Polymyositis and dermatomyositis belong to the group of inflammatory muscle diseases. This chapter deals only with the “idiopathic” polymyositis and dermatomyositis syndromes; parasitic, bacterial, spirochetal, and viral infectious myopathies will not be discussed. For recent reviews of the general subject, the reader may wish to refer to Banker and Engel (1986), Dalakas (1991, 1992), Engel (1992)

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(03)14368-1.pdf

Polymyositis and Dermatomyositis

Clustering of aberrations to specific chromosomes in human neoplasms. IV. A survey of 1,871 cases.

Centronuclear myopathy (CNM) is an inherited neuromuscular disorder characterised by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy.The incidence of X-linked myotubular myopathy is estimated at 2/100000 male births but epidemiological data for other forms are not currently available.The clinical picture is highly variable. The X-linked form usually gives rise to a severe phenotype in males presenting at birth with marked weakness and hypotonia, external ophthalmoplegia and respiratory failure. Signs of antenatal onset comprise reduced foetal movements, polyhydramnios and thinning of the ribs on chest radiographs; birth asphyxia may be the present. Affected infants are often macrosomic, with length above the 90th centile and large head circumference. Testes are frequently undescended. Both autosomal-recessive (AR) and autosomal-dominant (AD) forms differ from the X-linked form regarding age at onset, severity, clinical characteristics and prognosis. In general, AD forms have a later onset and milder course than the X-linked form, and the AR form is intermediate in both respects.Mutations in the myotubularin (MTM1) gene on chromosome Xq28 have been identified in the majority of patients with the X-linked recessive form, whilst AD and AR forms have been associated with mutations in the dynamin 2 (DNM2) gene on chromosome 19p13.2 and the amphiphysin 2 (BIN1) gene on chromosome 2q14, respectively. Single cases with features of CNM have been associated with mutations in the skeletal muscle ryanodine receptor (RYR1) and the hJUMPY (MTMR14) genes.Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features; muscle magnetic resonance imaging may complement clinical assessment and inform genetic testing in cases with equivocal features. Genetic counselling should be offered to all patients and families in whom a diagnosis of CNM has been made.The main differential diagnoses include congenital myotonic dystrophy and other conditions with severe neonatal hypotonia.Management of CNM is mainly supportive, based on a multidisciplinary approach. Whereas the X-linked form due to MTM1 mutations is often fatal in infancy, dominant forms due to DNM2 mutations and some cases of the recessive BIN1-related form appear to be associated with an overall more favourable prognosis.

/pdf/centronuclear-myotubular-myopathy-22zrk2w5xj.pdf

Centronuclear (myotubular) myopathy

This survey of chromosomal aberrations in human neoplasms comprises 1,871 cases distributed on 15 groups of malignant disease, viz. 4 groups of myeloproliferative disorders with 1,328 cases, 5 groups of lymphoproliferative disorders with 369 cases and 6 groups of solid tumors with 174 cases. The material is presented in 17 tables, in which the variation of each chromosome is listed separately for each geographic region. In the discussion part a number of special problems are looked into. The difference in variation between the individual chromosomes was highly signifcant statistically. Within each tumor, all chromosomes which exceeded the average variation with more than 1 standard deviation were considered selectively involved. In all neoplasms taken together, the chromosomes selectively involved clustered to 15 of the 24 human chromosome types. Other topics taken up for discussion were the following: possible differences in chromosome variation between geographic regions; the specificity of certain marker chromosomes; the hypothesis of 2 essentially different kinds of chromosome aberration in cancer. The phenomena of genic amplification and recurrent translocation often found in cancer require the assumption of unorthodox cytogenetic mechanisms. One main conclusion of the paper is that the aberrations of the selectively involved chromosomes influence cancer development because of the genes they carry.

Clustering of aberrations to specific chromosomes in human neoplasms

Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation.

Oestrogen Replacement Therapy.

The debate concerning the side-effects of oestrogen therapy for post-menopausal women is currently causing much anxiety, but of no less importance is the need for a clear understanding of the symptomatology and the endocrine changes of the climacteric syndrome. It is a truism to state that the best way to prevent complications of treatment is to withhold such treatment particularly in patients where this therapy is inappropriate. It follows that the correct selection of patients and a general agreement about symptoms which are due to oestrogen deficiency, rather than the results of the many life stresses of the middle years, is vital. Any carelessness in the criteria for treatment will lead to the misuse of oestrogen replacement therapy which will then be in danger of becoming the therapeutic crutch of stressed womankind, such as has happened with tranquillizers in the last two decades.

The Climacteric Syndrome

Estrogen use and endometrial cancer.

Discussion about a possible association between estrogens and endometrial and breast cancer is almost as old as estrogen therapy itself Certainly there have been arguments which seem to point to a causal relationship, the result of pharmacological studies and some clinical observations But there have been many, if not more, data indicating that no such relationship exists

Estrogens and Endometrial Cancer

Successful treatment depends on the right medicament being prescribed for a specific disorder. When treating climacteric and post-climacteric complaints, the prescribing physician will be guided by the symptoms presented and by the character of the patient-the type of woman she is-when he is selecting the drug, the dose, the mode of administration, and the frequency of administration. Thereafter, the medication should be continued as long as is necessary, but no longer than is sensible.

R. B. Greenblatt

Papers

Oestrogen Replacement Therapy.

The Climacteric Syndrome

Estrogen use and endometrial cancer.

Estrogens and Endometrial Cancer

Management of the patient including the high-risk patient