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Biomedical subjects

D Moglia

Publications and source records attributed to D Moglia.

At least 19 recordsLinked to original sources

Differential patterns of performance impairment result from changed reinforcer efficacy or distracting stimulation in a two-choice rodent spatial signal detection task.

Measures of the discriminabililty of stimuli in signal detection tasks can be influenced by alterations of motivational state. In the present study, rats performed an operant signal detection procedure that required the completion of a fixed number of responses before a stimulus was presented at one of two front cue lamps to separately measure the motivation to respond from the ability to respond accurately. One manipulation, presession water access, affected the speed and frequency that trials were initiated, but did not affect response accuracy. In contrast, a flashing houselight during the session, and i.p. ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d,] cyclohepten-5,10-imine (dizocilpine or MK-801), a glutamate N-methyl-D-aspartate receptor antagonist, impaired response accuracy in a stimulus duration-dependent manner. These results suggest that it is possible to procedurally isolate the motivation to respond to stimuli from accuracy of detection, and thereby protect attending from side effects of drugs that influence the motivation to respond.

Animals↗

Clinical and dermatoscopic diagnosis of early amelanotic melanoma.

Amelanotic cutaneous melanoma (ACM) often defies clinical diagnosis because of the lack of pigmentation. In an attempt to find diagnostic clues, we retrospectively studied the clinical features of 15 thin (< 1 mm thick or Clark level I) ACM lesions. The clinical features of early ACMs are identified and illustrated to enable early diagnosis and cure of these lesions. The typical early lesion presents as an asymmetric macula, which may be uniformly pinkish or reddish or, more often, has faint light pigmentation (tan, brown or grey) at the periphery; it has borders that may be well- or ill-defined. In our study, these features suggested the correct clinical diagnosis in only a minority (40%) of cases. Nine cases in this series were also subjected to dermatoscopy. By this technique we identified, as constant feature, the presence of small red dots, evenly distributed or grouped on a whitish or pink-red background. Our results show the importance of dermatoscopy in the evaluation of equivocal pink or reddish lesions. Red dots seen with this technique can be an important sign for the diagnosis of thin ACM. Since this sign does not appear to be pathognomonic, the presence of an associated pigmentary network can be decisive in the differential diagnosis.

Adult↗

Small melanomas: a clinical study on 270 consecutive cases of cutaneous melanoma.

The ABCD (asymmetry, border, colour, dimension) criteria represent a commonly used clinical guide for the diagnosis of early cutaneous melanoma (CM). This guide stipulates that CMs usually are more than 6 mm in diameter. The purpose of this retrospective study was to establish the frequency of occurrence of small (< or =6 mm) melanomas in a clinical context. Our series consisted of 270 consecutive CMs (39 in situ and 231 invasive) in 267 patients. Of these 270 lesions, 47 (17%) were small lesions, ranging from 2 to 6 mm in maximum linear extent, with a median value of 5 mm. Of these small lesions, 14 were in situ and 33 Invasive CMs. The median thickness of the 33 small invasive lesions was 0.31 mm. The clinical features of CMs were sufficiently distinctive to suggest a diagnosis of CM in half of the cases, irrespective of the invasiveness or not of the lesions. Dermatoscopy was performed on 36 of the small lesions and achieved a correct diagnosis in 72% of the cases. The combination of simple visual examination with dermatoscopy allowed a higher rate of recognition (86%) than when the two methods were considered separately. Results of our study show that small CMs represent a considerable clinical subset of all CMs. Clinicians must be aware of this fact in their diagnostic activity.

Adult↗

Effects of short-term pre-operative tamoxifen on steroid receptor and Ki-67 expression in primary breast cancer: an immunocytochemical study.

The effects of the short-term pre-operative administration of tamoxifen (TAM, 20 mg once daily) on the tumor levels of steroid receptors and the nuclear proliferation Ki-67 antigen, were investigated in 32 elderly patients with hormone-sensitive, operable primary breast cancer by means of fine-needle aspiration biopsy (FNAB). The FNAB smears before (pre-TAM) and after six weeks of treatment (post-TAM) were stained immunocytochemically in order to obtain an H-score for steroid receptors, and the percentage of cellular nuclei containing Ki-67. The mean oestrogen receptor (ER) score between the pre- and post-TAM specimens fell from 181.2 9.7 ( SEM) to 148.1 7.9 (Wilcoxon's matched-pairs signed-rank test, p=0. 01) and there was also a significant decrease in both the mean progesterone receptor (PgR) score (178.4 10.6 vs 148.5 10.6; p=0.01) and mean Ki-67 index (8.2% 1.2 vs 4.9% 0.9; p=0.0002). The reliability of FNAB as a sampling method was checked by comparing the results of the immunocytochemical assay (ICA) of the post-TAM biopsies with those of the immunohistochemical assay (IHA) of the corresponding excised tumors. There was a positive correlation between the ICA and IHA scores: ER (Spearman's correlation coefficient, rho=0.66, p<0.001), PgR (rho=0.84, p<0.001) and Ki-67 (rho=0.96, p<0.001). We conclude that the sequential use of FNAB is a reliable means of assessing the behaviour of within-tumor biomarkers during endocrine therapy.

Aged↗

Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins.

BACKGROUND: Basal cell carcinoma (BCC), the most common malignancy of the eyelid margins, poses therapeutic problems. Surgery, radiation therapy, and cryotherapy are the currently accepted methods for the treatment of this affliction. To verify the technical and clinical effectiveness of the surgical laser method, a specific approach was developed by performing laser-combined procedures under microscopic control. METHODS: A series of 26 patients underwent carbon dioxide (CO2) laser microsurgical excision of 27 primary superficial BCCs of the eyelid margins. Eighteen tumors were T1 and 9 were T2. The lesions were located at the lid margins in 18 and at the canthus in 9 cases. The eyelash line was involved in all cases, whereas intermarginal space was involved in 17 cases, without extension to the conjunctival border. Six lesions were in the lacrimal region. Median linear extent of the lesion was 5 mm (range, 4-10 mm). Treatment was performed with the patient under local anesthesia in a Day Hospital regimen. The authors used the microscope-mounted CO2 laser as a scalpel to excise the tumor mass, thus obtaining the specimen for histologic evaluation. The authors treated the deep and lateral resection margins with laser vaporization and left the wound bed to heal by secondary intention. RESULTS: No significant complications were observed. As full-thickness eyelid resections were avoided, the authors noted conservation of lid function and cosmetic aspect in all patients. With a median follow-up of 73 months (range, 18-118), only one patient had tumor recurrence after 22 months. This tumor, located at the outer canthus, had a second microsurgical laser excision, and the patient is disease free 51 months after the last treatment. CONCLUSIONS: Laser microsurgery appears to be a safe and effective treatment method for primary superficial T1 and T2 BCC of the eyelid margins without conjunctival extension.

Adult↗

Effects of topical treatment with fenretinide (4-HPR) and plasma vitamin A levels in patients with actinic keratoses.

Eighteen patients with facial actinic keratoses were treated with the retinoid fenretinide (4-HPR), applied topically twice-daily for 3 months. After 3 months of treatment, complete regression was observed in 56% and partial regression in 44% of cases. Eight patients relapsed within 3 months after drug discontinuation. Six months later, only two patients (11%) showed a treatment response (complete regression). Blood samples showed that 4-HPR was not absorbed and no local or distant adverse effects were observed. Baseline plasma retinol levels were lower than in healthy subjects, thus suggesting that reduced retinol levels might be involved in this pathology. These encouraging preliminary results suggest the need for further studies to evaluate the best dosage schedules and duration of 4-HPR topical application in actinic keratoses.

Administration, Topical↗

Biological and clinical evaluation of lanreotide (BIM 23014), a somatostatin analogue, in the treatment of advanced breast cancer. A pilot study by the I.T.M.O. Group. Italian Trials in Medical Oncology.

Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.

Adult↗

Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.

Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.

17-Hydroxycorticosteroids↗

Surgical resection plus tamoxifen as treatment of breast cancer in elderly patients: a retrospective study.

Between March 1982 and May 1989, 151 women with primary breast cancer ranging in age from 70 to 91 years (median 79), were treated with conservative surgical procedure followed by adjuvant tamoxifen. Surgery was performed under local anaesthesia without axillary node dissection. The median duration of follow-up was 60 months (range 36-124). There were six local, six ipsilateral axillary node and six distant relapses. Local recurrences were successfully managed with further surgery whereas axillary node relapses required radiotherapy in 3 cases, surgery in 2 cases and hormonal treatment in 1 case. 2 patients died of progression of disease and one of unrelated conditions. The 5-year relapse-free survival rate was 0.82. This treatment option in elderly patients yields an acceptable local control and reduces the risks of major surgery.

Aged↗

Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations.

PURPOSE: Monitoring of fenretinide (4HPR) levels, kinetics, and effects on retinal was performed in patients who participated in a phase I trial and who continued to be treated for 5 years as phase III trial patients. Accumulation of 4HPR in the breast was also assessed. PATIENTS AND METHODS: Plasma concentrations of 4HPR, of its main metabolite N-(4-methoxyphenyl)retinamide (4MPR), and of retinol were assayed by high-performance liquid chromatography (HPLC) in breast cancer patients treated orally with 4HPR 200 mg/d for 5 years with a 3-day drug interruption at the end of each month. RESULTS: 4HPR, at 200 mg/d, resulted in average 4HPR plasma levels of approximately 1 mumol/L, which remained steady and caused steady retinol level reduction; 4MPR levels, similar to those of 4HPR, slightly but significantly increased during the first 35 months, but at 5 years they were similar to those at 5 months. During daily treatment, baseline retinol concentrations were reduced by 71%; after a 3-day drug interruption, all patients recovered and the mean reduction was 38%. After discontinuation of 5-year treatment, 4HPR and 4MPR half-lives (t1/2 beta) were 27 and 54 hours, respectively, similar to those reported after 28 daily treatments. After 6 and 12 months, the concentrations of 4HPR were at the limit of detectability (0.01 mumol/L), whereas those of 4MPR were five times higher. Baseline retinol concentrations were already recovered after 1 month. Accumulation of this retinoid in the breast was evidenced by concentrations of 4HPR and 4MPR in nipple discharge and in breast biopsies that were 10 and 20 times higher, respectively, than those found in plasma. CONCLUSION: 4HPR, at 200 mg/d for 5 years, resulted in constant drug plasma levels and constant retinol level reduction. After treatment interruption, 4HPR plasma concentrations decreased at the limit of detectability at 6 months and baseline retinol plasma concentrations were recovered after 1 month.

Adult↗

Cationic content in multiple mammary cysts.

One hundred and ninety-six breast cyst fluid samples from 78 consecutive patients with multiple cysts were subdivided according to the K+/Na+ ratio: type 1 (K+/Na+ ratio > 1) and type 2 (K+/Na+ ratio < or = 1). Cysts of the same type were found in 57.7% of patients (concordant group). Such a finding suggests that in patients bearing multiple cysts, all aspirated fluids need to be classified on the basis of their cationic composition. In the concordant group, type 1 cysts were more frequent than in the discordant group (80.3% vs 59.5%, P = 0.002). High K+/Na+ ratios (> 4.0) were present in 64% of type 1 cysts in the concordant group compared to 37.7% in the discordant group (P = 0.001), which suggests a different activity of the epithelium lining the cyst wall.

Adult↗

Treatment of breast cancer in elderly women: retrospective analysis of 111 wide lumpectomies performed in a day hospital regimen between 1982 and 1988.

Between 1982 and 1988, 111 elderly women with breast cancer but without clinical involvement of the axillary lymph nodes underwent wide lumpectomy in a Day Hospital regimen at the National Cancer Institute of Milan. The patients ranged in age from 70 to 92 years (median, 79). An adjuvant treatment was carried out in all but 9 cases: tamoxifen only in 84 cases, tamoxifen plus radiotherapy in 6 cases, radiotherapy alone in 12 cases. The median duration of follow-up was 44 months (range, 30-109 months). Four patients (3.6%) were lost to follow-up. In the remaining 107 patients, 10 local-regional relapses (9.1%) and 7 distant metastases (6.5%) occurred. Six patients died from the disease, 14 from unrelated conditions. This retrospective study showed that selected elderly patients with breast cancers can be treated successfully under local anesthesia on an outpatient basis. The treatment guarantees local control of the disease, meets the favor of elderly women and consequently improves their quality of life.

Actuarial Analysis↗

Accumulation of active androgens in breast cyst fluids.

80 breast cyst fluids (BCF) from 57 patients were divided by K+/Na+ ratio: 56 with ratio over 1 (type I) and 24 with ratio less than 1 (type II). Significantly higher amounts of testosterone, dihydrotestosterone and dehydroepiandrosterone sulphate (DHAS) were found in type I than in type II cysts. A positive relation was found between testosterone and dihydrotestosterone in both types. DHAS was significantly correlated with testosterone and dihydrotestosterone in type I casts only. In 52 patients, blood was sampled after cyst evacuation. Testosterone was significantly higher in blood than in BCF while dihydrotestosterone and androstenedione were significantly higher in BCF. No relation was observed between circulating levels of androgens and their intracystic concentrations. Women bearing type I cysts may be at increased risk of developing cancer. These findings support the hypothesis that androgens play a role in the hormonal aetiology of breast cancer.

Adult↗

Diagnostic efficacy of physical examination, mammography, fine needle aspiration cytology (triple-test) in solid breast lumps: an analysis of 1708 consecutive cases.

The clinical-radiologic-cytologic triplet was used for diagnostic evaluation in 1708 women over 30 years old with a breast lump. All the lumps were subjected to surgery except for 258 cases in which clinical resolution took place within 1-2 months. Seven-hundred and ninety-three out of 1450 nodules removed were cancers. Sensitivity of the clinical, mammographic and cytologic examinations was 82%, 73% and 68%, respectively. It increased to 95% when they were associated. Specificity was 63%, 80% and 97%, respectively. The predictive value of positive results of the triple test was 100%. No patient with malignant cytology was subsequently shown to have benign disease. The systematic use of the triple test in solid breast lumps for the early detection of cancer is recommended as a routine procedure. However, participation of experienced radiologists and pathologists as well as physicians skilled in fine needle puncture is required.

Biopsy, Needle↗

Excision of oral leukoplakias by CO2 laser on an out-patient basis: a useful procedure for prevention and early detection of oral carcinomas.

Several epidemiologic studies have shown that oral cancer develops among individuals with a prior diagnosis of an oral premalignant lesion. Canceration chance in these patients is 17%, with the greatest rate occurring in the second year of observation. Based on this data, since 1981, 92 leukoplakias have been treated by out-patient laser surgery at the Istituto Nazionale Tumori of Milano. The therapeutic technique was laser excision to obtain a specimen for histology. Two groups were distinguished according to the diagnostic procedure. Thirty-three lesions (December 1981 to December 1982) were operated on without preliminary histologic examination, on the basis of a simple clinical diagnosis. Since January 1983 all leukoplakias have been biopsied in a systematic way and those negative for cancer treated with laser. Histology of the specimen showed 5 squamous cell carcinomas (15%) in the group of patients who did not undergo preoperative biopsy. Postoperative histology showed malignancy in 6 of 59 (10.2%) cases in spite of negative preoperative biopsies. Speckled and erosive leukoplakias had the highest canceration rate. Three of 11 patients with cancer were treated by knife excision or interstitial needle implantation because of margins in tumoral tissue or because they were not evaluable for injury by heat. Results have been satisfactory, only 2 of 54 followed leukoplakias and none of the cancers recurred during a 2 year follow-up.

Adult↗

Influence of 2-deoxy-D-glucose on feeding in the rat at different times of the light-dark cycle.

Two concentrations of 2-deoxyglucose (2-DG) were injected into adult male Long-Evans rats at four times during the 12:12 light/dark cycle. At low concentrations (300 mg/kg) in the first 3 h of a 6-h test period, 2-DG significantly increased feeding (268%) in the early part of the light period (EL) when compared to uninjected and saline-treated controls. In the late light (LL), 2-DG increased feeding by 48% but this was not statistically significant. For the high-concentration groups (750 mg/kg), 2-DG increased feeding by 240% in the EL, 117% in the LL, 50% in the early dark (ED) and 45% in the late dark (LD). As there was no significant interaction, it was concluded that 2-DG facilities feeding at all times of the day. In the second 3 h of the recorded 6 h, 2-DG decreased feeding by 37-45% in the ED and middle dark (MD) when compared to controls, although the suppression was significant only for the low concentration of 2-DG. There was some support from data on water intake and latencies to eat and drink for the view that 2-DG-induced feeding was not secondary to thirst stimulated by hypertonic injection fluids. It is concluded that 2-DG injection facilitates feeding for a few hours but the net effect on food intake may be reduced in the light, and even nullified in the dark, by a subsequent reduction of intake in rats with free access to food.

Animals↗