Apoptosis in the pathogenesis of renal disease with a focus on tubulointerstitial injury

Renal cell apoptosis is important not only in normal physiological conditions of the kidney but also in pathological processes. In normal renal development, it removes unwanted, damaged or harmful cells, and in the healthy adult kidney, it maintains cellular homeostasis by regulating the balance between cell proliferation and cell loss. The apoptotic process has now been described in the pathogenesis and prognosis of certain renal diseases with both beneficial and detrimental roles. It causes deletion of cells intrinsic to the kidney after, for example, toxic, ischaemic, immune or radiation damage, and this loss can be destructive and can cause significant reduction of renal function. In contrast, it can control and limit inflammatory processes in both the acute and chronic phases of renal disease. Information on the positive and negative outcomes of renal cell apoptosis, plus the thousands of publications on more general aspects of apoptosis mechanisms, have now presented real opportunities for the development of therapies that selectively delete or protect certain renal cell populations. This review will discuss some of the more general aspects of renal cell apoptosis and then concentrate on the detrimental or beneficial roles of apoptosis in the initiation, progression or resolution of selected, mainly tubulointerstitial, renal diseases.

Self-awareness of Prospective Memory Failure in Adults with Traumatic Brain Injury

The frequency of prospective memory failure in individuals with severe traumatic brain injury (TBI) was investigated by comparison with a non-brain-injured control group. Self-awareness of prospective memory function was also assessed by comparing self-ratings with ratings by significant others. Study participants included 33 individuals with severe TBI and 29 non-brain-injured persons. Each participant nominated a close friend or relative who completed the informant's version of the questionnaire. Participants and their significant others both rated the participants' frequency of prospective memory lapses using the Comprehensive Assessment of Prospective Memory (CAPM). An independent groups design was adopted to compare the TBI and control groups. No significant difference was found between the TBI and control participants' self-ratings of frequency of prospective memory failure, but ratings by significant others were significantly different. The TBI group demonstrated less self-awareness (i.e. underestimated the frequency of prospective memory failure compared to significant others) than the control group.

Interlabial contact pressures exhibited in dysarthria following traumatic brain injury during speech and nonspeech tasks

A miniature pressure transducer was used to assess the interlabial contact pressures produced by a group of 19 adults (mean age 30.6 years) with dysarthria following severe traumatic brain injury (TBI) during a set of speech and nonspeech tasks. Ten parameters relating to lip strength, endurance, rate of movement and lip pressure accuracy and stability were measured from the nonspeech tasks. The results attained by the TBI group were compared against a group of 19 age- and sex-matched control subjects. Significant differences between the groups were found for maximum interlabial contact pressure, maximum rate of repetition of maximum pressure, and lip pressure accuracy at 50 and 10% levels of maximum pressure. In regards to speech, the interlabial contact pressures generated by the TBI group and control group did not differ significantly. When expressed as percentages of maximum pressure, however, the TBI group's interlabial pressures appeared to have been generated with greater physiological effort. Copyright (C) 2002 S. Karger AG, Basel.

Evidence from mitochondrial DNA that head lice and body lice of humans (Phthiraptera : Pediculidae) are conspecific

The specific status of the head and body lice of humans has been debated for more than 200 yr. To clarify the specific status of head and body lice, we sequenced 524 base pairs (bp) of the cytochrome oxidase I (COI) gene of 28 head and 28 body lice from nine countries. Ten haplotypes that differed by 1-5 bp at II nucleotide positions were identified. A phylogeny of these sequences indicates that these head and body lice are not from reciprocally monophyletic lineages. Indeed, head and body lice share three of the 10 haplotypes we found. F-ST values and exact tests of haplotype frequencies showed significant differences between head and body lice. However, the same tests also showed significant differences among lice from different countries. Indeed, more of the variation in haplotype frequencies was explained by differences among lice from different countries than by differences between head and body lice. Our results indicate the following: (1) bead and body lice do not represent reciprocally monophyletic lineages and are conspecific; (2) gene flow among populations of lice from different countries is limited; and (3) frequencies of COI haplotypes can be used to study maternal gene flow among populations of head and body lice and thus transmission of lice among their human hosts.

Iatrogenic bile duct injury: The scourge of laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy (LC) has become the first-line surgical treatment of calculous gall-bladder disease and the benefits over open cholecystectomy are well known. In the early years of LC, the higher rate of bile duct injuries compared with open cholecystectomy was believed to be due to the 'learning curve' and would dissipate with increased experience. The purpose of the present paper was to review a tertiary referral unit's experience of bile duct injuries induced by LC. Methods: A retrospective analysis was performed on all patients referred for management of an iatrogenic bile duct injury from 1981 to 2000. For injuries sustained at LC, details of time between LC and recognition of the injury, time from injury to definitive repair, type of injury, use of intraoperative cholangiography (IOC), definitive repair and postoperative outcome were recorded. The type of injury sustained at open cholecystectomy was similarly classified to allow the severity of injury to be compared. Results: There were 131 patients referred for management of an iatrogenic bile duct injury that occurred at open cholecystectomy (n = 62), liver resection (n = 5) and at LC (n = 64). Only 39% of bile duct injuries were recognized at the time of LC. Following conversion to open operation, half the subsequent procedures were considered inappropriate. When the injury was not recognized during LC, 70% of patients developed bile leak/peritonitis, almost half of whom were referred, whereas the rest underwent a variety of operative procedures by the referring surgeon. The remainder developed jaundice or abnormal liver function tests and cholangitis. An IOC was performed in 43% of cases, but failed to identify an injury in two-thirds of patients. The bile duct injuries that occurred at LC were of greater severity than with open cholecystectomy. Following definitive repair, there was one death (1.6%). Ninety-two per cent of patients had an uncomplicated recovery and there was one late stricture requiring surgical revision. Conclusions: The early prediction that the rate of injury during LC would decline substantially with increased experience has not been fulfilled. Bile duct injury that occurs at LC is of greater severity than with open cholecystectomy. Bile duct injury is recognized during LC in less than half the cases. Evidence is accruing that the use of cholangiography reduces the risk and severity of injury and, when correctly interpreted, increases the chance of recognition of bile duct injury during the procedure. Prevention is the key but, should an injury occur, referral to a specialist in biliary reconstructive surgery is indicated.

Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery injury and repair

Macrophages participate in the restenosis process through the release of cytokines, metalloproteinases and growth factors. Studies of peritoneal granulation tissue suggest that macrophages may be precursors of myofibroblasts. This study examined the contribution of monocyte/macrophage lineage cells to neointimal cellular mass in a porcine model of thermal vascular injury. Thermal coronary artery injury caused medial smooth muscle cell necrosis and transformation of the media into an extracellular matrix barrier. The neointimal hyperplasia that developed over the injury sites was evaluated by light microscopy, electron microscopy and immunohistochemistry. At day 3, blood monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At day 14, 42 +/- 3.9% of neointimal cells had a monocytic nuclear morphology and expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha-smooth muscle actin and had ultrastructural characteristics intermediate between macrophages and myofibroblasts. At day 28, 10.5 +/- 3.5%, of cells expressed SWC3 and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This study indicates that hematopoietic cells of monocyte/macrophage lineage abundantly populate the neointima in the process of lesion formation and may be precursors of neointimal myofibroblasts after thermal vascular injury. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Cold Storage Preservation and Warm Ischaemic Injury to Isolated Arterial Segments: Endothelial Cell Injury

Injury to endothelial calls is thought to be important to the development of the vascular lesion of chronic rejection. It was the aim of this study to develop a semiquantitative method to assess endothelial injury in arterial grafts and to document the injury produced by cold storage preservation and additional warm ischaemia. Twelve- and 24-h cold preservation of rat aortic segments, together with an additional 1 h of warm ischaemia, were assessed. Electron micrographs of representative endothelial cells were scored for cytoplasmic, nuclear and mitochondrial injury. The overall injury score was obtained by addition of the individual scores. Storage for up to 24 h in University of Wisconsin (UW) and Terasaki did not produce any injury. Twenty-four hours of storage in Euro-Collins resulted in endothelial cell death. Injury occurred after 12 h of storage in Ross, Collins and normal saline, and the injury increased following 24 h of storage. One hour of warm ischaemia did not increase the injury. Injury to endothelial cells varies with the preservation solution used and the time of cold storage, so that both the type of solution and the storage time should be taken into account in clinical studies looking at the influence of cold ischaemia time and graft outcome.

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Appropriate indicators for injury control?

Indicators are valuable tools used to measure progress towards a desired health outcome. Increased awareness of the public health burden due to injury has lead to a concomitant interest in monitoring the impact of national initiatives that aim to reduce the size of the burden. Several injury indicators have now been proposed. This study examines the ability of each of the suggested indicators to reflect the nature and extent of the burden of non-fatal injury. A criterion validity, population-based, prospective cohort study was conducted in Brisbane, a sub-tropical Metropolitan City on the eastern seaboard of Australia, over a 12-month period between 1 January and 31 December 1998. Neither the presence of a long bone fracture nor the need for hospitalisation for 4 or more days were sensitive or specific indicators for 'serious' or major injury as defined by the 'Gold Standard' Injury Severity Score (ISS). Subsequent analysis, using other public health outcome measures demonstrated that the major component of the illness burden of injury was in fact due to 'minor' not serious injury. However, the suggested indicators demonstrated low sensitivity and specificity for these outcomes as well. The results of the study support the need to include at least all hospitalisations in any population-based measure of injury and not attempt to simplify the indicator to a more convenient measure aimed at identifying just those cases of,serious' injury.