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PubMedDate not supplied

In vitro function of granulocyte concentrates following passage through an electromechanical infusion pump.

Six units of granulocytes stored for 18 hours at 20 to 24 degrees C without agitation were passed through an electromechanical infusion device pump system (test) (Abbott) and through a 170-micron filter (control). To determine the effect of needle gauge, a 19 or 23 gauge needle was attached to the end of the pump administration set. After passage through the pump, granulocytes were evaluated for signs of cytolysis and functional loss, red cells for hemolysis, platelets for release of beta-thromboglobulin, and plasma for C3a and C5a complement activation. There was no evidence (mean +/- 1 SD) of hemolysis (less than 1.0 vs. less than 1.0 mg/dl), loss of granulocytes (123 +/- 38 X 10(3)/microliters vs. 118 +/- 29 X 10(3)/microliters), changes in any of several tests of neutrophil function, increased release of beta-thromboglobulin (15.8 +/- 5.8 vs. 17.0 +/- 6.6%), or C3a complement activation (483 +/- 221 vs. 500 +/- 200 ng/ml) after passage through the pump system (p greater than 0.05). No significant differences were seen between the use of a 19 or 23 gauge needle. Based on these in vitro data, we conclude that this pump system is acceptable for use in clinical practice when control over rate and volume of granulocyte administration is important.

Cell Survival↗

PubMed2005

Topical dorzolamide increases pericentral visual function in age-related maculopathy: pilot study findings with short-wavelength automated perimetry.

PURPOSE: Numerous studies have confirmed the enhancement of ocular circulation by carbonic anhydrase inhibitors (CAIs). Topical CAI treatment with dorzolamide averts the significant pericentral visual function loss accompanying retinal and choroidal vasoconstriction during acute hyperventilation-induced hypocapnia. This study was designed to discern whether dorzolamide might similarly enhance macular function in patients with age-related maculopathy (ARM). METHODS: In a masked, placebo-controlled study, 40 patients with ARM and acuity > 20/50 were randomized to receive either dorzolamide or placebo for 12 weeks, thrice daily. After pre-study perimetric training, pericentral function (mean sensitivity) was quantified using Humphrey 10-2 short-wavelength automated perimetry (SWAP), before and after 12 weeks of topical therapy. RESULTS: Dorzolamide-treated eyes demonstrated a significant increase in mean sensitivity of + 1.55 dB (p = 0.04); placebo-treated eyes showed no significant change (+ 0.58 dB; p = 0.10). Given the non-significant increase of mean sensitivity in the placebo-treated group, fewer than 100 subjects per group would be required to afford > 70% power to yield a significant direct comparative difference between treatment and placebo in a prospective, randomized study of equally short duration. CONCLUSIONS: This study demonstrated a significant increase in short-wavelength sensitivity in ARM with dorzolamide and the lack thereof with placebo. These encouraging pilot study data suggest a potential role for topical CAIs in ARM patients, and establish objective parameters for prospective studies to further evaluate the effects of dorzolamide in ARM.

Administration, Topical↗

PubMed1999

Renal chloride channel, CLCN5, mutations in Dent's disease.

Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. Patients with Dent's disease may also suffer from rickets and other features of the renal Fanconi Syndrome. Patients may have mutations in the X-linked renal chloride channel gene, CLCN5, which encodes a 746-amino-acid protein with 12-13 transmembrane domains. We have investigated the 11 coding exons of CLCN5 for mutations in eight unrelated patients with Dent's disease. Leukocyte DNA was used for the polymerase chain reaction amplification of CLCN5 and the products analyzed for single-stranded conformational polymorphisms (SSCPs). Abnormal SSCPs were sequenced and revealed eight mutations. These consisted of three nonsense mutations (Arg34Stop, Arg648Stop, Arg704Stop), four deletions involving codons 40, 86, 157, and 241, and one acceptor splice consensus sequence mutation tgcag --> tgaag. The mutations were confirmed either by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis. In addition, an analysis of 110 alleles from 74 unrelated normal individuals demonstrated that the DNA sequence changes were not common polymorphisms. All of the mutations predict truncated chloride channels that are likely to result in a functional loss. Thus, our findings expand the spectrum of CLCN5 mutations associated with Dent's disease and the results will help to elucidate further the functional domains of this novel chloride channel.

Amino Acid Sequence↗

PubMed2005

Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results.

OBJECT: A Phase I, open-label nonrandomized study was conducted to assess the safety and tolerability of incubated autologous macrophages administered to patients with acute complete spinal cord injury (SCI). METHODS: This therapy was first tested in rat models of spinal cord transection and contusion, in which it was shown to promote motor recovery. The procedure developed for clinical use consists of isolating monocytes from patient blood and incubating them ex vivo with autologous dermis. The resulting incubated autologous macrophages were injected into the patient's spinal cord immediately caudal to the lesion within 14 days of injury. Patients underwent preoperative and follow-up neurological assessment (American Spinal Injury Association [ASIA] standards), electrophysiological monitoring (motor evoked and/or somatosensory evoked potentials), magnetic resonance imaging, and safety monitoring. Before macrophage administration, complete neurological functional loss (ASIA Grade A) was confirmed in all patients. Of the eight patients in the study, three recovered clinically significant neurological motor and sensory function (ASIA Grade C status). During the study period, some adverse events were encountered, the most serious of which involved two cases of pulmonary embolism and one case of osteomyelitis that were treated and resolved without further complication. These and other adverse events appear to be similar to those encountered in other spinal cord-injured patients and are not considered a consequence of the experimental therapy. CONCLUSIONS: It is concluded that incubated autologous macrophage cell therapy is well tolerated in patients with acute SCI. Further clinical evaluation is warranted.

Acute Disease↗

PubMed2002

Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas.

High-frequent silencing of hematopoietic cell-specific protein-tyrosine phosphatase SHP1 gene by promoter methylation was detected in various kinds of leukemias and lymphomas, as well as in many hematopoietic cell lines, which is supported by our previous observation of strong decrease of SHP1 mRNA and protein. The promoter methylation of the SHP1 gene was clearly correlated with the clinical stage. Loss of heterozygosity with microsatellite markers near the SHP1 gene was shown in 79% of informative acute lymphoblastic leukemia cases. These results suggest that functional loss of SHP1 is associated with the pathogenesis of leukemias/lymphomas.

Acute Disease↗

PubMed1991

Influence of excessive weight loss on respiratory function. A study of obese patients following gastroplasty.

The influence of excessive weight loss, with decreased muscle mass, on pulmonary function was evaluated in 16 obese patients without clinical evidence of respiratory disease. Weight loss was induced with vertical banded gastroplasty. Six nonobese age-matched patients undergoing elective cholecystectomy acted as controls. Preoperative values for static and dynamic lung function variables and for pulmonary gas distribution and respiratory muscle strength were compared with postoperative values after approximately 10% and 18% weight reduction. Before gastroplasty the dominant abnormality of respiratory function was slight restrictiveness, with reduced lung volumes. Body weight and lean body mass decreased significantly during the study period, and respiratory muscle strength was significantly reduced after 10% weight loss. Lung function tests nevertheless showed significant increase of vital capacity, functional residual capacity, total lung capacity and maximal voluntary ventilation. No correlation was found between the reduction of respiratory muscle strength and that of lean body mass. The controls did not diminish the body weight after surgery and the lung volumes and respiratory muscle strength was not changed.

Adult↗

PubMed2006

The pseudoautosomal regions, SHOX and disease.

The pseudoautosomal regions represent blocks of sequence identity between the mammalian sex chromosomes. In humans, they reside at the ends of the X and Y chromosomes and encompass roughly 2.7 Mb (PAR1) and 0.33 Mb (PAR2). As a major asset of recently available sequence data, our view of their structural characteristics could be refined considerably. While PAR2 resembles the overall sequence composition of the X chromosome and exhibits only slightly elevated recombination rates, PAR1 is characterized by a significantly higher GC content and a completely different repeat structure. In addition, it exhibits one of the highest recombination frequencies throughout the entire human genome and, probably as a consequence of its structural features, displays a significantly faster rate of evolution. It therefore represents an exceptional model to explore the correlation between meiotic recombination and evolutionary forces such as gene mutation and conversion. At least twenty-nine genes lie within the human pseudoautosomal regions, and these genes exhibit 'autosomal' rather than sex-specific inheritance. All genes within PAR1 escape X inactivation and are therefore candidates for the etiology of haploinsufficiency disorders including Turner syndrome (45,X). However, the only known disease gene within the pseudoautosomal regions is the SHORT STATURE HOMEBOX (SHOX) gene, functional loss of which is causally related to various short stature conditions and disturbed bone development. Recent analyses have furthermore revealed that the phosphorylation-sensitive function of SHOX is directly involved in chondrocyte differentiation and maturation.

Animals↗

PubMed2006

Applying Taguchi methods to health care.

PURPOSE: The aim of this article is to show how Taguchi methods can be applied to health care. DESIGN/METHODOLOGY/APPROACH: The quadratic loss function is at the heart of Taguchi methods. It is a powerful motivator for a quality strategy and can be used to adequately model the loss to society in health care. It also establishes a relationship between cost and variability. Therefore, it can be integrated with the performance and parameters of the design of medical applications. Signal-to-noise ratios give a sense of how close is the performance to the ideal. By maximizing the signal-to-noise ratio, quality-engineering activities can be aimed at identifying near-optimum levels of factors and making quality equal to zero. FINDINGS: This article shows that, when the patients' requirements are consistently met, lower losses can provide an impetus to improve patient satisfaction. ORIGINALITY/VALUE: The article outlines areas in health care where Taguchi methods can easily be applied.

Decision Making, Organizational↗

PubMed2003

Effects of a home exercise programme on shoulder pain and functional status in construction workers.

BACKGROUND: Repetitive or sustained elevated shoulder postures have been identified as a significant risk factor for occupationally related shoulder musculoskeletal disorders. Construction workers exposed to routine overhead work have high rates of shoulder pain that frequently progresses to functional loss and disability. Exercise interventions have potential for slowing this progression. AIMS: To evaluate a therapeutic exercise programme intended to reduce pain and improve shoulder function. METHODS: Construction worker volunteers were screened by history and clinical examination to test for inclusion/exclusion criteria consistent with shoulder pain and impingement syndrome. Sixty seven male symptomatic workers (mean age 49) were randomised into a treatment intervention group (n = 34) and a control group (n = 33); asymptomatic subjects (n = 25) participated as an additional control group. Subjects in the intervention group were instructed in a standardised eight week home exercise programme of five shoulder stretching and strengthening exercises. Subjects in the control groups received no intervention. Subjects returned after 8-12 weeks for follow up testing. RESULTS: The intervention group showed significantly greater improvements in the Shoulder Rating Questionnaire (SRQ) score and shoulder satisfaction score than the control groups. Average post-test SRQ scores for the exercise group remained below levels for asymptomatic workers. Intervention subjects also reported significantly greater reductions in pain and disability than controls. CONCLUSIONS: Results suggest a home exercise programme can be effective in reducing symptoms and improving function in construction workers with shoulder pain.

Adult↗

PubMed1977

[Group psychotherapy. Institutional group psychotherapy with a realistic aim].

It is of great emotional impact to lose upper or lower limbs; adequate psychological handling of such a loss is described. Mourning will bary if amputation was programmed or carried out without warning. In the group, individual conflict, depression and the problem of function loss are handled, more than problems of the patient vis-a-vis the institution. Characteristics of the group are described.

Amputation, Traumatic↗

PubMed1993

Addressing the ideal requirements by free flap phalloplasty: some reflections on refinements of technique.

Ideally, in phalloplasty one should aim at 1) a one-stage procedure that can be predictably reproduced, 2) creation of a competent neo-urethra to allow for voiding while standing, 3) return of both tactile and erogenous sensibility, 4) enough bulk to tolerate the insertion of a prosthetic stiffener, and 5) a result that is aesthetically acceptable to the patient. We consider 6) minimal scarring or disfigurement, and 7) no functional loss in the donor area further requirements for any ideal procedure. Thanks to ongoing refinements, microsurgical free flap phalloplasty techniques lead to the best results, both functionally and cosmetically. These refinements are presented and discussed, as are our experiences applying them.

Female↗

PubMed2005

Biophysics of aging and therapeutic interventions by entropy-variation systems.

The cell is thermodynamically an open system and aging is characterized by an increasingly higher structural disorder (increase of entropy) and functional loss. If a variation of negative entropy is introduced by an external source, an anti-clockwise effect leading to regenerative processes and/or increase of the functional reserve supporting regenerative tissue changes is theoretically expected. The achievement of a negative variation of entropy is the main principle of a new technology which implies an exogenous delivery of energy with higher performance than the physiological production. Promising clinical experiences in liver cirrhosis and in long-standing scarring lesions seem to confirm the clinical applicability of the theoretical model.

Aging↗

PubMed2001

Relationship between physiological loss, performance decrement, and age in master athletes.

BACKGROUND: The use of master athletes to describe an idealized rate of physiological loss associated with aging is quite common. The results of such studies suggest that older athletes may be able to reduce the rate of decline in functional loss. The findings of such studies have been questioned due to their limited sample size and the age range and gender of their subjects. METHODS: We examined a group of 146 male and 82 female master athletes over the age of 40 years. Physiological parameters included maximal oxygen uptake (VO2max), body composition, muscle strength, bone density, and blood chemistries. Medical histories and training records were obtained via questionnaire. RESULTS: Results demonstrated gender differences in body composition, blood chemistries, blood pressure, VO2max, muscle strength, bone density, and performance (p <.05). All metabolic parameters for men and most for women demonstrated significant losses across the age range (p <.05). In addition, strength and performance for men and women and bone density for women declined significantly with age (p <.05). The demonstrated loss rates did not differ by gender. CONCLUSIONS: Although limited by the lack of a sedentary comparison group, these data suggest that age-related losses in VO2max may not be different from data previously reported for older sedentary adults and that loss in muscle strength and performance with aging is not linear.

Absorptiometry, Photon↗

PubMed2006

Severity staging by early features of age-related maculopathy exhibits weak relationships with functional deficits on SWS grating acuity.

PURPOSE: To examine the relationship between short-wavelength-sensitive (SWS) resolution acuity and epidemiologically defined stages of early age-related maculopathy (ARM). METHODS: Subjects consisted of 88 adults aged 51 to 87 years. Psychophysical testing was undertaken in only one eye of each subject (the study eye). All study eyes had a LogMAR acuity of 0.30 (20/40 Snellen) or better. SWS and achromatic grating resolution acuity were measured at 6 degrees eccentricity from the fovea. Stereoscopic color fundus photographs centered on the macula were taken on both eyes of each subject and were graded using the Wisconsin Age-Related Maculopathy Grading System (WARMGS). After grading, features of ARM were combined to assign a severity stage from 0 to 5 using the methods described by the Rotterdam Eye Study. Relationships between visual function, study eye ARM stage, and fellow eye status were examined with the use of standard statistical analysis. RESULTS: Although SWS resolution acuity was significantly reduced in eyes classified as having any ARM compared with eyes classified as having no ARM (P = 0.002), there was no relationship between the severity of functional deficits and the morphologic severity from stage 1 to stage 4. On reassigning subject eyes to a revised severity staging (stage 0, stages 1 to 4 combined, and stage 5), SWS acuity was significantly different among these three groups (P < 0.001). No significant relationship was found between achromatic resolution acuity and ARM staging. The status of the fellow eye (advanced macular degeneration present or absent) was not significantly related to visual function in the study eye. CONCLUSIONS: Significant functional deficits in SWS resolution acuity were found in eyes with ARM features, but the severity of functional loss did not correlate well with the currently accepted method of assigning a morphologic severity stage. Longitudinal studies may reveal further information on the relationships between functional deficits, ARM status, disease progression, and outcome.

Aged↗

PubMed2003

Clinical outcomes of photodynamic therapy for head-and-neck cancer.

Head-and-neck cancers not only carry poor prognoses, but also reduced quality of life for the patients. Disease control is often achieved at the expense of substantial functional loss and disfigurement. Photodynamic therapy (PDT) is particularly well suited to the treatment of head-and-neck-tumors because it has little effect on underlying functional structures and has an excellent cosmetic outcome. Studies in the past decades have shown that PDT is of similar efficacy as traditional measures in the treatment of early-stage head-and-neck cancers with an overall response rate of 85%-100% with up to 75% of the complete responses sustained at 2 years after PDT. For advanced head-and-neck cancers, studies were also conducted to evaluate the palliative effects of PDT. Overall, 58%-70% palliative benefit can be observed in these patients. Using interstitial PDT, median survival of the patients with recurrent unresectable head-and-neck cancers can be improved to 14 months (cf. 226 days by using surface illumination PDT). PDT is thus a therapeutic option that may prove a useful addition to the armamentarium of the integrated head and neck oncology team.

Clinical Trials as Topic↗

PubMed2001

Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2.

Recent investigations in mouse lines either deficient for the CRH receptor 1 (CRHR1) or 2 (CRHR2) suggest that the CRH neuronal system may comprise two separate pathways that can be coordinately and inversely activated in stress-induced hypothalamic-pituitary-adrenal (HPA) response and anxiety-like behavior. We generated mice deficient for both CRHR1 (Crhr1(-/-)) and CRHR2 (Crhr2(-/-)) to investigate the HPA system regulation in the absence of known functionally active CRH receptors under basal conditions and in response to different ethologically relevant stressors. To elucidate possible gene dose effects on the action of both CRH receptors, our analysis included heterozygous and homozygous CRHR1- or CRHR2-deficient mice, mutants lacking both CRH receptors, compound mutants with homozygous and heterozygous deficiency for either of the receptors, and their wild-type littermates. Both male and female Crhr1(-/-)Crhr2(-/-) mutants were viable, fertile, and indistinguishable in size from wild-type littermates. We show that the endocrine phenotype of mice lacking both CRHRs is dominated by the functional loss of CRHR1. CRHR2 does not compensate for CRHR1 deficiency, nor does the lack of CRHR2 exacerbate the CRHR1-dependent impairment of the HPA system function. Within the intraadrenal CRH/ACTH system, our data suggest different roles for CRHR1 and CRHR2 in fine-tuning of adrenocortical corticosterone release.

Adrenal Cortex↗

PubMed1988

Specialization in membrane structure and metabolism with respect to polyunsaturated lipids.

The principal features of the hypotheses presented here are presented in a model (Figure 8). Polyunsaturated phospholipids are preferentially localized on the cytosolic leaflet of the plasma membrane and around proteins. They influence the physical state of these microenvironments and thereby help to regulate cellular functions. Losses of these species due to phospholipase attack, dietary deprivation or other pathological stimuli (such as alcohol), may lead to drastic alterations in some of these functions. The PUFA's released, including 22:6 omega 3, can be metabolised by a lipoxygenase enzyme in the brain and platelet and the products formed are biologically active.

Animals↗

PubMedDate not supplied

Augmented memory loss in aging mice after one embryonic exposure to alcohol.

Prenatal exposure to alcohol can produce behavioral and cognitive deficits even in the absence of dysmorphic facial features. In a mouse model, we tested whether embryonic exposure to alcohol could exacerbate functional loss as animals age. Normal-appearing offspring were selected from litters produced by C57Bl/6J mice that had been gavaged with one teratogenic dose (5.8 g/kg) of ethyl alcohol during organogenesis on the 9th day of gestation. In adulthood, the offspring suffered a deficit in long-term retention, but not acquisition, of a place learning task. Although barely detectable in young adults, the retention deficit was severe in aging mice. These findings demonstrate that the functional deficits resulting from embryonic exposure to alcohol can interact with those of aging.

Aging↗