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In cases of visual impairment due to an accident it is the ophthalmologist's task to assess the functional loss. For the purposes of legal equality norms have been established for functional loss. Differences in the assessment of disability and loss of integrity in various countries are discussed.
Direct evidence for substantial mobilization of copper in the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. In the first coronary flow fraction (CFF) of reperfusion (0.15 ml), after 35 min of ischemia, the level of copper (as well as of iron) was 8- to 9-fold higher than the preischemic value. The levels in subsequent CFFs decreased and reached the preischemic value, indicating that both metals appear in a burst at the resumption of coronary flow. When the first CFF was used in a reaction mixture containing ascorbate and salicylate, the latter underwent chemical hydroxylation and was converted to its dihydroxybenzoate derivatives. Likewise, this CFF promoted the ascorbate-driven DNA degradation. Subsequent 150 CFFs were serially collected and demonstrated low activities. Following 18 min of ischemia, the copper level in the first CFF of reperfusion was only 15% over the preischemic value. In contrast, the mobilization of iron into coronary flow was significant but markedly lower than after 35 min. The levels of copper and the redox activity of the first CFF correlated well with the degree of loss of cardiac function, after 18 and 35 min of ischemia, respectively. After 18 min of ischemia, cardiac function was about 50% and the damage is considered reversible, whereas after 35 min the functional loss exceeded 80% and is considered irreversible. These results are in accord with the causative role that copper and iron can play in heart injury following ischemia, by virtue of their capacity to catalyze the production of hydroxyl radicals, and could lead to the development of new modalities for intervention in tissue injury.
Through two-hybrid interactions, protein affinity and localization studies, we previously identified Yip1p, an integral yeast Golgi membrane protein able to bind the Ras-like GTPases Ypt1p and Ypt31p in their GDP-bound conformation. In a further two-hybrid screen, we identified Yif1p as an interacting factor of Yip1p. We show that Yif1p is an evolutionarily conserved, essential 35.5 kDa transmembrane protein that forms a tight complex with Yip1p on Golgi membranes. The hydrophilic N-terminal half of Yif1p faces the cytosol, and according to two-hybrid analyses can interact with the transport GTPases Ypt1p, Ypt31p and Sec4p, but in contrast to Yip1p, this interaction is dispensable for Yif1 protein function. Loss of Yif1p function in conditional-lethal mutants results in a block of endoplasmic reticulum (ER)-to-Golgi protein transport and in an accumulation of ER membranes and 40-50 nm vesicles. Genetic analyses suggest that Yif1p acts downstream of Yip1p. It is inferred that Ypt GTPase binding to the Yip1p-Yif1p complex is essential for and precedes vesicle docking and fusion.
BACKGROUND: Several controversies have developed over acute renal failure (ARF) definition and treatment: which approach to patient care is most desirable and which form of renal replacement therapy (RRT) should be applied is an everyday matter of debate. There is also disagreement on clinical practice for RRT including the best timing to start, vascular access, anti-coagulation, membranes, equipment and finally, if continuous or intermittent techniques should be preferred. In this lack of harmony, the epidemiology of ARF has recently displayed an outbreak of cases in the intensive care units and nephrologists and intensivists are now called to work together in the case of such a syndrome. SUBJECTS AND METHODS: We report on the responses of 560 contributors, mostly coming from Europe, to a questionnaire submitted during the third International Course on Critical Care Nephrology held in Vicenza, Italy in June 2004. The questionnaire was divided into several sections concerning demographic and medical information, definition of ARF, practice of RRT, current opinions about clinical advantages and problems related to different RRTs and modalities, and beliefs on alternative indications to extracorporeal treatments. RESULTS: More then 200 different definitions of ARF and about 90 RRT start criteria were reported. Oliguria and RIFLE (an acronym classifying ARF in different levels of severity: Risk of renal dysfunction; Injury to the kidney; Failure of kidney function; Loss of kidney function; End-stage kidney disease.) were the most frequent criteria used to define ARF. In 10% of centres all forms of renal replacement techniques are available, and in 70% of cases two or more different techniques are available: absolute analysis of different techniques showed that continuous renal replacement therapies are utilized by 511 specialists (91%), intermittent haemodialysis by 387 (69%) and sustained low efficiency dialysis by 136 (24%). Treatment prescription showed significant differences among specialists, 60% of intensivists being uncertain on RRT dose prescription compared to 40% of nephrologists (P = 0.002). The most frequently selected dosage was '35 ml/kg/h' for urea (25%) and creatinine targets (26%), and '2-3 l/h' for the septic dose (25%). Of the participants, 90% said that they used RRT for non-renal indications, 60% although responders admitted the lack of scientific evidence as a limiting factor to its use. CONCLUSIONS: New classifications such as RIFLE criteria might improve well-known uncertainty about ARF definition. Different RRT techniques are available in most centres, but a general lack of treatment dose standardization is noted by our survey. Non-renal indications to RRT still need to find a definitive role in routine practice.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with post-cardiotomy cardiogenic shock or life-threatening respiratory failure. Acute renal failure following ECMO support has an extremely elevated mortality rate. This study examined the outcomes of patients treated with ECMO and characterized the association between mortality and RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage renal failure) classification. METHODS: This retrospective study analysed the medical records of 46 critically ill patients-most had post-cardiotomy cardiogenic shock-treated by ECMO. Sixteen patients (34.8%) were treated with both ECMO and continuous renal replacement therapies. RESULTS: The overall mortality rate was 65.2% (30/46). A progressive and significant increase (chi(2) for trend, P < 0.001) was observed for mortality based on RIFLE classification severity. The Hosmer and Lemeshow goodness-of-fit test demonstrated that the RIFLE category has a good fit. By applying the area under the receiver operating characteristic curve (AUROC), the RIFLE classification tool had good discriminative power (AUROC 0.868 +/- 0.068, P < 0.001). Cumulative survival rates at 6 months follow-up following hospital discharge differed significantly (P < 0.05) for non-ARF vs RIFLE-I and RIFLE-F, and RIFLE-R vs RIFLE-F. CONCLUSION: This investigation confirms that the prognosis for critically ill patients supported by ECMO is grave. The RIFLE category is a simple, reproducible and easily applied evaluation tool with good prognostic capability that might generate objective information for patient families and physicians and supplements the clinical judgment of prognosis.
BACKGROUND: Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. METHODS: In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by >/=50% (R-criteria), by >/=100% (I-criteria), or by >/=200% (F-criteria). In analogy, ARF was detected when cystatin C increased by >/=50%, by >/=100%, or by >/=200%. RESULTS: Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by >/=50% 1.5 +/- 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T(3)- or T(3)/T(4) syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. CONCLUSION: Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine.
Data relating to motor loss and swallowing difficulties in a community sample of 976 patients who suffered an acute stroke have been analysed. About 17% of patients seen within one week had no paralysis; at 6 months 48% of survivors had no paralysis and 9% had severe paralysis. The Motricity Index used to study motor loss related to functional loss and walking ability; it seems to be a simple valid measure of motor loss. Severe paralysis was associated with a high fatality rate, and only 6%-10% of survivors of an initially severe paralysis made a full recovery by 6 months. If severe persisted at 3 weeks, full recovery was not observed. Loss of sitting balance was associated with a poor outcome. Of conscious patients seen within one week, 14% choked on attempting to swallow and a further 28% had abnormal swallowing: this 42% of patients had a high fatality rate.
AIMS: To describe the clinical picture and electrophysiological findings in Müller cell sheen dystrophy, a recently reported retinal dystrophy. METHOD: A basic ophthalmological evaluation as well as recording of standard electro-oculography and electroretinography were performed in one patient at the onset of visual loss and after 1 year of follow up. RESULTS: A 61 year old woman presented with visual loss in the right eye. Multiple folds at the level of the internal limiting membrane were seen at the posterior pole in both eyes. Macular oedema was present in the right eye. The visual acuity of the right eye was 6/30 and of the left 6/9. A paracentral scotoma was found in the right eye. Electro-oculographic examination of both eyes gave normal results. Electroretinography (ERG) revealed reduced b-wave and flicker amplitudes in the right eye; these potentials were normal for the left eye. The ON response in the right eye was reduced and delayed; it was normal in the left eye. A further loss of visual function was noted 1 year later in the right eye, but the ophthalmoscopic findings were unchanged. The ERG of the right eye had a negative waveform when dark adapted. Light adapted responses showed an unusual delayed b-wave, broad and delayed ON and OFF responses and a missing flicker response, suggesting a Müller cell dysfunction. Light adapted responses were slightly reduced in the left eye. CONCLUSIONS: Electrophysiological data indicate Müller cell dysfunction as a background of functional loss in Müller cell sheen dystrophy. This is in agreement with previously reported histological findings in this disorder.
OBJECTIVE: The aim of this meta-analysis was to review the existent evidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: Individual patient data on 738 subjects from the three randomized clinical trials published on this topic were analyzed using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves investigated included median, ulnar, tibial, and peroneal. RESULTS: The pooled analysis of NCV taken as a continuous measurement showed a significant treatment effect, the magnitude of this benefit being approximately equal to 1 m/s for all the nerves investigated. When looking at the proportion of patients experiencing a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves investigated, it emerged that treatment reduced by > 40% the risk of such outcomes after adjusting for patients' characteristics. The odds ratios relative to the placebo group were 1.82 (1.30-2.52) and 1.70 (1.15-2.48) for a decrease of 1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk for a loss of nerve function of 1 and 2 m/s, respectively. No statistically significant difference in treatment effect emerged after stratification according to baseline motor NCV and glycated hemoglobin levels. CONCLUSIONS: After a treatment duration ranging between 24-52 weeks, patients treated with tolrestat had a reduced risk for developing nerve function loss compared with placebo-treated patients. Future long-term trials are needed to evaluate the impact of the treatment on more clinically meaningful endpoints such as the development of foot complications.
A study was conducted to examine some of the factors that influence peoples' generation of likely consequences associated with a major hypothetical life event, involving the loss of the function of one of one's own limbs. The design included four limbs involving two inclusion relations, thumb-hand and foot-leg, and two viewpoints involving consequences for one-self or for others. The results indicated that subjects generate more numerous consequences for primary than for secondary consequences, more for short-term consequences than for medium- or long-term ones, more for an inclusive limb than for an included limb (e.g., hand vs thumb), and more pertaining to one-self than to others. Individual differences in the generation of consequences were not associated with prior experience involving functional loss of the limbs tested or with general differences in academic performance. The results permit inference about some of the mental processes that accompany consequence generation.
Seventy-eight traumatic neuropathies were seen in 94 patients with femoral nerve lesions; 54 of these were operated on because of persistent complete functional loss and/or pain. The most common mechanism of injury to the femoral nerve was iatrogenic due to inguinal herniorrhaphy, total hip replacement, intraabdominal vascular or gynecological operation, and, less commonly, appendectomy, lumbar sympathectomy, and laparoscopic procedures. Femoral nerve injuries also resulted from penetrating gunshot and stab wounds, laceration by glass, and stretch/contusive injuries associated with pelvic fractures. There were no signs of clinical or electrical recovery in 45 of 78 patients with traumatic nerve injuries. These and other partial injuries associated with pain were explored and evaluated by intraoperative nerve stimulation and recording of nerve action potentials (NAPs). Despite complete loss of nerve function preoperatively, 13 patients had recordable NAPs and underwent neurolysis; each recovered function to at least a Grade 3 level. Twenty-seven patients had sural graft repairs performed with graft lengths varying from 2.5 to 14 cm. Most patients had some nerve regeneration and regained function to Grade 3 to 4 levels by 2 years postoperatively. Four of five patients with suture repairs recovered to Grade 3 or better within 2 years postoperatively. Despite a proximal pelvic level for most of these injuries and, as a result, lengthy graft repairs, recovery of some useful function was the rule rather than the exception. Tumors involved the femoral nerve in 16 patients and included eight neurofibromas, four schwannomas, one neurogenic sarcoma, two ganglion cysts, and one leiomyosarcoma. All tumors were treated surgically and most were removed successfully.
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The vestibular findings in Meniere's disease show large variations. In the attack-free interval, with strict unilateral disease, very often there seems to be a vestibular hypoexcitability. This canal paresis is mostly manifesting itself by a reduction of the velocity of the slow phase, and not so much by the shortening of the duration of a calorically induced nystagmus. With vestibular end-organ-diseases the relative hypoexcitability is most pronounced with strong cold stimuli. The correlation between hearing loss and vestibular function loss of 16 Meniere patients was examined at different caloric stimuli from 44 degrees to 17 degrees C. The generally accepted mode for determining vestibular hypoexcitability (mean value of the 44 degrees and 30 degrees -stimulus) only showed a very slight correlation to hearing loss. The determination of vestibular hypofunction at different caloric stimuli--or, at least, the additional application of a strong cold stimulus--seems to give new and valuable vestibular diagnostic possibilities.
OBJECTIVE: To investigate the manifestation of head shaking nystagmus (HSN) and the relationship between HSN and vestibular bithermal test while cross-checking the HSN and vestibular bithermal test. METHODS: One hundred and twenty-four patients were examined by HSN and vestibular bithermal test. The latency and duration of HSN were observed and the dynamic changes of HSN were also investigated. The results of bithermal test were clarified by the values of canal paresis (CP). RESULTS: There were 3 types of HSN, including 41 monophasic HSN, 11 biphasic HSN and 7 perverted HSN. The latency of monophasic HSN was (2.75 +/- 1.41) ms and the duration of it was (32.16 +/- 20.30) ms; as for the biphasic HSN, the first phase had no latency and the duration was (12.33 +/- 4.42) ms which was shorter than that of the second phase (57.00 +/- 17.19) ms (P < 0.01) and the latency of second phase was (57.00 +/- 17.19) ms. The value of canal paresis in the patients without HSN was lower than that in the patients with HSN. CONCLUSIONS: The existence of HSN was dependent on the loss of the function horizontal canal and also on the stage of vestibular compensation. The variation of duration of HSN among individuals was great. In the acute stage of unilateral vestibular function loss, there appeared to be prominent HSN, and the direction of HSN is the same as that of spontaneous nystagmus. With the development of vestibular compensation, biphasic nystagmus would appear instead of monophasic HSN and the direction of first phase represent the direction of un-lesioned side. After compensation, HSN would not be elicited. However,when HSN existed, it suggested that the value of CP should exceed 25%. Perverted nystagmus pointed to central abnormality.
Statins are the most frequently used lipid-lowering drugs in all cardiovascular disease. It has been postulated that also patients with renal failure and end-stage renal disease (ESRD) may benefit from statin therapy. Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP). Statins reduce inflammation, cell proliferation, which leads to a reduction in cellular damage. Those effects are probably independent of cholesterol levels. Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. It is concluded on the basis of the CARE trial that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. Similar data were obtained from recently published HPS trial with simvastatin. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency. Statins vary in their pharmacological profiles, leading to distinct levels of systemic exposure and capacities to penetrate skeletal myocytes. Pharmacokinetic interactions with certain agents increase the likelihood of statin-induced myopathy and, in exceedingly rare instances, potentially fatal rhabdomyolysis with myoglobinuria and renal failure, therefore two statins have been suggested for renal failure patients. These are the ones that are not metabolised by the cytochrome P450 3A4 system--fluvastatin and pravastatin. The article summarizes the current therapeutic status of statin use in renal failure patients.
BACKGROUND: Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and magnetoencephalography are new techniques of brain functional imaging which can provide the information of excitation of neurons by measure the changes of hemodynamics and electrophysiological data of local brain tissue. The purpose of this study was to study functional brain areas evoked by pure tones in healthy and sensorineural hearing loss subjects with these techniques and to compare the differences between the two groups. METHODS: Thirty healthy and 30 sensorineural hearing loss subjects were included in this study. In fMRI, block-design paradigm was used. During the active epoch the participants listened to 1000 Hz, sound pressure level 140 dB pure tones at duration 500 ms, interstimulus interval 1000 ms, which presented continuously via a magnetic resonance-compatible audio system. None stimulus was executed in control epoch. In magnetoencephalography study, every subject received stimuli of 1000 Hz tone bursts delivered to the bilateral ear at duration 8 ms, interstimulus intervals 1000 ms. Sound pressure level in healthy subjects was 30 dB; in sensorineural hearing loss subjects was 20 dB above everyone's hearing threshold respectively. All subjects were examined with 306-channel whole-scalp neuromagnetometer. RESULTS: In fMRI, all subjects showed significant activations in bilateral Heschl's gyri, anterior pole of planum temporale, planum temporale, precentral gyri, postcentral gyri, supramarginal gyri, superior temporal gyri, inferior frontal gyri, occipital lobes and cerebellums. The healthy subjects had more intensive activation in bilateral Heschl's gyri, anterior pole of planum temporale, inferior frontal gyri, left superior temporal gyri and right planum temporale than the hearing loss subjects. But in precentral gyri, postcentral gyri and occipital lobes, the activation is more intensive in the hearing loss subjects. In magnetoencephalography study, both in the hearing loss and the healthy subjects, the most evident audio evoked fields activated by pure tone were N100m, which located precisely on the Heschl's gyrus. Compared with the hearing loss subjects, N100m of the healthy subjects was stronger and had longer latencies in right hemisphere. CONCLUSIONS: Under proper pure tone stimulus the activation of auditory cortex can be elicited both in the healthy and the sensorineural hearing loss subjects. Either at objective equivalent stimuli or at subjectively perceived equivalent stimuli, the auditory responses were more intensive in healthy subjects than hearing loss subjects. The tone stimuli were processed in a network in human brain and there was an intrinsic relation between the auditory and visual cortex. Blood oxygen level dependent fMRI and magnetoencephalography could reinforce each other.
The retinoblastoma (RB) gene was the first tumor suppressor gene isolated and its inactivation is associated with the pathogenesis of several types of human cancer. In this study, we investigated the involvement of the RB gene in bladder and renal cell carcinomas by determining the loss of heterozygosity (LOH) at the RB locus and by DNA, RNA, and protein analysis of the RB gene. Whenever possible, the latter included Western blotting and immunohistochemical staining of the RB protein. In bladder carcinoma, 2 of the 8 cell lines we studied had an inactivated RB gene; one cell line lacked RB expression without a gross RB deletion, whereas the other cell line expressed only the underphosphorylated form of the RB protein. None of 16 low-grade noninvasive bladder carcinomas showed an alteration in RB protein by direct Western blot analysis, whereas 2 of 14 high-grade, invasive tumors had no RB protein as measured by both Western blotting and immunohistochemical staining. This suggests that the loss of RB function may be more important in the progression of bladder cancer than in its initiation, although more extensive studies are required. LOH within the RB locus was observed in 5 of 27 informative cases of primary bladder, ureter, or renal pelvis carcinoma. However, none of the 5 cases with LOH at the RB locus had a functional loss of RB protein expression. In renal cell carcinoma, one of the 12 cell lines had a gross homozygous deletion of the RB gene, and 2 of 32 primary tumors were negative for RB protein expression. LOH at the RB locus also was found in only 2 of 30 informative cases, one of which lacked RB expression. These results are the first to demonstrate the involvement of RB inactivation in the development of advanced primary bladder carcinoma and suggest that RB loss could have a role in certain renal cell carcinomas. Our data, however, show no correlation between LOH at the RB locus in bladder cancer and actual inactivation of the RB gene at the protein level. This may suggest that there is a second tumor suppressor or recessive cancer gene on chromosome 13 in bladder cancer and/or that the mechanism of RB inactivation in bladder cancer frequently involves independent mutations of each RB allele.
Globoid cells leucodystrophy was diagnosed by specific enzyme assays in two siblings of one family. A male infant presented the typical symptoms of hyperirritability and progressive loss of psychomotor functions beginning at the age of 4 months. The progression of the disease lead to decerebration and death at 19 months of age. The elder sister had a normal development until her third year, when she developed exclusively symptoms of peripheral neuropathy. Up to the moment there are no symptoms of cortical function loss.