studies were independently extracted by the reviewers. MAIN RESULTS: Five studies were included. The methodological quality of the studies was generally poor and the study results could not be validated or pooled for further analyses. REVIEWERS' CONCLUSIONS: The methodological quality and the reporting of the included studies were too poor to draw any useful conclusions.

Localization of SCP2 and SCP3 protein molecules within synaptonemal complexes of the rat.

SCP2 and SCP3 are major protein components of the lateral elements (LEs) of synaptonemal complexes (SCs) of the rat, with Mrs of 173, 000 and 30,000. We performed a detailed immunocytochemical comparison of the localization of SCP2 and SCP3 within SCs at the electron microscopic level. The ultrastructural localization of SCP2 and SCP3 was analyzed by immunogold labeling of two types of preparations, namely surface-spread spermatocytes and ultrathin sections of Lowicryl-embedded testicular tissue of the rat. For each of the antisera used, the distribution of immunogold label over SCs in surface-spread spermatocytes differed significantly from the distribution of label on sections. We attributed this difference to artifacts caused by the surface-spreading technique, and therefore we relied on sections for the precise localization of epitopes. On sections, the distribution of label obtained with two antisera against nonoverlapping, widely separated fragments of SCP2 did not differ significantly. There was a small but significant difference between the labeling pattern obtained with an anti-SCP3 serum and the pattern obtained with either of the two antisera against fragments of SCP2; although for all three antisera the peak of the immunogold label coincided with the center of the LE, the distributions of label obtained with the antisera against fragments of SCP2 were asymmetrical, with a shoulder at the inner side of the LE, whereas the distribution of label obtained with anti-SCP3 serum was symmetrical. Furthermore, we observed fuzzy connections between the LEs that were labeled by anti-SCP2 but not anti-SCP3 antibodies. It is possible that labeling of these fuzzy bridges caused the shoulder in the gold label distributions obtained with anti-SCP2 antibodies.

Organization of SCP1 protein molecules within synaptonemal complexes of the rat.

SCP1, a major protein component of synaptonemal complexes (SCs), is probably a constituent of the transverse filaments (TFs). The protein consists of three domains: a short, proline-rich N-terminal part, a stretch of 700 amino acid residues capable of forming an amphipathic alpha-helix, and a C-terminal domain of 240 amino acid residues which is capable of binding to DNA. To analyze the orientation of SCP1 molecules within SCs, we elicited polyclonal antibodies against three non-overlapping fragments of SCP1, which comprise, respectively, the N-terminus, the C-terminus, and a fragment from the middle of the SCP1 molecule. Using these antibodies, we performed immunoelectron microscopy on SCs in two types of preparations, namely, surface-spread spermatocytes and ultrathin sections of Lowicryl-embedded testicular tissue of the rat. For each of the three antibodies used, the distribution of immunogold label on surface-spread spermatocytes differed significantly from the distribution of label on sections. Masking of SCP1 epitopes within the lateral elements (LEs) and the central element (CE) of SCs in surface-spread preparations and the influence of the surface morphology of the spreads on the labeling pattern were considered as possible explanations for these differences. We therefore relied on the results from sections for the localization of epitopes. On the basis of the distributions of immunogold label in Lowicryl sections and the predicted secondary structure and dimensions of SCP1 molecules, we present the following model: the C-terminus of SCP1 molecules lies in the inner half of the LE, the molecules protrude from the LE through the central region into the CE, and end up with their N-terminus between the center of the CE and the opposite LE, so that the N-termini of SCP1 molecules from opposite LEs overlap. The model has several implications for the assembly of SCs and the possible functions of SCP1.

The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes.

The lateral elements of synaptonemal complexes (SCs) of the rat contain major components with relative electrophoretic mobilities (M(r)S) of 30,000 and 33,000. After one-dimensional separation of SC proteins on polyacrylamide-sodium dodecyl sulfate gels, these components show up as two broad bands. These bands contain closely related proteins, as judged from their peptide maps and immunological reactivity. Using affinity-purified polyclonal anti-30,000- and anti-33,000-M(r) component antibodies, we isolated a cDNA encoding at least one of the 30,000- or 33,000-M(r) SC components. The protein predicted from the nucleotide sequence of the cDNA, called SCP3 (for synaptonemal complex protein 3), has a molecular mass of 29.7 kDa and a pI value of 9.4. It has a potential nucleotide binding site and contains stretches that are predicted to be capable of forming coiled-coil structures. In the male rat, the gene encoding SCP3 is transcribed exclusively in the testis. SCP3 has significant amino acid similarity to the pM1 protein, which is one of the predicted products of an X-linked lymphocyte-regulated gene family of the mouse: there are 63% amino acid sequence similarity and 35% amino acid identity between the SCP3 and pM1 proteins. However, SCP3 differs from pM1 in several respects, and whether the proteins fulfill related functions is still an open question.

Ultrastructural evidence for a triple structure of the lateral element of the synaptonemal complex.

This study describes composition and localization of several substructures of the synaptonemal complex (SC) using different techniques. The techniques which were used were surface spreading, critical point drying of isolated SCs, and sectioning of Lowicryl embedded testis material. The lateral elements (LEs) of the SC appear to be composed of three lateral substructures: two morphologically identical major strands and a third strand which is considerably thinner. The thinner strand is localized on the inner side of the two major strands of the lateral element. In late pachytene/early diplotene stages when the SC starts to disintegrate more than three strands can be observed in the LEs. A model is presented and the function of the different substructures is speculated upon.

The sequential appearance of components of the synaptonemal complex during meiosis of the female rat.

This paper describes the light microscopy (LM) and electron microscopy (EM) localization of synaptonemal complex (SC) antigens in oocytes of rats. For this purpose, we used monoclonal antibodies (Mabs) that recognize components of 30 + 33, 125, and 190 kDa antigens of SCs of rat spermatocytes. The LM localization was performed by immunofluorescence and the EM localization by immunogold staining. The reaction of the Mabs with oocytes was similar to the reaction with spermatocytes, but weaker. The 30 + 33 kDa as well as the 190 kDa antigens could always be demonstrated if axial elements of the SC were present, irrespective of whether these were paired or unpaired. Thus, these antigens could be detected from leptotene--early zygotene until diplotene. The 190-kDa antigen appeared in a diffuse manner just before the appearance of the 30 + 33 kDa antigens. The 30 + 33 kDa antigens were not only detected in the axial elements of SCs but also in characteristic aggregates, which appeared in zygotene and persisted until after the SCs had disappeared. Such aggregates had rarely been observed in spermatocytes. The 125 kDa antigen was only present in the tripartite segments of SCs, at the inner edge of the lateral elements. Thus, the reaction of the Mab against the 125 kDa antigen was detectable in zygotene, pachytene, and very early diplotene. It appeared later than 30 + 33 kDa and 190 kDa antigens and it disappeared earlier. We found that several steps of the immunostaining procedure could cause variation in the intensity of the Mab reaction.

Synaptonemal complex proteins.

Synaptonemal complexes were isolated from rate spermatocytes for the purpose of biochemical and morphological analysis. Several monoclonal antibodies were elicited against purified synaptonemal complexes to study the composition and assembly of these structures. Four classes of antibodies could be discriminated according to the polypeptides that they recognize on Western blots of purified synaptonemal complexes, namely antibodies recognizing (i) a 190-kDa polypeptide; (ii) a 30- and a 33-kDa polypeptide; (iii) two polypeptides with molecular weights of about 120 kDa; and (iv) polypeptides with molecular weights of 66-55 kDa. The localization of these antigens within spermatocytes was analyzed light microscopically, by means of the immunoperoxidase technique and ultrastructurally, by immunogold labelling of surface-spread spermatocytes. The 66- to 55-kDa polypeptides are not confined to synaptonemal complexes; rather, these polypeptides appear to be chromosomal components. The 190-, 30-, and 33-kDa polypeptides make part of the lateral elements of paired as well as unpaired segments of synaptonemal complexes. The 120-kDa polypeptides were localized on the inner edge of the lateral elements, specifically in paired segments of synaptonemal complexes. The distribution of the 190-, 120-, 30-, and 33-kDa polypeptides within the testis was analyzed by immunofluorescence staining of cryostat sections. All these polypeptides turned out to be specific for nuclei of zygotene up to and including diplotene spermatocytes. Only in some early spermatids could the 190-, 30-, and 33-kDa polypeptides be detected, presumably in remnants of synaptonemal complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Two major components of synaptonemal complexes are specific for meiotic prophase nuclei.

Monoclonal antibody II52F10 was elicited against purified synaptonemal complexes (SCs); it recognizes two major components of the lateral elements of SCs, namely an Mr = 30,000 and an Mr = 33,000 protein. We studied the distribution of the antigens of II52F10 within tissues and cells of the male rat by immunoblot analysis and immunocytochemical techniques. Nuclear proteins from various cell types, including spermatogonia and spermatids, did not react with antibody II52F10 on immunoblots; the same holds for proteins from isolated mitotic chromosomes. As expected, an Mr = 30,000 and an Mr = 33,000 protein from spermatocyte nuclei did react with the antibody. In cryostat sections of liver, brain, muscle and gut we could not detect any reaction with II52F10. In the testis the reaction was confined to SCs or SC fragments. Partly on the basis of indirect evidence we identified the antigen-containing cells as zygotene up to and including post-diffuse diplotene spermatocytes. The persistence of some antigen-containing fragments in the earliest stages of spermatids could not be excluded. We conclude that the lateral elements (LEs) of SCs are not assembled by rearrangement of pre-existing components of the nucleus: at least two of their major components are newly synthesized, presumably during zygotene. Furthermore we conclude partly from indirect evidence that the major components of the LEs of SCs are not involved in the chromosome condensation processes that take place during the earliest stages of meiotic prophase.

Development of the first meiotic prophase stages in human fetal oocytes observed by light and electron microscopy.

The development of the first meiotic prophase stages was studied in two series of human female embryos and fetuses aborted for social reasons. The first series (64 embryos or fetuses aborted at 6-24 weeks of gestation) was used mainly to perfect the methods applied to obtain chromosome preparations and synaptonemal complex spreads. The second series (37 embryos or fetuses aborted at 9-24 weeks of gestation) was used to establish the timing and to characterize the different stages of prophase I. Leptotene-zygotene figures were observed in some embryos at 10 weeks of gestation. Typical zygotene figures were seen at 11-22 weeks. Pachytenes were first observed at 12-13 weeks, and the proportion of these figures was usually lower than 40%. Diplotenes were seen in fetuses with a gestational age of 14 weeks or more. The duration of the process in the human female is thus about 3-4 weeks, a similar period to that described for the male.

Identification of two major components of the lateral elements of synaptonemal complexes of the rat.

This paper describes the identification of two major components of the lateral elements of synaptonemal complexes of the rat by immunocytochemical techniques. We prepared monoclonal antibodies against synaptonemal complexes (SCs) by immunization of mice with purified SCs. One of these antibodies, II52F10, reacts with a 30 and a 33 kDa polypeptide, which are major components of purified SCs. Using this antibody, we studied the localization of its antigens light microscopically, by means of the indirect immunoperoxidase technique, as well as ultrastructurally, by means of the immunogold labeling technique. The immunolocalization was carried out on whole-mount preparations of lysed spermatocytes. The antibody reacts with paired as well as unpaired segments of zygotene, pachytene and diplotene SCs. In light microscopic preparations, the attachment plaques, particularly those of late pachytene and diplotene SCs, also appear to react strongly. In electron micrographs the lateral elements in paired as well as unpaired segments could be seen to react. No reaction was observed in the attachment plaques; however, in late pachytene and diplotene SCs the swollen terminal segments of the lateral elements did react with the antibody. Thus, we conclude that a 30 and a 33 kDa polypeptide make part of the lateral elements of synaptonemal complexes of the rat.

Structure and composition of synaptonemal complexes, isolated from rat spermatocytes.

Synaptonemal complexes (SCs) (structures involved in chromosome pairing during meiosis) were isolated and purified from rat spermatocytes for the purpose of biochemical and morphological analysis. Spermatocytes were lysed in a medium, containing Triton X-100, EDTA and DTT; the resulting swollen nuclei were disrupted by DNAse II, and the suspension was centrifuged through 1.5 M sucrose. The resulting preparation consisted for at least 60% of free SCs, as judged from electron micrographs of agar filtrates. The purified SCs still possessed lateral and transversal elements and attachment plaques. A small fraction also contained a central element. Particularly in diplotene SCs, the lateral elements clearly consisted of two subelements, which are connected by thinner fibres. The lateral elements may fall apart into a network of thinner fibres, presumably as a result of degradation during isolation. On SDS-polyacrylamide gels, the major protein components of purified SCs had relative mobilities (Mrs) of 67 to 60 and 57 to 55 kDa; in addition, there were minor proteins with Mrs of 90, 35, 33, 28, and 26 kDa, and varying amounts of histones. The 67 to 60 kDa proteins comigrate with lamins of rat liver pore complexes and laminae. A possible relationship between SCs and pore complexes and laminae is discussed.

Testicular cell suspensions of the mouse in vitro.

A method is presented which allows survival and continued differentiation of male mouse germ cells for up to 12 days in culture. The system uses continuous flow perfusion at 20 degrees C in a completely chemically defined medium. To show differentiation through meiosis, mice were treated with hydroxyurea (HU) which creates a gap in the spermatogenic line. Suspensions of testicular cells of these mice, completely lacking pachytene/diplotene stages, were put into culture. After 7 or 10 days culturing, differentiation was demonstrated by the appearance of pachytene and diplotene stages and round spermatids. The velocity of the differentiation in vitro was found the same as would be expected in vivo. The number of cells which show differentiation throughout meiosis is less than would be expected in cultures of testicular cells of mice which were not treated with hydroxyurea.