Future doctors and brain death: what is the prognosis?

OBJECTIVE: To evaluate the knowledge and the opinion of medical students at the Pontifical Catholic University of S?o Paulo related to the general aspects of donation, organ and tissue procurement, and basic concepts of brain death (BD). MATERIALS AND METHODS: Questionnaires of 24 items were distributed among all students related to the concept and diagnosis of BD, personal aspects of tissue and organ donation, and general question concerning organ donation. The answers classified students as good versus bad experts of the concept and the diagnosis of BD. RESULTS: Of a total of 580 students, 361 (62.24%) answered the questionnaire. Although the concept of BD was known to 70%, only 35% had a good knowledge of the diagnosis. One percent of the students were opposed to the organ donation and 76% of them were donors. Approximately 90% would authorize organ retrieval from their family members but 27% had never discussed organ donation with their families. Most students were interested in the general aspects of donation and organ procurement (88.36%). CONCLUSION: The majority of the students know the concept of BD. General aspects regarding tissue and organ donation and diagnosis of BD might be improved with the continued education on the subject.     

Evaluation of the fluoride concentration and consumption of mineral water

OBJECTIVE: Considering that water is an importance source of fluoride intake, and that the consumption of mineral water and prevalence of dental fluorosis have been increasing, the aim of this study was to evaluate the consumption of mineral water and its fluoride concentration. METHODS: The study was performed in residential districts of the municipality of Bauru, State of S?o Paulo, by means of stratified sampling via clusters. Each cluster corresponded to one residential block. For randomization purposes, the residential blocks were numbered within the 17 districts established by the city plan. One thousand homes were thus visited. Mineral water samples were collected using previously labeled 50 ml plastic flasks. Fluoride analysis was done using an ion-sensitive electrode (Orion 9609), after buffering using TISAB II. Information on the consumption of mineral water was obtained by means of applying a questionnaire. RESULTS: Around 29.72% of the city's population was consuming mineral water. In the 260 samples analyzed from 29 different brands of water, the fluoride concentration ranged from 0.045 to 1.515 mg/l. For one brand, the label stated that the fluoride concentration was 0.220 mg/l, but analysis revealed a concentration of 1.515 mg/l. Moreover, some brands did not specify the fluoride concentration on the label and, for these, the analysis showed concentrations ranging from 0.049 to 0.924 mg/l. CONCLUSIONS: The results demonstrated wide variation in fluoride concentrations and reinforce the importance of the control of such waters by the sanitary surveillance agency.     

Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens

Galantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of nicotinic receptors, enhanced in a concentration-dependent manner the amplitude of purinergic twitch contractions of the electrically stimulated rat vas deferens (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine>tacrine>rivastigmine=donepezil. The potentiations seem to be unrelated to the ability to inhibit acetylcholinesterase, since the hierarchy of potencies to block the enzyme in vas deferens was tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also increased the twitches; such effect was produced by a low range of concentrations of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not by rivastigmine or donepezil. A striking enhancement of twitches was also caused by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a blocker of small-conductance Ca2+-activated K+ channels, induced a lower potentiation. The antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the potentiation by galantamine, indicating the involvement of nicotinic receptors. Therefore, it is suggested that, besides an inhibition of acetylcholinesterase, some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or activation of nicotinic receptors of nerve terminals, might be involved in twitch potentiation. These results are relevant in the context of the clinical use of galantamine to improve cognition and behaviour in patients with Alzheimer's disease.     

Comparative sequence analysis of the South African vaccine strain and two virulent field isolates of Lumpy skin disease virus

Summary.  The genomic sequences of 3 strains of Lumpy skin disease virus (LSDV) (Neethling type) were compared to determine molecular differences, viz. the South African vaccine strain (LW), a virulent field-strain from a recent outbreak in South Africa (LD), and the virulent Kenyan 2490 strain (LK). A comparison between the virulent field isolates indicates that in 29 of the 156 putative genes, only 38 encoded amino acid differences were found, mostly in the variable terminal regions. When the attenuated vaccine strain (LW) was compared with field isolate LD, a total of 438 amino acid substitutions were observed. These were also mainly in the terminal regions, but with notably more frameshifts leading to truncated ORFs as well as deletions and insertions. These modified ORFs encode proteins involved in the regulation of host immune responses, gene expression, DNA repair, host-range specificity and proteins with unassigned functions. We suggest that these differences could lead to restricted immuno-evasive mechanisms and virulence factors present in attenuated LSDV strains. Further studies to determine the functions of the relevant encoded gene products will hopefully confirm this assumption. The molecular design of an improved LSDV vaccine is likely to be based on the strategic manipulation of such genes. Received November 25, 2002; accepted February 17, 2003 Published online May 5, 2003     

The kinetic profile of gentamicin in premature neonates

The kinetic profile of gentamicin in premature infants has been studied to enable the development of optimized dosage schedules for neonatal intensive-care units and to stress the relationship between the pharmacokinetic parameters and several demographic, developmental and clinical factors which might be associated with changes in gentamicin disposition. Sixty-eight newborn patients of 24- to 34-weeks gestational age and 600-3,100 g current weight in their first week of life, undergoing routine therapeutic drug monitoring of their gentamicin serum levels, were included in this retrospective analysis. Gentamicin pharmacokinetic parameters were determined through non-linear regression by using a single-compartment open model. By regression analysis the current weight (g) was shown to be the strongest co-variate, and both gentamicin clearance (L h(-1)) and volume of distribution (L) had to be normalized. Additionally, gentamicin clearance depended on gestational age with a cut-off at 30 weeks, which allowed the division of the overall population into two subsets (< 30 weeks and between 30-34 weeks of gestational age). The younger neonates (<30 weeks of gestational age) showed a lower gentamicin clearance (0.0288 vs 0.0340 L h(-1) kg(-1)), a slightly higher volume of distribution (0.464 vs 0.435 L kg(-1)), and a longer half-life (11.17 vs 8.88 h) compared with the older subgroup (30-34 weeks of gestational age). On the basis of the pharmacokinetic parameters obtained, we suggest loading doses of 3.7 and 3.5 mg kg(-1) for the two subgroups of neonates (<30 weeks and 30-34 weeks of gestational age), respectively. The appropriate maintenance doses in accordance with the characteristics of the patients should be 2.8 mgkg(-1)/24h and 2.6 mg kg(-1)/18 h for neonates < 30 weeks and between 30-34 weeks of gestational age, respectively. Finally, when compared with previous studies, the information obtained on the pharmacokinetics and determinants of the pharmacokinetic variability of gentamicin in neonates was shown to be consistent.     

Therapeutic monitoring of warfarin: the appropriate response marker

Warfarin is a 4-hydroxycoumarin anticoagulant drug used for the prevention and management of thromboembolic and vascular diseases. It acts through the inhibition of the vitamin K-dependent transcarboxylation reactions that convert precursors of clotting factors into their active form. Appropriate use of warfarin requires patient monitoring and dosage adjustments, to ensure its safety and efficacy. The aim of this work was to clarify the relationship between traditional (prothrombin time, usually expressed as the international normalized ratio; INR) and alternative (clotting factors II and X) warfarin response markers to establish their usefulness for therapeutic drug monitoring. Seventy adult outpatients, aged between 31 and 86 years old, were involved in the study. All subjects received warfarin in a monotherapy regimen and had been on a stable dosing schedule for at least two weeks to assure a steady-state condition. A total of 81 prothrombin times (expressed as INR), and factor II and factor X activity were simultaneously determined. Eleven patients presented repeated measurements at different time periods under the same dosing regimen. The results obtained from regression and cluster analysis showed a close relationship between factors II and X (r = 0.73), a weak correlation between INR and both factor II (r = -0.35) and factor X (r = -0.36), and a very slight dependency between warfarin and the response markers used. In addition, it seems that independent of the selected response marker, in long-term warfarin therapy, reproducible responses can be obtained over time if a steady-state condition is achieved. The coefficients of variation for factors II and X were greater (35.44 and 37.93%, respectively) than INR (14.50%), indicating that INR is a more precise measure than either factor II or factor X. In conclusion, INR appears to be the most appropriate warfarin response marker for therapeutic drug monitoring due to its universality, objectivity as a direct physiological effect measurement, and the available information regarding appropriate endpoints. However, when INR values are not in accordance with patient response therapy, factor II and factor X should be considered as an alternative to optimize warfarin therapy.     

Human Herpesvirus-8 (HHV-8)-Associated Primary Effusion Lymphoma in two Renal Transplant Recipients Receiving Rapamycin

The Akt/mammalian target of rapamycin (mTOR) signaling cascade has been demonstrated to be constitutively activated in several malignancies, including Kaposi sarcoma (KS) and human herpesvirus-8 (HHV-8)-associated primary effusion lymphoma (PEL). In organ transplant recipients, therapeutic change from cyclosporin to the mTOR inhibitor rapamycin can lead to regression of KS lesions. Recent experiments using PEL cell lines and murine xenograft PEL models suggested that rapamycin could inhibit the growth of PEL cells. In the present report, we describe the cases of two HIV-1-negative males of African origin who underwent renal transplantation and developed PEL while receiving rapamycin as immunosuppressive treatment. Both patients were retrospectively found to be HHV-8 seropositive before renal transplantation. The present case report suggests that rapamycin may not protect HHV-8-infected renal transplant recipients from occurrence of PEL or progression of pre-existing PEL.     

Characteristics of a tandem system of ionization chambers in X-ray beams,mammography level

Two parallel plate ionization chambers (inserted in slab phantoms) recently assembled at IPEN were studied in relation to their operational characteristics for use in quality control of X-ray beams, mammography level. The chambers present only one difference: one has an inner collecting electrode made of graphite and the other, of aluminum. These chambers make up a tandem system, which may be employed to verify X-ray beams energy constancy, by the confirmation of half-value layers and effective energies, and to determinate air kerma rates. The chambers presented good results for the operational tests, as recommended internationally.     

Utilization of screening mammography: comparison of different physician specialties

Data obtained on 426 consecutive patients referred to a breast center by 122 physicians, including family practitioners, general surgeons, and other specialists, showed that the obstetricians-gynecologists referred the greatest average number of patients per physician, with more than 50% of these referrals for screening mammography. Internists referred fewer patients by nearly a factor of ten, with only one-third of these patients referred for screening mammography. Internists may be the weakest link in the utilization of screening mammography.