Acute hepatic failure in seven patients after prophylaxis and therapy with antituberculous agents. Successful treatment with orthotopic liver transplantation.
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Adult↗
Biomedical subjects
M Schwartz
Publications and source records attributed to M Schwartz.
[Screening for carriers of cystic fibrosis. Result of a pilot study among pregnant women].
Total prevention of cystic fibrosis (CF) is possible if all carrier women are found before pregnancy or early enough during pregnancy so that prenatal diagnosis can be offered. The delta 508 allele constitutes almost 90% of the mutations causing CF in the Danish population. We have examined 6599 pregnant women and found 172 carriers of delta F508. Partners of carrier women were examined for delta F508 and five other mutations. Three couples at risk and one foetus with CF were identified. Giving information to couples before and after testing is time consuming. A comprehensive questionnaire was sent to 200 non-carriers and all 172 carriers (response rate 72%). It can be concluded that the project has been very well accepted. However, the majority of carriers were shocked or very worried when they had the test result. Based on this pilot study we recommend nationwide screening for delta F508 early in pregnancy.
Cystic Fibrosis↗
Recovery of visual response of injured adult rat optic nerves treated with transglutaminase.
Failure of axons of the central nervous system in adult mammals to regenerate spontaneously after injury is attributed in part to inhibitory molecules associated with oligodendrocytes. Regeneration of central nervous system axons in fish is correlated with the presence of a transglutaminase. This enzyme dimerizes interleukin-2, and the product is cytotoxic to oligodendrocytes in vitro. Application of this nerve-derived transglutaminase to rat optic nerves, in which the injury had caused the loss of visual evoked potential response to light, promoted the recovery of that response within 6 weeks after injury. Transmission electron microscopy analysis revealed the concomitant appearance of axons in the distal stump of the optic nerve.
Animals↗
Presence of growth inhibitors in fish optic nerve myelin: postinjury changes.
This study shows that the fish optic nerve, which is able to regenerate after injury, contains myelin-associated growth inhibitors similar to the growth inhibitors present in mammalian central nervous system (CNS) myelin. The ability of nerves to regenerate was previously correlated with the ability of sections from these nerves to support neuronal attachment and axonal growth in vitro. Thus neuroblastoma cells or embryonic neurons became attached to and grew axons on sections of rat sciatic nerve or fish optic nerve, which are spontaneously regenerating systems, but not on sections of rat optic nerve, a nonregenerating system. Failure of the latter to support axonal growth has been attributed, at least in part, to growth inhibitors. Recently it was shown that adult neurons, which differ in their growth requirement from embryonic neurons, are unable to extend neurites on sections of normal sciatic nerve but are able to extend neurites on sections of sciatic nerve that was injured prior to its excision. We found a similar situation in the fish optic nerve, i.e., that the nerve is normally not permissive to growth of adult retinal axons but becomes growth permissive after injury. The nonpermissiveness of the normal fish optic nerve was found to correlate with the presence of myelin-associated growth-inhibitory molecules. This inhibitory activity of fish myelin was neutralized by IN-1 antibodies, known to neutralize rat myelin growth inhibitors. The results thus demonstrate that fish optic nerve myelin contains inhibitors apparently similar or even identical to those of rat, but possibly present in lower amounts than in the rat. Results are discussed with respect to the possibility that fish optic nerve, like the rat sciatic nerve and unlike the rat optic nerve, undergoes certain changes after injury that support regeneration of adult neurons. Such changes might include elimination or neutralization of growth inhibitors.
Animals↗
Mapping of the choroideremia-like (CHML) gene at 1q42-qter and mutation analysis in patients with Usher syndrome type II.
The human choroideremia-like (CHML) gene and a locus for Usher syndrome type 2 (USH2) were recently mapped to the 1q31-qter region employing physical mapping and genetic linkage studies, respectively. Using a human-rodent hybrid cell line, we could refine the assignment of CHML in this study to 1q42-qter. USH2 was shown to map to the same chromosomal segment as evidenced by the fact that D1S58, a polymorphic marker previously shown to be located proximal to the USH2 locus, was also assigned in the 1q42-qter segment. To investigate a possible role of the CHML gene in the pathogenesis of USH2, we investigated 10 Dutch and 9 Danish USH2 patients for point mutations in the open reading frame of the CHML gene. Employing polymerase chain reaction-single-strand conformation polymorphism analysis and direct sequencing, we found no disease-specific mutations. These results suggest that CHML is not involved in the pathogenesis of USH2.
Animals↗
Vimentin immunoreactive glial cells in the fish optic nerve: implications for regeneration.
The poor regenerative ability of neurons of the central nervous system in mammals, as compared with their counterpart in fish or amphibians, is thought to stem from differences in their immediate nonneuronal environment and its response to axonal injury. We describe one aspect of the environmental response to axonal injury in a spontaneously regenerating system--the fish optic nerve. The aspect under investigation was the reaction of glial cells at the injury site. This was examined by the use of antibodies that specifically recognize vimentin in fish glial cells. In the present study, affinity-purified vimentin antibodies were raised against a nonconserved N-terminal 14-amino acid peptide, which was predicted from the nucleotide sequence of vimentin. These antibodies were found to react specifically with glial cells in vitro. Moreover, the antivimentin antibodies stained both the optic nerve and the optic tract, but with different patterns. Specificity of the antibodies was verified by protein immunoblotting, tissue distribution, and labeling patterns. After injury, vimentin immunoreactivity initially disappeared from the site of the lesion due to cell death. Early signs of glial cell migration toward the injury site were evident a few days later. It is suggested that the reappearance of vimentin-positive glial cells at the site of injury is associated with axonal elongation across it, and that they contribute to the regenerative ability of the fish optic nerve.
Amino Acid Sequence↗
Early prenatal direct gene diagnosis of cystic fibrosis in a twin pregnancy and subsequent selective termination.
We present a case of prenatal diagnosis of cystic fibrosis (CF) in one twin at 11-12 weeks of gestation. The parents had previously had two children, one of whom is alive and healthy and one who died of CF at the age of 2 1/2 months. The parents were both known to be carriers of the delta F508 mutation. Chorionic villus sampling (CVS) was performed and direct gene analysis showed that one fetus was homozygous for the delta F508 mutation, while the other fetus did not have the mutation at all. Both fetuses had normal karyotypes. Selective termination was subsequently performed. The pregnancy continued without complications except for mild pre-eclampsia at term. The woman had a Caesarean section. The genetic diagnosis was confirmed after birth.
Abortion, Induced↗
Cytokines modulate the inflammatory response and change permissiveness to neuronal adhesion in injured mammalian central nervous system.
Axonal injury of peripheral nerves has been shown to be followed by rapid and massive invasion of the nerves by macrophages, which appear to play an important role in the subsequent ability of these nerves to regenerate. In contrast, macrophage invasion of injured nerves of the central nervous system is limited, and the relationship between the post-traumatic inflammatory response of central nervous system nerves and their poor ability to regenerate is not fully understood. We used the proinflammatory cytokine tumor necrosis factor-alpha and the macrophage growth factor, colony stimulating factor-1, to examine whether the inflammatory response can be augmented in the optic nerve following injury, and whether such augmentation is accompanied by regeneration-associated changes. It appeared that the two cytokines caused a significant increase in the number of macrophages invading the optic nerve immediately after injury. Interestingly, however, in the nerve treated with tumor necrosis factor-alpha (but not in the nerve treated with colony stimulating factor-1) this increase was accompanied by an increased permissiveness of the nerve to neuronal adhesion, which we examined in vitro using longitudinal sections of the nerve on which PC12 cells were seeded. The results are discussed with respect to the ability of tumor necrosis factor-alpha to modify the nonpermissive nature of central nervous system white matter.
Animals↗
Nonpermissive nature of fish optic nerves to axonal growth is due to presence of myelin-associated growth inhibitors.
Fish optic nerve sections were recently shown to be nonpermissive to growth of adult retinal axons. In addition, fish optic nerve myelin was found to inhibit growth of adult retinal axons and this inhibition was neutralized by IN-1 antibodies (known to block rat myelin-associated inhibitors). In this study we examined whether the growth nonpermissiveness of fish optic nerves which had not been injured prior to their excision results, at least in part, from the presence of myelin-associated growth inhibitors. It was found that preincubation of the sections with IN-1 antibodies, known to recognize and neutralize the myelin-associated growth inhibitors of the rat central nervous system, increases sixfold the number of axons that grow on these sections. This demonstrates that fish myelin-associated growth inhibitors, which are similar to those of rat, are at least partly responsible for the growth nonpermissiveness of normal fish optic nerves.
Animals↗
Intraoperative ultrasound and liver tumors.
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Hepatectomy↗
394delTT: a Nordic cystic fibrosis mutation.
In a systematic screening for mutations in the gene encoding the cystic fibrosis transmembrane regulator among Danish cystic fibrosis (CF) patients, we identified a mutation in exon 3 (394delTT); this mutation was found to be relatively common in Denmark. We therefore screened for 394delTT in Sweden and Norway, where it turned out to be the second most frequent mutation, accounting for 4% of all CF mutations. It also occurs with a high frequency in Finland, but has not been found in larger surveys of mutations in the CFTR gene. Thus, 394delTT seems to be a specific Nordic CF mutation.
Base Sequence↗
Evidence for the existence of low-energy laser bioeffects on the nervous system.
The reported effects of low-energy laser irradiation on the nervous system are manifested in alterations in cellular and extracellular biochemical constituents and reactions, as well as in changes in cell division rates. These bioeffects were observed in both in vivo and in vitro experiments. Other observed phenomena relate to the function of the nervous system and consist mainly of induced alteration in electrical conduction, stimulation thresholds, and behavioral effects. Clinical aspects of low-energy laser bioeffects relate mainly to pain mitigation and postponement of the posttraumatic neural degeneration processes. Many of the reported observations were obtained by experiments apparently conducted according to less than rigorous scientific criteria, and some could not be duplicated. On the whole, however, there is little doubt that low-energy laser irradiation exerts some effects on the nervous system under specific conditions of irradiation and tissue exposure via a mechanism which is probably photochemical in nature.
Action Potentials↗
Searching for mutations in the arylsulphatase A gene.
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Alleles↗
Coronary artery bypass grafting: the Society of Thoracic Surgeons National Database experience.
The need for accurate risk assessment has become an indispensable element in the practice of cardiac surgery. The Society of Thoracic Surgeons National Cardiac Surgery Database allows subscribing institutions to perform sophisticated patient risk assessment using traditional statistical tools and a newly developed risk model of operative mortality. The database experience with isolated coronary artery bypass grafting has been studied most closely at this point and serves as the basis for this report. The approach to operative risk assessment is presented along with an analysis of important risk factors in the practice of coronary artery surgery from 1980 through 1990. The database contains records of 80,881 patients undergoing coronary artery bypass grafting in numerous institutions from 1980 through 1990. These records were used to conduct a detailed analysis of risk factors associated with coronary operations in this time interval and to present statistical methods used to formulate a risk equation that allows one to predict the probability of operative death. In the course of this decade, there were clearly defined trends showing a statistically significant increase in adverse patient risk factors. The risk model has proven to be a reliable tool for predicting the probability of operative death in an individual patient and may be valuable in both patient counseling and medical decision making. Large multi-institutional databases of this type are key ingredients of modern operative risk assessment. A database containing a broad national experience of this type can represent an aggregate experience that may well approximate a universally accepted standard of care.
Adult↗
Impact of internal mammary artery conduits on operative mortality in coronary revascularization.
The long-term advantages of internal mammary artery (IMA) conduits in coronary artery bypass graft (CABG) procedures are widely recognized, but the immediate short-term impact of IMA grafts is not well defined. The purpose of this study was to investigate the influence of IMA conduits on CABG operative mortality (OM). A retrospective study of two groups of patients undergoing isolated CABG was performed. Patients having at least one IMA graft (group 1) were compared with those with only venous conduits (group 2). The patient population was taken from The Society of Thoracic Surgeons National Cardiac Surgery Database, which contains a broad multi-institutional experience. A total of 38,578 registered patients undergoing isolated CABG from 1987 through 1991 were studied. Of these, 18,614 patients had at least one IMA conduit (group 1), whereas 19,964 had CABG using entirely venous conduits (group 2). The OM for group 1 was 2.0% (365/18,614), whereas the mortality was 4.5% (903/19,964) for group 2 (p < 0.005). Patient subgroups were examined to determine if the improved OM associated with IMA grafting was present in these patient subsets. The population was broken down according to age, sex, ejection fraction, extent of coronary disease, and operative priority. For each subset, univariate analysis showed that group 1 OM was significantly less (p < 0.005) than the OM for group 2. Numerous combinations of these patient parameters were also analyzed. Group 1 patients had a significant (p < 0.05) improvement in OM in each combination except for patients more than 70 years of age requiring reoperations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Practical considerations in the management of large multiinstitutional databases.
Large multiinstitutional databases are excellent sources of information that provide clinically useful insight into the practice of cardiac surgery. Fully informed subscribers should be aware of the practical concerns associated with the management and interpretation of database results. During development of The Society of Thoracic Surgeons National Database, three such areas have become particularly important: the database population, the database quality, and the significance of results. Appreciation of the real and philosophical problems associated with these issues will allow for greater appreciation of the intricacies of the database and will enhance the users' ability to interpret information gained from the database.
Bias↗
Profile of preoperative characteristics of patients having CABG over the past decade.
The Society of Thoracic Surgeons' National Cardiac Database was used to determine the changes in preoperative characteristics and the predicted and observed risk of operative mortality of patients undergoing coronary artery bypass grafting during the decade of 1984 to 1993. During this period, the data show an increase of 2.5 years in age and decreases of 3% both in incidence of male patients and in incidence of first operation. There was little change in the percentages of urgent/emergent procedures or mean left ventricular ejection fraction. There was a significant 17.5% decrease in the proportion of lowest risk patients (0% to 2.5% predicted mortality) from 61.1% to 43.6%. Although no change in the next higher risk group (> 2.5% to 5.0% predicted mortality) occurred, the higher risk groups showed increases of 6.2%, 9.1%, 1.4%, and 1.1% for the > 5% to 10%, > 10% to 20%, > 20% to 30%, and > 30% to 50% risk groups, respectively. Over the past 2 years, there have been no significant changes in the distribution of the risk groups. These data will provide a base for comparison of future endeavors to lower complication rates and cost of coronary artery bypass graft operations.
Coronary Artery Bypass↗
Spinal subdural abscess: successful treatment with limited drainage and antibiotics in a patient with AIDS.
The authors present a case of Staphylococcus aureus spinal subdural abscess in a patient with AIDS. Although complete surgical drainage has been strongly advocated in the literature, this patient made a complete neurologic and symptomatic recovery and radiographically demonstrated resolution of the abscess with only limited surgical drainage and parenteral antibiotics. Magnetic resonance imaging findings of this unusual lesion are discussed. Relevant literature in the management of spinal subdural abscesses is reviewed.
AIDS-Related Opportunistic Infections↗