Personality of the parkinsonian. Clinical and psychometric approach

The personality of patients suffering from Parkinson's disease has been considered as the basis of a psychosomatic theory or more simply as a form of reaction. Between these two extremes the controversy continues and is modified by the use of dopaminergic agents. In this study, 30 patients suffering from parkinson's disease undergo a psychological examination and a M.M.P.I.; the results allow us to determine a pre-morbid obsessive personality coupled with agressivity and ambition. A transformation occurs with the arrival of illness; dependence, passivity, suggestibility evolve in a context where anxiety is relieved of all agressivity but acquires a depressive character. The people surrounding the patients play a part in this transformation. Moreover the pre-morbid characteristics of these patients remind the physician of H. Tellenbach's "typus melancholicus".     

The Relationship of Diastereomer Hydrolysis Kinetics to Shelf-Life Predictions for Cefuroxime Axetil

Cefuroxime axetil, an ester prodrug of cefuroxime, is comprised of a 50:50 mixture of diastereomers A and B. The first-order hydrolysis kinetics of cefuroxime axetil were investigated as a function of pH, temperature, buffers, and ionic strength. Chromatographically identified hydrolysis products were cefuroxime, ²-cefuroxime axetil, and ,-sulfoxides. Buffer catalysis was observed in acetate and phosphate buffers. No significant kinetic effect was observed for ionic strength in the range µ = 0.1-1.0. The pH–rate profiles for hydrolysis of cefuroxime axetil isomeric mixture were obtained at 45, 35, and 25°C. The equation defining the cefuroxime axetil hydrolysis rate constant as a function of pH was k _obs = k _H(a _H) + k _s + k _OH(K _w/a _H), exhibiting maximal stability in the pH range 3.5 to 5.5. The predicted profile at 5°C was in excellent agreement with experimental data in the pH range 3.6 to 5.5. In the pH range 1 to 9, the maximum difference observed for individual hydrolysis constants of isomers was 27%. Shelf-life estimates based on the hydrolysis rate constants for cefuroxime axetil as an isomeric mixture were shown to be equivalent to those based on individual hydrolysis rate constants for isomers A and B.     

Antibiotic sensitivity of enteric pathogens in Vietnam

The in vitro antimicrobial susceptibilities of 675 common enteropathogenic isolates from faecal specimens of patients with diarrhea (E. coli, Shigella, Salmonella and V. cholerae), and 568 E. coli isolates from faecal flora of healthy persons, which were collected as part of a National antibiotic resistance surveillance in Vietnam, were determined. The agar dilution method was used for the following nine antibiotics: ampicillin, doxycycline, chloramphenicol, gentamicin, nalidixic acid, kanamycin, trimethoprim, trimethoprim in combination with sulfamethoxazole (1/20), and sulfisomidin. Gentamicin was the most active of the antibiotics tested against all bacterial species with MICs in the range 0.125-4 mg/l. All strains were susceptible to nalidixic acid (0.125-8 mg/l) and more than 90% were susceptible to kanamycin. Among E. coli and Shigella isolates from patients the frequencies of resistance to commonly used antibiotics were high: ampicillin 73% and 84%, doxycycline 83% and 94%, chloramphenicol 71% and 91%, sulfisomidin 82% and 92%, respectively. Resistance to trimethoprin, as well as to the combination with sulfamethoxazole was found in 21% and 23%, respectively. The frequencies of multiple resistance (resistance to three or more antibiotics) were also high (77% and 89%, respectively). Less than 10% of Salmonellae and V. cholerae isolates were resistant to ampicillin, sulfisomidin or trimethoprim. Among E. coli from healthy people the frequencies of resistance were lower than in isolates from patients: ampicillin 23%, doxycycline 40%, chloramphenicol 21% and sulfisomidin 34%. However, the same patterns of multiple resistance were found in both groups.     

Cancer chemotherapy in the elderly: a series of 51 patients aged>70 years

Summary A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were>70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was 70% for 40 patients. Malignancies were hematopoietic in 24 cases (47%) and digestive in 15 patients (29%), and 12 subjects (24%) had other types of cancers. The first chemotherapy course was given at the full dose to 23/51 (45.1%) patients. The drug dose was reduced for 28/51 (54.9%) patients, due in 25 cases to the subjects being>70 years old. Neither age, KPS, pretreatment assessment, nor cancer extent was correlated with the modifications made to the first cycle. An overall toxicity of grade 3+4 (WHO grading scale) was noted in 10 subjects (19.6%). Although these elderly patients were probably selected, analysis of their charts did not evidence an increase in chemotherapy toxicity, regardless of the dose they received.Presented at the EORTC Pharmacokinetics and Metabolism Group Meeting, Bordeaux, November 1990     

Myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) with myelofibrosis.

Acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) enter rarely in the differential diagnosis of myelofibrosis (MF). MF of marked intensity, resulting in either "dry taps" or non-representative smears, is encountered in approximately 10% of cases. MF may be observed in any type of AML, most frequently in acute megakaryoblastic leukemia (M7). Apart from some typical cases of MDS, MF is associated with cases of acute myelodysplasia with myelofibrosis (and a major megakaryocytic component). This syndrome has been described under various headings: acute or malignant myelosclerosis, and acute MF. It should be distinguished from M7 and from myeloproliferative syndromes.     

Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations

The dopamine transporter (DAT) provides major regulation of the synaptic levels of dopamine and is a principal target of psychostimulant drugs. Associations between DAT gene polymorphisms and human disorders with possible links to dopaminergic neurotransmission, including attention-deficit/hyperactivity disorder (ADHD) and consequences of cocaine and alcohol administration, have been reported. We now report approximately 60000 bp of genomic sequence containing the entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons and several introns and analyze these amplification products by single-stranded sequence conformation (SSCP) and/or direct sequencing. These results define silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and 15. Rare conservative mutations are identified in amino acids encoded by DAT exons 2 and 8. Analyses of the common nucleotide variants and the previously reported VNTR in the non-coding region of exon 15 define the pattern of linkage disequilibrium across the DAT locus. These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are consistent with substantial evolutionary conservation of the DAT protein sequence. They suggest that gene variants that alter levels of DAT expression provide the best current candidate mechanism for reported associations between DAT gene markers, ADHD and other more tentatively associated neuropsychiatric disorders.     

Cochlear implantation

Cochlear implants are the single greatest advancement of the late 20th century for the deaf and hearing impaired. Recent expanding guidelines as well as surgical techniques are discussed. Cochlear implantation is currently the only means to restoring partial hearing to patients with severe-to-profound sensorineural loss not aidable with conventional amplification.     

Volumetrie der Harnblase mittels implantierbaren Ultraschallsensoren

Experimental studies revealed that the contractile response of the urinary bladder to sacral anterior root stimulation depends on the actual bladder volume. Furthermore, no clinical relevant technique is available for continuous monitoring of the bladder wall distension respectively bladder volume in paraplegic patients. The presented study investigates the reliability of especially developed implantable ultrasound sensors as a sensoric system for continuous monitoring of the bladder volume. In six anaesthesized pigs two ultrasound sensors, one transmitter and one receiver, were implanted on the bladder wall at different locations (latero-lateral, dorsal-ventral, rostral-caudal). After closing the abdominal wall, the bladder was filled in 50 ml steps up to 250 ml. After each filling step the running time of the ultrasound signal was measured. In all experiments reproducible results and a high correlation of the measured running times with bladder volume were observed. The latero-lateral configuration of the sensors seemed to be most confidential. The presented study indicates that bladder volumetry with implantable ultrasound sensors is possible with minimal technical prerequisites. This promising technique for continuous bladder volumetry could play an important role in the development of an intelligent and autoadaptive neurostimulator of the urinary bladder in paraplegic patients.     

Effects of intermittent exposure to aflatoxin B1 on DNA and RNA adduct formation in rat liver: dose-response and temporal patterns.

We studied the effects of intermittent exposure to aflatoxin B1 (AFB1) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm of AFB1 intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB1 continuously for 4, 8, 12, and 16 weeks. Control rats received AFB1-free NIH-31 meal diet. AFB1-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after 1 or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB1 after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB1-RNA adducts were three to nine times more sensitive than AFB1-DNA adducts but showed greater variability. These results suggest that binding of AFB1 to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA.