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Biomedical subjects

J A Daller

Publications and source records attributed to J A Daller.

14 recordsLinked to original sources

Conversion from cyclosporine to tacrolimus results in improved creatinine but does not alter lipid profile.

INTRODUCTION: While cyclosporine and tacrolimus use results in similar renal graft survival, the side effect profiles of the drugs are substantially different. We examined the electrolyte and lipid alterations that occurred in our patient population following conversion from cyclosporine to tacrolimus. METHODS: Data for electrolytes, lipid profile, and immunosuppression were analyzed from 98 patients with kidney or kidney-pancreas transplants who were converted from cyclosporine to tacrolimus between October 1994 and June 2001. Results, expressed as mean +/- SEM, were compared to baseline values using the Wilcoxon signed-rank test (P < .05 considered significant). RESULTS: Among these patients, there were 56 men, 42 women, 75 primary transplants, 15 repeat transplants, and 26 multiorgan transplants. The mean time to tacrolimus conversion was 769 +/- 122 days. Creatinine, BUN, and glucose improved after conversion to tacrolimus. Surprisingly, cholesterol, low-density lipoproteins, and high-density lipoproteins levels were not significantly altered, although triglyceride levels demonstrated a significant difference at 1 year. CONCLUSION: Significant improvements in creatinine and BUN were observed following conversion from cyclosporine to tacrolimus. While hypomagnesemia was also seen, there was surprisingly little alteration in lipid profile.

Blood Glucose↗

T-lymphocyte apoptosis is increased by non-interleukin-2-dependent induction in human mixed lymphocyte cultures.

INTRODUCTION: Transplant tolerance is dependent on the apoptotic deletion of allospecific T lymphocytes following interleukin-2 (IL-2)-dependent T-lymphocyte activation. Current immunosuppressive strategies block IL-2 and may prevent T-cell activation. We examined apoptotic alterations in mixed lymphocyte culture (MLC), a model of allospecific lymphocyte activation, by polyclonal rabbit antithymocyte antibody thymoglobulin (rATG) and monoclonal anti-IL-2 receptor antibody basiliximab. METHODS: Human lymphocytes were isolated using Ficoll-Paque gradient. Cesium-irradiated (2500 rad) stimulator cells (10(6) cells/mL) were cocultured with equal numbers of responder cells. Apoptosis was measured using annexin-V staining and propidium iodide exclusion using flow cytometry. Isolated protein was analyzed using Western blotting with densitometry. RESULTS: Apoptosis increased at days 3 and 7 in rATG MLC compared with control and basiliximab MLC. Fas was up-regulated in rATG MLC in a dose-dependent manner, whereas basiliximab did not alter fas. FasL was increased initially and at late time points in rATG MLC. CONCLUSIONS: Polyclonal rATG increased apoptosis and production of the proapoptotic proteins fas and fasL. In contrast, monoclonal basiliximab did not change lymphocyte apoptosis or apoptotic protein production. These results suggest that a specific IL-2 pathway blockade may prevent allospecific tolerance and that a non-IL-2 pathway blockade may encourage apoptosis of allospecifically activated T cells.

Antilymphocyte Serum↗

Disseminated Pseudallescheria boydii (Scedosporium apiospermum) infection in a renal transplant patient.

Transplant recipients receive a number of immunosuppressive medications that result in an increased risk of infection, including infections with microbes that are normally not pathogenic. We describe a patient with end-stage renal disease who underwent kidney transplantation. Six months postoperatively, he presented with a lesion on his ankle, multiple thigh nodules, and right testicular pain. Biopsy of the ankle lesion demonstrated Pseudallescheria boydii (Scedosporium apiospermum), a common environmental fungus. Following orchiectomy, multiple fungal elements were found that were initially described as Aspergillus species, but later identified as P. boydii. In addition, multiple brain abscesses were found on magnetic resonance imaging. Despite treatment with multiple antifungal medications, the patient died of cardiac dysrhythmia. Current diagnostic and therapeutic alternatives for P. boydii are reviewed.

Antifungal Agents↗

Progression of hepatic damage during cold storage after procurement in a liver and kidney donor with HELLP syndrome.

BACKGROUND: HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and acute fatty liver of pregnancy are associated with preeclampsia and fetal defects in fatty acid metabolism. This defect causes the accumulation of metabolites that are harmful to the maternal liver. CASE REPORT: We report a liver and kidney donor with HELLP syndrome and describe the progression of disease in the liver during cold storage. Before procurement, liver biopsy demonstrated minimal necrosis. However, after cold storage, repeat biopsy demonstrated more than 30% necrosis. The liver was not engrafted; the kidneys were transplanted without complication. CONCLUSION: Livers procured from patients with HELLP syndrome should be carefully evaluated for progression of hepatic damage during cold storage and transport.

Adult↗

Hepatic hemangioendothelioma: clinical experience and management strategy.

PURPOSE: This study sought to define management strategies based on clinical experience in treating infantile hepatic hemangioendothelioma. METHODS: A retrospective analysis of patients with hemangioendothelioma presenting to a tertiary liver transplantation center between 1989 and 1997 was performed. RESULTS: Thirteen patients (median age, 14 days) with hemangioendothelioma were identified. Congestive heart failure (P<.03) and abdominal mass (P<.081) were predictive of 5-month mortality rates. Ultrasonography and computerized axial tomography were the diagnostic modalities most commonly used. Treatment strategies consisted of medical management (steroids and alpha-interferon) and interventional modalities (hepatic artery ligation or embolization, resectional surgery, or orthotopic liver transplantation). Patients who underwent resectional surgery, with or without orthotopic liver transplantation, had a lower 5-month mortality rate (P<.02) and a greater 2-year survival rate (P<.003) than did those who underwent hepatic artery ligation or embolization. Early morbidity and mortality tended to be a consequence of the primary lesion, whereas late morbidity and mortality were reflective of the treatment modality used. CONCLUSIONS: In cases of failed medical management, resectional therapy should be used when possible. If partial hepatectomy is not technically achievable, hepatic artery embolization should be used either as definitive therapy or as a temporizing measure until orthotopic liver transplantation is possible.

Algorithms↗

Lack of hematologic effects of recent ethanol ingestion by trauma patients.

A retrospective investigation was conducted to determine if acute ethanol (EtOH) ingestion before injury leads to hematologic impairment as noted by coagulation and transfusion parameters. Patients older than 18 years of age were grouped according to the presence or absence of detectable EtOH concentrations in the blood, with further subdivision based on an Injury Severity Score of 8 or less or 9 or more. The following direct and indirect indicators of hematologic function were studied: volume of resuscitation fluids administered (including blood products), prothrombin time, partial thromboplastin time, and hematocrit. Of the 304 patients who were evaluated, 152 had detectable EtOH concentrations and 136 had undetectable EtOH concentrations; 16 patients had not been tested for blood EtOH concentrations and were excluded from the analysis. There were no significant differences between groups with regard to blood or fluid requirements or coagulation parameters. Detectable blood EtOH concentrations in trauma patients are not associated with significant changes in transfusion requirements or coagulation parameters compared to patients without detectable EtOH concentrations.

Adolescent↗

The hepatotoxicities of endotoxin and ethanol comparisons in vitro using the precision-cut rat liver slice model.

Using the precision-cut rat liver slice model, the in vitro toxicities of endotoxin and ethanol, independently and in combination, were evaluated. Hepatotoxicity was assessed by two measures: the leakage of LDH from slice to medium and the ability of slices to reduce a tetrazolium compound, MTT. Ethanol, in concentrations of 1% and greater, exhibited a time and dose dependent hepatotoxicity; MTT reductive capacity was more profoundly affected than LDH leakage. Endotoxin (0.1 to 100 micrograms/ml), however, had only a modest effect on MTT reduction and did not perturb LDH leakage. When combined in vitro, the toxicities of 2% ethanol and various concentrations of endotoxin were additive. Slices prepared from the livers of rats injected ip with endotoxin one day previously sustained considerably more injury (compared to normal rat liver slices) upon subsequent in vitro exposure to either endotoxin or ethanol. Prior in vivo exposure to ethanol, however, did not affect the subsequent in vitro toxicity of endotoxin. Thus, while endotoxin exhibits only subtle toxic effects upon liver slices in vitro, exposure to endotoxin in vivo renders the liver more susceptible to subsequent direct injury by endotoxin or ethanol.

Animals↗

Suramin, a protein kinase C inhibitor, impairs hepatic regeneration.

Previously we have shown that partial hepatectomy (PH) or exposure of the liver to the mitogen prolactin induces activation of hepatic protein kinase C (PKC). Here, we used suramin, an antitrypanosomal and chemotherapeutic drug which inhibits that enzyme, as a probe of PKC signal transduction in the regenerative response after PH in the rat. Suramin was administered i.p. in nonhepatotoxic doses of 20 to 160 mg/kg 14 days prior to PH. Three measures of hepatic DNA synthesis or cell division, thymidine kinase activity, [3H]thymidine incorporation, and mitotic index were inhibited in a dose-dependent fashion. Baseline PKC activity, in both the cytosolic and particulate fractions, was unchanged by suramin. After PH, PKC activation, signalled by an increase in activity in the particulate fraction, was observed in control rats at 30 and 60 min. However, rats which had previously received suramin demonstrated dose-dependent inhibition of PKC activation. Suramin is known to also disrupt the binding of certain growth factors to their receptors. But if inhibition of PKC activation were conferred by interference with growth factor-receptor binding by suramin, then the generation of diacylglycerol, the second messenger for PKC activation, should likewise be impaired. However, we observed that the diacylglycerol mass generated at 15, 30, and 45 min after PH was not altered by suramin pretreatment. We conclude that the diminution in DNA synthesis after PH by suramin is likely the consequence of direct inhibition of PKC, suggesting that PKC activation is an important, perhaps obligatory, signal transduction event in liver regeneration.

Animals↗

Hematologic effects of ethanol consumption in trauma patients.

OBJECTIVE: To determine the effects of ethanol (EtOH) ingestion by trauma patients on the hematologic system as evidenced by coagulation abnormalities and transfusion requirements. DESIGN: Retrospective chart review. The injury severity score (ISS) was determined for each patient. Patients were grouped according to presence of EtOH (+EtOH) and absence of EtOH (-EtOH) with further subdivision based on an ISS < or = 8 or > or = 9. SETTING: University medical center. PATIENTS: All adult trauma patients admitted during a one-month period. MAIN OUTCOME MEASURES: The volume of resuscitation fluids (including blood products) administered, laboratory parameters indicative of bleeding, and length of stay. RESULTS: Of 104 evaluable patients, 38 had measurable EtOH concentrations, 46 had undetectable EtOH concentrations, and the remaining 20 patients had not been tested. Although isolated, statistically significant differences were found among groups for some of the outcome measures, there were no clinically important differences. CONCLUSIONS: EtOH ingestion prior to injury did not appear to cause significant alterations in the hematologic system of trauma patients, but a larger study is needed to confirm these findings.

Adolescent↗

Falsely decreased total serum calcium concentration associated with iron dextran injection.

We cared for a patient in whom iron dextran administration interfered with the determination of total serum calcium concentration. An unexpected elevation in serum phosphorus concentration also occurred after the iron dextran infusion. A MEDLINE search from 1966 to present was conducted, and the manufacturer of the iron dextran was contacted for information related to these findings. Several drugs and diseases were found that may decrease serum calcium and increase phosphorus concentrations. We found one anecdotal citation of iron dextran interfering with serum calcium concentrations, but no reports of interference with serum phosphorus concentrations. Doses of iron dextran in excess of 250 mg may cause a false decrease in total calcium concentration more than 4 hours after the infusion is completed. A false increase in serum phosphorus concentrations after the infusion requires further investigation.

Antiviral Agents↗