Homologous central limbo-keratoplasty in limbus stem cell damage. Retrospective study of 3 years' experience

BACKGROUND: Problems with epithelial healing are the main cause of corneal graft failure in patients with limbal stem cell deficiency. This post-operative complication cannot be eliminated by conventional penetrating keratoplasty alone, but only by additional limbal grafting, which is, however, highly immunogenic. We report here our 3 years' experience with a new surgical procedure which we developed called homologous central limbokeratoplasty. PATIENTS AND METHODS: We have performed 52 homologous central limbo-keratoplasties in patients with limbal stem cell deficiency since February 1993. We report here the results of the first 18 transplantations with the longest follow-up periods (mean 22 months). The unmatched donor cornea was trephined in a way such that 40% of its circumference contained limbus. These grafts were then sutured centrally into the host cornea. Systemic cyclosporin A (CSA) was administered for at least 1 year after all transplantations. RESULTS: Fourteen of the 18 grafts failed during the follow-up period. The reasons for graft failure were severe surface disorders (7), severe surface disorders in combination with endothelial immune reactions (5) and endothelial immune reactions alone (2). The four patients with centrally clear grafts no longer receive systemic CSA with follow-up periods between 20 and 30 months. CONCLUSIONS: Central limbo-keratoplasty is a very promising procedure. However, the average results are not yet satisfying, because the majority of limbal stem cells undergo rejection within 2 years. Improved results will be achievable in the future by using well-matched instead of non-matched transplants and by further improving immune modulation beyond the effectiveness of current CSA treatment.     

The risk of pancreatic cancer following pancreatitis: an association due to confounding?

BACKGROUND & AIMS: Chronic pancreatitis has been suggested as a causal risk factor for pancreatic cancer in a recent study. The aim of this study was to clarify the relationship between chronic pancreatitis and pancreatic cancer. METHODS: All patients in the Swedish inpatient Register with a discharge diagnosis of pancreatitis from 1965 to 1983 were identified. They were stratified into subcohorts as follows: (1) one episode of unspecified pancreatitis (n = 823); (2) one episode of acute pancreatitis (n = 24,753); (3) recurrent pancreatitis (n = 7328); and (4) chronic pancreatitis (n = 4546). We also identified those with associated diagnoses indicating gallbladder disease or alcoholism. The patients were followed up through record linkage to the nationwide Swedish Cancer Register, Death Register, and Migration Register. RESULTS: After exclusion of cancers occurring in the first year, there were excess risks for pancreatic cancer in all subcohorts. However, the risks declined with time in all subcohorts. A persistent excess risk after 10 years was restricted to patients with associated alcohol abuse (standardized incidence ratio, 3.8; 95% confidence interval, 1.5-7.9). CONCLUSIONS: The findings are not consistent with reports that pancreatitis is causally associated with a long-term risk of pancreatic cancer. Selection bias, alcohol consumption, and smoking may contribute to some of the patterns of risk that have been observed.     

Streptococcal protein H forms soluble complement-activating complexes with IgG, but inhibits complement activation by IgG-coated targets

Protein H, a surface protein of Streptococcus pyogenes interacting with the constant Fc region of IgG, is known to be released from the streptococcal surface by a cysteine proteinase produced by the bacteria. Poststreptococcal glomerulonephritis and rheumatic fever are conditions in which immune complexes and autoimmune mechanisms have been suggested to play pathogenetic roles. The present study demonstrates that addition of protein H to human serum produces complement activation with dose-dependent cleavage of C3. The activation was IgG-dependent and the result of complexes formed between IgG and protein H. These complexes were size heterogeneous with molecular masses of 400 kDa to 1.4 MDa. Using complement-depleted serum reconstituted with complement proteins, the activation by protein H was found to be dependent of the classical, but independent of the alternative pathway of complement. In contrast to results of experiments based on soluble protein H.IgG complexes, complement activation was inhibited by protein H when IgG was immobilized on a surface. The interaction between C1q and immunoglobulins represents the first step in the activation of the classical pathway, and protein H efficiently inhibited the binding of C1q to IgG immobilized on polyacrylamide beads. Protein H reduced C3 deposition on the IgG-coated beads and inhibited immune hemolysis of IgG-sensitized erythrocytes. Finally, significantly less C3 was deposited on the surface of protein H-expressing wild-type streptococci than on the surface of isogenic mutant bacteria devoid of protein H. The results demonstrate that protein H.IgG complexes released from the streptococcal surface can produce complement breakdown at the sites of infection, whereas complement activation on bacterial surfaces is inhibited. This should have important implications for host-parasite relationships. In addition, soluble protein H.IgG complexes might contribute to immunological complications of streptococcal infections.     

Mechanical energy contribution of the metatarsophalangeal joint to running and sprinting

Despite the fact that a number of studies have investigated lower extremity energy generation during locomotion, the influence of the metatarsophalangeal (MP) joint remained unknown. The purpose of this study was to determine the relative contribution of the MP joint to the total mechanical energy in running and sprinting. A sagittal plane analysis was performed on data collected from 10 trained male athletes (five runners and five sprinters). The MP moment was assumed to be negligible until the ground reaction force acted distal to the joint. During running, once the ground reaction force crossed the MP joint, the MP moment was plantarflexor for the remainder of ground contact with average peak values of 59.9 Nm. The MP joint moment was plantarflexor throughout the stance phase for sprinting with average peak values of 112.4 Nm. Since the MP joint was dorsiflexing throughout the majority of the stance phase the joint absorbed large amounts of energy, on average 20.9 J during running and 47.8 J during sprinting. A lack of plantarflexion of the MP joint resulted in a lack of energy generation during take-off. Thus, the energy that was absorbed at the joint was dissipated in the shoe and foot structures.     

Horizontal ultrathin-layer multi-zonal electrophoresis of DNA: an efficient tool for large-scale polymerase chain reaction (PCR) fragment analysis

A rapid and efficient procedure for large-scale analysis of polymerase chain reaction (PCR) fragments in the range of 200-3000 base pairs is presented. The procedure is based on horizontal ultrathin-layer multi-zonal (HUME) electrophoresis of PCR fragments in polyacrylamide gels followed by silver staining. HUME gels can be prepared rapidly using a simple procedure called the flap technique. The electrophoretic set-up allows the use of multi-channel pipettes for sample loading. Separation and detection of the PCR fragments from sample preparation to silver staining can be carried out in 2 h. Using four electrophoresis units, one technician can analyze 400 PCR fragment samples in 2 h.     

Candesartan cilexetil reduces chronic renal allograft injury in Fisher-->Lewis rats

OBJECTIVES: To determine the effects of the angiotensin II receptor antagonist, candesartan cilexetil, on glomerular and systemic blood pressures and the development of renal injury in Lewis rat recipients of a single Fisher kidney (F334--> LEW transplantation), an established rat model of chronic renal allograft failure. DESIGN: Recent studies have shown that chronic injury of renal allografts in F334-->LEW rats may be virtually abrogated by supplying the Lewis recipients with two Fisher kidneys or, alternatively, by retaining a native kidney. These findings imply a major contribution from processes associated with nephron loss to the pathogenesis of chronic renal allograft failure, a notion supported by the observation that transplanting two kidneys also normalizes glomerular capillary pressure (PGC) in F344-->LEW rats. Thus, a pharmacological reduction in PGC, by blocking the effects of angiotensin II, should also lessen renal injury in F344-->LEW rats. MATERIALS AND METHODS: Bilaterally nephrectomized F344--> LEW rats were treated with the angiotensin II receptor blocker candesartan cilexetil (TCV-116) at 40 mg/l or with vehicle, administered in drinking water. Proteinuria and systolic blood pressure were assessed monthly, and histological studies were carried out after 24 weeks. The glomerular filtration rate and glomerular pressures were determined after 10 weeks in additional rats by clearance and micropuncture studies. RESULTS: Treatment with candesartan cilexetil lowered systemic blood pressure, normalized PGC at 10 weeks and greatly reduced proteinuria and allograft glomerulosclerosis at 24 weeks. CONCLUSIONS: These data indicate that the development of renal injury in F344-->LEW renal allografts can be prevented by the pharmacological blockade of angiotensin II receptors using candesartan cilexetil. This suggests that angiotensin-dependent processes contribute significantly to chronic injury in this model of late renal allograft failure.     

Metacarpophalangeal joint dislocation: indications for open surgical reduction

In complex dislocations of the metacarpophalangeal joint, the volar plate is separated from the proximal phalanx and the metacarpal head is entrapped within surrounding tissue structures. These complex dislocations must be managed by open surgical reduction to reduce the dislocation and realign the volar plate. A 58-year-old male presented to the emergency department with a complex dislocation of the metacarpophalangeal joint of the left little finger, which was successfully treated by open reduction in the operating room. The indications for open reduction of metacarpophalangeal joint dislocations are reviewed.     

Hsp70 and Hsc70 are preferentially expressed in differentiated epithelial cells in normal human endometrium and ectocervix

This paper addresses parametric system identification of linear and nonlinear dynamic systems by analysis of the input and output signals. Specifically, we investigate the relationship between estimation of the system using a feedforward neural network model and estimation of the system by use of linear and nonlinear autoregressive moving-average (ARMA) models. By utilizing a neural network model incorporating a polynomial activation function, we show the equivalence of the artificial neural network to the linear and nonlinear ARMA models. We compare the parameterization of the estimated system using the neural network and ARMA approaches by utilizing data generated by means of computer simulations. Specifically, we show that the parameters of a simulated ARMA system can be obtained from the neural network analysis of the simulated data or by conventional least squares ARMA analysis. The feasibility of applying neural networks with polynomial activation functions to the analysis of experimental data is explored by application to measurements of heart rate (HR) and instantaneous lung volume (ILV) fluctuations.