Cystine stones treated by percutaneous ultrasonic lithotripsy.
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Adolescent↗
Biomedical subjects
C C Tan
Publications and source records attributed to C C Tan.
Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia.
Erythropoietin (EPO) mRNA levels were measured by ribonuclease (RNase) protection in organs from unstimulated rats and from animals after normobaric hypoxia or hemorrhagic anemia. Both liver and kidney responded to stimulation with large increases in EPO mRNA, but the response characteristic to graded stimulation was different. The liver responded poorly to mild normobaric hypoxia, accounting for only 2 +/- 1% of total EPO mRNA at 11% O2, but hepatic EPO mRNA levels increased steeply with more severe hypoxia so that at 7.5% O2 the liver contributed to 33 +/- 7% of the total. After hemorrhagic anemia, the liver also responded more strongly to more severe stimulation, but at all points it accounted for a significant proportion of total EPO mRNA, contributing 18 +/- 6% after removal of 2.5 ml (hematocrit 37.2 +/- 1.3%), increasing to 37 +/- 14% after venesection of 10.5 ml (hematocrit 15.8 +/- 0.8%). Studies of EPO mRNA in other organs confirmed that EPO production outside the liver and kidney were quantitatively insignificant in stimulated animals. However, the hypoxia-induced increases in EPO mRNA in brain, testis, and spleen suggest the existence of an oxygen-sensing mechanism at other sites.
Acute Disease↗
Renal innervation plays no role in oxygen-dependent control of erythropoietin mRNA levels.
To assess the role of renal innervation in O2-dependent control of erythropoietin (EPO) formation, we have determined EPO mRNA levels in both kidneys of unilaterally denervated rats and sham-operated controls using RNase protection. To investigate whether possible effects of renal nerve input are related to the type of hypoxic stimulus and the degree of stimulation, animals were studied under basal conditions, after exposure to normobaric hypoxia (8% O2, 4 h) or CO (0.1%, 4 h), and after acute hemorrhage (decrease in hematocrit from 40.8 +/- 0.5 to 12.7 +/- 0.5% within 7 h; mean +/- SE, n = 6). Serum EPO levels rose on average 22-, 49-, and 48-fold under the three stimuli and were unaffected by unilateral denervation. Renal EPO mRNA levels in unilaterally denervated animals, when expressed in arbitrary units revealed by comparison with an external standard, were 7.0 +/- 1.5 vs. 6.3 +/- 2.0 (normoxia), 432 +/- 136 vs. 451 +/- 156 (normobaric hypoxia), 971 +/- 93 vs. 930 +/- 120 (CO), and 604 +/- 170 vs. 689 +/- 203 (hemorrhagic anemia) in the intact vs. the denervated kidney (mean +/- SE, n = 3). Furthermore, there was no difference between EPO mRNA levels of either kidney of unilaterally denervated animals and levels in sham-operated controls. We conclude that renal nerve input plays no significant role in the control of the EPO gene under both basal and stimulated conditions.
Anemia↗
Age-dependent expression of the erythropoietin gene in rat liver and kidneys.
Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism.
Age Factors↗
Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults.
PURPOSE: The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively. PATIENTS AND METHODS: Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis. RESULTS: Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024). CONCLUSIONS: The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.
Adult↗
Functional analysis of an oxygen-regulated transcriptional enhancer lying 3' to the mouse erythropoietin gene.
Erythropoietin, the major hormone controlling red-cell production, is regulated in part through oxygen-dependent changes in the rate of transcription of its gene. Using transient transfection in HepG2 cells, we have defined a DNA sequence, located 120 base pairs 3' to the poly(A)-addition site of the mouse erythropoietin gene, that confers oxygen-regulated expression on a variety of heterologous promoters. The sequence has the typical features of a eukaryotic enhancer. Approximately 70 base pairs are necessary for full activity, but reiteration restores activity to shorter inactive sequences. This enhancer operates in HepG2 and Hep3B cells, but not in Chinese hamster ovary cells or mouse erythroleukemia cells, and responds to cobalt but not to cyanide or 2-deoxyglucose, thus reflecting the physiological control of erythropoietin production accurately.
Animals↗
Quantification of 32P-labeled samples in gel fragments using the flat-bed liquid scintillation counter.
Quantification of 32P in bands after gel electrophoresis was performed using the flat-bed scintillation counter (Betaplate). The most convenient system involved placing fragments of dried gel between two glass fiber sheets, each previously sealed in a thin plastic bag with liquid scintillant. Good pulse-height spectra and counting efficiencies were obtained with low cross talk and background. The method has been used to quantify mRNA in RNA antisense-protection assays that were linear over a wide range (1-20000 cpm). Cross talk and background could be reduced further by an alternative technique utilizing plastic trays with shallow wells in which a solid scintillant had been melted. Fragments were immersed in the molten scintillant (90 degrees C), which was allowed to solidify, by cooling, before counting.
Animals↗
Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989).
Twenty-eight of 124 (23%) advanced germ cell tumor (GCT) patients who were treated on four successive platin-based induction regimens and who failed to achieve a durable complete response (CR) remain alive (median follow-up, 50 months). An analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy. Survival and/or response to salvage therapy were significantly enhanced for patients with a prior CR to induction chemotherapy, treatment with a cisplatin-based salvage regimen, a testis primary site, a normal serum human chorionic gonadotropin level, a normal serum lactate dehydrogenase level, one site of metastasis, and an Indiana Class of 6 or less. Patients with a prior incomplete response (IR) had a particularly poor prognosis (P = 0.00007) with only 4 of 52 (9%) patients alive (median follow-up, 37 months) compared with 15 of 42 (36%) patients with a prior best response of a CR (median follow-up, 35 months). The poor survival of patients who fail to achieve a durable CR to induction chemotherapy warrants the continued investigation of new salvage therapy. The identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens.
Adolescent↗
Organ distribution of erythropoietin messenger RNA in normal and uremic rats.
We used RNAase protection assays to measure low levels of erythropoietin messenger RNA (EPO mRNA) in the organs of unstimulated rats, and to compare basal and stimulated levels of EPO mRNA in the kidneys and extrarenal organs of rats rendered uremic by subtotal nephrectomy, with pair-fed controls. Using this sensitive assay, EPO mRNA was measured in the kidneys of unstimulated control animals and was detectable, at lower levels, in the liver and lung. After exposure to hypoxia, there was a 150-fold increase in renal EPO mRNA. Hepatic EPO mRNA was also greatly increased and accounted for 39 +/- 10% of the total. The small quantity of EPO mRNA in lung did not increase, but EPO mRNA became detectable in spleen. Animals subjected to subtotal nephrectomy became uremic and anemic (hematocrit 0.32 +/- 0.04 vs. 0.43 +/- 0.04 in controls, P = 0.002), but serum EPO concentrations were not significantly increased (32 +/- 9 vs. 24 +/- 6 mU/ml, P = 0.14). However, after hypoxic exposure, uremic animals increased serum EPO concentrations greatly, although the response was less than in controls (349 +/- 82 vs. 1009 +/- 238 mU/ml, P = 0.002). After hypoxia, extrarenal EPO mRNA levels in uremic animals were similar to controls. In particular, the large hepatic potential for EPO mRNA synthesis was unchanged but accounted for a greater proportion (84 +/- 5%) of the total EPO mRNA. The renal EPO mRNA content was reduced, as expected, after subtotal nephrectomy, but increased 50-fold after hypoxia. In this model of chronic renal failure, despite anemia, a large potential for EPO synthesis exists in liver and remnant kidney.
Amino Acid Sequence↗
Multiple arterial thromboses in nephrotic syndrome.
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Adult↗
Effect of inhibitors of oxidative phosphorylation on erythropoietin mRNA in isolated perfused rat kidneys.
We have used RNase protection to measure oxygen-dependent changes in erythropoietin (EPO) mRNA in isolated perfused kidneys and to compare the effect of hypoxia with the response to inhibitors of oxidative phosphorylation. In well-oxygenated kidneys perfused for 2 h at 12 ml/min, with hematocrit of 0.09 +/- 0.005 and PO2 of 443 +/- 67 mmHg, EPO mRNA levels were similar to the baseline levels measured in nonperfused contralateral kidneys from the same animals. When perfusions were performed under identical conditions but at a PO2 of 32 +/- 4 mmHg, EPO mRNA increased approximately 16-fold. In contrast, graded concentrations of cyanide (10, 100, and 300 microM and 1 mM), antimycin (0.01, 0.1, 0.5, and 1 microM), and oligomycin (0.01, 0.1, and 1 microM) did not alter EPO mRNA in well-oxygenated perfused kidneys. However, in kidneys perfused at low PO2 with a high concentration of each inhibitor, EPO mRNA levels were increased, demonstrating that the ability to respond to hypoxia was retained. Thus inhibitors of oxidative phosphorylation did not mimic the effects of hypoxia, indicating that oxygen-dependent expression of the EPO gene in the kidney is not effected through hypoxic compromise of oxidative phosphorylation.
Animals↗
Occupational health problems among nurses.
Nurses are an integral component of the health care delivery system. In discharging their duties, nurses encounter a variety of occupational health problems which may be categorized into biological hazards, chemical hazards, physical hazards, and psychosocial hazards. A review of some examples of each of these four types of hazards is presented in this article. Particular attention has been devoted to hepatitis B, acquired immunodeficiency syndrome, tuberculosis, cytotoxic drugs, anesthetic agents, needlestick injury, back pain, and stress.
Communicable Diseases↗
Occupational health in sawmills of Sarawak.
A self-administered questionnaire survey was conducted among sawmill managers in Sarawak to explore certain health and safety aspects of workers in this industry. The survey reveals that many sawmills are lacking in the provision of occupational health facilities and activities for their employees.
Humans↗
The diagnostic yield of upper gastrointestinal endoscopy in the investigation of anaemia.
Computer records of patients endoscoped over a 34-month period were studied to assess the diagnostic yield of gastrointestinal endoscopy in patients with anaemia. Patients with obvious gastrointestinal bleeding and known gastrointestinal pathology were excluded. On hundred and thirty-six patients were endoscoped for anaemia. Eighty-three of them (61%) had iron deficiency anaemia and 53 (39%) had other types of anaemia. The ages of the patients with iron deficiency anaemia (mean 56 years) were significantly lower than those of other anaemias (means 65 years), (p less than 0.003). Patient characteristics were otherwise comparable. There were significant endoscopic findings (ulcers, carcinoma and haemorrhagic or erosive gastritis) in 26 of 83 patients (31%) with iron deficiency anaemia, in 11 of 53 patients with other anaemias (21%) and 37 of 136 patients (27%) combined. Significant endoscopic findings were found in 506 of 2224 patients (23%) endoscoped during this period who were not anaemic, did not have obvious gastrointestinal haemorrhage and were not known to have gastrointestinal diseases. The diagnostic yield for iron deficiency anaemia was significantly higher than for the non anaemic group (p less than 0.05). There was no difference between the diagnostic yields of iron deficiency and other anaemias, other anaemias and the non anaemic group, or total anaemias and the non anaemic group. Gastrointestinal symptoms and history of analgesic or steroid usage did not appear to increase the incidence of gastrointestinal lesions in either iron deficiency anaemia or other anaemias. Twenty-three of 41 patients (56%) who had no cause for anaemia found at the end of all investigations were colonscoped.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Pharmacokinetics of intravenous vancomycin in patients with end-stage renal failure.
The pharmacokinetics of a 500-mg dose of i.v. vancomycin were studied in six Chinese patients with end-stage renal failure. Serum vancomycin concentrations were determined by high-performance liquid chromatography. Observed peak and trough (at 168 h postinfusion) concentrations were in the range of 14.2-35.0 micrograms/ml and 2.8-5.5 micrograms/ml, respectively. The data were analyzed using the PCNONLIN. In all six patients, the data could be fitted well by both the biexponential and triexponential models, but in three patients the latter model provided a better fit. Two-compartment pharmacokinetic parameters obtained from the six patients were t 1/2 alpha 1.13 +/- 0.25 h (mean +/- SEM), t 1/2 beta 121.3 +/- 8.2 h, Vc 0.45 +/- 0.09 L/kg, Vss 1.00 +/- 0.12 L/kg, ClT 5.90 +/- 0.69 ml/kg/h, and the calculated Cmax 25.0 +/- 6.1 micrograms/ml. The mean vancomycin serum protein binding was 18.5 +/- 12.0% as compared with a mean of 46.0% in pooled serum from normal controls. Hemodialysis had no significant effect on vancomycin protein binding or clearance. On the basis of our kinetic study, 500 mg of vancomycin given every seven days is probably adequate treatment for methicillin resistant Staphylococcus aureus infection in end-stage renal failure patients, but further clinical studies are necessary to confirm this.
Aged↗
Right chest electrocardiographic patterns in normal subjects.
Right-sided chest lead ECGs (V3R to V6R) were recorded in 110 normal male subjects who were between the ages of 17 and 22 years old (mean, 17.9 years). The prevalence of the rS pattern decreased from V3R (89 percent) to V6R (37 percent). However, the opposite was the case for the rSr pattern (10 percent in V3R and 36 percent in V6R). The amplitudes of the r wave, S wave and secondary r wave all progressively decreased from V3R to V6R. The prevalence of the qr and qS patterns was 0 and 1 percent, respectively in V3R and 14 and 2 percent, respectively in V6R. A positive ST segment deviation of 0.5 to 1 mm was present in 13 percent of subjects in V3R and 5 percent in V4R. T wave inversion was common and the prevalence increased from V3R (60 percent) to V6R (79 percent).
Adolescent↗
Pasteurella multocida osteomyelitis of the cervical spine in a patient on chronic haemodialysis.
Osteomyelitis due to Pasteurella multocida has been frequently documented but virtually all previous cases have resulted from direct inoculation of the organism or contiguous spread of local infection, following animal bites or scratches. Infections often occur in patients with serious underlying illnesses. Haematogenous osteomyelitis due to P multocida has very rarely been reported particularly in patients with chronic renal failure. We describe a patient on chronic haemodialysis who developed an acute febrile illness, two months following a monkey bite, caused by haematogenous cervical vertebral osteomyelitis due to P multocida.
Animals↗
The nucleotide sequences of two rice histone H3 genes.
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Amino Acid Sequence↗