[Off-label antibiotic use: malpractice or good clinical practice?]. / La prescrizione off-label di antibiotici: malpractice o buona pratica clinica?

In Italy, off-label drug use has been forbidden since 1998. However, Italian law allows off-label treatment for single cases only if treatment is considered irreplaceable, and completely under physician responsibility. To assess the consequences of such regulations for the infectious diseases specialist, we listed the indications of intravenous and oral antibiotics available in our hospital pharmacy service, and discussed them in a pool of nine infectious diseases specialists. Indications were compared with the recommended treatment of major bacterial syndromes as suggested by the major guidelines and textbooks. We found that standard treatment for several bacterial infections is off-label. The pool of specialists concluded that some off-label use of antibiotics is vital to daily practice in infectious diseases. Scientific societies should promote guidelines as the standard reference for good clinical practice, which should not be based only on the respect of drug labels.

Simian virus 40 footprints in normal human tissues, brain and bone tumours of different histotypes.

SV40 footprints were investigated by PCR in normal human tissues and tumours of different histotypes, followed by Southern blot hybridization with a specific internal oligoprobe for SV40 DNA. Specific SV40 amplification products were detected at high prevalence in primary human brain tumours: 83% of choroid plexus papillomas, 75% ependymomas, 47% astrocytomas and 37% glioblastomas. SV40 footprints were also revealed in primary bone tumours: 35% osteosarcomas and Ewing's tumours. Positive normal tissue samples ranged from 45% of sperm fluids to 8% of brain tissue. Normal bone tissue specimens were SV40 negative. These results indicate that SV40 is associated with human brain and bone neoplasms, whereas normal bone and brain tissues were either SV40 negative or positive at low grade. SV40 footprints were found in other normal samples such as PBC, B- and T-lymphocytes and sperm fluids, indicating that SV40 is latent in these cells. Therefore, these cells may be vectors of SV40 in other host tissues and may spread SV40 infection by blood transfusion and sexual transmission in the human population.

[SV40 as a possible cofactor in the etiopathogenesis of mesothelioma and other human tumors]. / SV40 come possible cofattore nell'eziopatogenesi del mesotelioma e di altri tumori umani.

Simian virus 40 (SV40) has been introduced into the human population with contaminated polio vaccines between 1955 and 1963. Previous research conducted by southern blot hybridization and recent analysis by PCR have shown the presence of SW0 sequences in human brain tumors, mesotheliomas and osteosarcomas as well as in normal tissues such as blood and sperm fluids. SV40 RNA and T antigen were detected in the same tissues. All the samples were coinfected by BK Virus (BKV), suggesting that BKV may have a helper function for SV40 replication in human cells. The presence of SV40 in human tumors suggests that the virus may be a cofactor in the etiopathogenesis of human neoplasia. In addition, blood and semen may represent the vectors for transmission of SV40 by horizontal infection in the human population.

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants.

UNLABELLED: The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. CONCLUSION: This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity.

Contraception in diabetic women.

There is a very strong need for an effective and reliable method of contraception in the diabetic woman. An unplanned pregnancy that occurs when her diabetes is not under good control can have disastrous consequences, ranging from abortion to a congenitally malformed fetus. The most important factor in the contraceptive decision for the diabetic patient, especially the IDDM patient, is that the choice be made not by the clinician alone or the patient alone, but through a carefully through-out process that involves both patient and physician.

PIP: Diabetic women are in special need of effective, reliable contraception. A pregnancy that occurs when the diabetes is not under control is at risk of congenital fetal malformations. Since diabetic women require a method with a minimum risk of failure, their choices are limited largely to the IUD and oral contraceptives (OCs). In women with insulin-dependent diabetes mellitus, OC use does not appear to disrupt diabetes control and may require only a mild alteration of insulin requirements. Low-dose monophasic OCs that limit the amount of androgenic activity of the progestin may be the best choice for women with a history of gestational diabetes or insulin-dependent diabetes mellitus.

SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals.

SV40 T antigen (Tag) coding sequences were detected by PCR amplification followed by Southern blot hybridization in human brain tumors and tumor cell lines, as well as in peripheral blood cells and sperm fluids of healthy donors. SV40 early region sequences were found in 83% of choroid plexus papillomas, 73% of ependymomas, 47% of astrocytomas, 33% of glioblastoma multiforme cases, 14% of meningiomas, 50% of glioblastoma cell lines, and 33% of astrocytoma cell lines and in 23% of peripheral blood cell samples and 45% of sperm fluids from normal individuals. None of the 13 normal brain tissues were positive for SV40 DNA, nor were seven oligodendrogliomas, two spongioblastomas, one neuroblastoma, one meningioma, or four neuroblastoma cell lines. Expression of SV40 early region was found by reverse transcription PCR, and SV40-specific Tag was detected by indirect immunofluorescence in glioblastoma cell lines. DNA sequence analysis, performed in four positive samples, confirmed that the amplified PCR products belong to the SV40 early region. Sixty-one % of the neoplastic patients positive for SV40 sequences had an age excluding exposure to SV40-contaminated polio vaccines, suggesting a contagious transmission of SV40. The possible role of SV40 Tag in the etiopathogenesis of human brain tumors and the spread of SV40 by horizontal infection in the human population are discussed.