The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

Synaptic plasticity in the dentate gyrus of aged rats is altered after chronic nimodipine application.

We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this compound improves hippocampal neuronal physiology and enhances cognitive function during aging. In the supragranular layer of the dentate gyrus we found a 24% decrease in synaptic density (Nv) in aged animals, while synaptic size (S) was not significantly altered. After nimodipine treatment Nv in aged rats was not significantly different from young adults, thus being significantly increased compared to age-matched controls. The size of synapses was not significantly altered after nimodipine administration. Total synaptic surface area (Sv) in nimodipine-treated animals was significantly increased compared to aged controls, however, Sv remained significantly lower than in young adults. These data indicate that chronic administration of nimodipine enables granular cells in the dentate gyrus to maintain its number of synaptic contacts during the aging process. Furthermore, the presented influence of nimodipine on synaptic plasticity processes may underlie previously reported improved cognitive functioning of aged animals treated similarly with nimodipine.     

Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transportedPhaseolus vulgaris leucoagglutinin

The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). After immunocytochemical visualization of labeled efferents, the distribution of projections over the cortical mantle, olfactory regions and amygdala were studied by light microscopy. Based on differences in cortical projection patterns, the MBN was subdivided in anterior, intermediate and posterior portions (MBNa, MBNi and MBNp). All subdivisions maintain neocortical projections and are subject to an anterior to posterior topographic arrangement. In the overall pattern, however, the frontal cortex is the chief target. Furthermore, all MBN parts project to various regions of meso- and allocortex, which are progressively more dense when the tracer injection is more anteriorly placed. The most conspicuous finding, however, was a ventrolateral to dorsomedial cortical projection pattern as the PHA-L injection site moved from posterior to anterior. Thus, the posterior MBN projects predominantly to lateral neo- and mesocortex while the anterior MBN sends more fibers to the medial cortical regions. Furthermore, the MBNa is a source of considerable afferent input to the olfactory nuclei and as such should be regarded as a transition to the HDB. The HDB, apart from projecting densely to olfactory bulb and related nuclei, maintains a substantial output to the medial prefrontal cortical regions and entorhinal cortex, as well. Comparison of young vs aged cases indicate that aging does not appear to have a profound influence on cortical innervation patterns, at least as studied with the PHA-L method.     

Post-ischemic administration of diazoxide attenuates long-term microglial activation in the rat brain after permanent carotid artery occlusion

Diazoxide is a putative mitochondrial, ATP-sensitive potassium channel opener that has been implicated in neuroprotection in cerebral ischemia. Administered as pretreatment, diazoxide can attenuate ischemia-related neuronal injury, but little is known about the potential neuroprotective properties of the drug when it is given after the onset of an ischemic insult. In a previous study, we applied diazoxide after imposing chronic cerebral hypoperfusion by means of permanent, bilateral occlusion of the common carotid arteries (2VO) in rats. We observed that ischemia-induced learning impairment assessed in the Morris water maze, and microglial activation visualized by immunocytochemistry, were prevented by diazoxide as determined at 13 weeks after 2VO. However, dimethyl sulfoxide, the organic solvent of diazoxide also prevented memory deficits, without any effect on microglial activity. Therefore, we have repeated our experiments with the use of an inorganic solvent, aqueous NaOH solution in order to clarify the effect of diazoxide independent of dimethyl sulfoxide. The present results demonstrated that diazoxide alone did not improve learning performance, but it prevented microglial activation in the hippocampus 13 weeks after the onset of 2VO. These data provide evidence that post-treatment with diazoxide is not effective in impeding a long-term memory deficiency, but it can attenuate ischemia-induced microglial activation, independently of the solvent used.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Cholinergic fiber aberrations in nucleus basalis lesioned rat and Alzheimer's disease.

Innervation density and morphological aberrations of cholinergic fibers were studied with choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry in 30-35 month-old aged rats and rats with long-term bilateral lesions of the magnocellular basal nucleus (MBN). In addition, AChE histochemistry was performed on human cortical sections derived from autopsy brains of normal aged and Alzheimer's disease (AD) patients. A limited but variable number of morphological alterations were observed in ChAT-immunoreactive fibers in the cortex and the hippocampus of the aged control rats. The aged MBN-lesioned rats displayed a severely reduced number of cholinergic fibers in the denervated areas of the neocortex, whereas the surviving fibers showed a strongly increased number of aberrations. Fiber anomalies were also observed in the cortex of the aged human subjects and Alzheimer patients, the latter showing a higher incidence of such aberrations. Only a part of these distended profiles were seen in close association with senile plaques as detected in the AChE-stained material. These findings suggest that experimental MBN lesions combined with aging share with AD the induction of large quantities of fiber malformations. Implications of possible mechanisms in both conditions are discussed.     

Colour Doppler changes and thromboxane production after ovarian stimulation with gonadotrophin-releasing hormone agonist

The objective of this study was to evaluate the Doppler flow variations which occur following the use of different protocols of ovarian stimulation in an IVF programme, and to investigate the thromboxane production by cultured endometrial cells and its influence on embryo implantation. A total of 60 patients underwent three different ovarian stimulation protocols: long gonadotrophin-releasing hormone agonist (GnRH-a), short GnRH-a and no GnRH-a. Transvaginal ultrasonography and colour Doppler analysis were performed before and during the treatment. On the day that the Doppler examination took place, luteinizing hormone, follicle stimulating hormone, plasma oestradiol and thromboxane concentrations were assayed. On the day of oocyte retrieval, endometrial cells were collected and cultured, and their thromboxane production evaluated. No significant differences in hormonal, ultrasonographic or Doppler parameters were observed between the three groups. Ten out of 56 patients who had a successful embryo transfer became pregnant. In the group of pregnant women the pulsatility index values of both uterine and spiral arteries was lower than in non-pregnant patients, and was associated with significantly lower thromboxane concentrations from cultured endometrial cells. It is concluded that thromboxane plays a role in embryo implantation, and that Doppler flow analysis of uterine and spiral arteries in infertile patients may be important in the management of ovarian stimulation.      

A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy

Maternal serum concentrations of inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids and gonadotrophins were measured longitudinally in six normal singleton pregnancies. Maternal venous blood was collected randomly during a spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11, 16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the early puerperium. Steroid and gonadotrophin profiles conformed to previous reports. While at week 5 of gestation inhibin-A, activin-A and follistatin concentrations were similar to those at the follicular phase, all three increased progressively (P < 0.001) to maximal concentrations in week 36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately 22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/- 418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was undetectable (<12 pg/ml) between week 5-16 of gestation but increased slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was undetectable throughout pregnancy. Post-partum concentrations of inhibin-A (41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml), pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were substantially lower than at week 36 of gestation. The activin-A:follistatin ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more free activin-A is available in the maternal circulation during late pregnancy.