Andrea Hofmann

Monitoring the Virus Load Can Predict the Emergence of Drug-Resistant Hepatitis B Virus Strains in Renal Transplantation Patients during Lamivudine Therapy

The development of resistant hepatitis B virus (HBV) strains during lamivudine treatment has been described repeatedly. To investigate whether the development of such resistant HBV strains can be predicted in an early phase of therapy, the HBV loads of 11 renal transplantation patients were screened at 3-month intervals by a quantitative HBV polymerase chain reaction (PCR) assay. Lamivudine resistance was detected by sequence analysis. Five patients developed resistance to lamivudine in the 12-15-month follow-up period. In all of them, a virus load of 1x103 HBV DNA copies still was detectable after 3 months of therapy. This was statistically significantly different from those patients who did not develop lamivudine resistance within the observation period, all of whom had no HBV DNA detectable after 3 months of treatment (P=.0022). Thus, virus load testing by use of a sensitive PCR assay allows the early prediction of the emergence of lamivudine-resistant HBV strains.

Increased prevalence of sublinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis?

objectives  Hashimotos encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimotos encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimotos encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis.

A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease

This work describes a microdosing study with an investigational, carbon 11‐labeled antiamyloid drug, 1,1′‐methylene‐di‐(2‐naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimers disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single‐dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose. After intravenous bolus injection of 341 ± 21 MBq [11C]ST1859 (containing <11.4 nmol of unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total plasma radioactivity being in the form of unchanged parent drug at 10 minutes after administration. In both the control and patient groups, uptake of radioactivity into the brain was relatively fast (time to reach maximum concentration, 9–17 minutes) and pronounced (maximum concentration [standardized uptake value], 1.3–2.2). In both healthy volunteers and patients, there was a rather uniform distribution of radioactivity in the brain, including both amyloid‐beta‐rich and ‐poor regions, with slow washout of radioactivity (half‐life, 82–185 minutes). In conclusion, these data provide important information on the blood‐brain barrier penetration and metabolism of an investigational antiamyloid drug and suggest that the PET microdosing approach is a useful method to describe the target‐organ pharmacokinetics of radiolabeled drugs in humans.

Incidence and predictability of amiodarone-induced thyrotoxicosis and hypothyroidism

ZusammenfassungEINLEITUNG: Ziel dieser Studie war die Erfassung von Inzidenz und Prädiktabilität der Amiodaron-induzierten Hyperthyreose (AIT) und Hypothyreose (AIH) bei Patienten mit Kardiomyopathie. METHODEN: 72 Patienten (mittleres Alter 69 ± 11 Jahre) aus einem ehemaligen Jodmangelgebiet wurden hinsichtlich der Schilddrüsenfunktionsparameter vor, während und nach einer Amiodarontherapie untersucht. Alle Patienten wurden dabei zum ersten Mal mit Amiodaron behandelt. Der mediane Beobachtungszeitraum betrug 8 Monate bei 71 (98,6%) Patienten. ERGEBNISSE: Nur 18 von 72 Patienten (25,0%) hatten eine morphologisch unauffällige Schilddrüse. Die Prävalenz der Schilddrüsenfunktionsstörungen vor Amiodarontherapie betrug 37,6% (27 von 72) mit gleichem Verhältnis von Hypo- und Hyperthyreose (14 bzw. 13 Fälle). Eine Funktionsstörung nach Therapiebeginn wurde bei 56,8% (25 von 44) der Patienten ohne präexistente Schilddrüsenerkrankung diagnostiziert. Davon entwickelten 36,0% (9 von 25) der Patienten entweder eine subklinische oder klinisch manifeste AIH, 64,0% (16 von 25) eine subklinische oder manifeste AIT. Der Anteil der Patienten mit normaler Schilddrüsenfunktion sank von 61,1% (44 von 72) vor Therapiebeginn auf 26,7% (19 von 71, p < 0,001) unter Therapie. Die Entwicklung beider Funktionsstörungen war weder mit einer Schilddrüsenautoimmunerkrankung, dem 99mTc-Pertechnetat Uptake, höherem Lebensalter, Schilddrüsenautonomie noch einer abnormen Schilddrüsenmorphologie signifikant assoziiert. SCHLUSSFOLGERUNG: Es findet sich eine hohe Prävalenz von Schilddrüsenfunktionsstörungen bei älteren Patienten mit Kardiomyopathie, die mit Amiodaron behandelt werden. Über- oder Unterfunktion zeigten sich sowohl bei Patienten mit präexistenten Schilddrüsenfunktionsstörungen, als auch bei initial euthyreoten Patienten. Aufgrund der hohen Inzidenz von Schilddrüsenfunktionstörungen empfehlen sich regelmäßige Funktionskontrollen während und im Anschluss an eine Amiodarontherapie.SummaryOBJECTIVES: To determine the incidence and predictability of amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism (AIH) in patients with cardiomyopathy. PATIENTS AND METHODS: A total of 72 patients (mean age 69 ± 11 years) living in an area previously endemic for thyroid disease but with currently sufficient iodine intake were enrolled in this prospective study. All participants were treated with amiodarone for the first time. The course of thyroid function in patients with normal thyroid morphology and in those with goiter was monitored over a median follow-up period of eight months in 71 (98.6%) patients. RESULTS: Of 72 participants, 18 (25.0%) had a morphologically normal thyroid gland as evidenced by sonography. The prevalence of thyroid dysfunction before initiation of amiodarone was 37.6% (27 of 72) with almost equal distribution between hypothyroidism and hyperthyroidism (14 and 13 patients). After treatment with amiodarone, thyroid dysfunction was diagnosed in 56.8% (25 of 44) of the patients without preexisting dysfunction. Of these 25 patients, nine (36%) developed either subclinical or overt AIH and 16 (64.0%) developed either subclinical or overt AIT. Although 61.1% (44 of 72) had normal thyroid function before initiation of amiodarone, this number decreased to 26.7% (19 of 71, P < 0.001) after treatment. Factors such as 99mTc-pertechnetate scan uptake, thyroid autoimmunity, age, thyroid autonomy or abnormal thyroid morphology were not significantly associated with the development of thyroid dysfunction. CONCLUSIONS: Prevalence of thyroid dysfunction was high in elderly patients treated with amiodarone. Cases of AIT and AIH occurred in patients with and without preexisting thyroid disorders. Because of the high incidence of amiodarone-induced thyroid dysfunction, regular testing of thyroid function is mandatory during and following amiodarone treatment.

Higher Frequency of Thyroid Tumors in the Right Lobe

Recently, using ultrasonography, we observed that the right lobe usually is larger compared with the left thyroid lobe. Since the higher cell number in a larger right lobe may confer a higher tumor risk, we investigated the location of benign and malignant lesions to test the hypothesis of a more frequent occurrence in this lobe. In 1,001 consecutive patients with benign thyroid lesions, tumors more frequently occurred in the right lobe (+21.5%, p = 0.0022). Furthermore, in 1,277 thyroid cancer patients with 1,302 thyroid cancers, the right lobe more often harbored the tumor initially (+22.9%, p = 0.0009). Our data show a larger proportion of both benign and malignant tumors in the right thyroid lobe.