Osteochondritis dissecans of the patellofemoral joint

Osteochondritis dissecans of the patellofemoral joint is an uncommon condition that may be the cause of anterior knee pain or crepitus. We present the clinical features of 37 patients with osteochondritis dissecans lesions of the patellofemoral joint (24 on the patella, 13 on the trochlear groove), including two patients with medial trochlear groove lesions, which have not, to our knowledge, been previously reported. The osteochondral lesions involved the convex articular surfaces. The median age of patients when first examined was 15 years, and 54% of patients had open epiphyses. These lesions were more common in male patients than in female patients (four-to-one ratio). Osteochondritis dissecans of the patellofemoral joint can be overlooked unless quality radiographs are viewed with care and, at arthroscopy, both the patella and trochlear groove are assessed. Treatment depends on the symptoms, site, and nature of the lesion and the patient's age. Nonoperative management includes patellar taping and vastus medialis obliquus muscle exercises. Operative intervention is indicated for patients with mechanical symptoms and includes arthroscopy, consisting of chondroplasty and removal of loose bodies, and lateral retinacular release. In this study treatment generally improved the symptoms, but patients with articular cartilage loss had persistent patellofemoral crepitus and discomfort.     

Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases

To date qualitative studies of IgA in the cerebrospinal fluid in neurological disease, particularly multiple sclerosis, have been few and given mixed results. The aim of this study was to identify local synthesis of IgA by detection of clonal IgA bands, in a large cohort of patients with a variety of neurological disorders, using polyacrylamide gel electrophoresis, transfer of protein to nitrocellulose membranes and specific staining. Of 2,097 sequentially analysed patients with suspected neurological disease 54 (2.6%) had locally synthesised IgA; most notably, IgA was present in 39 of 291 (13%) patients with suspected multiple sclerosis. The latter group also had a significant excess of light-chain production, particularly free kappa, when compared to multiple sclerosis patients without local synthesis of IgA. Locally synthesised IgA was also demonstrated in inflammatory, infectious and autoimmune diseases of the central nervous system. This qualitative technique is simple and suitable for routine analysis of cerebrospinal fluid, and further qualitative studies of IgA may be useful in investigating the pathophysiology of certain neurological disorders.     

Structural mass spectrometry: rapid methods for separation and analysis of peptide natural products

A significant challenge in natural product discovery is the initial discrimination of discrete secondary metabolites alongside functionally similar primary metabolic cellular components within complex biological samples. A property that has yet to be fully exploited for natural product identification and characterization is the gas-phase collision cross section, or, more generally, the mobility-mass correlation. Peptide natural products possess many of the properties that distinguish natural products, as they are frequently characterized by a high degree of intramolecular bonding and possess extended and compact conformations among other structural modifications. This report describes a rapid structural mass spectrometry technique based on ion mobility-mass spectrometry for the comparison of peptide natural products to their primary metabolic congeners using mobility-mass correlation. This property is empirically determined using ion mobility-mass spectrometry, applied to the analysis of linear versus modified peptides, and used to discriminate peptide natural products in a crude microbial extract. Complementary computational approaches are utilized to understand the structural basis for the separation of primary metabolism derived linear peptides from secondary metabolite cyclic and modified cyclic species. These findings provide a platform for enhancing the identification of secondary metabolic peptides with distinct mobility-mass ratios within complex biological samples.     

Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation

Retinoblastoma, when it kills by metastasis, almost always does so within 5 years of enucleation. The median time to death was 6.4 months in unilateral cases and 14.2 months in bilateral cases. Multivariate statistical analysis of 361 cases of retinoblastoma indicated that histologic detection of invasion of the tumor into the optic nerve or orbit were the risk factors most highly predictive of death from retinoblastoma. Choroidal invasion was not significantly associated with a fatal outcome. Histologic evidence of a cataract, failure to diagnose retinoblastoma clinically, and bilaterality were also significant risk factors. The authors believe that in at least two of the cases of bilateral retinoblastoma death did not result from metastasis to the brain as was originally diagnosed, but resulted from the development of an independent primary intracranial neuroblastic tumor, a syndrome designated "trilateral retinoblastoma."     

Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

Summary Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called ‘Z’ mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols. Competing interests: None declared References to electronic databases: Alpha 1-antitrypsin deficiency: +107400. C.M. Greene and S.D.W. Miller contributed equally to the work.     

From responsible users to recalcitrant dope fiends: Mapping modes of engagement with harm reduction

This article considers individuals' diverse modes of engagement with an increasingly medicalised strain of harm reduction that emphasises individual accountability for personal health and welfare. Drawing upon 1 year of ethnographic research at a New York City-based syringe exchange (“NYC Harm Reduction”, a pseudonym), I describe how drug users themselves made sense of harm reduction, negotiated its discourses of risk and responsibility, and incorporated its behavioural directives into their own body projects – or did not. While suggesting some participants' apparent absorption of risk reduction into a dominant, and enabling identity, I focus mainly upon individuals' “on-stage” performances and apparent depth of service use and acceptance while at NYC Harm Reduction. Building upon recent critiques of contemporary harm reduction's de-contextualised neoliberal subject, I discuss the crucial roles of public housing assistance and peer worker employment in incentivising participants' uptake of pro-risk reduction attitudes, and (presumably) practices. Ultimately, participants' multiplicity of approaches to harm reduction hinged upon differences in not only personality or stage of drug use, but also current living circumstances; moreover, individuals' differential engagement with NYC Harm Reduction reflected the ways in which the organisation and its government funders prioritised the material investment of certain “risky” bodies – namely, HIV-positive drug users.     

Further characterization of the androgen receptor in rat testis.

Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules.