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Biomedical subjects

R Grilli

Publications and source records attributed to R Grilli.

At least 37 records · Page 2Linked to original sources
PubMed1998

Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release.

Growth hormone-releasing peptides (GHRPs) are a class of small peptides that stimulate growth hormone (GH) release in several animal species, including the human. Moreover, GHRPs injected into the brain ventricles stimulate feeding in the rat. The aim of this study was to evaluate the GH-releasing properties of a series of novel GHRP analogs and the possible existence of functional correlations between the GH-releasing activity and the effects on feeding behavior. Two well-known hexapeptides, GHRP-6 and hexarelin, given s.c., dose dependently stimulated both GH release and feeding behavior in satiated rats. However, in a series of tri-, penta- and hexapeptide analogs of hexarelin, some compounds were active either on GH release or on eating behavior. Interestingly, even minor structural modifications resulted in major changes of the pharmacological profile. We conclude that GHRPs have orexigenic properties after systemic administration which are largely independent from the effects they exert on GH release.

Animals↗
PubMed1998

GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.

BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. METHODS: The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. CONCLUSIONS: Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated, effective 6-month adjuvant regimen for patients with colon carcinoma that has no detrimental effect on their quality of life.

Adult↗
PubMed1998

Acquired hypertrichosis lanuginosa: case report and review of the literature.

Acquired hypertrichosis lanuginosa is a rare cutaneous disorder usually associated with internal malignancy that consists of the development of abnormal hair growth of the lanugo type, often confined to the skin of the face and neck, although other areas also may be involved. We report on a 66-year-old woman with a metastatic ductal infiltrating carcinoma of the breast who developed growth of fine lanugo type hair on her face and progressive growth of the hair of eyebrows and eyelashes. We review the literature on this uncommon paraneoplastic cutaneous disorder emphasizing the pathogenic mechanisms that have been proposed to explain the striking overgrowth of lanugo type hair.

Aged↗
PubMed1998

Practice guidelines: a more rational approach to diagnosis and treatment and a more effective use of health care resources.

Practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The implementation of practice guidelines is justified by factors such as variations in clinical practice, malpractice and its associated costs, and the need to contain health care expenditures. In this context, practice guidelines promote a more rational approach to clinical decision making and better quality of care. Although there are several limitations to the use of guidelines in current practice, different organizations (professional societies, government agencies, licensing authorities, educational institutions) have a potential interest in their development. A working group on the development of practice guidelines endorsed by the Italian Society of Neurology has been active since 1995. The aims of this group include the development of guidelines to be accepted by the medical community and to be placed within the framework of initiatives of the Italian Ministry of Health.

Health Care Costs↗
PubMed1998

Promoting consumers' demand for evidence-based medicine.

The widespread implementation of rationing and priority-setting policies in health care opposes the stochastic practice of medicine induced by professional uncertainty and professional vested interests in market-oriented clinical environments. It also clashes with consumers' overly optimistic and "mythical" view of the effectiveness of medicine, which is bound to support a potentially unlimited provision of health services. Thus, for consumers and society at large, it is necessary to create conditions favorable for a more conscious demand of evidence-based health care. In pursuit of this goal, we suggest the adoption of a community-oriented strategy based upon delivery of information to the public in order a) to generate greater awareness ("healthy skepticism") among consumers, through disclosure of data on the true effectiveness of health care interventions and on the existing variation in their utilization, and b) to provide tools to empower consumers in dealing better with both the uncertainty in their own individual patient-physician relationships and with the health policy issues to be faced in the future. Such a community-oriented strategy could also reinforce and support, through the generation of a "bottom-up" pressure from consumers toward physicians, a wider adoption of evidence-based interventions by health care professionals. This paper, using data from surveys on public opinions and attitudes toward the practice of medicine, focuses on how consumer demand for more evidence-based medical practice can be promoted.

Consumer Advocacy↗
PubMed1998

Do specialists do it better? The impact of specialization on the processes and outcomes of care for cancer patients.

OBJECTIVE: To assess the impact of specialization on processes and outcomes of care for cancer patients. DATA SOURCE: Papers published in English between 1980 and 1995 and identified through MEDLINE and Embase (MeSH terms: NEOPLASM (exploded), and PHYSICIAN PRACTICE PATTERNS (or DECISION MAKING, ATTITUDE OF HEALTH PERSONNEL, QUALITY OF HEALTH CARE, DELIVERY OF HEALTH CARE, HEALTH EDUCATION or OUTCOME ASSESSMENT HEALTH CARE), or through the reference lists of review articles. STUDY SELECTION: Studies providing information on the association between quality of care indicators for cancer patients and clinician/centre degree of specialization. A total of 47 papers concerning 46 empirical studies were considered. DATA EXTRACTION: For studies using process of care indicators, the proportion of specific procedures performed by specialists and non-specialists was abstracted. For studies using outcome indicators (e.g., mortality), the effect of specialization was quantified in terms of odds ratio (OR) expressing relative reduction in risk of death. The quality of individual studies using process or outcome indicators was assessed according to study design, avoidance of selection bias in patient identification and data analysis, degree of adjustment of the comparison between clinicians/centres with different levels of specialization. DATA SYNTHESIS: Specialized centres/clinicians fared better both when process and outcome indicators were used. While the former varied widely in different studies and their clinical relevance was often questionable, mortality was consistently lower when care was provided by specialized centres/clinicians, with the effect size being greater in smaller studies. For breast cancer, where all the studies were of sufficiently good quality, a pooled estimate of the effect of specialization was performed which showed that specialized cancer care was associated with an 18% (95% CI: 12%-23%) reduction in mortality. CONCLUSIONS: Despite the fact that care provided by specialized centres/clinicians appeared to be better both when assessed in relation to process indicators and to mortality, this evidence should be considered far from conclusive because of major methodological flaws in these studies. Relative to current efforts to promote evidence-based policy-making, this review underscores the limited capability of scientific information to provide reliable guidelines for structuring better health care systems.

Confidence Intervals↗
PubMed1998

Spinulosis of the face as a manifestation of demodicidosis.

We describe a 78-year-old woman with polycythaemia rubra vera who had multiple tiny follicular hyperkeratotic spicules on the cheeks. She was receiving treatment with oral hydroxyurea, but no topical agents had been applied to her face. Histopathological study demonstrated numerous Demodex folliculorum mites within dilated follicular infundibula, and we consider that the mites were playing a part in the aetiology of the skin lesions.

Aged↗
PubMed1998

Cutaneous manifestations of infection by nontuberculous mycobacteria.

Cutaneous infections by nontuberculous mycobacteria (NTM) are not usual but their relative importance has changed during the last few years and still further changes are expected. This study comprised 13 patients from whom NTM were recovered from skin biopsy specimens, sinus exudates or cutaneous abscesses. All samples were processed according to standard methods, and the isolates were identified by biochemical testing. Skin biopsy specimens, when available, were processed for histopathological study. The clinical records of the patients were reviewed, and the relevant clinical, microbiological and epidemiological data collected. The clinical manifestations were noted to be relatively nonspecific and consisted of draining sinuses, abscesses, ulcers and nodules with multicentric or sporotrichoid patterns. Tissue culture isolated Mycobacterium fortuitum complex in nine patients, M. avium in three, and M. marinum in one. In the nine patients studied by histopathology, various patterns were observed. These included dermo-hypodermal abscesses, suppurative granulomas, tuberculoid granulomas and granulomas with a perifollicular distribution. Cutaneous lesions can thus be the first and the only sign of NTM disease, and culture still remains the definitive diagnostic procedure.

Adult↗
PubMed1998

Cost effectiveness of screening for subclinical hypothyroidism in the elderly. A decision-analytical model.

OBJECTIVE: The value of early detection of subclinical hypothyroidism is the object of a long lasting debate. In this study, we assessed the cost effectiveness of a policy based upon screening for this condition through thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) serum level measurements in the elderly. DESIGN: A Markov model was developed where hypothetical elderly patients (i.e. > or = 60 years of age), who attend general practitioner (GP) clinics for periodic health examinations in a primary-care setting in Italy, made transitions between health states at annual interval for 15 years, thus allowing an estimation of the average cost and of the expected average number of quality-adjusted life-years (QALY). In this model, patients were assumed to be seen at annual intervals by GPs for clinical examination and serum cholesterol level measurement, to which a TSH, T3 and T4 serum measurement was added. In the base-case analysis, TSH was measured every 5 years and, if abnormal, T3 and T4 serum levels were also determined. Costs were analysed from the perspective of the Italian National Health Service (NHS) and reflected 1996 values. MAIN OUTCOME MEASURES AND RESULTS: In the base-case analysis, the additional benefit estimated from testing a female population for subclinical hypothyroidism every 5 years was 0.36 QALY, with a cost per QALY gained of 668,298 lire (L). The expected gain in QALY for men was 0.20 and the cost per QALY gained was L270,322. In general, the best cost-effectiveness profile was seen with testing every 3 years. Results were sensitive to variations in the prevalence of disease among the target population, both in men and women. CONCLUSIONS: Our study indicates that a screening policy for subclinical hypothyroidism in the elderly population could be worthwhile. However, as the costs could be significant when applied at the population level, this policy deserves further assessment through well-designed primary research.

Aged↗
PubMed1997

Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: I. A study on ad libitum fed and starved adult male rats.

The individual role played by GH and IGF-I in the regulation of hypothalamic GHRH and SRIF gene expression is still object of debate. We have investigated the effect of exogenously administered recombinant hGH (rhGH) and recombinant hIGF-I (rhIGF-I) in ad libitum fed control and starved rats, the latter an animal model which is characterized by low circulating levels of endogenous GH and IGF-I. Adult male rats were fed ad libitum (C) or food-deprived (S) for 72 hours; rats in either C or S groups were treated with systemic administration of rhGH and rhIGF-I for 3 days. GHRH, SRIF and GH mRNA levels were evaluated by Northern and slot blot hybridization. Administration of rhGH (250 micrograms/kg/twice daily, sc) induced a significant inhibition of GHRH and a significant stimulation of SRIF mRNA levels in C rats; GH treatment was, however, ineffective on both neuropeptide mRNA levels in the S group. Continuous infusion of rhIGF-I (300 micrograms/kg/day, sc) induced a significant increase of SRIF levels in both C and S rats but did not modify GHRH mRNA levels in either group. In the pituitary, GH mRNA levels followed a pattern very similar to that of GHRH. These results provide evidence for a direct role of GH in the inhibition of GHRH mRNA levels; IGF-I appears more involved in the direct stimulation of SRIF mRNA levels.

Animals↗
PubMed1997

Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: II. A study in the infant rat.

It is generally accepted that growth hormone influences its own secretion by modulating the activity of GHRH and SRIF neurons. To investigate if GH feedback mechanisms are already operating in the early postnatal life of the rat, we have studied in 10-day-old pups the effects of rhGH and rhIGF-I administration on GHRH and somatostatin mRNA levels. The same experiment was also performed in pups passively immunized with an anti-GHRH antiserum from the day of birth. The latter animal model had been previously characterized for presenting reduced levels of circulating GH and IGF-I. In control pups, neither rhGH (250 micrograms/kg, b.i.d., sc) nor rhIGF-I (150 micrograms/kg, b.i.d., sc) administration induced significant changes of GHRH and SRIF gene expression. The passive immunization against GHRH induced per se a trend toward an increase and a reduction of GHRH and SRIF mRNA levels, respectively. Also in these rats the treatment for 3 days with rhGH and rhIGF-I did not further modify the GHRH and SRIF mRNA levels. Based on these results, we conclude that in the 10-day-old rat GH feedback mechanisms are poorly operative, though a direct ultra-short loop mechanism involving the GHRH and SRIF systems seems already operating.

Animals↗
PubMed1997

Hexarelin stimulation of growth hormone release and mRNA levels in an infant and adult rat model of impaired GHRH function.

Hexarelin, a GH-releasing peptide, is an effective GH secretagogue in man and a variety of experimental animals. In the present study, we sought to characterize the effects of short-term Hexarelin treatment on GH release and GH mRNA levels in infant and young-adult rats and in rats of either age passively immunized with an antiserum against GHRH (GHRH-Ab). Hexarelin (80 micrograms/kg, b.i.d. s.c.), administered for 3, 5 or 10 days to 8-, 6- and 1-day-old rats, respectively, induced a progressive enhancement of the plasma GH rise elicited by a subsequent acute Hexarelin (80 micrograms/kg s.c) challenge when pups were 10 days old. As expected, GHRH-Ab treatment decreased GH concentrations in 10-day-old pups. In GHRH-Ab-treated pups, Hexarelin administration for 3-10 days significantly enhanced the GH response to the acute Hexarelin injection, though the mean plasma GH values remained significantly lower than in the respective control group. Hexarelin treatment did not alter GH mRNA levels in control pups. In GHRH-Ab-treated pups Hexarelin treatment for 3 and 5 days, but not 10 days, restored GH mRNA levels to control values. In young-adult male rats, regardless of antiserum treatment, Hexarelin administration for 5 or 10 days significantly suppressed the GH response to a subsequent acute challenge with the peptide. Yet, 5-10 days of Hexarelin treatment did not alter GH mRNA in control young-adult rats. In adult rats GHRH-Ab also decreased GH mRNA levels, but 10 days of Hexarelin treatment were necessary to return GH mRNA back to normal levels. These results indicate that: (1) the effects of Hexarelin on GH release and GH mRNA levels may be unrelated events; (2) deprivation of GHRH function discloses the ability of Hexarelin to stimulate GH mRNA levels; (3) age plays a crucial role in setting the pituitary responsiveness to short-term Hexarelin treatment, and (4) the different ability of Hexarelin to stimulate GH release and GH synthesis in neonatal and young-adult rats may have clinical relevance in the chronic administration of the peptide.

Aging↗
PubMed1997

Dermatomyositis with a pityriasis rubra pilaris-like eruption: a little-known distinctive cutaneous manifestation of dermatomyositis.

A pityriasis rubra pilaris-like eruption has been described in patients with dermatomyositis. These patients showed generalized follicular hyperkeratosis and diffuse thickening of the palms and soles. Histopathological findings consisted of keratotic plugging of the follicular infundibulum and features of erector pili myositis. We report on an 18-year-old woman with dermatomyositis. The diagnosis was established by characteristic enzymatic alterations, electromyographic pattern of myositis and the findings in a muscle biopsy, although the patient had no evidence of muscular weakness during a follow-up of 14 years. She developed an erythematosus and squamous eruption associated with diffuse palmoplantar keratoderma. Histopathological features consisted of a papillomatous epidermis with spicules of compact eosinophilic hyperkeratosis over the tips of papillae that were not related to hair follicles. Pityriasis rubra pilaris-like eruption seems to be a characteristic although uncommon cutaneous manifestation in dermatomyositis.

Adolescent↗
PubMed1996

Physicians' view of practice guidelines. A survey of Italian physicians.

After more than 10 years of development, two different views of practice guidelines are emerging: either as an educational tool for the medical profession, or as a forum where health care issues can be debated by physicians and non-medical groups. Physicians use practice guidelines in the former model to set their own standards of good quality care, while the latter approach needs contributions from other components in order to decide what should be provided by our health care systems. In a survey of Italian physicians' opinions and attitudes toward practice guidelines, responders supported the "narrowest" model. More than 80% stated that improvement of quality of care and reduction of variation in clinical and practice styles should be the aim of practice guidelines, without representatives from outside the medical profession being involved (61%, 79% and 86% disagreed with a possible involvement, respectively, of patients, health care administrators and representatives of the public at large). Overall, 38% of physicians had a positive attitude toward guidelines viewed as a quality assurance tool for the medical profession. Overall, physicians seem to ignore that the need to rationalize health care calls for input from other professions and members of society. Indeed, most of the issues facing medicine today are mainly a matter of how much value our societies attach to the benefit expected from the available health services. The answers as to what should be done in health care probably cannot be left to the medical profession alone.

Adult↗