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Biomedical subjects

R W Jansen

Publications and source records attributed to R W Jansen.

At least 19 recordsLinked to original sources
PubMed2005

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

Cohort Studies↗
PubMed2001

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older.

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day-to-day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70-84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6.7 +/- 15.4 mmHg (P<0.05, mean +/- SD) and 8.2 +/- 6.4 mmHg (P<0.01), respectively, whereas HR increased by 9.5 +/- 5.0 bpm (P<0.01) and SV decreased by -8.3 +/- 7.4 ml (P<0.01) during standing on the first occasion. [O2Hb] decreased by -3.9 +/- 2.9 micromol l-1 (P<0.01), while [HHb] increased by 1.8 +/- 2.2 micromol l-1 (P<0.01). Group-averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group-averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day-to-day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.

Aged↗
PubMed2001

The influence of low-, normal-, and high-carbohydrate meals on blood pressure in elderly patients with postprandial hypotension.

BACKGROUND: Postprandial hypotension (PPH) is a common and serious disorder of blood pressure (BP) regulation in elderly people. It has been suggested that primarily the carbohydrate (CH) content of a meal induces the BP decrease. Therefore, we examined the relationship between the CH content of meals and postprandial BP responses in elderly patients diagnosed with PPH. METHODS: Twelve geriatric patients (aged 75 to 91 years; 6 men) who were previously diagnosed with PPH received standardized liquid meals with low- (25 g), normal- (65 g), and high- (125 g) CH content in random order on three separate days. Systolic BP (SBP), diastolic BP, and heart rate were measured every 5 minutes from 20 minutes before until 75 minutes after each meal. Postprandial symptoms were recorded every 15 minutes. RESULTS: The maximum decrease in SBP was significantly smaller after the low-CH meal (-28 +/- 5 mm Hg) than after the normal- (-39 +/- 7 mm Hg) and high-CH meals (-40 +/- 5 mm Hg) (p <.050 between groups). In addition, the duration of PPH was significantly shorter (p <.010), and postprandial symptoms were less frequent and less severe after the low-CH meal. CONCLUSIONS: Reducing the CH amount in meals induces significantly smaller decreases in SBP, shorter duration of PPH, and reduction of PPH-related symptoms. Therefore, limiting the CH content of an elderly patient's meal can be a clinically effective nonpharmacological treatment for PPH in elderly patients and can reduce the risk of developing symptomatic PPH.

Aged↗
PubMed2001

Effect of levodopa on orthostatic and postprandial hypotension in elderly Parkinsonian patients.

BACKGROUND: This study describes orthostatic and postprandial hypotension in elderly Parkinsonian patients and evaluates the effect of levodopa therapy on orthostatic and postprandial hypotension in these patients. METHODS: Seventeen elderly patients with a clinical diagnosis of Parkinson's disease or Parkinsonism based on the U.K. Parkinson's Disease Society Brain Bank criteria (age range, 66-84 years) participated in the study. Blood pressure was continuously monitored during standardized standing and meal tests, after starting 125-mg b.i.d. doses of levodopa/benserazide (Madopar) or placebo, in a double-blind, randomized, cross-over design. Seventeen age- and sex-matched healthy subjects served as controls. RESULTS: Orthostatic hypotension was infrequently found in Parkinsonian patients (13%) and healthy subjects (6%; p =.58, between groups), whereas postprandial hypotension was more frequent in Parkinsonian patients (82%) than in healthy subjects (41%; p <.05, between groups). Doses of levodopa/benserazide, administered 2 times per day, did not result in significantly larger blood pressure decreases after standing or eating, or in higher frequencies of orthostatic or postprandial hypotension in the Parkinsonian group. Postprandial hypotension was related to disease severity (r = -.56, p <.05). CONCLUSIONS: Postprandial hypotension, but not orthostatic hypotension, was more common in elderly Parkinsonian patients than in healthy subjects. Therapy with 125-mg b.i.d. doses of levodopa/benserazide did not significantly aggravate orthostatic or postprandial hypotension.

Aged↗
PubMed2000

Furosemide withdrawal in elderly heart failure patients with preserved left ventricular systolic function.

To explore the possibilities of furosemide withdrawal in elderly heart failure (HF) patients with intact left ventricular (LV) systolic function and assess its effects on functional status and orthostatic blood pressure homeostasis, we performed a placebo-controlled pilot trial of furosemide withdrawal with 3 months of follow-up in 32 HF patients (aged 75.1 +/- 0.7 years [mean +/- SEM]) with a LV ejection fraction of 60 +/- 2% and without overt congestion. Investigations included repeated clinical assessment, spirometry, standardized 6-minute walking test, and chest x-rays. Measurements of blood pressure response on active standing and Doppler echocardiography were performed before and 3 months after furosemide withdrawal. Recurrent congestive HF occurred in 2 of 21 patients (10%) who discontinued furosemide use, and in 1 of 11 patients (9%) who continued furosemide (p = NS). Three patients restarted furosemide for ankle edema and 1 for blood pressure levels >180/100 mm Hg. After 3 months, there were no differences regarding HF symptom scores, blood pressure, heart rate, spirometric results, 6-minute walking distance, or quality of life scores between patients who discontinued use and patients who continued the therapy. In patients successfully withdrawn, Doppler E/A ratio increased from 0.68 +/- 0.05 to 0.79 +/- 0.06 after withdrawal (p <0.01), and maximum blood pressure decrease on active standing changed from -8 +/- 5 mm Hg to +5 +/- 3 mm Hg systolic (p <0.05). Thus, in this pilot investigation of furosemide withdrawal in elderly HF patients without overt congestion and with a normal LV systolic function, withdrawal was successful in almost all patients and was associated with improvement of LV diastolic filling and blood pressure homeostasis on active standing.

Aged↗
PubMed2000

Achieving haemodynamic baseline values with Finapres in elderly subjects during supine rest.

BACKGROUND: Clear guidelines for the resting time necessary to achieve stable blood pressure (BP) levels are scant in gerontology research. Therefore, we aimed to determine the minimum period required for obtaining haemodynamic baseline values in elderly subjects during supine rest. In addition, we evaluated the effect of cardiovascular morbidity, such as diastolic heart failure, and the effect of complex comorbidity of geriatric patients, on haemodynamic changes during supine rest. METHODS: A total of 17 healthy subjects, 18 heart failure patients with normal systolic function and 24 geriatric patients, aged 70 years and more, participated. After an overnight fast, changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR), and stroke volume (SV) were determined by Finapres beat-to-beat non-invasive BP monitoring during a 20-min supine rest. The procedure was repeated in the healthy subjects and geriatric patients on a second day. RESULTS: Complete BP stabilization was reached in each group within 5 min of supine rest, as SBP remained essentially unchanged and DBP did not change significantly anymore after the fourth minute. In the heart failure patients, HR decreased and SV increased until the twelfth minute of rest. The SBP, DBP, HR, and SV changes during supine rest showed good reproducibility. CONCLUSIONS: A span of 5 min of supine rest ensured achievement of reliable and reproducible baseline BP values by Finapres in elderly subjects. However, we recommend at least 12 min of rest to obtain full haemodynamic stability in elderly patients with diminished cardiac compliance and diastolic function.

Adaptation, Physiological↗
PubMed2000

Cerebral oxygenation declines in healthy elderly subjects in response to assuming the upright position.

BACKGROUND AND PURPOSE: With increasing age, assuming the upright position is more often accompanied by symptoms such as dizziness and lightheadedness, possibly as a result of a diminished oxygen supply to the brain due to impaired cerebral autoregulation. We aimed to quantify postural changes in cerebral oxygenation and systemic hemodynamics in healthy elderly and young subjects. METHODS: In 18 healthy elderly subjects (aged 70 to 83 years) and 10 healthy young subjects (aged 22 to 45 years), frontal cortical oxygenation and hemodynamic responses were continuously monitored by near infrared spectroscopy and Finapres, respectively, before and during 10 minutes of active standing. RESULTS: -Cortical oxyhemoglobin concentration [O(2)Hb] decreased by -4.6+/-2.2 micromol/L (P<0.001) and cortical deoxyhemoglobin concentration increased by 1.5+/-2.4 micromol/L (P<0.05) in the elderly subjects after posture change, whereas these variables did not change significantly in the young subjects. The postural hemodynamic changes tended to be attenuated in the elderly subjects, except for the increases in systolic blood pressure (BP). Smaller postural increases in diastolic BP were related to larger [O(2)Hb] decreases (r=0.53, P<0.01, corrected for the age effect). CONCLUSIONS: Assuming the upright position evokes an asymptomatic decrease in frontal cortical oxygenation in healthy elderly subjects but not in healthy young subjects. Cortical [O(2)Hb] changes are affected by diastolic BP changes. These findings may indicate that regulation of cerebral oxygenation alters with increasing age.

Adult↗
PubMed2000

Diuretic therapy in elderly heart failure patients with and without left ventricular systolic dysfunction.

Long term prescription of diuretics for heart failure is very prevalent among elderly patients, although the rationale for such a treatment strategy is often unclear, as diuretics are not indicated if volume overload is absent. The concept of diastolic heart failure in the elderly might particularly change the role of diuretic therapy, since diuretics may have additional adverse effects in these patients. This paper reviews the effects of diuretic therapy in elderly patients with heart failure, emphasising the differences between patients with normal and decreased left ventricular systolic function. Studies on diuretic withdrawal in elderly patients with heart failure are discussed, with emphasis on issues involved in decision making such as diuretic dose reduction and withdrawal in elderly patients and factors that have been established to predict successful withdrawal. Existing guidelines on the prescription of diuretics in elderly patients with heart failure with normal and decreased left ventricular systolic function and in those with diastolic heart failure are also discussed. By reducing intravascular volume, diuretics may further impair ventricular diastolic filling in patients with diastolic heart failure and thus reduce stroke volume. Indeed, preliminary studies demonstrate that diuretics may provoke or aggravate hypotension on standing and after meals in these patients. Therefore, it is suggested that elderly patients with heart failure with intact left ventricular systolic function should not receive long term diuretic therapy, unless proven necessary to treat or prevent congestive heart failure. This implies that physicians should carefully evaluate the opportunities for diuretic dose tapering or withdrawal in all of these patients, and that a cautiously guided intermittent diuretic treatment modality may be critical in the care for older patients with heart failure with intact left ventricular systolic function.

Aged↗
PubMed1999

Furosemide withdrawal improves postprandial hypotension in elderly patients with heart failure and preserved left ventricular systolic function.

OBJECTIVE: To assess the effects of furosemide withdrawal on postprandial blood pressure (BP) in elderly patients with heart failure and preserved left ventricular systolic function. METHODS: Noninvasive measurement of blood pressure (BP) and heart rate, computation of stroke volume and cardiac output (after a 1247-kJ (297-kcal) meal, and Doppler echocardiography before and 3 months after placebo-controlled withdrawal of furosemide therapy. RESULTS: Of 20 patients with heart failure (mean+/-SEM age, 75+/-1 years; left ventricular ejection fraction, 61%+/-3%), 13 were successfully able to discontinue furosemide therapy. At baseline, 11 (55%) of the 20 patients (had maximum postprandial systolic BP declines of 20 mm Hg or more. In the withdrawal group, the maximum systolic BP decline lessened from -25+/-4 to -11+/-2 mm Hg (P<.001) and the maximum diastolic BP from -18+/-3 to -9+/-1 mm Hg (P= .01), compared with no changes in the continuation group. In the withdrawal group, maximum postprandial declines in stroke volume and cardiac output decreased from -9+/-1 to -4+/-2 mL (P =.01) and from -0.6+/-0.2 to -0.2+/-0.1 L/min) (P = .04), respectively. The baseline maximum postprandial systolic BP decrease was correlated with the ratio of early to late flow (n = 20; Spearman rank correlation coefficient, 0.58; P = .007). For patients in the withdrawal group, the changes in postprandial systolic BP response were independently related to changes in peak velocity of early flow (n = 13; r2= 0.61; P = .003). CONCLUSIONS: Postprandial hypotension is common in elderly patients with heart failure and preserved left ventricular systolic function. The withdrawal of furosemide therapy ameliorates postprandial BP homeostasis in these patients, possibly by improving left ventricular diastolic filling.

Aged↗
PubMed1999

Monitoring hypovolemia in healthy elderly subjects by measuring blood pressure response to Valsalva's maneuver.

Quantification of hypovolemia by physical examination has limited validity. We explored the use of non-invasive measurement of blood pressure (BP) response to Valsalva's maneuver in monitoring hypovolemia in nine healthy elderly volunteers, recruited from participants of the Nijmegen Annual Four-Days Marches. Heart rate (HR), systolic and diastolic BP, and mean arterial pressure (MAP) response (Finapres) to a Valsalva's maneuver as well as clinical and laboratory assessment of fluid balance were determined 5 minutes before, and 3, 5, and 48 hours after administration of 40 mg furosemide orally. Subjects' (4 males aged 74.2 +/- 3.0 years) weight was 66.1 +/- 9.7 kg, mean BP was 139 +/- 21 over 76 +/- 12 mm Hg. A maximum weight loss of -2.8 +/- 0.9% occurred 5 hours after furosemide administration. Systolic and diastolic BP, HR, clinical assessment scores, and serum creatinine and urea nitrogen did not change during the total study period. Significant changes occurred in Valsalva phase I to phase II systolic BP response (difference +14.2 +/- 11.3 mm Hg, ratio difference -0.09 +/- 0.07 after 5 hours, P < 0.01). Changes after 48 hours did not differ from baseline values. Finapres measurement of Valsalva BP response may be useful in monitoring hypovolemia in the elderly.

Aged↗
PubMed1998

Loop diuretics in patients aged 75 years or older: general practitioners' assessment of indications and possibilities for withdrawal.

OBJECTIVE: To examine the indications for prescription and possibilities for withdrawal of loop diuretics in community-dwelling patients aged 75 years or older, as reported by their general practitioners (GPs). METHODS: Analysis of dispensary data to identify patients aged 75 years or older using loop diuretics on 1 February 1996. Questionnaires were sent to the GPs of these patients to inquire about the indications for loop diuretic prescription and the necessity for continuation. We subsequently determined loop diuretic prescription rates in the survey population over the next 9 months. SETTING: A panel of nine Dutch community pharmacies. RESULTS: Questionnaires were returned for 338 out of 667 patients (50.7%) using loop diuretics on 1 February 1996. Reported indications for loop diuretic use were heart failure in 223 patients (66.0%), hypertension in 35 patients (10.4%), and a combination of both in 23 patients (6.8%). Loop diuretics were used for ankle edema in 27 patients (8.0%) and for unknown reasons in another 27 patients (8.0%). Continuation of treatment was considered unnecessary by GPs in 66 out of 338 patients (19.5%). However, prescription rates for these 66 patients in the following months were no different from rates for the remaining 272 patients. Loop diuretics were still prescribed to 47 of 66 patients (71.2%) after 12 weeks, and to 26 patients (39.4%) after 36 weeks. CONCLUSIONS: GPs reported substantial opportunities for withdrawal of loop diuretics in patients over 75 years of age, but this did not influence actual prescription rates in these patients. Future studies should explore means of facilitating withdrawal of these medications in this population.

Age Factors↗
PubMed1998

Use of diuretics and opportunities for withdrawal in a Dutch nursing home population.

BACKGROUND: Diuretics are frequently used by elderly patients and overprescription has been suggested. However, the present withdrawal patterns of these medications in clinical practice elderly patients are unclear. METHODS: Retrospective medical record analysis of all 584 patients aged 75 years or older admitted to a 240-bed nursing home facility in the years 1990-1994. One-year follow-up by record review and collection of updated information from nursing home physicians. RESULTS: Two hundred and twenty patients (37.7%) used diuretics, and use increased with age (p < 0.05). Reported indications for prescription were heart failure (n = 77), hypertension (n = 38), ankle edema without heart failure (n = 21), or not reported (n = 84). Diuretics were withdrawn in 82 of 220 patients (37.3%), but a doubtful actual indication for diuretic use was found in 72 of the remaining 138 patients (52.2%). After withdrawal, the probability of remaining free from diuretics for at least one year was 0.47. There were no reports of life-threatening or fatal incidents after withdrawal. Mortality rates for the patients whose diuretics were withdrawn did not differ from patients continuing on diuretics. CONCLUSIONS: Withdrawal of diuretics was frequently performed and often successful. In addition, doubtful indications for diuretics were found in half of the patients continuing on these medications, suggesting additional opportunities for diuretic withdrawal.

Aged↗
PubMed1998

Prescription patterns of diuretics in Dutch community-dwelling elderly patients.

AIMS: To describe age- and gender-related prescription patterns of diuretics in community-dwelling elderly, and to compare diuretics to other cardiovascular (CV) medications. METHODS: Cross-sectional study of patient-specific prescription data derived from a panel of 10 Dutch community pharmacies. Determination of proportional prescription rates and prescribed daily dose (PDD) of diuretics, cardiac glycosides, nitrates, angiotensin converting enzyme (ACE) inhibitors, beta-adrenoceptor blockers, and calcium channel blockers in all 5326 patients aged 65 years or older dispensed CV medications between August 1st, 1995 and February 1st, 1996. RESULTS: Diuretics were prescribed to 2677 of 5326 patients (50.3%), 1325 patients (24.9%) using thiazides and 1198 patients (22.5%) using loop diuretics. Prescription rates of loop diuretics increased from 15.1% in patients aged 65-74 years to 37.2% in patients aged 85 years or older. Rates also increased for digoxin and nitrates. Rates for thiazide diuretics remained unchanged with age; rates for beta-adrenoceptor blockers, ACE inhibitors and calcium channel blockers declined with age. Thiazides were prescribed to 30.1% of women compared with 16% of men (P < 0.001). Average PDD was 135 +/- 117% of defined daily dose (DDD) for loop diuretics, and highest for bumetanide (245 +/- 2.01% of DDD, equivalent to 2.5 +/- 2.0 mg). Average PDD was 74 +/- 40% of DDD for thiazides, and highest for chlorthalidone (100 +/- 49% of DDD, equivalent to 25 +/- 12 mg). CONCLUSIONS: Important characteristics of diuretic usage patterns in this elderly population were a steep increase in loop diuretic use in the oldest old, a large gender difference for thiazide use, and high prescribed doses for thiazides.

Age Factors↗
PubMed1998

Use of the Valsalva manoeuvre to identify haemodialysis patients at risk of congestive heart failure.

BACKGROUND: In the presence of elevated cardiac filling pressures, the decline of blood pressure (BP) during the straining phase of a Valsalva manoeuvre is blunted or absent. We compared the use of non-invasively measured BP response to a Valsalva manoeuvre with clinical assessment and bioimpedance measurements to identify haemodialysis patients at risk of acute congestive heart failure (CHF). METHODS: Continuous BP response (Finapres) to a Valsalva manoeuvre, clinical assessment by nephrologists, and bioimpedance estimations of extracellular fluid volume were determined before and after haemodialysis, once every week during a 5-week period. Acute CHF was defined according to preset clinical and radiological criteria. RESULTS: Participants (age 60+/-19 years, six females, nine males) had an average predialysis weight of 66.8+/-11.8 kg. Patients were dialysed for 3.8+/-0.8 h with a mean ultrafiltration of 2.4+/-1.1 litres. Valsalva systolic BP ratios (phase 2 to 1) decreased significantly during dialysis from 0.81+/-0.11 to 0.73+/-0.10 (P<0.05). Five patients experienced an episode of acute CHF. The Valsalva BP ratios for these patients before and after dialysis (0.89+/-0.05 and 0.78+/-0.05 respectively) were higher than for the remaining ten patients (0.77+/-0.10 and 0.70+/-0.11, respectively) (P<0.05). A cutoff Valsalva BP ratio of 0.82 resulted in positive and negative predictive values for CHF of 62 and 100% respectively. No differences in clinical assessment or bioimpedance parameters were found, with the exception of postdialysis diastolic BP and predialysis ankle oedema. After treatment of CHF, Valsalva BP ratios decreased significantly without changes in the other hydration parameters. CONCLUSIONS: Non-invasive assessment of the BP response to a Valsalva manoeuvre appears to be a potential tool for identifying patients at risk of acute CHF during maintenance haemodialysis.

Acute Disease↗
PubMed1998

[Recruitment and selection of test subjects for scientific research in geriatrics: literature review and experiences of the Nijmegen NESTOR study].

The conduct of research in geriatric medicine differs from that in other medical specialties in a number of ways. In geriatric research it is almost impossible to study a large, homogeneous group of subjects, suffering solely from the problem to be studied. Moreover, measurements and questionnaires should be short, simple and not very troublesome. These differences are due to the heterogeneity of geriatric patients and the high prevalence of multimorbidity, often resulting in impaired physical, psychological and social performance. In this article a number of issues which are important for successful recruitment and selection of subjects for geriatric research are discussed. First, a review of relevant literature is given, and subsequently, experiences concerning recruitment and selection appreciated in the Nijmegen geriatric research programme' are described. This programme was part of the governmental Netherlands Programme for Research on Ageing (NESTOR). According to the literature the efficacy of recruitment may be improved by: personal contact between researcher and subject in view, introduction of the selection criteria already at the time of subjects' recruitment, a balance between research burden and profit, sufficient rewards for participation, both financially and non-financially, maximal effort in the subjects' transport, and also piloting of the recruitment procedure. In the NESTOR-studies the average number of subjects who were recruited and who completed the studies was low (23%), because a lot of the recruited subjects did not meet the selection criteria or considered participation as too troublesome. Subjects who agreed to participate showed high research compliance.

Aged↗
PubMed1997

Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation.

BACKGROUND: Orthotopic liver transplantation for end-stage hepatitis-B-virus (HBV) infection is commonly complicated by recurrence of HBV. Lamivudine, a cytosine nucleoside analogue, has been shown to suppress HBV infection. We report the development of resistance to lamivudine in three patients who underwent transplantation for end-stage liver disease secondary to hepatitis B. METHODS: Two of the patients received lamivudine for recurrent HBV infection after transplantation, whereas the third patient began treatment 1 month before transplantation in an attempt to prevent HBV recurrence after transplantation. The three patients initially responded well to treatment, but viral recurrence occurred after 9-10 months of treatment in all patients. HBV DNA was amplified from serum and sequenced through a conserved polymerase domain-the tyrosine, methionine, aspartate, aspartate (YMDD) locus. We assessed the susceptibility of HBV to lamivudine by infecting primary human hepatocytes with serum taken before the start of treatment and after recurrence in varying concentrations of lamivudine. FINDINGS: DNA sequencing showed a common mutation within the YMDD locus of the HBV polymerase gene in all patients during lamivudine treatment. In hepatocyte cultures infected with pretreatment serum, HBV DNA concentrations were reduced to less than 6% of those in control cultures by addition of lamivudine in concentrations as low as 0.03 mumol/L. By contrast, in cultures treated with serum taken after recurrence, HBV DNA concentrations did not fall below 20% of control values, even with lamivudine at 30 mumol/L. INTERPRETATION: Resistance to lamivudine has been reported in HIV patients with mutations in the YMDD locus of the polymerase gene. Our findings indicate a common mechanism of lamivudine resistance for HIV and HBV that involves similar point mutations in homologous domains of the viral polymerases.

Antiviral Agents↗