Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

What community measurements can be used to predict bone disease in patients with COPD?

BACKGROUND: Osteoporosis is common in patients with COPD. Previously we have reported that loss of fat-free mass (FFM), measured by dual X-ray absorptiometry (DXA) is associated with loss of bone mineral density (BMD). In addition, in patients with a low body mass index (BMI) and a low FFM, all had evidence of bone thinning, 50% having osteopenia and 50% osteoporosis. We explored the utility of different anthropometric measures in detecting osteoporosis in a community-based COPD population. METHODS: Patients with confirmed COPD and not on long-term oral corticosteroids (n=58) performed spirometry. They underwent nutritional assessment by skinfold anthropometry, midarm circumference, calculation of both % ideal body weight (IBW) and BMI. All had DXA assessment of BMD. RESULTS: A total of 58 COPD patients had anthropometric measurements taken, with a mean age of 66.8 (SD 8.7) years, 31 (58%) were male, with a forced expiratory volume in 1s (FEV(1)) of 54.17 (20.18)% predicted. Osteoporosis was present at either the hip or lumbar region in 14 patients (24%). The useful anthropometric measurements identifying those with osteoporosis were both % IBW and BMI. The adjusted odds ratio for %IBW was 0.93 (95% confidence interval (CI) 0.87, 0.99), p=0.016 and for BMI: 0.79 (0.64-0.98), p=0.03. The receiver operating characteristics (ROC) score for both was 0.88, indicating a good fit. CONCLUSION: Osteoporosis is common, even in patients with mild airways obstruction. Nutritional assessment, incorporating a calculation of their BMI or %IBW may confer an additional benefit in detecting those at risk of osteoporosis and guide referral for BMD measurement.

Seasonality and breeding success of captive and wild Tasmanian devils (Sarcophilus harrisii).

The synchrony and timing of reproductive events are crucially important factors to maximize individual and offspring survival, especially in seasonal environments. To increase our understanding of the physiological basis of seasonality and the influence of associated environmental factors (maximum temperature, day length and rate of day length change associated with different latitudes) on reproduction in Tasmanian devils, we reviewed records and research data from captive facilities throughout Australia in comparison to those from a wild population study (1974-1987). Overall, breeding activity began 2 weeks earlier in the captive than the wild population (week 5.7 ± 0.6 versus week 7.7 ± 0.5 for devils entering into estrus during the first two week phase; n = 24 and n = 23 respectively). If the timing of reproductive activity is considered against absolute day length rather than date, both the captive and wild populations displayed similar distributions (12.9 ± 0.7 h versus 13.0 ± 0.7 h respectively; P < 0.01) confirming day length as a proximal cue involved in eliciting a physiological response to trigger seasonal reproductive activity regardless of location. Wild devils had a higher breeding success (75%; n = 169 versus 43%; n = 115) and larger litter size (3.4 ± 0.9 versus 2.8 ± 1.1 joeys per litter) than captive devils (P < 0.05). Mean maximum temperature at the onset of reproductive activity (P < 0.05) was higher for the captive than the wild population (28.1 ± 4.0 °C versus 22.3 ± 2.7 °C respectively). The drivers for reproductive success in captive Tasmanian devils are likely multifactorial, but our results suggest that elevated temperatures associated with shifts in breeding activity and geographical location should be examined further.

Attaining a correct diagnosis of COPD in general practice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common. Diagnosis should include objective evidence of airways obstruction and spirometry is recommended in guidelines and the general medical services contract in the UK. We assessed the impact of spirometry in general practice. METHOD: We determined by questionnaire the availability, staff training, use and the interpretation results of spirometry in 72% of general practices in Wales. We reviewed the diagnosis of COPD previously made in two general practices without spirometry. RESULTS: Most practices had a spirometer (82.4%) and used it (85.6%). Confidence in use and interpretation of results varied widely: 58.1% were confident in use and 33.8% confident in interpretation. Spirometry was performed more often if confident in use and interpretation (both P<0.001) and was related to greater training periods (P<0.001). Spirometric confirmation of COPD varied widely (0-100%, median 37%). Of the 125 patients previously diagnosed with COPD 61 had spirometric confirmation, while 25 had reversible obstruction (range 210-800 mls), 34 had normal and 5 had restrictive spirometry. CONCLUSION: Despite incentives to perform spirometry in general practice, lack of adequate training in use and interpretation suggests use is confounded and the diagnosis of COPD is likely to be made on imprecise clinical grounds.

Controlled trial of the sequential use of streptokinase and ancrod in the treatment of deep vein thrombosis of lower limb.

Treatment with streptokinase ('Kabikinase') was given to 26 patients with venographically confirmed deep vein thrombosis extending into the popliteal vein or above. Treatment was continued for 4 days and the patients were allocated randomly to oral anticoagulant therapy or a course of treatment with ancrod ('Arvin') for 6 days followed by oral anticoagulant therapy. The degree of thrombolysis as judged by further venographic examination at 10 days was not significantly different between the 2 groups. The majority of patients showed clinical improvement but there was no appreciable difference between the groups at 3 and 6 months. Haemorrhagic complications were a more serious problem during the period of treatment with ancrod than during the equivalent period in the control group.

The effects of prenatal tertiary butanol administration in CBA/J and C57BL/6J mice.

Pregnant mice of the CBA/J and C57BL/6J strains were given either tertiary butanol (10.5 mmoles/kg, p.o.) or an equivalent volume of tap water twice daily from day 6 through day 18 of gestation. Examination on day 18 revealed significantly more resorptions per litter in the t-butanol-treated animals but no interstrain difference. Tertiary butanol did not significantly affect the body weight of the survivors nor produce significant abnormalities in either strain. Subsequent blood concentration profiles in female C57BL/6J mice indicated that the treatment regimen produced blood levels equivalent to teratogenic ethanol treatment. Mice receiving 3 days of t-butanol treatment did not eliminate the drug more rapidly than control animals, indicating that tolerance was not a factor in the treatment regimen. Since t-butanol shares membrane disordering effects with ethanol but is not metabolized by the same pathway, a role for acetaldehyde or the process of ethanol metabolism is suggested in ethanol teratogenicity.

Ultrasound: a simple noninvasive examination of cervical swellings.

Ultrasound scanning is a simple investigation that is recommended for preoperative diagnosis of cervical swellings. Its clinical utility has been demonstrated by use in four cases: a parotid cyst, an abscess, a lymph node metastasis, and a branchial cyst.

Charge and reimbursement analysis for intensive care unit patients in a large tertiary teaching hospital.

Hospital charge and reimbursement data were analyzed for 115 patients admitted to the surgical intensive care and burn-trauma units at Brigham and Women's Hospital over a two-month study period. A skewed distribution of hospital charges resulted in mean and median charges of $43,068 and $29,081, respectively. Major differences were observed in total charges among major diagnostic groups. The median charge was highest in orthopedic trauma and neurosurgery patients. The median charge across major diagnostic groups correlated with the length of stay in the unit and in the hospital, and the number of drugs used. The median percent reimbursement from private providers, Medicaid, Medicare, and health maintenance organizations was 93, 55, 40, and 30 percent, respectively, and 55 percent overall. Reimbursement was high from private providers regardless of major diagnostic group. Medicare reimbursement through the diagnostic reference group system was considerably higher in cardiothoracic patients (77 percent) than in other major diagnostic groups. The discrepancy between charge and Medicare reimbursement in these patients was consistent with that reported for intensive care units in other hospitals, thereby underscoring the need for cost containment and more realistic reimbursement methods.

The pharmacokinetics of tertiary butanol in C57BL/6J mice.

Doses of 5.0, 10.0, and 20.0 mmoles/kg of t-butanol were given to C57BL/6J mice in order to study the in vivo pharmacokinetics of the alcohol in this strain. A pseudozero order decline in blood concentrations which was directly proportional to dose suggested Michaelis-Menten kinetics. PCNONLIN analysis of the data, however, yielded Vmax estimates which increased with dose and VD estimates which decreased with dose. These results are inconsistent with the Michaelis-Menten model and suggest either multiple elimination pathways or dose related effects on distribution or elimination.

Drug usage patterns in the ICU: profile of a major metropolitan hospital and comparison with other ICUs.

Drug use patterns observed in an intensive care unit (ICU) at a large tertiary teaching hospital (Brigham & Women's Hospital [BWH], Boston) were documented and compared with patterns reported from ICUs of hospitals at two other sites. Antibiotics, analgesics, and H2 antagonists were the most frequently prescribed classes of drugs. Despite the variability in ICU populations studied, similar patterns of drug use (drug classes and frequency of use) were seen at all three institutions. Pharmacy charges for ICU care at BWH were calculated with respect to total hospitalization charges and were found to account for 10% of total charges. Identifying drug use patterns in ICUs--an area of potentially high drug use, risk, and cost--provides valuable information for P & T Committees as well as for medical staff quality assurance and usage evaluation functions.

Comparative pharmacokinetics of ethanol in inbred strains of mice using doses based on total body water.

The mean total body water was determined by desiccation in DBA/2J, CBA/J, and C57BL/6J mice to be 60.6, 65.6, and 68.6 percent of body weight, respectively. The pharmacokinetics of ethanol was subsequently studied in mice of these strains given an intraperitoneal dose of 116 mmoles/l of total body water based on the desiccation study. This dose was equivalent to 70, 76, and 80 mmoles/kg in the DBA/2J, CBA/J, and C57BL/6J strains, respectively. The zero time concentrations were nearly identical between strains; therefore volume of distribution (VD) estimates based on mmole/kg doses reflected interstrain differences in total body water. The apparent zero order elimination rate was significantly greater in the DBA/2J strain versus the other two strains using this regimen. Interstrain differences in ethanol sleep time paralleled the differences in anesthetic sensitivity evidenced by blood concentrations at the time of regaining the righting reflex. The results demonstrate the importance of considering differences in total body water and hence ethanol VD when comparing the effects of ethanol in inbred mouse strains.

Assessment of the efficacy of activated charcoal following gastric lavage in acute drug emergencies.

The efficacy of administering a slurry of 100 g of activated charcoal (AC) via the gastric tube following lavage was assessed in 25 treated and 37 control patients presenting to the emergency room with chemical evidence of sedative-hypnotics or aspirin in the blood. Efficacy was evaluated as the ability of AC to prevent further absorption as determined by subsequent blood drug concentration changes. Although fewer patients in the AC group showed increased blood drug concentrations, the differences were not statistically significant. Comparison of the mean percent change in blood drug concentrations at various times following treatment produced similar results. Comparisons using subgroups of patients based on the individual drugs, the treatment delay time, and entering functional decompensation showed significant benefit from AC only in the less symptomatic patients. Comparing these results with other studies demonstrating the unequivocal efficacy of early (e.g., 30 min) treatment, it is concluded that the use of AC following lavage may often be too late to benefit most patients. The authors suggest that AC be given in the home, emergency vehicle, or immediately upon admission.

Measurement of fibrinogen-fibrin-related antigen in serum as aid to diagnosis of deep vein thrombosis in outpatients.

A study of serum levels of fibrinogen-fibrin-related antigen (F.R.-antigen) in outpatients presenting with clinical features suggesting deep vein thrombosis was undertaken. A raised serum level of this antigen (greater than 12 mg/1) is strong evidence in favour of the diagnosis of deep vein thrombosis. It is virtually conclusive evidence if other known causes of a raised level of the antigen are absent. On the other hand, a normal serum level of F.R.-antigen does not exclude even extensive thrombosis, and other objective techniques are required to substantiate the diagnosis.

Dose-response studies on tolerance to multiple doses of secobarbital and methaqualone in a polydrug abuse population.

Patients from a polydrug abuse treatment program were titrated with either secobarbital or methaqualone, their primary drug of abuse, to a state of mild intoxication, consisting of lateral and vertical nystagmus, ataxia, slurred speech, and drownsiness. The mean dose required to produce each sign was compared to that determined in a similarly treated control group. Tolerance to secobarbital was more easily demonstrated than tolerance to methaqualone, and nystagmus was the least sensitive indicator of patient tolerance. The individual signs were also cumulated into a graded rating scale of central nervous system depression which would be related to the dose administered. Tolerence was easily demonstrated at the higher stages of toxicity for secobarbital in the overall patient population, but tolerance to methaqualone was only unequivocal in the subjects indicating a relatively high frequency of abuse. Tolerance to methaqualone occurred at the lower stages of toxicity, suggesting that there is a difference between tolerance to secobarbital and tolerance to methaqualone. There was no indication that patients who also abuse alcohol are more tolerant than their patient counterparts. The patients who also had a history of amphetamine abuse, however, were less tolerant than the nonusers of these drugs.