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.     

Short-term morbidity and mortality of implantation of automatic implantable cardioverter-defibrillator

Over the 3-year period from Jan. 1, 1986, through Dec. 31, 1988, we have implanted 101 automatic implantable cardioverter-defibrillators into patients with life-threatening ventricular arrhythmias. There were 82 male patients and 19 female patients. The mean age was 58 years with a range of 25 to 82 years. The indication for implantation was ventricular fibrillation in 89 patients and recurrent ventricular tachycardia in 12 patients. Seventy-seven patients had a history of prior myocardial infarction or coronary artery disease, or both. Eighteen patients had nonischemic cardiomyopathy. One patient had a prolonged QT syndrome and five patients had no evidence of preexisting structural heart disease. The mean injection fraction was 37% +/- 17%. Forty-one of the automatic implantable cardioverter-defibrillator implantations were associated with procedures necessitating cardiopulmonary bypass. The hospital mortality rate was 4% and the morbidity rate was 15%. The only statistical difference between those patients who did and did not have postoperative complications was a history of a prior myocardial infarction (90% versus 54%, p less than 0.05). Twenty percent of patients had new-onset postoperative atrial fibrillation after implantation of the device. Eleven percent of patients had sustained ventricular tachycardia postoperatively. Although there was a trend toward a higher complication/death rate in the patients whose automatic implantable cardioverter-defibrillator was inserted in association with cardiopulmonary bypass (24% versus 15%) and the occurrence of new-onset postoperative atrial fibrillation (27% versus 15%), these findings were not statistically significant. Automatic implantable cardioverter-defibrillator implantation with and without concomitant cardiopulmonary bypass is associated with a clinically important morbidity and mortality rate and development of postoperative arrhythmias.     

Protein binding of antiepileptic drugs during pregnancy, labor, and puerperium

Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, alpha 1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days postpartum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum.     

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.      

Modulatory effect of substance P to the brain stem locomotor command in lampreys

Substance P initiates locomotion when injected in the brain stem of mammals. This study examined the possible role of this peptide on the supraspinal locomotor command system in lampreys. Substance P was bath applied or locally injected into an in vitro isolated brain stem, and the effects of the drug were examined on reticulospinal cells and on the occurrence of swimming in a semi-intact preparation. Bath applications of substance P induced sustained depolarizations occurring rhythmically in intracellularly recorded reticulospinal cells. Spiking activity was superimposed on the depolarizations and swimming was induced. The sustained depolarizations were abolished by tetrodotoxin, and substance P did not affect the membrane resistance of reticulospinal cells nor their firing properties, suggesting that it did not directly effect reticulospinal cells. To establish where the effects were exerted, successive lesions of the brain stem were made as well as local applications of the drug in the brain stem. Removing the mesencephalon abolished the sustained depolarizations, whereas large ejections of the drug in the mesencephalon excited reticulospinal cells and elicited bouts of swimming. More local injections into the mesencephalic locomotor region (MLR) also elicited swimming. After an injection of substance P, the current threshold needed to induce locomotion by MLR stimulation was decreased, and the size of the postsynaptic responses of reticulospinal cells to MLR stimulation was increased. Substance P also reduced the frequency of miniature spontaneous postsynaptic currents in reticulospinal cells. Taken together, these results suggest that substance P plays a neuromodulatory role on the brain stem locomotor networks of lampreys.     

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.