Search PubMed⌕ Search

Biomedical subjects

P Hoff

Publications and source records attributed to P Hoff.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synthesis, purification, and in vitro stability of 211At- and 125I-labeled amidobisphosphonates.

A method is described for preparing 211At- and radioiodinated amidobisphosphonates. The active esters N-succinimidyl 3-(tri-methylstannyl) benzoate (ATE) and N-succinimidyl 5-(tri-methylstannyl)-3-pyridinecarboxylate (SPC) were used as precursors. The isolated and purified radiolabeled intermediates were coupled to 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APB) in high yields ranging from 60% to 97%. The lipophilicity of the compounds was found to depend on the nature of the labeled template and the halogen. High in vitro stability in mouse, fetal calf, and human serum was documented by high performance liquid chromatography.

Animals↗
PubMed1999

Influence of pretreatment with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APB) on organ uptake of 211At and 125I-labeled amidobisphosphonates in mice.

To minimize nontarget organ uptake in animals receiving radiolabeled amidobisphosphonates, the influence of pretreatment with cold 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APB, pamidronate) was studied. Three groups of animals were given pure 3-[125I]iodobenzamide-N-3-hydroxypropylidene-3,3-bisphosphonate (IBPB) and 3-[211At]astatobenzamide-N-3-hydroxypropylidene-3,3-bisphosphonate (ABPB) (control); co-injection of APB and IBPB/ABPB; and 1 h preinjection of APB followed by IBPB/ABPB, respectively. A significant reduction of uptake in normal tissue was observed, whereas the bone uptake remained constant at 35-50%ID/g tissue. This study suggests that co- or preinjection of pamidronate may reduce the normal organ radiation doses when using these radiohalogenated bisphosphonates for endoradiotherapeutic procedures.

Animals↗
PubMed1999

The electrically elicited startle blink reflex in patients with schizophrenia: A threshold study of different reflex components.

The electrically elicited blink reflex consists of three components (R1, R2, R3). In humans the excitability of these components is influenced by attentional states. In particular, distraction from the stimulus leads to facilitation of the bilateral R2 and R3. The present study was performed in order to investigate the excitability of the different components of the electrically evoked blink reflex in 13 patients with schizophrenia and 13 normal controls under standard conditions. Therefore, the thresholds of the distinct components were determined without any inhibitory or facilitatory procedure. There was no significant difference in R1 and R2 thresholds between patients and controls. In contrast, the R3 threshold was significantly reduced in schizophrenic patients (R3 threshold = 17.5 mA in normal subjects, 10.5 mA in patients, p = 0. 0001). In recent studies the R3 magnitude was found to be highly susceptible to changes in the attentional state of normal subjects. The lower threshold of R3 in patients with schizophrenia might therefore be a neurophysiological marker of attentional dysfunctions in schizophrenia.

Adult↗
PubMed1999

211At- and 131I-labeled bisphosphonates with high in vivo stability and bone accumulation.

UNLABELLED: Bisphosphonates were synthesized for use as carriers for astatine and iodine radioisotopes to target bone neoplasms. METHODS: Radiohalogenated activated esters were coupled to the amino group in the side chain of the bisphosphonate. The bisphosphonate 3-amino-1-hydroxypropylidene bisphosphonate was combined with four different acylation agents: N-succinimidyl 3-[211At]astatobenzoate, N-succinimidyl 3-[131I]iodobenzoate, N-succinimidyl-5-[211At]astato-3-pyridinecarboxylate and N-succinimidyl-5-[131I]iodo-5-pyridinecarboxylate. The products, 3-[131I]iodobenzamide-N-3-hydroxypropylidene-3,3-bisphosphonate (IBPB), 3-[211At]astato-benzamide-N-3-hydroxypropylidene-3,3-bisphosphonat e (ABPB), 5-[131I]iodopyridine-3-amide-N-3-hydroxypropylidene-3,3-bisphospho nate (IPPB) and 5-[211At]astatopyridine-3-amide-N-3-hydroxypropylidene-3,3-bisphos phonate (APPB), were injected intravenously into Balb/c mice. MIRD and Monte Carlo methods were used on the basis of cumulated activity calculated from biodistribution data to estimate dose to organs and bone segments. RESULTS: All 131I- and 211At-labeled analogs were strongly incorporated into osseous tissue and retained there at stable levels, while a rapid clearance from blood was observed. The bone uptake was found to be similar for 211At- and 131I-labeled bisphosphonate when compared in paired label experiments. Bone uptake and bone-to-tissue ratios were better for IBPB compared with IPPB, and ABPB compared with APPB. All four compounds appeared to be highly resistant to in vivo dehalogenation as indicated by low uptake of 131I/211At in the thyroid gland and stomach. According to dosimetric estimates, the bone surface-to-bone marrow ratio was three times higher with 211At than with 131I. CONCLUSION: Both the beta-particle- and alpha-particle-emitting compounds showed high in vivo stability and excellent affinity for osseous tissue. Further preclinical evaluation is therefore warranted.

Animals↗
PubMed1998

Emil Kraepelin and forensic psychiatry.

Kraepelin's main positions in forensic psychiatry, that are understandable only in the context of his underlying psychiatric and, especially, nosological theory, are the following: (1) Criminal behavior, especially if repeatedly shown by the same individual, should be regarded as (or, in the strongest version possible, is) mental illness; (2) above all, this viewpoint is due to Kraepelin's broad acceptance of degeneration theory in general, whereas he rejected simplifying concepts like Lombroso's early hypothesis of clinically observable "stigmata degenerations"; (3) Kraepelin voted for the acceptance of diminished responsibility to provide a more differentiated spectrum for the psychiatric expert and the judge; (4) because delinquency, in his view, was closely linked with mental illness, which should be treated instead of (only) being punished, he strictly objected to the death penalty; and (5) he suggested significantly increasing psychiatry's influence on decisions regarding the kind and length of imprisonment.

Crime↗
PubMed1998

[Development of the AMDP module for identification of obsessive- compulsive symptoms. Conceptualization and empirical results].

Results of epidemiology and comorbidity studies have recently demonstrated the psychopathological relevance of obsessive-compulsive symptoms. Therefore the "Arbeitsgemeinschaft für Methodik und Diagnostik in der Psychiatrie" (AMDP) has started to develop a rating scale for a quick and precise assessment of obsessive-compulsive symptoms. The actual version of the scale comprises 20 items on the dimensions "description", "distress and impairment" and "emotion and cognition". The results of a first empirical study (n = 137, psychiatric in- and outpatients) demonstrated excellent internal consistency (Cronbach's alpha = 0.92), a split-half reliability of 0.89 (Spearman-Brown), a test-retest reliability of r = 0.86 and good convergent validity with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamburger Zwangsinventar (HZI). The factor-analytical distribution of the 20 items revealed a 4-factor structure of the scale. The results are presented and their implications on further steps of the development of the scale are discussed.

Adult↗
PubMed1998

Genetic identification of multiple loci that control breast cancer susceptibility in the rat.

We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.

Alleles↗
PubMed1998

Predicting detectability in radioguided surgery: a study based on physical characterization of the probe and on tissue uptake ratios of 125I-, 153Sm- and 165Er-labelled radiopharmaceuticals.

We performed measurements of the sensitivity in water of the radioguided surgery system, Neoprobe 1000. Point sources of 125I, 153Sm and 165Er were measured to a geometric accuracy of 0.1 mm. These measurements were performed with the detector uncollimated and with two different collimators; the results were used to construct three-dimensional sensitivity matrices from which isosensitivity curves could be derived. The matrices were used to simulate the reliability of detecting tumours of various sizes, at various depths, and with variable uptake ratios and activity levels of the three radionuclides investigated. Simulations showed improved tumour detection with a conical collimator, demonstrating that collimator design is important. To minimize the radiation dose during diagnostic work-up, a novel bone-seeking radiopharmaceutical, 165Er-EDTMP, was developed and tested. It showed rapid bone localization, especially in growth zones, and rapid clearance from blood and non-osseous tissues. Its biodistribution was similar to that of 153Sm-EDTMP. Based on these results and previous clinical data, the simulations predicted that lung metastases with a radius of 1 mm might be reliably detected with the Neoprobe 1000 system, if equipped with a suitable collimator.

Animals↗
PubMed1998

[Quality indicators of patient treatment of schizophrenic patients. Results of a pilot study for external quality assurance using tracer diagnosis].

PURPOSE: In Germany, measures for assuring the quality of inpatient treatment are regulated by legislation. Treatment quality must be presented in comparison with other hospitals. Tracer diagnosis is an established method for external quality assurance in the sphere of somatic medicine. METHOD: To evaluate this method of external quality assurance in psychiatry, the German Society for Psychiatry, Psychotherapy and Nervous Diseases (DGPPN) defined and operationalised quality indicators for the treatment of schizophrenic inpatients. RESULTS: of a multicentre project supported by the German Federal Ministry of Health (BMG) using this inventory in 96 schizophrenic inpatients (ICD-10) from 4 hospitals are presented. The qualification of these indicators of structure, process and outcome while comparing the treatment quality of different hospitals as well as their applicability for internal quality management are discussed.

Adult↗
PubMed1997

[Multi-axial system of chapter V (F) of ICD-10. Initial results of a multicenter practicability and reliability study].

With the introduction of operationalized diagnostic systems the multiaxial approach became a more important issue. The proposed multiaxial system of ICD-10 consists of three axes: on axis I psychiatric diagnoses are made according to the ICD-10 Clinical Guidelines or Diagnostic Criteria for Research. Axis II (Disability Diagnostic Scale, DDS) deals with impairment of psychosocial functioning. On axis III environmental/circumstantial and personal lifestyle management factors are rated. As part of the WHO international field trial, applicability and inter-rater reliability of the system were examined in seven German-speaking centers. In addition axis II was compared with the corresponding axis of DSM-III-R (Global Assessment of Functioning Scale). 45 German clinicians rated 12 case histories written in English (provided by WHO) with 488 ratings altogether. Diagnoses on axis I with an average percentage agreement of 65.6% and a mean kappa of 0.50 showed a moderate inter-rater reliability. For axis II the intraclass coefficient was 0.62, and that for the corresponding DSM-III axis was 0.65: both these axes thus also had a moderate inter-rater reliability. There was a close correlation between the subscales and the global assessment of axis II there was. Wide variation was found in the psychosocial circumstances on axis III, the mean kappa value being 0.16. In the discussion proposals for the revision process for the multiaxial ICD-10 system are made.

Adult↗
PubMed1997

[Mianserin-induced hypertension 2 weeks after discontinuation of tranylcypromine].

As compared to other tri- and tetracyclics, antidepressant therapy in patients suffering also from cardiac disease with mianserin is known to be relatively safe. Hypertensive effects of mianserin have not been described so far. We report a case of 64 years old patient with a dilatative cardiomyopathy and left anterior hemiblock, who developed hypertension (maximum: 180/125 mmHg) during mianserin treatment. Previous treatment with tranylcypromine has been stopped two weeks before. After discontinuance of mianserin blood pressure rapidly came back to normal values. The possible noradrenergic and serotonergic mechanisms of this phenomenon are discussed in relation to pretreatment with tranylcypromine.

Antidepressive Agents↗
PubMed1997

Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis.

In 1911, Alois Alzheimer published a detailed report (Zbl. ges. Neurol. Psych. 4: 356-385) on a peculiar case of the disease that had been named after him by Emil Kraepelin in 1910. Alzheimer describes a 56-year-old male patient (Johann F.) who suffered from presenile dementia and who was hospitalized in Kraepelin's clinic for more than 3 years. Post-mortem examination of the patient's brain revealed numerous amyloid plaques but no neurofibrillary tangles in the cerebral cortex, corresponding to a less common form of Alzheimer disease which may be referred to as 'plaque only'. We have identified well-preserved histological sections of this case and performed mutational screening of exon 17 of the amyloid precursor protein gene and genotyping for apolipoprotein E alleles. The patient was shown to be homozygous for apolipoprotein allele epsilon3 and lacked APP mutations at codons 692, 693, 713 and 717. This case is of historical importance as it may have convinced Kraepelin to name the disease after his co-worker, Alois Alzheimer.

Alzheimer Disease↗
PubMed1997

212Bi-DOTMP: an alpha particle emitting bone-seeking agent for targeted radiotherapy.

The synthesis and in vivo stability of the bone-seeking alpha-particle emitting compounds 212Bi-DOTMP and 212Pb/212Bi-DOTMP are described. 212Bi-DOTMP, injected i.v. into Balb/c mice, showed prominent bone localization and a rapid clearance from blood and other organs. Femur/blood ratios increased from 13 at 15 min up to 490 at 2.0 h postinjection. Enhanced uptake of 212Bi-DOTMP was demonstrated in regions with high bone turnover. A comparison between 212Bi-DOTMP and [153Sm]Sm-EDTMP showed essentially no differences in biodistribution. 212Pb/212Bi-DOTMP followed a similar biodistribution, except for slightly elevated levels of 212Bi in the kidneys. The present study has shown 212Bi-DOTMP to be an in vivo stable bone-seeking radiopharmaceutical with promising biological properties for the treatment of sclerotic metastases and osteoblastic osteosarcoma.

Alpha Particles↗
PubMed1996

Dysmorphophobia: differential-diagnostic aspects.

The case of a patient presenting with a depressive-suicidal syndrome and dysmorphophobia, which also showed a delusional character, is discussed concerning the differential-diagnostic difficulties. The nosology of the disorder is discussed especially regarding the variants in the new classification systems.

Adult↗