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PubMedDate not supplied

Repeated intraportal injections of subtherapeutic islet cell isografts restore normoglycemia in streptozotocin-diabetic rats.

Poor engraftment and consequent loss of beta-cell mass could be one of the factors that are responsible for function loss after intraportal islet transplantation (Tx). Streptozotocin-diabetic rats were transplanted with syngeneic islets, which were injected into the portal vein via an indwelling catheter connected to a subcutaneous port. In Group I (n = 6), 1,000 islets were injected in a single dose into the liver. In Group II (n = 6), five doses of 200 islets were repeatedly injected over a period of 14 days, for a total of 1,000 islets. In Group III (n = 4), five decreasing doses of islets were injected over a period of 14 days, for a total of 750 islets. Nonfasting blood glucose (n-FBG) and body weight (b.wt.) were determined twice a week and an intravenous glucose tolerance test (IVGTT) was performed at 30 and 90 days. In Group I, n-FBG decreased in 2 wk from the time of first islet injection, averaging 110 +/- 21.9 mg/dl at 1 mo (p < 0.05 vs. normal controls); this value was maintained throughout the 3-mo duration of the study. In Group II, n-FBG was normalized in 2 wk averaging 90.2 +/- 25 mg/dL on day 12 (p = NS vs. normal controls) and 75.8 +/- 14.6 mg/dL at 1 month (p = NS vs. normal controls); this value was maintained throughout the 3-mo duration of the study. In Group III, n-FBG decreased to normal values in 2 wk, averaging 77 +/- 15.7 mg/dL at 1 mo (p = NS vs. normal controls), but normoglycemia was maintained for 40 days and then followed by a progressive increase. Only in Group II, KG (percent/min decline in glucose level) was not significantly different from that of normal controls (1.702 +/- 0.531 at 1 mo and 1.676 +/- 0.891 at 3 mo), while it was significantly lower than normal controls in both Group I and III animals. Body weight increase after Tx correlated with the number of transplanted islets and at 90 days, Group III rats showed less increase than Groups I and II (p < 0.05), while no significant differences in b.wt. were recorded between Group I and II. The findings indicate that intraportal islet Tx, injected repeatedly and in small doses, produced better metabolic effects than injection of the same total number of islets in a single dose.

Animals↗

PubMed2005

Bowel and bladder continence, wound healing, and functional outcomes in patients who underwent sacrectomy.

OBJECT: Total or partial sacrectomy is a rare procedure in patients with locally invasive tumors involving the sacrum; it may be associated with functional loss, such as bowel and bladder dysfunction and gait abnormality. In this study the authors examined functional outcome following sacrectomy. METHODS: The authors reviewed the charts of 50 consecutive patients who had undergone sacrectomy between July 1993 and August 2002. There were 23 male and 27 female patients whose mean age was 46 years (range 13-86 years). Twelve patients with rectal cancer underwent a separate analysis. The patients without rectal cancer were divided into two groups: those who had undergone colostomy for bowel diversion (Group 1, six cases), and those who had not (Group 2, 32 cases). In Group 1 patients the median hospital length of stay (LOS) was 48.5 days (the 25th% and 75th percentiles are 26 and 58, respectively), and in Group 2 patients the median LOS was 18.5 days (the 25th and 75th percentiles are 8 and 41, respectively; p = 0.14). In Group 2 (non-rectal cancer without colostomy), LOS was greater in patients in whom a myocutaneous flap was used compared with those in whom no flap was used (36 days compared with 8.5 days, respectively; p = 0.0012); in patients with bowel incontinence the median LOS was significantly longer than that in patients with bowel continence (39 days compared with 8 days, respectively; p = 0.0026). The incidence of bowel incontinence in Group 2 was closely related to the integrity of the S-3 nerve root (p = 0.05). CONCLUSIONS: Awareness of the association between S-3 nerve root resection and bowel and bladder incontinence may help surgeons' decision-making process.

Adolescent↗

PubMed2002

Osteoporosis: trends and intervention.

Osteoporosis is a skeletal disorder in which bone strength is compromised due to loss of bone density and bone quality. It is the leading cause of serious morbidity and functional loss in the elderly. At times, it is difficult for the clinician to distinguish between the disease and normal skeletal aging, but advances in the scientific understanding of the underlying disease process have made management of osteoporosis a preventable disease for the most part. Defining the point at which these age-related skeletal changes require intervention presents a major challenge to researchers and clinicians alike. There are several reasons for these difficulties. There is a long period of bone loss before the onset of clinically apparent disease. Also current diagnostic procedures have been shown to distinguish those at risk of fracture and those not at risk, there is a large overlap in bone density between persons who experience fractures and those who do not. Research efforts directed at these issues have increased dramatically, as have developing technologies in the measurement and screening of bone mineral density. Ongoing advances in the therapeutic modalities have promoted new methods to treat this disorder. The foregoing review will describe the mechanisms responsible for osteoporosis and the modalities used to screen and diagnose this common disorder. Various therapeutic approaches now in use, and some promising experimental trials, will be discussed.

Bone Density↗

PubMed1976

[Aggravation of hearing loss (author's transl)].

Functional hearing loss is defined as a syndrome in which audiologic responses are found lacking. Such phenomena are related to capacities of the auditory system which are not fully understood (and include constant functional threshold levels as well as decreasing functional overlay with steeper discrimination scores). Examples are given for symptoms which characterize functional hearing losses, and variable timing for degrees of functional hearing loss described. In addition, etiologic factors are tabulated from a literature survey.

Audiometry↗

PubMed2001

Rehabilitation following bone marrow transplantation.

Bone marrow transplantation and stem cell transplantation are increasingly used to treat hematologic malignancies and some solid tumors. The treatment entails bone marrow-ablative therapies and intensive medical support to sustain the patient through pancytopenia and other complications of the disease, transplantation process, or drug side effects. Patients who develop graft-versus-host disease are the most difficult subset of transplant recipients to manage. Most transplant recipients perform at normal or near-normal functional levels at the inception of the transplantation process but are at high risk for developing functional deficits as a result of cumulative impairments. These impairments arise from their disease, their prior cancer treatment, transplant induction, graft-versus-host disease, immobility, infection, steroid-related side effects, and other sequelae of transplantation. Preventive and preemptive rehabilitation interventions can minimize functional loss and facilitate recovery, but the transplantation team must be sensitive to and regularly assess for early functional declines in these patients. The physiatrist and the other members of the rehabilitation team must be thoroughly acquainted with the unique needs and challenges of the bone marrow transplantation population in order to design and modify treatment programs effectively and safely. Outcome research has shown that some patients have continued limitations in function despite successful transplantation. Few evidence-based data are available that addresses factors correlating with poor functional outcomes other than graft-versus-host disease. However, this disease has not been investigated utilizing objective functional instruments. Future research should more clearly elucidate the functional impact of allogeneic and autologous transplants by using standardized physical performance measures as well as thorough function-based symptomatology questionnaires.

Bone Marrow Transplantation↗

PubMed2003

Prions prevent brain damage after experimental brain injury: a preliminary report.

The physiological function of the normal cellular form of prion protein (PrPC) is not yet fully understood. In the current study we used prion protein gene knock-out mice (Prnp-/-) to assess the role of PrPC in traumatic brain injury. Prnp+/- and Prnp-/- mice were subjected to weight-drop contusional brain injury over the left parietal cortex. Prnp-/- mice manifested a significantly larger lesion volume and worse neuromotor scores than did their Prnp+/- littermates. IgG immunostaining revealed that in Prnp-/- mice the breakdown in the blood-brain barrier (BBB) was more extensive at 1 month after brain injury. Our results are in agreement with previous in vitro findings of the neuroprotective role of PrPC and further support the hypothesis that functional loss of PrPC plays a pathogenic role in prion diseases. We also suggest that PrPC modulates BBB function.

Animals↗

PubMed2006

Cerenkov losses: a limit for bandgap determination and Kramers-Kronig analysis.

Measuring low energy losses in semiconductors and insulators with high spatial resolution becomes attractive with the increasing availability of modern transmission electron microscopes (TEMs) equipped with monochromators, C(s) correctors and energy filters. In this paper, we demonstrate that Cerenkov losses pose a limit for the interpretation of low energy loss spectra (EELS) in terms of interband transistions and bandgap determination for many materials. If the velocity of a charged particle in a medium exceeds the velocity of light, photons are emitted leading to a corresponding energy loss of a few electronvolt. Since these losses are strong for energies below the onset of interband transitions, they change the apparent loss function of semiconductors and insulators, with the risk of erroneous interpretation of spectra. We measured low energy losses of Si and GaAs with a monochromated TEM demonstrating the effect of sample thickness on Cerenkov losses. Angle resolved EELS and energy filtered diffraction patterns (taken without a monochromator) show the extremely narrow angular distribution of Cerenkov losses. The latter experiment provides a method that allows to decide whether Cerenkov radiation masks the very low loss signal in EELS.

Journal Article↗

PubMed2002

Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson's disease.

Adenosine A2A receptors are abundant in the caudate-putamen and involved in the motor control in several species. In MPTP-treated monkeys, A2A receptor-blockade with an antagonist alleviates parkinsonian symptoms without provoking dyskinesia, suggesting this receptor may offer a new target for the antisymptomatic therapy of Parkinson's disease. In the present study, a significant neuroprotective effect of A2A receptor antagonists is shown in experimental models of Parkinson's disease. Oral administration of A2A receptor antagonists protected against the loss of nigral dopaminergic neuronal cells induced by 6-hydroxydopamine in rats. A2A antagonists also prevented the functional loss of dopaminergic nerve terminals in the striatum and the ensuing gliosis caused by MPTP in mice. The neuroprotective property of A2A receptor antagonists may be exerted by altering the packaging of these neurotoxins into vesicles, thus reducing their effective intracellular concentration. We therefore conclude that the adenosine A2A receptor may provide a novel target for the long-term medication of Parkinson's disease, because blockade of this receptor exerts both acutely antisymptomatic and chronically neuroprotective activities.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2003

Functional rescue of N-methyl-N-nitrosourea-induced retinopathy by nicotinamide in Sprague-Dawley rats.

PURPOSE: A single intraperitoneal injection of 60 mg/kg body weight of N-methyl-N-nitrosourea (MNU) into rats results in retinal degeneration over a 7-day period in all treated animals. The purpose of this study was to determine whether nicotinamide (NAM) can lead to a functional rescue of the MNU-induced retinopathy. METHODS: NAM, a water-soluble B-group vitamin (vitamin B( 3)), was administered immediately after MNU injection, and retinas were examined morphologically and functionally. RESULTS: Morphologically, 1000 mg/kg NAM completely suppressed and 50 mg/kg NAM partially suppressed the photoreceptor cell loss. Functionally, scotopic and photopic electroretinographic (ERG) recordings showed that both rod and cone photoreceptor cells were well protected from MNU damage by 1000 mg/kg NAM and partially protected by 50 mg/kg NAM. CONCLUSIONS: NAM can protect photoreceptor cells from MNU-induced retinopathy both structurally and functionally.

Alkylating Agents↗

PubMed1999

Predicting 'normal' grip strength for rheumatoid arthritis patients.

OBJECTIVE: An ability to predict accurately 'normal' grip strength in rheumatoid arthritis (RA) patients would facilitate a more accurate assessment of the degree of their functional loss. This, in turn, would allow the setting of more meaningful treatment goals aimed at restoring hand function towards normal. This study carefully measures three modalities of hand grip strength and their correlation with multiple simple anthropometric parameters in normal subjects. We aim to determine which of these parameters are best correlated to grip strength, and whether this correlation is strong enough to allow the accurate prediction of what normal grip strength should be in RA patients. METHODS: In 81 normal subjects (67 female), power, pinch and tripod grip strength measurements were made using an MIE digital pinch grip analyser. These strength data were correlated with specific local forearm anthropometric measurements: forearm circumference, forearm length, forearm volume, hand circumference, hand length, hand volume, hand and forearm volume, and various general anthropometric parameters (weight, height and age). These normal subjects had been chosen so as to be age and sex matched with 83 RA patients (67 female) in whom the same strength and anthropometric parameters were assessed and correlated. In patients, the grip strength results were additionally correlated with two markers of disease activity: a modified Ritchie Articular Index local to the hand and forearm (mRAI) and a visual analogue scale (VAS) assessing subjective pain severity. RESULTS: In normal subjects, clear correlations were demonstrated between hand grip strengths and all specific anthropometric variables, the strongest correlation being with forearm and hand volume (r = 0.729 and 0.638 for dominant and non-dominant hands, respectively; P < 0.01 for both). The patients were considerably weaker than normal subjects. Markers of disease activity showed a negative correlation with grip strength. In normal subjects, the dominant hand was significantly stronger than the non-dominant hand, and on average by 8%, while the opposite was true in patients, who were 20% weaker on the dominant side. CONCLUSION: Simple anthropometric measurements, and forearm and hand volume in particular, would be useful at baseline for predicting 'normal' hand grip strength in RA patients, both in the clinical setting and in research trials aimed at improving grip strength and hand function.

Aged↗

PubMed2000

Effects of core body temperature on changes in spinal somatosensory-evoked potential in acute spinal cord compression injury: an experimental study in the rat.

STUDY DESIGN: Acute spinal cord injury was induced by a clip compression model in rats to approximate spinal cord injury encountered in spinal surgery. Spinal somatosensory-evoked potential neuromonitoring was used to study the electrophysiologic change. OBJECTIVES: To compare and correlate changes in evoked potential after acute compression at different core temperatures with postoperative neurologic function and histologic change, to evaluate current intraoperative neuromonitoring warning criteria for neural damage, and to confirm the protective effect of hypothermia in acute spinal cord compression injury by electrophysiologic, histologic, and clinical observation. SUMMARY OF BACKGROUND DATA: With the increase in aggressive correction of spinal deformities, and the invasiveness of surgical instruments, the incidence of neurologic complication appears to have increased despite the availability of sensitive intraoperative neuromonitoring techniques designed to alert surgeons to impending neural damage. Many reasons have been given for the frequent failures of neuromonitoring, but the influence of temperature-a very important and frequently encountered factor-on evoked potential has not been well documented. Specifically, decrease in amplitude and elongation of latency seem not to have been sufficiently taken into account when intraoperative neuromonitoring levels were interpreted and when acceptable intraoperative warning criteria were determined. METHODS: Experimental acute spinal cord injury was induced in rats by clip compression for two different intervals and at three different core temperatures. Spinal somatosensory-evoked potential, elicited by stimulating the median nerve and recorded from the cervical interspinous C2-C3, was monitored immediately before and after compression, and at 15-minute intervals for 1 hour. RESULTS: Spinal somatosensory-evoked potential change is almost parallel to temperature-based amplitude reduction and latency elongation. Significant neurologic damage induced by acute compression of the cervical spinal cord produced a degree of effect on the amplitude of spinal somatosensory-evoked potential in normothermic conditions that differed from the effect in moderately hypothermic conditions. Using the same electromonitoring criteria,moderately hypothermic groups showed a significantly higher false-negative rate statistically (35%) than normothermic groups (10%). CONCLUSIONS: Systemic cooling may protect against the detrimental effects of aggressive spinal surgical procedures. There is still not enough published information available to establish statistically and ethically acceptable intraoperative neuromonitoring warning and intervention criteria conclusively. Therefore, an urgent need exists for further investigation. Although a reduction of more than 50% in evoked potential still seems acceptable as an indicator of impending neural function loss, maintenance of more than 50% of baseline evoked potential is no guarantee of normal postoperative neural function, especially at lower than normal temperatures.

Acute Disease↗

PubMed2003

A Bayesian A-optimal and model robust design criterion.

Suppose that the true model underlying a set of data is one of a finite set of candidate models, and that parameter estimation for this model is of primary interest. With this goal, optimal design must depend on a loss function across all possible models. A common method that accounts for model uncertainty is to average the loss over all models; this is the basis of what is known as Läuter's criterion. We generalize Läuter's criterion and show that it can be placed in a Bayesian decision theoretic framework, by extending the definition of Bayesian A-optimality. We use this generalized A-optimality to find optimal design points in an environmental safety setting. In estimating the smallest detectable trace limit in a water contamination problem, we obtain optimal designs that are quite different from those suggested by standard A-optimality.

Bayes Theorem↗

PubMed2026

Convergent latitudinal erosion of circadian systems in a rapidly diversifying order of fishes.

Biological clocks allow organisms to anticipate cyclical environmental changes, yet in high-latitude or deep-sea habitats, the diel cues that entrain these rhythms are often seasonally diminished or absent. Fishes of the order Perciformes have rapidly diversified across these arrhythmic ecosystems, raising the question of whether changes to circadian rhythms and biological clock genetic architecture are a component of their evolutionary success. Here, we used a comparative genomic approach to investigate patterns of core biological clock gene loss across 96 perciform and five outgroup species. We found widespread and lineage-specific loss in core clock genes, particularly in the convergently evolving polar and deep-sea suborders Notothenioidei and Cottoidei. This trend of clock gene loss was significantly amplified with higher-latitude species. To determine if these genomic signatures reflect a functional loss of rhythmicity, we performed metabolic phenotyping on three notothenioid species. We found a consistent lack of circadian metabolic oscillations during the late austral fall across all notothenioids, including the sub-Antarctic sister lineage to the cryonotothenioid adaptive radiation, Eleginops maclovinus. Experimental data across Perciformes, combined with suborder-wide patterns of gene loss, suggest that a release from circadian constraints occurred early in their diversification, potentially facilitating the repeated expansion of these fishes into polar and deep-sea habitats.

Animals↗

PubMed2005

Senescence of hematopoietic stem cells and bone marrow failure.

Functional failure in hematopoietic stem cells (HSCs) may bring fatal consequences because HSCs are the ultimate source of mature blood cells, which need continuous replenishment. One potential cause of HSC dysfunction is senescence, in which HSCs and progenitor cells enter a state of proliferative arrest. HSC senescence is genetically regulated and one particular regulator is the telomerase gene. Mutations in the telomerase gene complex have been found in patients with bone marrow failure syndromes. During a normal lifetime, HSC clones function over the long term and may not show any functional loss under normal circumstances. However, pathologic environments may limit HSC proliferation, accelerate HSC turnover, and shorten the functional life of HSCs, leading to HSC clonal exhaustion and senescence.

Animals↗

PubMed1992

Occurrence of reactions, their diagnosis and management in leprosy patients treated with multidrug therapy; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

This paper reports on reactions in leprosy patients who were treated with multidrug therapy (MDT) in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Only those reactions which occurred in patients who had not been treated with dapsone before MDT and which required treatment with prednisolone were included. Until the end of the second year of MDT a reversal reaction had been diagnosed in 43.6% of 266 borderline lepromatous (BL) patients and in 19.2% of 109 lepromatous leprosy (LL) patients, and an erythema nodosum leprosum (ENL) reaction in 2.7% and 11.1% of the patients, respectively. The reversal reactions were observed in 4.9% of the BL patients and in 0% of the LL patients at the time of diagnosis of leprosy, in 26.3% and 12.8% of the patients during the first year of MDT, and in 12.4% and 6.4% during the second year of MDT. ENL reactions were seen in 0.8% of BL patients at diagnosis, 1.1% in the first year and 0.8% in the second year and 2.8% at diagnosis, 5.5% in the first year, and 2.8% in the second year for LL patients. During a 3 1/2-year period, a total of 405 reactions were diagnosed among multibacillary (MB) patients on MDT; 365 of these reactions (90.1%) were reversal reactions and only 40 (9.9%) were ENL reactions. The point in time of the reversal reactions showed that the risk of reversal reaction is highest during the first year of MDT. Thereafter there is a gradual decline, although reactions were still observed during the fifth year of MDT. A reversal reaction was diagnosed in 21.0% of 438 BT patients; in 3.4% of the patients the reaction was present at the time of diagnosis of leprosy; in 10.3% it occurred during MDT, and in 7.3% during the first year after release from MDT. During a period of 3 1/2 years a total of 183 reversal reactions were diagnosed among BT patients. The point in time showed a declining trend in the risk of reversal reaction after starting MDT. The risk is highest during MDT, followed by the first 6 months after stopping MDT. However, reactions, although few, still occurred during the fourth year after stopping MDT. The analysis of the results of prednisolone treatment in 161 patients who were treated for nerve function loss in the field showed that 142 patients (88.2%) regained complete or partial recovery of the nerve function(s), while no improvement was observed in 19 patients (11.8%).(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Therapy, Combination↗

PubMed1996

[Genetic alterations in stomach cancer].

The scenario of multistep of stomach carcinogenesis differs depending on the two histological types, well differentiated adenocarcinoma and poorly differentiated adenocarcinoma, because the two types may have different genetic pathways. Genetic instability, reactivation of telomerase and abnormal transcript of CD44 including intron 9 are common events of both well and poorly differentiated type carcinomas. These occur at early stage of carcinogenesis, even in precancerous lesions such as intestinal metaplasia and adenoma. Inactivation of APC, activation of K-ras, amplification of c-erbB2, and allelic loss of DCC locus are associated with well differentiated type, while amplification of K-sam and functional loss of cadherin/catenin are characteristics of poorly differentiated type. HGF/c-met system plays a pivotal role in morphogenesis of both histological types through interaction with cell-cell adhesion molecules. Reactivation of telomerase or genetic instability may be an initial event for accumulation of multiple genetic alterations during the progression of stomach carcinogenesis.

Adenocarcinoma↗

PubMed1992

Accelerated loss of lung function and alveolitis in a longitudinal study of non-smoking individuals with occupational exposure to asbestos.

Long-term asbestos workers who insulate pipes and boilers may develop interstitial lung disease associated with loss of lung function. To quantitate annual loss of lung function, 77 individuals with chest X-rays greater than or equal to 1/0 ILO category who were life-long non-smokers or ex-smokers for greater than 5 years were evaluated. Study parameters included pulmonary function tests and bronchoalveolar lavage for a mean of 3 visits over 30 +/- 2 months. The study participants were 56 +/- 1 years old and had 31 +/- 1 years' occupational exposure to asbestos. At the first visit, multiple regression analysis revealed significant associations between rales or radiographic opacities and VC, FEV1, and total lung capacity; significant associations were also found between neutrophils/ml lavage fluid with FEV1 and diffusing capacity (all p less than 0.05). Annual declines for the asbestos-exposed were VC -92 +/- 28 ml/yr and FEV1 -66 +/- 21 ml/yr. Declines in VC and FEV1 were less in those with reduced lung function at the initial visit. There were no significant associations between any of the annual declines and cells recovered by bronchoalveolar lavage. Compared to other asbestos-exposed cohorts followed longitudinally, asbestos insulators with radiographs greater than or equal to 1/0 and exposure greater than or equal to 20 years have larger rates of FVC and FEV1 decline for both non-smokers and ex-smokers.

Asbestos↗

PubMed1978

[Compensatory processes during unilateral loss of vestibular function].

Changes in the compensation of the sequences of the unilateral loss of the labyrinthine function were studied in rabbits. Destruction of the labyrinth was accompanied by ocular nystagmus, increase of frequency of respiration and heart contractions, and EEG-activation. Investigations carried out showed these reactions to be extinguished at different time. At the late periods of labyrinthectomy a considerable asymmetry of nystagmus reaction to the angular accelerations equal in intensity, but opposite in direction was revealed. Stimulation of an intact otolith labyrinth was accompanied by the appearance of positional nystagmus. The results obtained indicated imperfection of the compensatory mechanisms during complete unilateral loss of the vestibular function.

Animals↗