Specific matrix metalloproteinase expression in focal myositis: an immunopathological study

OBJECTIVES: The aim of our study was to investigate immunoexpression of matrix metalloproteinases MMP2, MMP7 and MMP9 in muscle specimens from patients with focal myositis (FM) vs polymyositis (PM) and dermatomyositis. MATERIALS AND METHODS: We studied muscle biopsy samples from seven patients affected by FM; samples from five patients each with PM and dermatomyositis were studied as disease controls. RESULTS: MMP2 immunoreactivity was present in PM and dermatomyositis, MMP7 only in PM, and MMP9 in PM, dermatomyositis and FM. CONCLUSIONS: Our results confirm that increased MMP9 immunoreactivity in muscle fibres is a common feature of all inflammatory myopathies and suggest that MMP2 and MMP7 cannot be implicated in the inflammatory events of FM.     

Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene

Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, give rise to Emery-Dreifuss muscular dystrophy and to limb-girdle muscular dystrophy 1B (EDMD and LGMD1B). With one exception, all the reported EDMD and LGMD1B mutations are confined to the first 10 exons of the gene. We report four separate cases, with mutations in the same codon of LMNA exon 11, characterized by remarkable variability of clinical findings, in addition to features not previously reported. One patient had congenital weakness and died in early childhood. In two other patients, severe cardiac problems arose early and, in one of these, cardiac signs preceded by many years the onset of skeletal muscle weakness. The fourth case had a mild and late-onset LGMD1B phenotype. Our cases further expand the clinical spectrum associated with mutations in the LMNA gene and provide new evidence of the role played by the C-terminal domain of lamin A.     

Correlates of Human Herpesvirus-8 DNA detection among adults in Italy without Kaposi sarcoma

BACKGROUND: The presence of Human Herpesvirus-8 (HHV8) DNA is predictive of Kaposi sarcoma (KS) among patients with HIV-associated or iatrogenic immunosuppression. However, correlates of HHV8-DNA detection in the general population remain undefined. METHODS: We assessed correlates of HHV8-DNA detection among Italian adults without KS who had antibodies against HHV8-latent nuclear antigen by immunofluorescence assay. HHV8-K6 DNA sequences were detected in peripheral blood mononuclear cells using TaqMan PCR. RESULTS: Of the 158 subjects 26 (16.5%) had detectable HHV8-DNA [median copies/million cells, 53; (13-2128)]. Adjusted for age, sex, and laboratory, HHV8-DNA was detected more frequently in participants with >7 total residents in the childhood home [OR = 3.7 (1.5-9.1)], >2 younger siblings [OR = 2.6 (1.1-6.5)], and current cardiovascular [OR = 3.6 (1.3-9.7)] or renal [OR = 3.1 (1.2-8.0)] disease. Excluding the participants using immune modulating drugs, HHV8-DNA was more frequent among those with low red blood cells (RBC) [<4.5 10(6)/microl; OR = 5.3 (1.7-16.2)], slightly elevated mean corpuscular volume [>92 microm3/red cell; OR = 2.8 (1.0-7.8)], and mild thrombocytopenia [<151 K/microl; OR = 5.6 (1.9-16.3)]. CONCLUSIONS: Presence of HHV8-DNA in elderly Italians is associated with childhood crowding, low RBCs, and platelets, perhaps indicating roles for early infection and chronic inflammation. These risk factors are the first to be reported for non-immunosuppressed HHV8-seropositive adults.     

Neuroendoscopic management of hydrocephalus secondary to midline and pineal lesions

AIM: In patients with space-occupying lesions of the pineal region, increased intracranial pressure is due to direct compression of the sylvian aqueduct. Based on results of the recent literature, neuroendoscopic management of obstructive hydrocephalus, secondary to tumors of the pineal gland, has gained a preeminent role respect to shunting procedures. METHODS: In 14 select cases, hydrocephalus was secondary to midline and pineal lesions. The patient's age ranged from 1 to 56 years (mean 47.3+/-12.5), with a follow-up ranged from 3 months to 5 years after discharge. In 9 cases the endoscopic procedure represented the only surgical treatment. In 5 cases, microsurgical removal of the lesions and/or ventriculo-peritoneal shunts placement were performed, as additional treatment, while adjuvant radiotherapy was utilized in 4 cases; high dose chemotherapy followed by bone marrow transplantation was performed in 3 cases. RESULTS: In our series, obstructive hydrocephalus secondary to midline and pineal lesions, was successful treated by neuroendoscopic approach alone in 9 cases, with an unremarkable course and good outcome, except in 1 case. CONCLUSIONS: Neuroendoscopic approach affords a minimally invasive way to obtain 4 objectives by one-step surgical approach, such as resolution of obstructive hydrocephalus by endoscopic third ventriculostomy (ETV), cerebrospinal fluid sample to detect tumor markers and to perform cytological analysis, biopsy specimens and tissue diagnosis, associated to absence of shunt-related complications. Therefore, in experienced hands, ETV should be the treatment of first choice, in cases of hydrocephalus secondary to lesions of the pineal gland.     

Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings

The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ER alpha and ER beta) (although they preferentially bind to and activate ER beta) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.