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.     

Primary gastric non-Hodgkin's lymphoma in a population-based registry.

BACKGROUND. The incidence of primary gastric non-Hodgkin's lymphoma (NHL) appears to have increased worldwide in recent years, and this seems to be confirmed by large-sample population studies. METHODS AND RESULTS. We derived our data from the Lombardy Cancer Registry, which provides the incidence of cancer in the province of Varese, Northern Italy. From 1978 to 1987 we identified 3261 cases of gastric neoplasms, 119 of which were gastric NHL: 32 (1.87%) from 1978 to 1982, and 87 (5.32%) from 1983 to 1987. The difference in the age and sex standardized incidence trend between these two time periods was statistically significant (p < 0.001). The overall survival rate of the 112 evaluable patients was 54% at 5 years and 45% at 10 years. A multivariate analysis was performed. Age (p < 0.0005), clinical stage (p < 0.04) and therapy (p < 0.0005) were found to be significant prognostic factors for survival. CONCLUSIONS. This study stresses the utility of prospective randomized clinical trials that could indicate the optimal management of patients with primary gastric lymphoma.     

Rehabilitation: the Cinderella of neurological research? A bibliometric study

Rehabilitation is under-represented in the neurological literature on disabling diseases. A Medline search was conducted to retrieve the articles published between January 1991 and June 1994 under the main headings of Stroke, Parkinson's disease, Multiple sclerosis, Brain injury, Ataxia and Dementia. These were then combined with the sub-heading Rehabilitation. The former search yielded 27724 articles, the latter 1272 (4.6%). In 1992, the Journal of Citation Reports (JCR) assigned to Journals publishing rehabilitation papers an average Impact Factor (IF) of 0.7–2.8 (median 1.8): that is, 31–90% (depending on the various main headings, median 68%) of the average IF given to Journals publishing non-rehabilitation papers. In the present study, the weight of the literature was defined as the product of the number of articles multiplied by the IF of the corresponding Journal (IF=0 for non-JCR Journals). Across the various neurologic conditions, the weight of the Rehab literature was 0.1–7% (median 2%) of the weight of the non-Rehab literature. The results suggest that neurology is still reluctant to face the disability challenge.

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Sommario La riabilitazione è scarsamente rappresentata nella letteratura neurologica sulle patologie che causano disabilità. Gli Autori hanno interrogato la banca-dati Medline nella ricerca degli articoli pubblicati fra il Gennaio 1991 ed il Giugno 1994 sotto le parole-chiave Stroke, Parkinson's disease, Multiple Sclerosis, Brain injury, Ataxia e Dementia. È stato poi eseguito un incrocio con la parola-chiave secondaria Riabilitazione.La prima ricerca ha prodotto 27724 articoli mentre la seconda ne ha prodotti 1272 (4.6%). Nel 1992 il Journal of Citation Reports (JCR) ha attribuito alle Riviste che hanno pubblicato articoli con tema riabilitativo un Impact Factor (IF) medio di 0.7–2.8 (mediana 1.8), pari al 31–90% (a seconda della parola-chiave principale: mediana delle percentuali 68%) dell'IF medio attribuito alle Riviste che hanno pubblicato soltanto articoli su temi non riabilitativi. In questo studio è stato definito come peso della letteratura il prodotto del numero di articoli per l'IF delle rispettive Riviste (IF=0 per le Riviste non censite dal JCR). A seconda delle diverse patologie neurologiche, il peso della letteratura riabilitativa variava fra 0.1 e 7% (mediana 2%) del peso della letteratura non riabilitativa.I risultati suggeriscono che la Neurologia sia ancora riluttante ad affrontare la sfida che le pone la disabilità.

     

Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters

Electroneutral cation-Cl^– cotransporters compose a family of solute carriers in which cation (Na⁺ or K⁺) movement through the plasma membrane is always accompanied by Cl^– in a 1:1 stoichiometry. Seven well-characterized members include one gene encoding the thiazide-sensitive Na⁺–Cl^– cotransporter, two genes encoding loop diuretic-sensitive Na⁺–K⁺–2Cl^– cotransporters, and four genes encoding K⁺–Cl^– cotransporters. These membrane proteins are involved in several physiological activities including transepithelial ion absorption and secretion, cell volume regulation, and setting intracellular Cl^– concentration below or above its electrochemical potential equilibrium. In addition, members of this family play an important role in cardiovascular and neuronal pharmacology and pathophysiology. Some of these cotransporters serve as targets for loop diuretics and thiazide-type diuretics, which are among the most commonly prescribed drugs in the world, and inactivating mutations of three members of the family cause inherited diseases such as Bartter's, Gitelman's, and Anderman's diseases. Major advances have been made in the past decade as consequences of molecular identification of all members in this family. This work is a comprehensive review of the knowledge that has evolved in this area and includes molecular biology of each gene, functional properties of identified cotransporters, structure-function relationships, and physiological and pathophysiological roles of each cotransporter.     

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.      

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.      

Hoechst staining and exposure to UV laser during flow cytometric sorting does not affect the frequency of detected endogenous DNA nicks in abnormal and normal human spermatozoa

Controlling the sex of offspring by the separation of X and Y chromosome-bearing spermatozoa using flow cytometry has been reported as a clinical technique aiding prevention of X-linked diseases. Although this technique has resulted in several hundred normal births in animals and at least one human birth, there is still concern over its genetic safety due to the involvement of two potentially mutagenic agents: UV light and the fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly those considered abnormal, may be more likely to suffer DNA damage following exposure to mutagenic agents, compared with other mammalian species. The stability of normal fresh and decondensed human spermatozoa were examined after exposure to a range of levels of UV and H33342 staining, using an assay that detects endogenous nicks in the DNA of spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed human spermatozoa was examined following UV laser, H33342 staining and flow cytometry treatments utilizing the same assay. There was an increase in the presence of endogenous nicks when spermatozoa were decondensed compared with fresh spermatozoa. There was no increase in the incidence of nicks in any group of spermatozoa after UV and fluorochrome exposure compared with controls without exposure.