Chronic wrist pain: indications for wrist arthroscopy

Although arthroscopy represents a new and dynamic diagnostic technique for evaluating the wrist, specific indications for arthroscopic intervention in the wrist are not defined. To place this technique in perspective, we review our experience with 54 consecutive arthroscopies of the radiocarpal and midcarpal joints in 53 patients with chronic wrist pain. On the basis of this review, we believe arthroscopy is indicated for the diagnosis of wrist pain of longer than 3 months' duration. Defects of the triangular fibrocartilage and lesions of the articular cartilage, including loose bodies, are detectable and easily treated with wrist arthroscopy.     

Extracellular matrix components in Kimmelstiel Wilson nodules

Summary: The distribution of collagen types I, III, IV, V, VI, fibronectin laminin, tenascin, heparan sulfate proteoglycan and chondroitin sulphate proteoglycan was examined by light microscopy immunocytochemistry (ICC) in paraffin-embedded renal biopsies with nodular diabetic glomeruloscierosis. Immunoglobulin A, G and M, complement (C3c and C1q), fibrinogen and k and γ light chain deposition was also sought by ICC in the same tissue.
Kimmelstiel Wilson (KW) nodules were graded as either evolving (>3 nuclei present +/ - fibrillary appearance) or as late stage (amorphous and acellular). the extracellular matrix (ECM) components present in the evolving KW nodules were the same as those present in normal mesangial matrix but with an increased density. Late stage nodules displayed negative binding for all antibodies in their core with accentuated expression of the normal mesangial matrix components together with complement and 1gM at their periphery. Occasionally, when ruptures in Bowman's capsule (BC) were detected and adhesions between the capsule and the nodular tuft occurred, the interstitial collagens I and III were detected within laminations of Bowman's capsule, in Bowman's space, at adhesion sites and within some nodules.
The results suggest nodular lesions are initially formed by aggregation and/or increase in the normal components of mesangial matrix. the normal mesangial matrix constituent proteins are subsequently relocated to the periphery by amorphous material in which these ECM components are not detected. When BC is disrupted, interstitial collagens I and III may appear in Bowman's space and within nodules.     

Replantation of completely amputated distal forearm--1965

Although replantation of completely amputated wrists and forearms is now commonplace, in 1965 the replantation of this "wrist level" amputation was the first reported in the western world. The details of the technique used are contrasted with current standard of care.     

New insights into ROS dynamics: a multi-layered microfluidic chip for ecotoxicological studies on aquatic microorganisms

Reactive oxygen species (ROS) play an important role in the life of every cell, including cellular defense and signaling mechanisms. Continuous and quantitative ROS sensing can provide valuable information about the cell state, but it remains a challenge to measure. Here, we introduce a multi-layered microfluidic chip with an integrated optical sensor for the continuous sensitive detection of extracellular hydrogen peroxide (H₂O₂), one of the most stable ROS. This platform includes hydraulically controlled microvalves and microsieves, which enable the precise control of toxicants and complex exposure sequences. In particular, we use this platform to study the dynamics of toxicity-induced ROS generation in the green microalga Chlamydomonas reinhardtii during short-term exposures, recovery periods, and subsequent re-exposures. Two cadmium-based toxicants with distinct internalization mechanisms are used as stress inducers: CdSe/ZnS quantum dots (Qdots) and ionic cadmium (Cd²⁺). Our results show the quantitative dynamics of ROS generation by the model microalga, the recovery of cell homeostasis after stress events and the cumulative nature of two consecutive exposures. The dissolution of quantum dots and its possible influence on toxicity and H₂O₂ depletion is discussed. The obtained insights are relevant from ecotoxicological and physiological perspectives.     

Effect of saturable binding on the pharmacokinetics of drugs: a simulation

The time-courses of both total and unbound drug concentrations with time were simulated under conditions of saturable binding to either plasma proteins or tissues, or both, following a single intravenous dose. The curves were either linear, convex, or concave, depending upon the extent of distribution and the intrinsic ability of an eliminating organ to remove drug from the body. Saturable binding should therefore be considered whenever data showing nonlinear semilogarithmic decline are to be interpreted.     

Dietary fats and cancer

The mono-unsaturated non-essential fatty acid oleic acid (OA) has been shown to stimulate malignant cell proliferation in culture significantly. In contrast, the essential fatty acids (EFAs) linoleic acid (LA) and alpha-linolenic acid (ALA) and their longer chain metabolic derivatives have been shown to have potent proliferation suppressive effects on malignant cells in culture. OA is normally synthesized in the body and present in most vegetable oils and therefore also in most experimental polyunsaturated fatty acid diets used for assessing the effects of dietary fatty acids on tumorigenesis in rats. Dietary OA could therefore specifically account for the general observation that diets containing polyunsaturated fatty acids (PUFAs) are tumorigenic (1). It has been repeatedly demonstrated that many EFAs and EFA metabolites suppress proliferation of a wide range of malignant cells in culture. These cytotoxic effects of EFAs do not inhibit the proliferation of nonmalignant cultured cells. The EFAs which have proliferation-suppression activities are components of cell membranes and many are also eicosanoid precursors. It is proposed that the membranes of malignant cells are inherently unstable. Thus the EFAs may have effects which either fluidise or stabilise these membranes. This results in either cytolysis or inhibition of proliferation. The relative quantities of the different EFAs may be critical for these effects. Eicosanoid metabolites may further compound these actions. It is suggested that one pathway for these actions could be a metabolic imbalance of EFA metabolites and their eicosanoid products. This would arise due to a combination of inhibited desaturase enzymes and a concomitant free cellular supply of dietary arachidonic acid (AA). This imbalance also could be causally involved in the promotion of malignancy. A simple procedure, which only involves dietary supplementation with gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA), is proposed as prophylaxis against the possible tumorigenic effect of dietary fats. "By some estimates, as much as 90% of all cancer in humans has been attributed to various environmental factors, including diet. The evidence reviewed by the committee suggests that cancers of most of the major sites are influenced by dietary patterns. The committee concluded that of all the dietary components it studied, the combined epidemiological and experimental evidence is most suggestive for a causal relationship between fat intake and the occurrence of cancer" - (1).     

Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis leading to renal failure is the most severe complication in untreated patients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different ethnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a high frequency of carriers among Jews from the various ethnic groups. In North African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations among healthy individuals (M694V 29%, V726A 16%, M6801 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84.4%, V726A 9.0%, M6801 0% and E148Q 6.6%). Six healthy asymptomatic individuals were found to carry mutations in both alleles: two homozygotes for E148Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mutation E148Q is associated with a milder phenotype, which explains the lower prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises the question of the need for molecular screening for M694V homozygotes in the Israeli North African Jewish community.     

Characterization of genes encoding translation initiation factor eIF- 2gamma in mouse and human: sex chromosome localization, escape from X- inactivation and evolution

The Delta Sxrb interval of the mouse Y chromosome is critical for spermatogenesis and expression of the male-specific minor transplantation antigen H-Y. Several genes have been mapped to this interval and each has a homologue on the X chromosome. Four, Zfy1 , Zfy2 , Ube1y and Dffry , are expressed specifically in the testis and their X homologues are not transcribed from the inactive X chromosome. A further two, Smcy and Uty , are ubiquitously expressed and their X homologues escape X-inactivation. Here we report the identification of another gene from this region of the mouse Y chromosome. It encodes the highly conserved eukaryotic translation initiation factor eIF-2gamma. In the mouse this gene is ubiquitously expressed, has an X chromosome homologue which maps close to Dmd and escapes X-inactivation. The coding regions of the X and Y genes show 86% nucleotide identity and encode putative products with 98% amino acid identity. In humans, the eIF-2gamma structural gene is located on the X chromosome at Xp21 and this also escapes X-inactivation. However, there is no evidence of a Y copy of this gene in humans. We have identified autosomal retroposons of eIF-2gamma in both humans and mice and an additional retroposon on the X chromosome in some mouse strains. Ark blot analysis of eutherian and metatherian genomic DNA indicates that X-Y homologues are present in all species tested except simian primates and kangaroo and that retroposons are common to a wide range of mammals. These results shed light on the evolution of X-Y homologous genes.