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PubMedDate not supplied

Postprocedural aspiration test to predict adequacy of dialysis following tunneled catheter placement.

The objective of the study was to determine if a timed aspiration technique with a 20-ml syringe can be used to predict adequacy of blood flow in tunneled dialysis catheters. Sixteen patients referred for de novo placement or manipulation of failing tunneled hemodialysis catheters had the time it takes to fill a 20-ml syringe with the plunger fully withdrawn measured to the nearest tenth of a second. These measurements were correlated with flow rates recorded in dialysis just prior to (if failed catheter) and in the following dialysis session with adequacy determined as at least 300 ml/min. Syringe-filling time (22 catheters in 16 patients) was plotted against adequacy of dialysis. The mean time to fill a 20-ml syringe was 2.2 sec, with a range of 1.0-4.7 sec. The mean time to fill syringes for catheters with adequate dialysis was 1.7 +/- 0.5 sec, and for inadequate catheters, it was 2.8 +/- 0.8 sec. These differences are statistically significant (p < 0.001). Using a filling time of greater than or equal to 2 sec as a threshold gives the highest sensitivity (100%) for predicting inadequate dialysis while maintaining high specificity (75%). To achieve a specificity of 100%, a 3-sec cutoff would be necessary, but would lead to a sensitivity of only 20%. A simple and objective aspiration technique can be performed at the time of tunneled dialysis catheter placement/manipulation to reasonably predict adequacy of subsequent dialysis.

Adult↗
PubMed1997

The limits of generalized cardiac screening tests for predicting cardiac complications after infrainguinal arterial reconstruction.

We examined the relative efficacies of different cardiac screening strategies for infrainguinal arterial bypass. The outcomes of 205 elective leg bypass procedures over a 10-year period, including myocardial infarction (MI), total cardiac complications, and mortality were tallied. Clinical risk factors popularized by Goldman and Eagle, and the results of dipyridamole thallium myocardial imaging (DThal) were recorded. The overall mortality rate was 3.4%, with a 3.4% incidence of MI and a 5.4% total cardiac complication rate. Both abnormal DThal (p = 0.011) and Goldman class II-IV (p = 0.030) were significant predictors of MI and cardiac death, but both suffered from poor specificity and positive predictive value. Because logistic regression analysis identified a correlation between angina, CHF, and an abnormal DThal, a customized screening strategy was developed to include the presence of angina, CHF and an abnormal DThal. Eighty-eight percent of patients suffering MI or death met these criteria, while only 11% of the complication-free group did. This screening strategy provided a superior sensitivity of 88%, specificity of 89%, positive predictive value of 25%, and 99% negative predictive value. A customized screening strategy (angina, CHF, abnormal DThal), developed from a 10-year experience with a single patient group, provided better predictive accuracy than any generalized screening formula.

Adult↗
PubMed1999

Non-Alcoholic Steatohepatitis (NASH).

Non-alcoholic steatohepatitis (NASH) is an increasingly common cause of persistently abnormal liver tests. Establishing a diagnosis of NASH requires the secure exclusion of alcohol abuse and hepatitis C as an alternate cause of liver injury. The gold standard of diagnosis is liver biopsy. Unfortunately, NASH, although a common entity, is without a satisfactory treatment. Weight reduction, optimum blood glucose control, and elimination of medications implicated in causing the disorder are sensible first steps in treatment. Drug therapy should not be used unless there is histologic evidence of necro-inflammatory injury and/or fibrosis. Ursodeoxycholic acid (UDCA) has been reported to be of benefit in non-controlled trials and anecdotal case reports. Our approach is to use ursodeoxycholic acid in a dose of 15 mg/kg, and to monitor serial liver enzyme tests. Predictable normalization of liver tests often results, but relentless progression of liver injury can occur in the face of consistently normal liver tests. Close follow-up is mandatory after establishing a diagnosis of NASH. Newer, more effective drugs are needed to treat NASH in a controlled trial environment.

Journal Article↗
PubMed1993

In vitro tests to predict in vivo performance of liposomal dosage forms.

Design of liposome-based formulations for clinical use can be assisted by employing in vitro assays to predict pharmacokinetics and bioavailability of the drug before employing costly and time-consuming in vivo studies. For such formulations of the anti-cancer drug doxorubicin (DXR) we developed two assays. (A) An assay which determines the dilution-induced DXR release in buffers and plasma. This assay was employed to evaluate two liposomal DXR formulations: (i) membrane-associated liposomal doxorubicin (L-DXR), and (ii) sterically-stabilized liposomes which encapsulate DXR in the aqueous phase of the liposomes (S-DXR). The agreement between the dilution-induced release assay in vitro and the pharmacokinetics of DXR administrated either as L-DXR or as S-DXR in humans suggests that the dilution release assay can be used as a predictor for the pharmacokinetic performance of liposomal formulations. (B) An assay which determines intracellular drug release induced by liposome degradation in the presence of mouse liver lysosome lysate. This assay was used to assess bioavailability of DXR when delivered via L-DXR, which are taken up by the reticuloendothelial system (RES). (C) An assay which complements conventional chromatographic analyses (HPLC or TLC) of the drug, in which a DXR adduct or aggregate was determined by using Sephadex LH-20 gel exclusion chromatography.

Animals↗
PubMed2004

Donor non-specific IFN-gamma production by primed alloreactive cells as a potential screening test to predict the alloimmune response.

UNLABELLED: In order to devise an in vitro experimental system that predicts the in vivo generation of T lymphocytes capable of initiating the rejection process and thereby to individualize the immunosuppressive strategy in a rational way, we studied the in vitro strength of alloresponses to non-specific donors as a surrogate tool to identify patients with heightened alloimmunity. We measured interferon gamma (IFN-gamma) produced by primed alloactivated peripheral blood lymphocytes (p-allo-PBL) against third party stimulator PBLs in four groups by the enzyme linked immunospot (Elispot) assay: 16 with excellent renal transplant function (group 1); nine with chronic rejection (group 2); 11 allo-sensitized (PRA>60%) by graft loss on dialysis (group 3) and 36 normal controls (group 4). The Elispot assay was performed using 10(6) irradiated stimulator PBLs and 10(5) responder PBLs for 24 and 48 h. Each responder was challenged by 2-4 independent stimulators. RESULTS: At 24 h, mean+/-S.D. and 95% confidence intervals (CI) of spots/10(5) responder cells were 12.8+/-8.7 (10-15.5); 57.8+/-116 (11.9-103.7); 77.5+/-91.3 (39.8-115.2); and 20.7+/-17.9 (17.4-24.1) in groups 1-4, respectively. P<0.01 between groups 1 or 4 vs. 2 or 3. An arbitrary spot level of >or=30 has positive and negative predictive values of 58% and 95%, respectively, sensitivity of 94% and specificity of 65% to identify patients with enhanced immunity. CONCLUSION: Chronic allogeneic stimulation is associated with enhanced p-allo-PBL. IFN-gamma producing frequencies against third party stimulators. Significant variation in IFN-gamma spots produced by p-allo-PBL may be useful to choose less allogeneic donors. Diminished p-allo-PBL alloresponse to third party stimulators may predict transplant patients with decreased alloresponses who may benefit from lesser immunosuppressive drugs.

Cells, Cultured↗
PubMed1999

Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children.

BACKGROUND: Patients with multiple endocrine neoplasia (MEN) type 2 are at risk for early medullary thyroid carcinoma (MTC). Recently, the cloning of the ret oncogene has made it possible to identify patients at risk for MEN 2 syndrome with a high degree of reliability before presenting any symptoms. METHODS: Children of families with MEN 2 were screened genetically if one of the parents was a known gene carrier of the RET proto-oncogene. If they were carriers, thyroidectomy was performed. RESULTS: The authors report five children with MEN 2 who underwent prophylactic thyroidectomy irrespective of the results of calcitonin screening tests after genetic screening had shown that they were carrier of the RET proto-oncogene. Apart from a temporary hypocalcemia in one, the operations were uneventful. Pathology results showed MTC in three children of one family with MEN 2A at age 2, 3, and 6 years. In two families with MEN 2B the thyroidectomy specimen showed bilateral MTC in a 1-year-old and a 3-year-old child. CONCLUSIONS: These findings show that MTC occurs at very young age in children with MEN 2. The authors advocate performing prophylactic thyroidectomy in the first year of life in children with MEN 2B and at age 2 years in children with MEN 2A to obtain an optimal cure rate.

Carcinoma, Medullary↗
PubMed1988

A new test to predict reversibility of hydronephrotic atrophy after stable partial unilateral ureteral obstruction.

In previous studies we showed that hydronephrotic atrophy develops only in the first weeks after stable partial ureteral obstruction, and does not progress thereafter. Relief of obstruction only in the "destructive phase" and not in the later "steady-state phase" seems to improve or prevent hydronephrotic atrophy. Since the duration of partial ureteral obstruction is often not known, we studied urinary enzymes of rat kidneys after stable partial unilateral ureteral obstruction to identify the destructive phase. We chose as an example of the tubular lysosomal enzyme N-acetyl glucosaminidase (NAG) and as an example of the brush border enzyme gamma-glutamyl-transferase (Gamma-GT). NAG concentration but not so much Gamma-GT concentration was higher in the urine of the obstructed kidneys than in the urine of the contralateral control kidney, in the first two weeks after operation, and then returned to normal. These observations lead to the conclusion that the "destructive phase" after ureteral obstruction can be identified by the appearance of high urinary tubular lysosomal enzyme content. The clinical implication is that the timing of relief of asymptomatic stable partial ureteral obstruction of unknown duration can be based on the concentrations of urinary lysosomal enzymes.

Acetylglucosaminidase↗