Memory, reconstruction, and mourning in the analysis of a 4-year-old child: maternal bereavement in the second year of life.
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Biomedical subjects
Publications and source records attributed to T Lopez.
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Although myocardial actomyosin ATPase specific activity determined at Ca2+ levels of 1 x 10(-3) to 1 x 10(-2) M is consistently higher in two-month old male Fischer rats than in twelve-month old individuals, this difference can be eliminated if the enzyme is assayed at lower calcium concentrations. This suggests that the previously reported, declining actomyosin ATPase activity in the rat myocardium with advancing age may represent an age-related diminished ability of calcium to reverse the known inhibition upon actomyosin ATPase by the regulatory proteins.
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The function of the kidney in adult subjects with Cooley's disease has been hitherto inadequately investigated. In 10 patients suffering from thalassemia major, glomerular filtration rate, renal plasma flow, renal blood flow have been studied, together with urine concentration capacity. The authors emphasize certain pathological changes, such as the increase in renal plasma flow and the failure of the urine concentration ability. On the basis of renal biopsies, two pathogenetic theories are discussed: the functional impairment of the coutercurrent system and fibrosis of the medullary tissue.
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Cultures of embryonic day 17 (E17) rat adrenal and neonatal bovine adrenal cells were conditionally immortalized with the temperature-sensitive allele of SV40 large T antigen (tsTag) and chromaffin cell lines established. Indicative of the adrenal chromaffin phenotype, these cells expressed immunoreactivity (ir) for tyrosine hydroxylase (TH), the first enzyme in the synthetic pathway for catecholamines. At permissive temperature in vitro (33 degrees C), these chromaffin cells are proliferative, have a typical rounded chromaffin-like morphology, and contain detectable TH-ir. At nonpermissive temperature in vitro (39 degrees C), these cells stop proliferating and express increased TH-ir. When these immortalized chromaffin cells were transplanted in the lumbar subarachnoid space of the spinal cord I week after a unilateral chronic constriction injury (CCI) of the rat sciatic nerve, they survived longer than 7 weeks on the pia mater around the spinal cord and continued to express TH-ir. Conversely, grafted chromaffin cells lost Tag-ir after transplant and Tag-ir was undetectible in the grafts after 7 weeks in the subarachnoid space. At no time did the grafts form tumors after transplant into the host animals. These grafted chromaffin cells also expressed immunoreactivities for the other catecholamine-synthesizing enzymes 7 weeks after grafting, including: dopamine-beta-hydroxylase (DbetaH) and phenylethanolamine-N-methyltransferase (PNMT). The grafted cells also expressed detectable immunoreactivities for the opioid met-enkephalin (ENK), the peptide galanin (GAL), and the neurotransmitters y-aminobutyric acid (GABA) and serotonin (5-HT). Furthermore, after transplantation, tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI were significantly reduced during a 2-8-week period, related to the chromaffin cell transplants. The maximal antinociceptive effect occurred 1-3 weeks after grafting. Control adrenal fibroblasts, similarly immortalized and similarly transplanted after CCI, did not express any of the chromaffin antigenic markers, and fibroblast grafts had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that embryonic and neonatal chromaffin cells can be conditionally immortalized and will continue to express the phenotype of primary chromaffin cells in vitro and in vivo; grafted cells will ameliorate neuropathic pain after nerve injury and can be used as a homogeneous source to examine the mechanisms by which chromaffin transplants reverse chronic pain. The use of such chromaffin cell lines that are able to deliver antinociceptive molecules in models of chronic pain after nerve and spinal cord injury (SCI) offers a novel approach to pain management.
The use of cell lines utilized as biologic "minipumps" to provide antinociceptive molecules, such as GABA, in animal models of pain is a newly developing area in transplantation biology. The neuronal cell line, RN33B, derived from E13 brain stem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat GAD67 cDNA (glutamate decarboxylase, the synthetic enzyme for GABA), and the GABAergic cell line, 33G10.17, was isolated. The 33G10.17 cells transfected with the GAD67 gene expressed GAD67 protein and synthesized low levels of GABA at permissive temperature (33 degrees C), when the cells were proliferating, and increased GAD67 and GABA during differentiation at nonpermissive temperature (39 degrees C) in vitro, because GAD67 protein expression was upregulated with differentiation. A control cell line, 33V1, transfected with the vector alone, contained no GAD67 or GABA at either temperature. These cell lines were used as grafts in a model of chronic neuropathic pain induced by unilateral chronic constriction injury (CCI) of the sciatic nerve. Pain-related behaviors, including cold and tactile allodynia and thermal and tactile hyperalgesia, were evaluated after CCI in the affected hind paw. When 33G10.17 and 33V1 cells were transplanted in the lumbar subarachnoid space of the spinal cord 1 week after CCI, they survived greater than 7 weeks on the pia mater around the spinal cord. Furthermore, the tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI was significantly reduced during the 2-7-week period after grafts of 33G10.17 cells. The maximal effect on chronic pain behaviors with the GABAergic grafts occurred 2-3 weeks after transplantation. Transplants of 33V1 control cells had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that a chronically applied, low local dose of GABA presumably supplied by transplanted cells near the spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of neural cell lines that are able to deliver inhibitory neurotransmitters, such as GABA, in a model of chronic pain offers a novel approach to pain management.
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PURPOSE: The dialysis dose is usually assessed by Kt/V urea; however, it is possible that middle molecule (MM) removal could play a role in optimal treatment. Vitamin B12 is a classical MM marker and Kd-B12 is used to compute a MM-based dialysis index, requiring a weekly total clearance (Kd-B12 + renal creatinine clearance (CrCl) > or =30 L, corresponding to IDB12> or =1 (Babb et al, Kidney Int, 1975). Recently, it was demonstrated that by increasing the total Kd-B12 per session (TCV) from 10 to 16 and to 26 L, the relative risk (RR) of death was reduced from 1 to 0.79 and to 0.62, respectively (Leypoldt et al, Am J Kidney Dis 1999). This implies that a minimum TCV of 16 L, but preferably of 26 L per session, should be delivered, for anuric HD patients on a 3x/wk schedule. To extend these results to the whole hemodialysis (HD) population, we suggest transforming TCV into the corresponding IDB12 values: i.e. a TCV=10 L on 3x/wk corresponds to IDB12=1, a TCV=16 and 26 L corresponds to IDB12=1.6 and 2.6, respectively. METHODS: This study aimed to assess Kd-B12 and IDB12 for all stable patients in our unit. There were 62 patients (33 males, 29 females): five patients were being dialyzed once per week (1x), nine patients twice (2x), 46 patients three (3x) and two patients four times (4x) per week (wk); the session length was 232+/-18 min. Most dialyzers had a large surface area (mean 1.9+/-0.3 m2), with KoA-B12=211+/-92 mL/min. Eleven patients, 3x/wk, were on hemodiafiltration (HDF): the reinfusion rate was 33+/-3 mL/min in five patients (sHDF) and 76+/-12 mL/min in six patients (HDF on-line (OL). Kd-B12 was computed as a function of KoA-B12, effective plasma flow, Qd and ultrafiltrate (UF). IDB12 was computed from Kd-B12, ses-sion length and schedule, CrCl and body surface area. RESULTS: The main results are given below: [table: see text] On average, Kd-B12 was 105 +/- 13 mL/min on HD and 152+/-34 mL/min on HDF. A significant difference was found only for HDF-OL and was essentially due to the higher UF. Of note, the presence of renal function allowed good IDB12 values for 1x/wk and 2x/wk patients, even better than for the standard 3x/wk patients. CONCLUSIONS: We have demonstrated that most available dialyzers provide high Kd-B12 values (but HDF-OL performs significantly better) and that IDB12, by quantifying the impact of UF, session length, schedule and renal function, allows the assessment of dialysis adequacy beyond Kt/V urea, for all HD or HDF patients, on a routine basis and at no added cost.
Regional clinical Audit, guideline Targets and local and regional Benchmarks In order to improve the quality of dialysis treatment, we have devised some routines, particularly suitable for electronic data management systems. First, we suggest a systematic monthly analysis of 10 common clinical performance measures (CPM), with the following guideline based targets: predialysis systolic blood pressure (SBP) < 140 mmHg; session length >/= 240 min; dialysis dose (spKt/V) >/=1.3; normalized protein catabolic rate (NPCR) >/=1.2 g/kg/d; hemoglobin (Hb) >/=11 g/dL; serum calcium (Ca) 8.4-9.5 mg/dL; serum phosphorus (P) 3.5-5.5 mg/dL; Ca x P </=55 mg 2 /dL 2 ; serum bicarbonate (HCO3) >/=20 mmol/L; serum potassium (K) 3.5-6.0 mmol/L. The Hb target should be reached in at least 85% of all maintenance hemodialysis (HD) patients in the unit; for all other targets, an arbitrary >/=80% is proposed. Since the above percentages are quite difficult to reach on a short-term basis, an intermediate local or regional standard (benchmark) could be devised as an average of the percentage of patients who actually reach the targets for each CPM at any dialysis unit in a given regional area; and therefore, from truly comparable patients. As an example, we simulated a regional audit by using the above targets with available data from 398 patients from southern Italy. A further step in this process was to find the cause(s) of failure in each patient who did not reach the targets. To this end, we suggest a systematic search of the well-known factors that could affect each CPM, for each failed patient. As an example, we screened all patients with Hb < 11 g/dL at a single unit, to establish the presence/absence of any common cause associated with inadequate response to epoetin treatment. Moreover, by using criteria for prescribing iron therapy or increasing epoetin dose, we found that some patients did not receive the appropriate therapy after blood sampling results. To avoid this possible common problem, we suggest the need for a monthly report of failure cases for any particular CPM and a check that the appropriate treatment has been delivered to all patients at the dialysis unit. This should also favor guideline implementation.
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Bone densitometry using I125 is a very easy method of investigation; it may be used repeatedly and simultaneously at different bone levels without distress to patients. The problems involved were those of the value, semeiological significance and possible limitations of this method in the investigation of uraemic osteopathy. These problems were solved successfully in tests carried out on 87 patients of both sexes suffering from various degrees of chronic nephropathy and on chronic haemodialysis patients. The method is reliable: reproducibility tests in normal and uraemic subjects were satisfactory; the indexes remain constant, usually in normal subjects. The parameters are "Bone Mineral Content" and "Bone Index". Trabecular bone is more sensitive than cortical bone, although comparisons between the two types of bone produce interesting data. There are difference dependent on sex. The method which is more sensitive than others enables: 1) Normal and nephropathic subjects, to be distinguished from one another. The latter generally show a lower mineral content and bone index (clinical picture of osteomalacia, osteoporosis, hyperparathyroidism) seldom a higher or a normal one. 2) The same bone sites to be examined over a given period. 3) Treatment of patients to be monitored.