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D J Kramer

Publications and source records attributed to D J Kramer.

At least 19 recordsLinked to original sources
PubMed2002

Clinical and laboratory evaluation of the safety of a bioartificial liver assist device for potential transmission of porcine endogenous retrovirus.

BACKGROUND: The potential risk of transmission of porcine endogenous retroviruses (PERV) from xenogeneic donors into humans has been widely debated. Because we were involved in a phase I/II clinical trial using a bioartificial liver support system (BLSS), we proceeded to evaluate the biosafety of this device. MATERIALS AND METHODS: The system being evaluated contains primary porcine hepatocytes freshly isolated from pathogen-free, purpose-raised herd. Isolated hepatocytes were installed in the shell, which is separated by a semipermeable membrane (100-kD nominal cutoff) from the lumen through which the patients' whole blood is circulated. Both before and at defined intervals posthemoperfusion, patients' blood was obtained for screening. Additionally, effluent collected from a clinical bioreactor was analyzed. The presence of viral particles was estimated by reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assays. For the detection of pig genomic and mitochondrial DNA, sequence-specific PCR (SS-PCR) was used. Finally, the presence of infectious viral particles in the samples was ascertained by exposure to the PERV-susceptible human cell line HEK-293. RESULTS: PERV transcripts, RT activity, and infectious PERV particles were not detected in the luminal effluent of a bioreactor. Culture supernatant from untreated control or mitogen-treated porcine hepatocytes (cleared of cellular debris) also failed to infect HEK-293 cell lines. Finally, RT-PCR, SS-PCR, and PERV-specific RT assay detected no PERV infection in the blood samples obtained from five study patients both before and at various times post-hemoperfusion. CONCLUSION: Although longer patient follow-up is required and mandated to unequivocally establish the biosafety of this device and related bioartificial organ systems, these analyses support the conclusion that when used under standard operational conditions, the BLSS is safe.

Animals↗
PubMed2001

High detection rate of breast ductal carcinoma in situ calcifications on mammographically directed high-resolution sonography.

OBJECTIVE: To assess the high-frequency sonographic characteristics of ductal carcinoma in situ of the breast. METHODS: In a retrospective review, we identified 18 patients with biopsy-proven pure ductal carcinoma in situ who had received mammographic and high-frequency sonographic examinations at transducer frequencies of 8-15 MHz, 8-5 MHz and 5 to 13 MHz [corrected]. RESULTS: All 18 patients had mammographically identified calcifications. Four (22%) of the 18 had either asymmetric focal mammographically identified densities or masses with the calcifications. These calcifications were identified sonographically in 17 (94%) of the 18 patients. In 9 (50%) of 18 patients, the calcifications were associated with sonographically detected malignant masses, and in 3 (17%) of 18 patients the calcifications were within focally dilated ducts. Lesions that had masses or dilated ducts visible on sonography represented 9 (82%) of 11 of the grade 3 neoplasms and only 2 (28%) of 7 of the grade 1 and 2 tumors. This difference was statistically significant (P < .039). CONCLUSIONS: Our study showed that ductal carcinoma in situ may appear on sonography as calcifications, masses, or focally dilated ducts. Those lesions that were associated with masses or dilated ducts on sonography were more likely high-grade histologic specimens.

Breast Neoplasms↗
PubMed2001

Comparison of fever treatments in the critically ill: a pilot study.

BACKGROUND: Fever in critically ill patients is often treated with antipyretics or physical cooling methods. Although fever is a host defense response that may benefit some critically ill patients, others may not tolerate the cardiovascular demands associated with fever. OBJECTIVES: To compare antipyretics and physical cooling for their effects on core body temperature and cardiovascular responses in critically ill patients. METHODS: The antipyretic administered was 650 mg of acetaminophen. Physical cooling was accomplished by anterior placement of a cooling blanket at 18 degrees C. Core temperature and cardiovascular responses were measured in 14 febrile (body temperature, 38.8 degrees C) critically ill patients at baseline before treatment and up to 3 hours after treatment. Patients able to receive acetaminophen were randomly assigned to receive either acetaminophen only (n = 5) or acetaminophen in combination with a cooling blanket (n = 3). Patients not able to receive acetaminophen were treated with physical cooling only (n = 6). RESULTS: Mean body temperature decreased minimally from baseline to 3 hours after treatment in the physical-cooling-only group (from 39.1 degrees C to 39.0 degrees C) and in the physical cooling and acetaminophen group (from 39.1 degrees C to 38.6 degrees C), but the mean body temperature increased in the acetaminophen-only group (from 39.2 degrees C to 39.4 degrees C). Other notable findings included a slight increase in systemic vascular resistance index in the physical-cooling-only group and in the physical-cooling-plus-acetaminophen group. CONCLUSIONS: Although the study included only 14 subjects, the findings will provide information for future studies in febrile critically ill patients.

Acetaminophen↗
PubMed2000

Short-term and long-term outcome prediction with the Acute Physiology and Chronic Health Evaluation II system after orthotopic liver transplantation.

OBJECTIVE: To evaluate the relationship between the postoperative Acute Physiology and Chronic Health Evaluation (APACHE) II score and mortality at hospital discharge and at 1 yr in liver transplant recipients. POPULATION: Adult orthotopic liver transplant (OLTX) recipients (n = 599) admitted to the intensive care unit postoperatively at a university hospital. METHODS: The cohort was split randomly into development and validation sets. Three models were compared for each end point: a) the original APACHE II slope with the original APACHE II postgastrointestinal surgery intercept; b) the original APACHE II slope with an OLTX-specific intercept generated from the development set; and c) an OLTX-specific slope and intercept generated from the development set. Goodness-of-fit and calibration were assessed by the Hosmer-Lemeshow C statistic (where p>.05 suggests good fit) and standardized mortality ratios. Discrimination was assessed by receiver operator characteristic area under the curve analysis. MEASUREMENTS AND MAIN RESULTS: Hospital and 1-yr mortality rates were 9.9% and 15.9%, respectively. The APACHE II score was strongly associated with mortality (chi-square, p<.0001), but when used with the original equation, it significantly overestimated hospital mortality (standardized mortality ratio, 0.73 [confidence interval, 0.58-0.99]). Using the OLTX-specific approaches, goodness-of-fit for both hospital and 1-yr mortality was good (p = .2-.57) but discrimination was only moderate (receiver operator characteristic area under the curve, 0.675-0.723). CONCLUSIONS: APACHE II is a good predictor of short- and long-term mortality after liver transplantation, especially when using OLTX-specific coefficients. Because fit and calibration were better than discrimination, APACHE II will be most useful in the prediction of risk for groups of patients (e.g., in clinical trials or institutional comparisons) rather than for individuals. This study raises the possibility that APACHE II may be useful for long-term mortality prediction in other critically ill populations. The overestimation of mortality using the original equation suggests that orthotopic liver transplantation, by reversing the underlying pathophysiology, may modify risk.

APACHE↗
PubMed1999

Novel bioartificial liver support system: preclinical evaluation.

Preclinical safety and efficacy evaluation of a novel bioartificial liver support system (BLSS) was conducted using a D-galactosamine canine liver failure model. The BLSS houses a suspension of porcine hepatocytes in a hollow fiber cartridge with the hepatocytes on one side of the membrane and whole blood flowing on the other. Porcine hepatocytes harvested by a collagenase digestion technique were infused into the hollow fiber cartridge and incubated for 16 to 24 hours prior to use. Fifteen purpose-bred male hounds, 1-3 years old, 25-30 kg, were administered a lethal dose, 1.5 g/kg, of D-galactosamine. The animals were divided into three treatment groups: (1b) no BLSS treatment (n = 6); (2b) BLSS treatment starting at 24-26 h post D-galactosamine (n = 5); and (2c) BLSS treatment starting at 16-18 h post D-galactosamine (n = 4). While maintained under isoflurane anesthesia, canine supportive care was guided by electrolyte and invasive physiologic monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, urinary catheter, and end-tidal CO2. All animals were treated until death or death-equivalent (inability to sustain systolic blood pressure > 80 mmHg for 20 minutes despite massive fluid resuscitation and/or dopamine administration), or euthanized at 60 hours. All animals developed evidence of liver failure at 12-24 hours as evidenced by blood pressure lability, elevated ICP, marked hepatocellular enzyme elevation with microscopic massive hepatocyte necrosis and cerebral edema, elevated prothrombin time, and metabolic acidosis. Groups 2b and 2c marginally prolong survival compared with Group 1b (pairwise log rank censored survival time analysis, p = 0.096 and p = 0.064, respectively). Since survival times for Groups 2b and 2c are not significantly different (p = 0.694), the groups were combined for further statistical analysis. Survival times for the combined active treatment Groups 2b and 2c are significantly prolonged versus Group 1b (p = 0.047). These results suggest the novel BLSS reported here can have a significant impact on the course of liver failure in the D-galactosamine canine liver failure model. The BLSS is ready for Phase I safety evaluation in a clinical setting.

Animals↗
PubMed1999

Fulminant hepatic failure.

Fulminant hepatic failure is a disease of varied causes and a high mortality rate. A sudden onset, jaundice, hepatic encephalopathy, and multiorgan failure are the hallmarks of this syndrome. The management of patients with FHF requires a multidisciplinary approach and intense monitoring. The availability of liver transplantation has provided the means to rescue such patients from near-certain death. Early prognostication and timely availability of donor livers are requirements for a successful outcome. The development of effective artificial liver support devices may greatly prolong the window of opportunity to provide a donor liver, or alternatively, to allow the native liver to regenerate.

Acetaminophen↗
PubMed1999

Early complications after orthotopic liver transplantation.

The cost and impact of early post-transplant complications continue to be high. Diagnosis and management involves a high index of suspicion, rapid diagnostic and therapeutic interventions, and elimination of technical problems. Preoperative assessment of the donor and recipient medical condition and meticulous attention to detail during the technical performance of OLTx are the mainstays in achieving a good outcome.

Bacterial Infections↗
PubMed1998

Mononeuropathies associated with liver transplantation.

Mononeuropathies associated with orthotopic liver transplantation were evaluated in a prospective manner. Ten percent of liver transplant recipients were noted to have focal peripheral nerve lesions in the postoperative period. The ulnar nerve was most commonly involved, with intraoperative compression or postoperative trauma as possible mechanisms of injury. Other upper extremity mononeuropathies were likely a result of vascular cannulations. No brachial plexus injuries occurred. Diabetes and alcoholism were not risk factors for the development of a mononeuropathy.

Adult↗
PubMed1998

Impact of acute renal failure on mortality in end-stage liver disease with or without transplantation.

BACKGROUND: Acute renal failure (ARF) is traditionally considered a poor prognostic factor in end-stage liver disease and is associated with a mortality approaching 90%. While the increased use of orthotopic liver transplantation (OLTX) has changed the outcome for patients with end-stage liver disease (ESLD), it is not clear whether this has affected the outcome of patients with ESLD and ARF. METHODS: We prospectively followed the course of ARF in 177 patients with ESLD being evaluated for OLTX. Of these patients 111 received OLTX. In-hospital mortality was compared to that of 316 ESLD patients without ARF, of these 196 received OLTX. Variables include severity of illness as assessed by APACHE II, co-morbid conditions, oliguria, need for renal replacement therapy, and etiologies of ESLD and ARF. These variables were evaluated with respect to the outcome in-hospital mortality by multiple regression analysis for patients with ARF. RESULTS: Mortality was significantly higher in oliguric versus non-oliguric patients and in patients who required renal replacement therapy. Mortality correlated strongly with the number of co-morbid conditions, especially sepsis, encephalopathy, respiratory failure, and DIC. For OLTX recipients who developed ARF, no significant difference in survival occurred whether the ARF was pre-OLTX or post-OLTX. CONCLUSION: ARF was associated with an increased mortality consistent with the known adverse prognostic effect of ARF in ESLD. However, the effect of ARF on mortality was remarkably reduced in patients who received a functioning OLTX. Since expected mortality generated from APACHE II scores was higher in the ARF groups, it is not clear that there is an additional effect of ARF beyond the physiologic derangements captured by APACHE II. ARF per se should not necessarily be a contraindication to liver transplant.

Acute Kidney Injury↗
PubMed1998

Quantitative analysis of respiratory, motor, and sensory function after supraclavicular block.

UNLABELLED: The incidence and clinical significance of hemidiaphragmatic paresis after supraclavicular block of the brachial plexus is unknown. Eight healthy volunteers received a supraclavicular block with a standard technique using 30 mL of 1.5% lidocaine. Respiratory function was assessed with ultrasound of the diaphragm, respiratory inductive plethysmography (RIP), and pulmonary function tests (PFT) every 20 min. Sensory block was assessed with pinprick and motor block with isometric force dynamometry every 20 min. Four of eight subjects demonstrated hemidiaphragmatic paresis on both ultrasound and RIP. No subject experienced changes in PFT values or subjective symptoms of respiratory difficulty. Motor and sensory blockade outlasted hemidiaphragmatic paresis. These results are contrasted to the often symptomatic, 100% incidence of hemidiaphragmatic paresis seen after interscalene block. In this study of healthy volunteers, supraclavicular block was associated with a 50% incidence (95% confidence interval 14-86) of hemidiaphragmatic paresis that was not accompanied by clinical evidence of respiratory compromise. IMPLICATIONS: Interscalene block is always associated with diaphragmatic paralysis and respiratory compromise. The significance of these side effects after supraclavicular block is unknown. Using sensitive measures of respiratory function, we determined that diaphragmatic paralysis occurs less often with the supraclavicular approach and is not associated with respiratory difficulties in healthy subjects.

Adult↗
PubMed1998

Etiology of metabolic acidosis during saline resuscitation in endotoxemia.

We sought to understand the mechanism of metabolic acidosis that results in acute resuscitated endotoxic shock. In six pentobarbital-anesthetized dogs, shock was induced by Escherichia coli endotoxin infusion (1 mg/kg) and was treated with saline infusion to maintain mean arterial pressure > 80 mmHg. Blood gases and strong ions were measured during control conditions and at 15, 45, 90, and 180 min after endotoxin infusion. The mean saline requirement was 1833+/-523 mL over a 3 h period. The total acid load from each source was calculated using the standard base deficit. The mean arterial pH decreased from 7.32 to 7.11 (p < .01); pCO2 and lactate were unchanged. Saline accounted for 42% of the total acid load. However, 52% of the total acid load was unexplained. Although serum Na+ did not change, serum Cl-increased (127.7+/-5.1 mmol/L vs. 137.0+/-6.1 mmol/L; p=.016). We conclude that saline resuscitation alone accounts for more than one-third of the acidosis seen in this canine model of acute endotoxemia, whereas lactate accounts for less than 10%. A large amount of the acid load can be attributed to differential Na+ and Cl- shifts from extravascular to vascular spaces.

Acidosis↗
PubMed1998

Acute myopathy after liver transplantation.

Acute myopathy is a cause of weakness and additional morbidity in a variety of critically ill patients, including transplant recipients. We report the incidence of and risk factors associated with acute myopathy after orthotopic liver transplantation (OLTx). One hundred consecutive adult patients were prospectively assessed for muscle weakness after OLTx. Electrodiagnostic studies and muscle biopsies were performed on consenting affected patients. Potential risk factors for myopathy were evaluated in patients with myopathy versus control subjects. Seven patients developed acute persistent weakness after OLTx. Electrodiagnostic studies were consistent with a necrotizing myopathy. Histopathologic evaluation in five revealed a necrotizing myopathy with loss of myosin thick filaments. A higher initial index of illness severity, dialysis requirement, and higher doses of glucocorticoids were associated with development of myopathy. Patients with myopathy subsequently remained in the intensive care unit (ICU) longer than unaffected patients. In conclusion, acute substantial weakness was a source of additional morbidity in 7% of patients after OLTx. Most had myopathy with loss of myosin thick filaments. Patients with greater severity of illnesses and renal failure requiring dialysis were more likely to be affected. The effect of reducing exposure to corticosteroids in high-risk patients warrants further investigation.

Acute Disease↗
PubMed1997

Splanchnic buffering of metabolic acid during early endotoxemia.

PURPOSE: We sought to determine the sites of metabolic acid production and clearance during acute endotoxemia. MATERIALS AND METHODS: In 10 pentobarbital-anesthetized dogs, flow was measured (ultrasonic probes) for the protal vein, hepatic artery, and renal artery. Catheters were inserted into the hepatic vein, pulmonary artery, renal vein and portal vein. Measurements of blood gases and strong ions were obtained from each site during control conditions and after 30 minutes of intravenous infusion of 1 mg/kg of Escherichia coli endotoxin. The total metabolic acid flux across each organ was calculated using the standard base excess formula and the effective strong ion difference method. PaCO2 was maintained by controlled ventilation. RESULTS: Mean arterial pH decreased from 7.34 to 7.22 with acute endotoxemia. Although transvisceral pH gradients revealed net acid release, the source of this was purely respiratory (carbon dioxide). During early endotoxemia, the gut significantly increased metabolic acid uptake (36.60 +/- 6.60 mmol/h, P < .05). CONCLUSIONS: We conclude that during early endotoxemia in the dog, the gut is a major site of metabolic acid removal.

Acid-Base Equilibrium↗
PubMed1997

Effect of quinupristin/dalfopristin on the outcome of vancomycin-resistant Enterococcus faecium bacteraemia: comparison with a control cohort.

Serious infection with vancomycin-resistant Enterococcus faecium (VREF) strains has no proven effective antimicrobial therapy. We compared the clinical and bacteriological outcomes of 20 patients with VREF bacteraemia treated with quinupristin/dalfopristin (RP 59500), an investigational streptogramin, with a historical cohort of 42 patients with VREF bacteraemia treated with other agents. Quinupristin/dalfopristin demonstrated in-vitro bacteriostatic activity against all 20 initial VREF blood isolates (MIC range 0.03-0.50 mg/L) by macrobroth dilution. The clinical characteristics of both groups were comparable for major outcome-dependent variables. There were five cases of recurrent VREF bacteraemia in the quinupristin/dalfopristin-treated cohort and 21 in the controls (P = 0.11); persistence of VREF at the primary site was found in six and 18 of the evaluable patients with follow-up cultures in these two cohorts (P = 0.06). In-hospital mortality was high in both groups: 65% in the quinupristin/dalfopristin group and 52% in the control group; however, VREF-associated mortality was significantly lower in the quinupristin/dalfopristin group (five and 17 respectively; P = 0.05). Follow-up susceptibility testing of five VREF isolates in the quinupristin/ dalfopristin group did not demonstrate resistance to quinupristin/dalfopristin. Quinupristin/ dalfopristin may be a useful agent for the therapy of serious VREF infection. Further clinical investigations are warranted to confirm or refute its clinical efficacy.

Adult↗