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PubMed1998

[Intestinal transplantation: a clinical reality in 1998].

Each year, thousands of peoples die, suffering from an anatomical or functional loss of their intestine; these patients would benefit from bowel transplantation; the difficulties of bowel transplantation are as follows: 1. the physiological characteristics of the small bowel, and the fact that denervation, lymphatics interruption and ischemia, independently from rejection, may disturb its function; 2. secondly, the organ is septic; thus, its transplantation causes major infectious problems; 3. at last, the immunological characteristics of the intestinal allograft. Bowel transplantation causes a two-way immunological conflict, not only a standard rejection response, but also a graft-versus-host disease, similar to that observed after bone marrow transplantation; this reaction is caused by the lymphoid tissue conveyed within the bowel graft. The introduction of a new immunosuppressive molecule, FK 506, in combination with profound antibiotic prophylactic regimens, decontamination protocols and vigorous anti-viral protection (against cytomegalovirus and Epstein-Barr), have significantly improved the results. Bowel transplantation has recently reached clinical application. The one-year survival rate of intestinal grafts reaches now 70%. Still, there is no doubt that, due to its microbiological and immunological characteristics, the small bowel will remain the most challenging abdominal organ to transplant.

Drug Monitoring↗

PubMed1998

[Repeat kidney transplantation].

BACKGROUND: The objective of the study was an analysis of results of repeated kidney transplantations (Tx2, Tx3) implemented during the first 29 years of activities of the Transplantation Centre of the Institute of the Clinical and Experimental Medicine in subjects with a different maintenance immunosuppression. METHODS AND RESULTS: The retrospective study pertains to 134 Tx2 and 17 Tx3 in 134 non-diabetic subjects: 43 of them had during Tx1 and Tx2 (1966-1981 and 1966-1985 resp.) immunosuppression on the basis of azathioprin (Aza, sub-group AA), 42 during Tx1 (1972-85), Aza, while during Tx2 (1984-85) immunosuppression on the basis of cyclosporin (CyA, subgroup AC) and 49 both during Tx1 and Tx2 (1985-93 and 1986-95 resp.) CyA (subgroup CC). Compared was survival of grafts by the actuarial method (with regard to all losses regardless of cause) by the end of the 4th year inside the subgroups (Tx2, vs. Tx1 and Tx3 vs. Tx2 in the same subjects) and between subgroups (Tx1 vs. Tx1 and Tx2 vs. Tx2 in different subjects). Moreover in paired investigations the survival of recipients and grafts after Tx2 was compared after immunosuppression on the basis of CyA with the same parameters after Tx1 in different subjects with the same immunosuppression, operated at approximately the same time (n = 81) and survival of subjects with Tx1 + Tx2 on the CC regime regardless whether the second grafts functioned at the time of the last examination, with survival of subjects after Tx1 where after graft failure Tx2 was not performed (n = 34). Prophylaxis with antilymphocyte globulins was not used. Survival of second and first grafts did not differ in any of the subgroups, third grafts survived at the end of the third year more frequently than second grafts (66 vs. 18%, p < 0.01). Second grafts in CC survived more than in AA (55 vs. 28%, p < 0.01). In the paired study Tx2 vs. Tx1 the survival of grafts and recipients was the same (88 vs. 89%, N.S. and 47 vs. 62% resp.), in the paired study Tx1 + Tx2 vs. Tx1 more subjects with Tx1 + Tx2 survived 10 years after Tx1 than subjects who did not have Tx2 (82 vs. 49%, p < 0.05). CONCLUSIONS: A further transplantation of the kidney after functional loss of the first graft is the method of choice: the mortality is low, the probability of several years' function is considerable and the prognosis as regards quality and length of life better than with regular dialysis treatment.

Adult↗

PubMed1997

Neurogenic bladder may be a side effect of focus resection in an epileptic patient.

A 34-year-old man with intractable epilepsy was treated by focus resection. The resected volume of neocortex in the left supracallosal part of the medial frontal gyrus was 7 x 1 x 2.5 cm. The treatment was effective and epileptic attacks completely disappeared. However, the patient developed urinary incontinence postoperatively without any other new neurological abnormalities. Urodynamic study revealed loss of bladder sensation, increased bladder capacity, involuntary detrusor contraction, and synergic external sphincter. The suprcallosal part of the medial frontal gyrus has been reported to include 1 of the suprapontine micturition centers. In this case, resection of this area significantly affected bladder function. Loss of bladder sensation and increased threshold volume on micturition are characteristic signs of deficit in this area.

Adult↗

PubMed1989

Impotence and aging.

Taking into account the normal changes that occur with aging and the large number of pathologies, pharmacologic agents, and social situations that the elderly are subject to, it is perhaps more surprising that 25 per cent of those over 80 years of age do report normal sexual functioning. Loss of erectile capability appears to be multifactorial in many patients, although the exact degree is uncertain due to unsystematic assessment in the majority of current studies. Unfortunately, impotence is often ignored by the patients' physicians. Physicians do not routinely ask about erectile functioning in their patients, perhaps because they do not know how to systematically evaluate and treat the complaint. Any follow through that might result from a complaint is often chaotic. And, rarely are treatment possibilities systematically and clearly presented to the patient. This is particularly true for the elderly patients whose physicians may be surprised that an elderly patient would still be interested in sexual behavior. No matter how subtle, this "dirty old man" response by the physician does not foster a good therapeutic environment. Inappropriate and unsystematic evaluations of impotent patients leads to a literature replete with contradictory statements. Because of the prevalence of impotence in the elderly, as a group they are hurt the most by unsystematic evaluation techniques and therefore have the most to gain from the application of systematic evaluation and treatment procedures.

Adult↗

PubMedDate not supplied

[The efficacy of transcutaneous electrostimulation of the visual system in partial optic atrophy].

Effects of transcutaneous electric stimulation of the eyes on vision acuity, visual field, electric sensitivity, electric lability, Hanzfeld ERG and macular ERG were studied in 260 patients with partial atrophy of the optic nerve of various origins and with different degrees of visual function loss. Dispersion analysis of random samples showed that changes in each characteristic after electric stimulation depended on the initial value of this parameter: in general, the more manifest were deviations from the norm, the more marked was the improvement of this or that function. A conclusion is made on physiological nature of electric stimulation method used for the treatment of optic nerve atrophy.

Adolescent↗

PubMed2005

Differential respirable dust related lung function effects between current and former South African coal miners.

Dust-related dose-response decrements in lung function among coal miners have been reported in several studies, with varying magnitudes across populations. Few studies have compared differences between current and former coal miners. No studies on dose response relationships with lung function have been conducted in South African coal mines, one of the top three producers of coal internationally. The objectives of this study were (1) to describe the relationship between respirable dust exposure and lung function among current and former South African coal miners and to determine whether differential dust related effects were present between these employment categories; (2) to examine dust related dose response relationships, controlling for potential confounding by smoking and a history of tuberculosis (TB). Six hundred and eighty-four current and 188 ex-miners from three bituminous coal mines in Mpumalanga Province were studied. Interviews assessing work histories, smoking profiles and other risk factors were conducted. Work histories were also obtained from company records. Standardised spirometry was performed by trained technicians. Cumulative respirable dust exposure (CDE) estimates were constructed from company-collected sampling and measurements conducted by the researchers. Regression models examined the associations of CDE with per cent predicted FEV(1) and FVC, controlling for smoking, past history of TB and employment status. A statistically significant decline in FEV(1) of 1.1 and 2.2 ml/mg-year/m(3) was found in representative 40-year-old, 1.7-m tall current and former miners, respectively. Significant differences were found between the highest and medium exposure categories. Ex-miners had a lower mean per cent predicted lung function than current miners for each cumulative exposure category, suggesting a "healthy worker" effect. Past history of TB contributed to 21 and 14% declines in per cent predicted FEV(1) and FVC, respectively. Thus, in this cohort, a dose-related decline in lung function was associated with respirable dust exposure, with a magnitude of effect similar to that seen in other studies and important differences between current and former employees. A "healthy worker" effect may have attenuated the magnitude of this relationship. TB was a significant contributor to lung function loss.

Adult↗

PubMed1987

Caloric vertical nystagmus: the vertical semicircular canal in caloric testing.

Vertical nystagmus elicited by caloric testing does not necessarily mean there is central pathology. In a patient with confirmed peripheral vestibular disease, caloric stimulation produced an intense vertical nystagmus, which showed all the features of a caloric nystagmus. The patient had bilateral mastoid cavities, allowing easy stimulation of the posterior semicircular canal, using air. At the same time, a unilateral horizontal semicircular canal functional loss was observed, raising the possibility of dissociated canal dysfunction.

Adult↗

PubMed1979

Selective neutrophil desensitization to chemotactic factors.

In the presence of extracellular calcium and magnesium, a series of chemotactic oligopeptides and C5a caused aggregation of human polymorphonuclear neutrophils (PMNs). This cellular response developed rapidly and began to reverse 2 min after exposure to the chemotactin. In the absence of the bivalent cations, none of the chemotactins stimulated the aggregation response. If cells were first exposed to a chemotactin and then treated with calcium and magnesium, aggregation was detected only after addition of the cations, and the magnitude of the response fell sharply as the interval between the addition of chemotactin and addition of cations was lengthened: when this interval exceeded 2 min, aggregation was barely detectable. This loss of reactivity persisted even when cells were re-exposed to fresh chemotactic factor and washed between the first and second exposures. In all instances, however, loss of cellular reactivity was highly selective: cells preincubated with any chemotactic oligopeptide were hyporesponsive to subsequent stimulation with an oligopeptide but remained fully responsive to C5a; cells preincubated with C5A were hyporesponsive to C5a but retained their responsitivity to the oligopeptides. Because this selectivity parallels the known specificities of these chemotactic factors for their receptors in or on the neutrophil, desensitization may reflect functional loss of receptors after stimulation. Alternatively, this selectivity may indicate that morphologically identical neutrophils contain subpopulations of cells with varying reactivities to receptor-bound chemotactic factors. In either event, desensitization may be useful in functionally defining chemotactic factors and their respective receptors. The rapidity of development of desensitization suggests that it may operate to limit or moderate various in vitro and in vivo neutrophil responses to chemotactic factors.

Calcium↗

PubMed1988

Regulation of the mid-blastula transition in amphibians.

The cleavage cycles during early amphibian development are synchronous, rapid, and biphasic. There is no transcription and no growth of the embryo, and the nuclear cycle is independent of the cytoplasmic cleavage cycle. All components necessary for development through the blastula stage are provided by maternal stores. At the twelfth cleavage division, a major transition occurs that involves initiation of transcription, an elongation of the cell cycle, an increase in cell movement, and asynchrony of cell division. It is probable that the major controlling factor in the regulation of all the aforementioned events is the cell cycle. During early cleavage stages, the cell cycle is both rapid (30-35 min) and synchronous. There is evidence that the cycling time may be controlled by the presence of several mitotic factors, such as MPF, CSF (cytostatic factor), and a titratable component that binds to nuclear membranes. The rapid rate of DNA synthesis may inhibit the formation of transcription complexes, resulting in the absence of detectable transcription before the MBT. Cellular movement may also be inhibited in the rapidly dividing cell. As the cell cycle elongates (possibly due to the functional loss or sequestration of one or more of the mitotic control factors), the G1 and G2 phases are incorporated into the cell cycle. Under conditions of slower rates of DNA replication and the presence of the G1 and G2 phases, the transcriptional machinery becomes functional. It is apparent that at the MBT, not all classes of transcripts are activated simultaneously in every cell, nor is their expression regulated by a common mechanism. Incorporation of the G1 and G2 phases in the cell cycle may also permit the synthesis and assembly of microtubules and cytoskeletal components necessary for the initiation of the cell movements characteristic of this stage of development. The role of the cell cycle in controlling events at the MBT is supported by evidence from studies in which perturbation of the cell cycle that results in its elongation or arrest produces subsequent initiation of events that occur normally at the MBT. The MBT therefore appears to be a window in the developmental time frame, during which a number of molecular and morphogenetic events occur independently of one another, but all are necessary for subsequent morphogenesis and cellular differentiation. It is a transition from the strict reliance on the maternal program to a dependence on the new transcription from the embryonic genetic program. It is probable that the major regulatory mechanism involved in the occurrence of this constellation of cellular events is the change in the cell cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Open reduction and internal fixation of ipsilateral fractures of the scapular neck and clavicle.

Ipsilateral fractures of the scapular neck and clavicle disrupt the suspensory mechanism of the shoulder, resulting in functional loss and deformity. Fifteen patients who had such fractures were managed with open reduction and internal fixation and were followed for an average of twenty-five months (range, fourteen to forty-seven months). All but one patient had a good or excellent functional result according to the scoring system of Rowe. All fractures healed at an average of eight weeks postoperatively. Complications from concomitant fractures of the ribs were treated uneventfully. We concluded that operative treatment of these complex fractures is safe and yields predictably good results.

Adolescent↗

PubMedDate not supplied

Comprehensive functional assessment.

A diagnosis-centered approach has limited value when describing the health status of the elderly. Functional losses often stem from many interacting health and social problems, and therefore, successful treatment is dependent on evaluation of an individual's overall capacity to meet his own needs in everyday community life. A systematic and multidimensional assessment should cover physical, cognitive, and emotional functioning, including the instrumental activities of daily living, as well as economic resources, informal social supports, and utilization and perceived need for services. Comprehensive functional assessment at the primary care level can be a very valuable tool not only for patient care, but also for administrative management.

Activities of Daily Living↗

PubMed1998

Resection and graft repair for localized hypertrophic neuropathy.

OBJECTIVES: Formulation of surgical management recommendations for localized hypertrophic mononeuropathy has been difficult because of the infrequency of the lesion, lack of precise pathological diagnosis, and uncertainties regarding its cause. The purpose of this retrospective review of the Louisiana State University (LSU) experience with this unusual neuropathy was to evaluate the efficacy of lesion resection and interposition grafting in its management. METHODS: The charts of 15 patients operated on at LSU during a 15-year period with a pathological diagnosis of localized hypertrophic neuropathy were reviewed. RESULTS: Hypertrophic lesions were located on major named peripheral nerves of the extremities, distributed equally to the upper and lower extremities. Family history was negative for all patients, and entrapment or trauma, other than previous surgery, were unlikely by symptom location or history. Weakness was the most common presentation. The mean length of symptoms was 76 months. Atrophy, sensory loss, Tinel's sign, focal tenderness, and a mass were found in the majority of patients. Preoperative electrophysiological studies showed chronic denervational changes in all patients. At surgery, if no action potential or one of low amplitude was recorded across the lesion, the lesion was resected and an autologous nerve graft measuring from 3.5 to 8.5 cm in length was interposed. During follow-up periods of 1 or more years, seven of nine patients with localized hypertrophic mononeuropathy treated with graft repairs were either unchanged or improved. CONCLUSION: Localized hypertrophic mononeuropathy is a progressive process associated with pathological nerve changes that correlate with eventual severe functional loss. If intraoperative histological examination shows onion bulb neuropathy and intraoperative nerve action potentials confirm a nonfunctioning or poorly functioning segment, lesion resection with interposition graft repair provides the possibility of some degree of recovery.

Action Potentials↗

PubMed2000

Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Adolescent↗

PubMed2000

Care of the older adult following hip fracture.

Proximal femoral (hip) fractures are the leading cause of hospitalization for injuries among older persons and constitute a serious health problem. Research shows significant functional losses among older persons following surgery for hip fracture related to a wide range of problems. Because of the physiological, emotional, social, and psychological complications inherent in this particular population, a team approach using a holistic model of care is efficacious when attempting to improve functional outcomes and reduce morbidity and mortality.

Activities of Daily Living↗

PubMed2006

Improvement of sexual function in male patients treated surgically for cervical spondylotic myelopathy.

STUDY DESIGN: A prospective follow-up study. OBJECTIVE: To analyze the recovery of sexual function loss in surgically treated male patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Cervical spondylotic myelopathy is common in the elder population and can lead to sexual dysfunction. Although numerous studies have shown that surgical treatment of cervical spondylotic myelopathy achieved satisfactory neurologic and functional improvement, only few researchers mentioned sexual dysfunction. METHODS: A total of 22 patients with combined cervical spondylotic myelopathy and sexual dysfunction on admission were treated with surgery. The patients' preoperative and postoperative neurologic status was recorded according to the Japanese Orthopedic Association (JOA) Scoring System. The sexual function was assessed using the International Index of Erectile Function (IIEF). Special attention was also given to the preoperative and postoperative presence or absence of a reflexogenic and psychogenic erection. RESULTS: In most cases, there was significant improvement in neurologic status after surgery, with a mean improvement of JOA score of 3.6. The difference between the preoperative and postoperative JOA score was significant (P < 0.05). Most of these patients had an abnormal psychogenic erection (18/22, 82%) before surgery, but only few had an abnormal reflexogenic erection (4/22, 18%). After surgery, most patients had improvement in sexual function, and the average IIEF score was 28.5 before and 60.2 after surgery. The difference between preoperative and postoperative IIEF scores was statistically significant (P < 0.05). CONCLUSIONS: In addition to neurologic deficits, cervical spondylotic myelopathy also causes sexual dysfunction. Most of these patients had an abnormal psychogenic erection and normal reflexogenic erection. Along with neurologic recovery, most patients had improvement in sexual function after surgery.

Adult↗

PubMed2025

Alcohol-induced KDM5B activation in hepatocytes drives pathogenic cell-cell communication, leading to loss of liver function.

BACKGROUND: Alcohol-associated liver disease (ALD) is a major cause of alcohol-associated mortality. Previously, we identified KDM5B as a sex-specific mediator of ALD development; however, the mechanism behind KDM5B-induced pathological changes is not established. METHODS: Kdm5b flox/flox female mice were fed a western diet and 20% alcohol in the drinking water for 8-16 weeks (WDA). To induce KO, mice received 2×1011 genome copies of AAV8-CMV-Cre, AAV8-TBG-Cre, or AAV8-control. To test the role of myeloid C/EBPβ, Cebpbfl/fl, or Cebpbfl/fl Lyz2-Cre mice were fed WDA for 16 weeks. RESULTS: We found that Kdm5b KO prevented alcohol-induced liver fibrosis and liver inflammation in female mice. These changes were in part mediated by hepatocyte-to-non-parenchymal cell communication changes. KDM5B in hepatocytes promoted pro-inflammatory and pro-fibrotic changes in liver macrophages, endothelial cells, and stellate cells. Moreover, KDM5B promoted alcohol-induced early increase in EpCAM-positive liver progenitors and loss of liver function at later time points of alcohol feeding. We found that loss of liver function was dependent on a hepatocyte-to-macrophage communication feedback loop. KDM5B in hepatocytes inhibited macrophage C/EBPβ expression, which in turn resulted in loss of the mature KCs phenotype and prevented the ability of KCs to support hepatocyte differentiation, ultimately leading to loss of liver synthetic function. CONCLUSIONS: KDM5B activation in hepatocytes drives pathogenic cell-cell communication, leading to alcohol-induced loss of liver function in ALD.

Animals↗

PubMed1992

Genetic and biochemical analysis of the adenylyl cyclase-associated protein, cap, in Schizosaccharomyces pombe.

We have identified, cloned, and studied a gene, cap, encoding a protein that is associated with adenylyl cyclase in the fission yeast Schizosaccharomyces pombe. This protein shares significant sequence homology with the adenylyl cyclase-associated CAP protein in the yeast Saccharomyces cerevisiae. CAP is a bifunctional protein; the N-terminal domain appears to be involved in cellular responsiveness to RAS, whereas loss of the C-terminal portion is associated with morphological and nutritional defects. S. pombe cap can suppress phenotypes associated with deletion of the C-terminal CAP domain in S. cerevisiae but does not suppress phenotypes associated with deletion of the N-terminal domain. Analysis of cap disruptants also mapped the function of cap to two domains. The functional loss of the C-terminal region of S. pombe cap results in abnormal cellular morphology, slow growth, and failure to grow at 37 degrees C. Increases in mating and sporulation were observed when the entire gene was disrupted. Overproduction of both cap and adenylyl cyclase results in highly elongated large cells that are sterile and have measurably higher levels of adenylyl cyclase activity. Our results indicate that cap is required for the proper function of S. pombe adenylyl cyclase but that the C-terminal domain of cap has other functions that are shared with the C-terminal domain of S. cerevisiae CAP.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Ocular findings in patients with autosomal dominant retinitis pigmentosa and Cys110Phe, Arg135Gly, and Gln344stop mutations of rhodopsin.

This report describes ocular findings obtained in four patients from three families with autosomal dominant retinitis pigmentosa (adRP) due to missense mutations in the rhodopsin gene. Phenotypes were characterized by standard ophthalmologic examinations, visual fields, electroretinography (ERG), dark adaptation, and two-color dark-adapted threshold perimetry. Two patients aged 38 and 45 years, respectively, from a family with the Cys110Phe mutation showed mild fundus changes without bone spicules as well as small arcuate scotomas in the inferior quadrants of their visual fields but displayed severe functional loss of rods and cones in the ERG. Two-color dark-adapted threshold perimetry revealed a regional type of degeneration. A 48-year-old patient with an Arg135Gly mutation had typical RP with concentrically narrowed visual fields and nondetectable ERG responses. Central visual functions were well preserved for a long time. Two-color dark-adapted threshold perimetry indicated a diffuse type of retinal degeneration. An 18-year-old patient with a Gln344stop mutation has been followed for 13 years. His ERG was clearly reduced at the age of 5 years; since that time, disease progression has been very slow. Currently, there are relatively mild alterations in visual acuity, rod sensitivity, and visual fields. Our findings confirm that there is a large phenotypic variety among patients with adRP and different rhodopsin mutations.

Adolescent↗