Prediction of chemical absorption into and through the skin from cosmetic and dermatological formulations.

BACKGROUND: To date, risk assessment following topical exposure to cosmetic/dermatological formulations cannot be precisely evaluated. OBJECTIVES: To provide a tool for optimization of active permeation into/through skin and for risk assessment. METHODS: A predictive model was developed for estimating the cumulative mass of a chemical absorbed into and across the skin from a cosmetic/dermatological formulation. Account was taken of (i) the ionization state of the chemical, to correct the skin/vehicle partition coefficient; and (ii) the nature of the cosmetic/dermatological formulation. Three specific assumptions were made: firstly, steady-state transport across the skin was achieved despite application of a finite dose of chemical; secondly, vehicle effects were small relative to the precision of the prediction; and, thirdly, each formulation could be treated as an oil-in-water emulsion, in which only that fraction of the chemical in the aqueous phase was available to partition into the stratum corneum. A database of 101 ex vivo human skin experiments involving 36 chemicals was analysed. RESULTS: For 91% of the data, the difference between predicted and experimental values was less than a factor 5; when the aforementioned corrections were not used, on the other hand, only 26% of the data was well predicted. The model was successfully applied to predict skin absorption of two compounds not included in the database, for which in vitro percutaneous penetration from cosmetic vehicles have been measured. CONCLUSION: A model has been developed to predict the mass of a chemical absorbed into and through the skin from a cosmetic or dermatological formulation.

Brain metastases from unknown primary tumour: a prospective study.

The best management of patients with brain metastases from an unknown primary tumour is still unclear, as data are scarce and studies are retrospective. We report 33 patients with biopsy-proven brain metastases from a primary tumour not found at the first investigations, who were treated by surgery and/or radiotherapy and followed with serial CT until death. Median survival time for all patients was 10 months and survival rates at 6 months, 1 year and 2 years were 76 %, 42 % and 15 % respectively. Patients with single brain metastasis treated by gross total resection and whole-brain radiotherapy (WBRT) had a median survival of 13 months with 76% alive at 6 months, 57 % at 1 year and 19% at 2 years. Patients with multiple brain metastases who underwent either WBRT alone or WBRT preceded by gross total resection of the symptomatic lesions had a poorer prognosis: median survival of 6-8 months with 50-100% alive at 6 months, 17-20% at 1 year and none alive at 2 years. In 85% of patients with a single brain metastasis a significant improvement in neurological functions was observed after surgical resection; among patients with multiple brain metastases a neurological improvement was observed in all patients who had a resection of symptomatic lesions and only in a half of patients who had WBRT alone. During the follow-up the primary tumour was found in 27/33 patients (82 %) and was located in the lung in 78%. Between 1987 and 1991 (with limited screening for the primary tumour in the follow-up) the unknown tumours were 6/15 (40%); in the more recent period (1992-1996) (CT-based screening for the primary tumour in the follow-up) no primary tumour remained unknown but overall survival has not significantly improved. The number of brain metastases was the only significant factor affecting survival after both univariate and multivariate analysis. This study suggests that, in patients with both single and multiple brain metastases from an undetected primary site when first studied, surgery and/or WBRT enable the control of the brain disease, partly because the systemic disease may be silent for a prolonged time. Only a few asymptomatic patients may benefit from an early detection and treatment of the primary tumour during the follow-up.

Atypical and polymorphic angioblastic tumors of the central nervous system.

Five central nervous system (CNS) polymorphic angioblastic tumors have been studied. Four were located in the posterior fossa and one involved the temporal lobe. In reviewing the literature, the authors point out the rarity of the supratentorial locations and of malignant hemangioblastomas. The clinical and anatomopathological peculiarities are discussed, as is the uncertain classification of two cases. The discrepancy between histology and outcome is focused upon in the other three cases. Finally, the diagnostic, prognostic, and nosographic difficulties posed by CNS angioblastic neoplasms are discussed.

Treatment of cerebral arterio-venous malformations with laser.

The surgical application of the laser in the treatment of vascular diseases of the brain is based on its characteristic to perform an immediate or delayed modification of the vessel wall either by shrinking the collagenous fibres or by intraluminal thrombosis. Personal researches have been carried out to study the histological modifications of the vessel wall in normal arteries following laser irradiation with Nd:YAG. On this basis we have treated arterio-venous malformations (AVMs) in man. The laser enables radical surgery with a complete preservation of the healthy tissue surrounding the lesion because of reduced manipulation and the absence of intraoperative haemorrhage. Doppler technique and real-time ultrasonography are mostly suitable in the identification of the small deep-seated AVMs localizing the site of the malformation and the reactive glial tissue surrounding the lesion. The main indications are small AVMs located in critical areas of the brain.

Medulloblastoma with lipidized cells versus lipomatous medulloblastoma.

BACKGROUND: Lipomatous medulloblastoma is a recently identified clinicopathological entity, characterized by areas of lipomatous differentiation, manifestation in adults, and apparently by a favorable prognosis. MATERIAL AND METHODS: In our series of medulloblastomas of adults and children we have found lipidized cells within the tumor in 6 out of 78 cases of adults and in 8 out of 44 cases of children. In 3 adult cases and 3 children cases, lipidized cells were particularly numerous and clustered. RESULTS: Neuronal differentiation was found in 4/6 cases; no case showed GFAP-positive tumor cells. Lipidized cells were constantly immunopositive for vimentin and some of them also for KP-1 and CR3/43. The proliferation potential was evaluated by the immunohistochemical demonstration of MIB-1; MIB-1-labeling index (LI) ranged from 20.8% to 40.5%. No case survived longer than 7 years after diagnosis and postoperative radiotherapy. CONCLUSION: The present 6 cases of heavily lipidized medulloblastoma are not uniform as for age of occurrence, proliferation potential and survival. They do not share the clinical and pathologic features of "lipomatous medulloblastoma". Therefore, the finding of large numbers of lipidized cells in a medulloblastoma does not authorize to diagnose the tumor as "lipomatous medulloblastoma", for which a favorable clinical prognosis is foreseen.

MIB-1 immunoreactivity in craniopharyngiomas: a clinico-pathological analysis.

BACKGROUND: Craniopharyngiomas are epithelial tumors of the suprasellar region, unanimously defined as benign. Despite the benign histological aspect and apparent gross total resection achieved in a proportion of cases, recurrence rate remains about 30% at 10 years. The role of 7 pathological factors as predictors of recurrence and clinical outcome in craniopharyngioma patients is controversial, as well as the prognostic role of the evaluation of proliferation potential. MATERIAL AND METHODS: In the present study, the proliferation potential of 37 craniopharyngiomas was investigated by analyzing the pattern of Ki-67-MIBI immunoreactivity; the data have been analyzed in relation to age of the patient, histologic type (adamantinomatous/squamous papillary), microscopic and cytochemical features. RESULTS: Craniopharyngiomas operated in adults have a higher MIB-1-LI than those of children; the epithelial cells abutting the stromal cysts are engaged in the cell cycle, while this is not the case for the cells abutting the nervous tissue; MIB-1-LIs of adamantinomatous craniopharyngiomas are not different from those of squamous papillary craniopharyngiomas, the localization of MIB-1-positive nuclei is different in the 2 craniopharyngioma types, non-epithelial cells proliferate in the stromal component of craniopharyngiomas. CONCLUSIONS: By analyzing these data while considering all available information on the efficacy of surgery and radiotherapy, the proliferation potential of craniopharyngiomas, when evaluated by MIB-1, has no role in the outcome. The very low MIB-1-LI of the intracerebral tumor growth indicates that uncompletely resected tumor remnants do not represent an active starting point of recurrence.

Thermal effects on nervous human tissues under electro or laser surgery.

A series of experiments has been carried out with the aim of determining the temperature distribution in nervous tissues after coagulation, vaporization and cutting, using electrosurgical unit (monopolar mode and bipolar mode) and laser beam (CO2, Argon and Nd:YAG). It was found that, at a surface distance of 2 mm from the heated point, the superficial temperature reaches different values, ranging from 100 degrees C, to 15 degrees C, 8 degrees C, 6 degrees C, 10 degrees C using monopolar mode, bipolar mode, CO2 laser, Argon laser and Nd:YAG, respectively. At a depth of 2 mm below the target point, however, the temperature increase is drastically reduced.

[Controlled hypotension with nitroglycerin in neurosurgery (author's transl)]. / L'hypotension controlée avec la nitroglycérine en neurochirurgie.

Controlled hypotension with nitroglycerin has been used n 30 neurosurgical procedures for aneurysms clipping, artero-veinous malformations, cerebral vascularised tumours and in some cases in the course of serial carotido-cerebral angiography. Farmacodynamic aspects of this drug and its effects on intracranial pressure are compared with sodium nitroprusside. Controlled hypotension was induced with prepared solution of nitroglycerin via an infusion pump in order to achieve a mean arterial blood pressure from 70 to 40 torr. All patients during hypotension were monitored by continuous blood pressure, pulse rate and intracranial pressure records. First results of our clinical evaluation indicate that this drug produce a rapid fall in blood pressure without harmful effect and does not significantly modify intracranial pressure. Its potential benefit in spasm of intracranial arteries associated with subarachnoid bleeding is investigated.

Retrosigmoid approach for vestibular neurectomy in Meniere's disease.

BACKGROUND: Vestibular nerve section is considered to be the most effective surgical procedure to control intractable symptoms secondary to Meniere's disease (MD). This study was developed to analyze the adequacy of retrosigmoid vestibular neurectomy in terms of vertigo control, hearing preservation and clinical complications of this procedure. METHODS: A retrospective review was carried out on 14 patients affected by definite unilateral MD who underwent vestibular neurectomy via the retrosigmoid approach. FINDINGS: One patient was lost from follow-up; another one had only a short postoperative observation. At follow-up performed on 12 cases, no patients reported any crisis of acute vertigo. Four patients were free from any vestibular symptoms, while 8 reported some slight gait disturbances. Hearing function was preserved in 10 patients and improved in 2. 1 year postoperative vestibular function was absent at the side operated on and unchanged on the other side in all the cases. CONCLUSIONS: Vestibular neurectomy via the retrosigmoid approach can be considered a safe and effective procedure in relieving medically refractory vertigo in Meniere's disease, while preserving hearing.

Observations on the simultaneous use of CO2 and Nd:YAG lasers in neurosurgery.

Seven cases of cerebral tumors (four deep-seated sovratentorial gliomas located in motor area, occipital region, parietal region and frontal region; one deep-seated cystic cerebellar spongioblastoma; one sphenoidal wing meningioma, and one spinal cord intradural tumor) were simultaneously irradiated in the same area with two sources (CO2 and Nd:YAG). Using CO2 and Nd:YAG simultaneously, a larger and deeper lesion was obtained. The main bulk was irradiated with two sources free hand. The implant with the two sources was connected to the operating microscope. The rise in temperature, 3 mm from the border of the lesion, was similar to that obtained with Nd:YAG alone. Hemostasis was not impaired. In comparison with the single sources, this method allows a more rapid demolition of the tumor without additional damage to the surrounding tissues.

Effects of laser sources (argon, Nd:YAG, CO2) on the elastic resistance of the vessel wall: histological and physical study.

The function of elastic elements of the vessel wall is to produce a tension suitable to resist the distension strength made by blood pressure. By producing a modification in the morphologic and structural configuration of such elastic elements, it is possible to obtain changes of the elastic resistance of the wall. The paper reports the histological and physical modifications of blood vessel walls irradiated with different laser sources.