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Objectives: To examine the prevalence of temporomandibular disorders (TMD) in patients with juvenile fibromyalgia syndrome (JFS) and identify TMD characteristics specifically associated to JFS., Methods: Signs and symptoms of TMD were assessed using a novel clinical tool specifically devised for children that consists of: 1. a self-report multiple-choice questionnaire; 2. a protocol for the clinical examination of the orofacial region. Multivariate logistic regression model was used to identify TMD features associated with JFS., Results: Thirty JFS patients (median age 15.5 years) and 45 healthy controls (median age 15.0 years) were included in this cross-sectional study. Orofacial pain was reported by 26 of 30 JFS patients (86.7%) and by 3 of 45 controls (6.7%; p<0.001). Pain on TMJ palpation was present in 18 of 30 JFS patients (60%) and in 5 of 45 controls (11.1%; p<0.001). Median values of maximum spontaneous mouth opening, voluntary active opening and assisted passive opening were significantly higher in JFS patients than in controls. On multiple regression analysis spontaneous orofacial pain (OR: 21.0; p=0.005), diffuse tenderness on palpation of the masticatory muscles (OR: 14.9; p=0.026) and TMJ hypermobility (OR 1.42; p=0.008) were independently associated with JFS., Conclusions: The high prevalence of TMD in JFS highlights the need for a broader interdisciplinary evaluation of JFS patients. TMJ hypermobility, in addition to orofacial and masticatory muscle pain, is an important clue for the diagnosis of TMD in adolescents with JFS. Elucidating the link between these disorders will advance individualised management and improve treatment efficacy.

Background and Objective: Studies on the prevalence of anaemia in chronic kidney disease in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain., Materials and Methods: Multicentre, non-interventional, retrospective study with CKD-ND stage 3a-5 and CKD-D patients treated in Spain between 2015 and 2017 (RIKAS study)., Results: The prevalence of anaemia in CKD-ND and CKD-D in 2015 was 33.8% and 91.5%, respectively, with similar results during 2016-2017. The prevalence of systemic inflammation in anaemic patients (18.1% and 51.8% for CKD-ND and CKD-D, respectively) was higher, especially in those treated with erythropoiesis-stimulating agents (ESA), compared to the general population with CKD-ND. After 12 months of follow-up, mean ferritin and transferrin saturation index (TSI) values in anaemic patients with CKD-ND were 187.1 ng/mL and 22.2%, respectively, while in CKD-D were 254.6 ng/mL and 20.2%. In ESA-treated patients, mean values were 190.6 ng/mL and 22.0% in ND-CKD, and 255.0 ng/mL and 20.2% in D-CKD., Conclusions: The prevalence of anaemia and inflammation increased with the disease severity, being higher in D-CKD. Iron parameters in anaemic patients treated or not with ESA are insufficient according to the guidelines, so there is room for improvement in the treatment of anaemia associated with CKD., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Action tremor in Parkinson's disease may present in up to 46% of patients, either as postural or kinetic tremor. How action tremor may affect handwriting has been the object of some investigations; however, clinical features of writing tremor in Parkinson's disease are still not well-characterised. One hundred consecutive patients with idiopathic Parkinson's disease were included in the study. Demographic and clinical data were collected through a standardized questionnaire. Patients were assessed for the presence of rest, action and writing tremor in on condition. The effect of a standardised sensory trick (gently touching the wrist of the upper limb manifesting tremor with the contralateral hand) was also investigated in all patients with action tremor. Writing tremor was found in 10% of patients (26% of patients with postural/kinetic tremor, either alone or in combination with rest tremor). Severity of writing tremor did not correlated with that of the other tremor variants and to the other clinical variables. Writing tremor was task-specific in 4/10 patients, no task-specific in 6/10. Sensory trick was effective on writing tremor in two patients but did not improve action tremor in any of the study patients. Results showed that writing tremor in Parkinson's disease is less common than other tremor variants, may be associated with other forms of action tremor, and may sometimes have dystonic features, including task-specificity and sensitivity to sensory trick., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Loss of olfaction is a well-established early feature of Parkinson's disease (PD). Although olfactory dysfunction has been widely described as a prodromal feature of PD in the literature, whether it can be considered a biomarker of PD progression is still a matter of debate., Objective: The aim of this work is to define the possible relationship between the progression of olfactory dysfunction and other putative clinical hallmarks of PD over time, through a systematic review of the current literature., Methods: We conducted a systematic review of the literature on PubMed from inception to March 2022. We included only longitudinal studies conducted on patients with diagnosis of idiopathic PD who underwent olfactory function testing at baseline and repeated it at least once during follow-up., Results: Among 5740 records identified through database searching, nine longitudinal studies met full criteria and underwent data extraction., Conclusions: Olfaction seemed to decrease over time, albeit with a degree of fluctuation. Moreover, smell detection ability seems to deteriorate more rapidly in the early phase of disease, indicating a possible association with disease progression. More studies are needed to better understand the role of olfaction as a biomarker of PD progression over time.

Aim and Background: There is increasing evidence that statins and oral anti-diabetic drugs, such as metformin, can have a favorable role in advanced prostate cancer treatment.Metformin has been shown to inhibit proliferation of tumor cells in vitro and statins inhibit carcinogenesis by suppressing angiogenesis/invasion mechanisms. However, clinical evidence on the protective effect of these drugs is still weak.The purpose of this study is to analyze if these drugs have an impact on Biochemical-Failure-Free-Survival (BFFS) and on Distant-Failure-Free-Survival (DFFS) in localized high-risk prostate cancer., Material and Methods: From 2002-2016, 447 patients with histologically confirmed high-risk prostate cancer were retrospectively evaluated. All patients received radiotherapy and androgen deprivation therapy. Biochemical recurrence was determined by the Phoenix criteria and metastatic patients were defined by the presence of radiological metastasis. Survival analysis was performed using the Kaplan-Meier method., Results: 175 patients were treated with statins (65.3 % with a dose ≤ 20 mg/day) and 70 with metformin (75.7 % with a dose ≤ 1700 mg/day). Median follow-up was 88 months (1-194) with no differences in BFFS and DFFS between metformin and non-metformin patients (77.4 % versus 80 %, p = 0.91 and 89.4 % versus 88.7 %, p = 0.56, respectively). We did not find a statistical difference in BFFS and DFFS in patients taking higher doses of those drugs., Conclusion: Metformin and statins were not associated with BFFS or DFFS improvement in our analysis. However, the small number of patients treated with these drugs limits the reliability of the results and prospective studies are needed., (© 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)

We report a measles outbreak in Sardinia, Italy, that originated in a cruise ship passenger. The outbreak showed extensive nosocomial transmission (44 of 80 cases). To minimize nosocomial transmission, health care facilities should ensure that susceptible health care workers are vaccinated against measles and should implement effective infection control procedures.

Introduction: We report the case of a multiple drug interaction involving clozapine, antifungals and oral contraceptives, which resulted in an increased clozapine plasma level, pericarditis with pericardial effusion and eosinophilia in a young Caucasian woman. These symptoms and signs disappeared a few days after discontinuation of clozapine. At present, we are not aware of reports of clozapine-antifungals interaction, whereas there is only one other case report on the interaction between oral contraceptives and clozapine. The purpose of this case report is to show the risk of potentially serious adverse effects stemming from drug interactions involving medications routinely used in clinical practice., Case Presentation: A 29-year-old Caucasian woman diagnosed with a schizoaffective disorder was admitted to a psychiatric unit for acute psychosis (hallucinations, delusions and catatonic behavior). She denied smoking tobacco products and was on long-term oral contraceptives. During the first month of hospitalization she was treated with antipsychotics and for 1 week she took simultaneously fluconazole and miconazole gel, after being diagnosed with oral candidiasis. On the last day of antifungals treatment, 29 days after admission, clozapine was started with resolution of psychotic symptoms. After 3 weeks, her clozapine plasma level had increased to 542 ng/mL and eosinophilia was observed. She complained of nausea, vomiting and palpitations; echocardiography showed echocardiographic abnormalities and pericardial effusion. Oral contraceptives were discontinued and after 1 week clozapine was interrupted, with a complete resolution of side effects and pericardial effusion within 4 days., Conclusions: Clozapine is metabolized by cytochrome P450. The use of inhibitors or other substrates of cytochrome P450, such as antifungals and oral contraceptives, can cause long-lasting interactions and clozapine toxicity. The Naranjo algorithm shows clozapine is a definite cause of pericarditis (score 9) and both clozapine-antifungals and clozapine-contraceptives interactions resulted probable (score 5) in Drug Interaction Probability Scale. A good knowledge on drugs that act as substrates, inhibitors or inducers of cytochrome P450 is mandatory. When those drugs are used in patients taking clozapine, blood level monitoring of clozapine should be recommended, since a lower dose of clozapine might be required to prevent clozapine toxicity.

Purpose: Targeted therapies using the anti-EGFR antibodies panitumumab (Pmab) or cetuximab (Cmab) are currently restricted to patients with metastatic colorectal adenocarcinoma whose tumours do not show a mutation in KRAS. However, recent retrospective studies indicated that patients with tumours mutated in codon 13 of KRAS may benefit from treatment with Cmab in contrast to patients with tumours mutated in KRAS codon 12., Methods: To study the functional impact of the subtype of KRAS mutations on the efficiency of EGFR-targeted therapies, we correlated the KRAS mutation status of 15 colorectal carcinoma cell lines with the in vitro sensitivity of these cells to Cmab/Pmab. Mutations in the potential predictive biomarkers BRAF and PIK3CA as well as protein expression of EGFR and PTEN were also determined., Results: Four out of seven KRAS-mutated cell lines were characterised by the p.G13D mutation. Treatment of these cells using Cmab/Pmab induced a significant growth inhibition in contrast to cell lines showing a KRAS mutation at codon 12 or 61. Out of the eight KRAS wild-type cell lines, five were insensitive to Cmab/Pmab. These cell lines were characterised either by BRAF mutation or by absence of EGFR or PTEN protein expression., Conclusions: Since KRAS p.G13D-mutated tumour cells may respond to EGFR-targeted therapy, we suggest including subtype analysis of KRAS mutations in prospective clinical trials. In KRAS wild-type tumour cells, BRAF mutations and loss of EGFR or PTEN expression may lead to resistance to EGFR-targeted therapy and should be considered as additional negative predictive biomarkers.

In anurans, fecundity (clutch size) is the most important determinant of female reproductive success. We investigated three possible causes responsible for fecundity variation in female Italian treefrogs, Hyla intermedia, during four breeding seasons: (i) variation in morphological (body size and condition) and life-history (age) traits; (ii) variation in the tradeoff between the number and the size of eggs; (iii) seasonal effects and within-season differences in the timing of deposition. At the population level, we found no evidence for a tradeoff between the number and the size of eggs, because they both correlated positively with females' body size. Conversely, neither age nor post-spawning body condition showed any effect on female reproductive investment. Independent of body size, we found no evidence for variation in reproductive effort among different breeding seasons, but strong evidence for a decrease of clutch size and an increase of egg size with the advancing of a breeding season. To test for the functional significance of the observed temporal variation in allocation strategy, we carried out a rearing experiment in semi-natural conditions on a random sample of ten clutches. The experiment showed a negative effect of clutch size and a positive effect of egg size on both tadpole growth and developmental rates, suggesting that reproductive investment, although constrained by body size, can be adjusted by females to the time of deposition to increase the chances of offspring survival., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

The present review is based on the thesis that mate choice results from information-processing mechanisms governed by computational rules and that, to understand how females choose their mates, we should identify which are the sources of information and how they are used to make decisions. We describe mate choice as a three-step computational process and for each step we present theories and review empirical evidence. The first step is a perceptual process. It describes the acquisition of evidence, that is, how females use multiple cues and signals to assign an attractiveness value to prospective mates (the preference function hypothesis). The second step is a decisional process. It describes the construction of the decision variable (DV), which integrates evidence (private information by direct assessment), priors (public information), and value (perceived utility) of prospective mates into a quantity that is used by a decision rule (DR) to produce a choice. We make the assumption that females are optimal Bayesian decision makers and we derive a formal model of DV that can explain the effects of preference functions, mate copying, social context, and females' state and condition on the patterns of mate choice. The third step of mating decision is a deliberative process that depends on the DRs. We identify two main categories of DRs (absolute and comparative rules), and review the normative models of mate sampling tactics associated to them. We highlight the limits of the normative approach and present a class of computational models (sequential-sampling models) that are based on the assumption that DVs accumulate noisy evidence over time until a decision threshold is reached. These models force us to rethink the dichotomy between comparative and absolute decision rules, between discrimination and recognition, and even between rational and irrational choice. Since they have a robust biological basis, we think they may represent a useful theoretical tool for behavioural ecologist interested in integrating proximate and ultimate causes of mate choice., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The innate immune system limits viral replication via type I interferon and also induces the presentation of viral antigens to cells of the adaptive immune response. Using infection of mice with vesicular stomatitis virus, we analyzed how the innate immune system inhibits viral propagation but still allows the presentation of antigen to cells of the adaptive immune response. We found that expression of the gene encoding the inhibitory protein Usp18 in metallophilic macrophages led to lower type I interferon responsiveness, thereby allowing locally restricted replication of virus. This was essential for the induction of adaptive antiviral immune responses and, therefore, for preventing the fatal outcome of infection. In conclusion, we found that enforced viral replication in marginal zone macrophages was an immunological mechanism that ensured the production of sufficient antigen for effective activation of the adaptive immune response.

Background: detecting chronic kidney disease (CKD) may have important implications for the management of older and frail people. We aimed at investigating whether clinical setting (nursing home: NH versus hospital: H) affects the agreement between glomerular filtration rate (GFR) values estimated by Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations., Design: observational study., Setting: comparison between NH residents and H patients., Subjects: we used data from 177 NH residents, and 439 H patients., Methods: the agreement between estimating equations and the odds of a discrepancy >25% between formulas in relation to setting (NH versus H) were investigated., Results: the agreement between MDRD and CKD-EPI formulas was good either in NH (k = 0.82) or H (k = 0.87) patients, while corresponding figures for CG indicate only a fair agreement with CKD-EPI (k = 0.50 for both populations). Setting (NH versus H) was associated with discordance between MDRD and CKD-EPI (OR = 3.97; 95% CI = 1.75-9.01), but not between CG and EPI (OR = 1.25; 95% CI = 0.87-1.81)., Conclusions: in NH residents, MDRD and CKD-EPI formulas yield highly concordant GFR values, but CG behaves differently in up to one-third of patients. Such findings have important implications in dosing drugs cleared by the kidney. Setting should be taken into consideration in studies for validation of GFR equations.

Long-term care is a hospital unit, designed for frail elderly people, with ongoing physical challenges and in difficult social situations who have been suffering from multiple not-yet-stabilized pathologies. These subjects need medical-nursing and continuing care and/or treatments of rehabilitation which cannot be performed in extra-hospital situations. The aim of our study was to estimate a geriatric assessment of an old population hospitalized in a long-term care unit, using psychometric scales, paying attention to clinical, cognitive, functional, nutritional and social status. Two-hundred and ninety-seven patients of both sexes (middle age 81.3 +/- 8.6 years) divided into two groups of age (> or = 80 and < 80 years) were evaluated. The most important result of our study is a high index of disability (about five daily living activities were lost). These "functional deficits" were related to age, comorbidity, dementia, institutionalization and mortality. The study group showed a multiple pathology with various pharmacology therapy and, in 23.9% of cases, pressure ulcers were found and were related to mortality, as statistically noted. A serious cognitive impairment was found in 41.4% of the group (dementia was related to aging). As for residential destination, the most significant result is that almost half of the discharged patients went back to their home with a caregiver, who often was a woman. We finally underline the importance of increasing long-term care unit and the need for a higher integration in the territorial social-sanitary system, in order to guarantee care continuity for the frail and elderly.

The aims of the present open, randomized, single-blind (patient), single institution, phase II study were: i) to compare the therapeutic effectiveness and toxicity of two dosages and schedules of ifosfamide (IFO) in combination with cisplatin (CDDP) mainly in the neo-adjuvant setting of patients (pts) with locally advanced (stage III-IV) head and neck squamous cell cancer (HNSCC) (primary endpoint); ii) to assess the quality of life (QL) of pts included in the study before and after treatment (secondary endpoint). From July 1996 to June 1997, 28 pts, all males (mean age 56.79 years, range 37-72), hospitalized in the Department of Medical Oncology, University of Cagliari, were enrolled in the study. Twenty pts (M/F 20/0, mean age 53.6, range 37-71 years; stage III 1 pt, stage IV 19 pts) were evaluable for response and all 28 pts enrolled were evaluable for toxicity. Arm A: IFO 2.2 g/m2 i.v. as a 4 h infusion on days 1-5, Mesna 600 mg i.v. as push injection at 0 h, 4 h, 8 h on days 1-5, CDDP 20 mg i.v. as a 60 min infusion on days 1-5. The regimen was repeated every 28 days for 2 cycles. Fifteen pts (11 of whom were evaluable) were enrolled in this Arm. Arm B: IFO 1.5 g/m2 i.v. as a 4 h infusion on days 1-5, Mesna 600 mg i.v. as push injection at 0 h, 4 h, 8 h on days 1-5, CDDP 20 mg i.v. as a 60 min infusion on days 1-5. The regimen was repeated every 28 days for 3 cycles. Thirteen pts (9 of whom were evaluable) were enrolled in this Arm. The two Arms were well-balanced for sex, age, site of primary, ECOG PS and clinical stage. After completion of 2 (Arm A) or 3 (Arm B) cycles of chemotherapy, the pts were assessed for response. All evaluable pts received treatment as planned. Six pts (54.5%) of Arm A and 4 pts (44.5%) of Arm B had partial response (PR) with an overall response rate (ORR) of 54.5% and 44.5%, respectively: it is worth noting that all (100%) pts who had PR in Arm B achieved a high-grade PR, i.e. >/=70%, whereas only one pt (16.7%) who had PR in Arm A achieved a high-grade PR. Three pts (27.3%) in Arm A and 2 pts (22.2%) in Arm B had stable disease (SD); 2 pts (18.2%) in Arm A and 3 pts (33.3%) in Arm B had progressive disease (PD). The actual dose intensity was over 80% of the projected dose intensity for both drugs and for both Arms. Over a total of 59 cycles administered, the total number of episodes of toxicity was 24 for Arm A and 17 for Arm B. Three pts out of 28 evaluable for toxicity (10.8%) died for Grade 5 hematological toxicity: all pts were included in Arm A. In Arm A, 2 pts (13.3%) experienced hematological Grade 3 toxicity and 2 pts (13.3%) hematological Grade 4 toxicity. In Arm B no pt experienced Grade 3-4 hematological toxicity. No Grade 3-4 toxicity of any other type was found in either Arm. The QL evaluation, using the Cella's FACT-G scale supplemented with disease-specific scale (FACT-H&N scale), did not show significant beneficial effect of neo-adjuvant chemotherapy treatment.

We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2 (rIL-2) in patients with advanced (stage III IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m(-2) day(-1) 5-FU on days 1-5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8-12 and 15-19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients (20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients (13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus, there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were 2 toxic deaths (6.7%), 1 from hematological causes in group A and I from cardiac causes in group B. Myelosuppression and gastrointestinal toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable that a clinically significant difference between the two treatment groups will be observed even if the calculated patient sample size is achieved.

The aim of the study is to evaluate, in a short case-report, the concomitant urinary tract infections in a group of institutionalized elderly people with urinary indwelling catheter. Mental, functional and sanitary status was determined. 61 subjects over 65 years old (23 male and 38 female) were recruited and subdivided into three groups. Streptococcus faecalis was the main cause of urinary tract infections, Gram negative infections were overall predominant. High levels of dysautonomia with strong, global cognitive ability compromise were present in 75% of pattern. DMI and RSS test showed a marked not self-contained in 77% of recruited people and a high stress in the relatives. A significant statistical correlation among functional, sanitary, status and outcome institutionalization was present.

The aim of our study is to evaluate the possible association between lower plasma cholesterol and depression in the elderly. 140 subjects over 65 years old of both sexes were enrolled, of which 60 were affected by depression (DSM-III-R and Hamilton test) and 80 composed a control group homogeneous for sex and age with the previous one. Plasma cholesterol, HLD-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides were measured. A statistically significant difference between cholesterol and LDL-C (p < 0.001) was noted in the total group, in both males and females. Such modifications were independent of sex. In the group with lower cholesterol (cut-off < = 160 mg/dl) a prevalence of depression three times greater than subjects with higher cholesterol was found. In conclusion, the authors recommended a prudent use of lipid-lowering medications in the elderly because of its uncertain benefits.

The aim of our study is to evaluate whether hyperuricemia may be considered a cardiovascular risk factor also in the elderly. 370 subjects over 60-years-old of both sexes were examined of which 148 presented an ischemic heart disease and 222, age and sex homogeneous, were considered as control group. Serum uric acid was determined. A strong difference among the two groups (p < 0.001) was statistically demonstrated. Such modifications were sex independent. A strict correlation of hyperuricemia and hyper trygliceridemia was present; in fact high uric acid levels were mostly found in the group with triglycerides > 200 mg/dl (p < 0.02). In the whole group and in males a stability of uric acid was noted. In females a significant increase among the first (60-69 years) and the second (70-79 years) age class was present. In conclusion, a positive role of hyperuricemia in the ischemic heart disease pathogenesis is possible.

The authors evaluated 406 patients affected by carpal tunnel syndrome diagnosed by clinical and electromyographic data. Diabetes mellitus was recognized in 57 subjects. The others constituted the control group. The severity of the syndrome was similar in both groups. Also similar was the interval between onset and clinical diagnosis. Such parameters and the severity of the syndrome showed no modification with age in the diabetic group. In the control group, carpal tunnel syndrome was more pronounced in the aged patients, presumably for the longest latency of disease. Carpal tunnel syndrome onset was later in diabetic subjects compared the control. At lastly we found a prevalence of bilaterality in diabetics, and an M/F rate comparable in both groups, as described by other authors.

A 67-year-old man affected by moderate weight loss, acral paresthesia and plantar burning sensation was admitted to our department. Electromyographic (EMG) and electroneurographic (ENG) studies confirmed a peripheral, asymmetrical, motor-sensorial polyneuropathy (PPN). Hematological data and bone marrow biopsy discovered a non-secerning multiple myeloma (MM). All other probable causes of peripheral neuropathy could be excluded, and the possible relationship between nerve damage and neoplasia was confirmed. Furthermore, all possibilities of association of MM with PPn, namely the osteosclerotic variant, the Crow-Fukase syndrome, and the amyloid one have been evaluated. The only finding of osteolytic bone areas by radiology, the absence of organomegaly, diabetes mellitus, skin alterations, and of amyloid deposition in muscles and nerves, exclude the possible connection of the case to any of the listed possibilities. On the other hand, some clinical aspects differ, in part, to others described in the literature. In conclusion, the association between PPN and MM as the result of multiform clinical variants could be considered.

The aim of the study is to evaluate thyroid serum levels in a geriatric community to confirm the presence of a low T3 syndrome during normal ageing. The authors consider 413 subjects (125 male and 288 female) admitted to our Geriatric Division. The group affected by thyroid and extrathyroid disease (such us malnutrition, diabetes mellitus, renal failure, etc.) was withdrawn. In the selected patients (271) was operated a statistical evaluation to correlate the hormonal parameters (T3, T4, TSH, FT3, FT4) with age and sex. According to international literature, we confirm a progressive T4 and FT4 reduction (p less than 0.05) during ageing, both in male and in female. These data range within normal values. On the contrary, TSH shows no modifications with age and sex. Unlike all other parameters, T3 presents a more evident decrement with age, confirming a low T3 syndrome.

While there are definite data showing the correlation between cholesterol level and cardiovascular disease in adults, so far we lack reliable evidence showing hypercholesterolemia to be an important risk factor in the elderly as well. Having examined all available data, the authors come to the conclusion that in elderly subjects, too, hypercholesterolemia should be treated after careful clinical evaluation of every individual case. Whenever possible therapy should be dietary but in light of recent results obtained with HMG-CoA reductase inhibitors which are effective and well tolerated also in the elderly, adequate pharmacological management should also be feasible in this type of patient.

Recent studies have shown that there is a relationship between an alteration of central neurotransmitters and the modification of some biohumoral parameters in Alzheimer's Disease (AD). In this study the authors evaluated, after metoclopramide (MTC) stimulation, the concentration curve of vasopressin (AVP), prolactin (PRL) and growth hormone (HGH) in the plasma of 34 subjects (20 males and 14 females, mean age 70.5+/-6.9 years; 17 were AD patients, the others constituted the control group). MTC increased AVP serum concentration in healthy (P <0.001), but not in AD patients. This result seemed to be due to the lack of 'procholinergic' action of the drug in the AD patients probably due to an alteration in their cholinergic pathways. The PRL response to MTC was reduced only in the AD female group (P <0.005), suggesting an alteration in dopaminergic control. Lastly, the HGH response in AD did not differ in the two groups, neither in basal conditions, nor after MTC stimulation. The absence of HGH response both in AD and in healthy subjects, demonstrated the ineffectiveness of MTC stimulation. We can conclude that AVP and PRL responses to MTC stimulation efficiently separated the two groups (AD and controls); the former test showing a higher discriminant power than the latter.

The distribution of mononuclear cell subsets has been studied in human adenoids, tonsils and peripheral blood (PB) by evaluating the presence of surface immunoglobulins, E-rosette formation, receptors for IgG Fc and for complement, alpha-naphthyl acetate esterase (ANAE) cytochemistry, reactivity with peanut lectin (PNA) and with monoclonal antibodies (McAb) (OK panel). Adenoids and tonsils, compared to PB, contain (1) fewer macrophages and T cells but more B cells; (2) higher proportions of ANAE negative, complement receptors and Ia-like antigens bearing T lymphocytes; (3) higher percentages of cells reacting with the McAbs OKT9 and OKT10 ("immature" lymphoid cells). In both adenoids and tonsils, clusters, formed by a central heavily ANAE stained interdigitating cell surrounded by lymphocytes with a sickle-shaped ANAE reaction, were found. Analogous clusters have been previously described in mice and human thymus. Two major hypotheses could be put forward: (1) adenoids and tonsils contain "immature" lymphoid cells undergoing education process, or (2) the above organs contain lymphocytes activated by a constant exposure to bacterial antigens or mitogens.

The morphological and phenotypical features of multicellular complexes formed by follicular dendritic cells and lymphocytes (FDC-LC) isolated from human hyperplastic tonsils and adenoids are described. FDC-LC obtained with this procedure were morphologically and immuno-phenotypically heterogeneous. In one type of FDC-LC, probably obtained from germinal centers, the lymphocytes exhibited ultrastructural features of centroblasts and centrocytes. In a second type, likely derived from follicular mantles, the enclosed lymphocytes were small in size and characterized by a condensed chromatin pattern. Similar heterogeneity was observed by immuno-phenotypical analysis, which revealed a prevalence of IgD+, CD3-, MT2+ small lymphocytes in a high proportion of FDC-LC. Both types of FDC-LC contained desmoplakin immunoreactivity in a typical punctate pattern corresponding to intercellular junctions when tested with a specific antibody. These findings confirm the importance of FDC in maintaining the follicular structure and also suggest that the different zones forming lymphoid follicles (mantle zone and germinal center) are formed by lymphocytes gathered in single "domains" by cytoplasmic processes of FDC. These domains have strong resistance to mechanical stress, such as that used in isolation procedures. FDC-LC have also been maintained as organized multicellular clusters for short periods (more than 48 h) in agarose gel cultures.

Epithelial cells filled with lymphocytes (nurse cells, NC), recently described in mouse, rat and human thymus, have been interpreted as mediators of direct contact ('stromal') induced thymocyte maturation. We describe analogous NC in trypsin-dissociated human adenoids and tonsils. NC from these organs show morphological characteristics analogous to those of thymic NC: they appear as large (diameter 30-35 micrometers) elements, containing peripherally situated tonofilament bundles, electrodense mitochondria and some vacuoles. Each NC contains 5-30 intact lymphoid cells, some of which appear in the activated state. NC show neither phagocytic ability, nor ANAE and peroxidase cytochemical reactions. The majority of NC from adenoids and tonsils react with the monoclonal antibody (McAb) OKIa1 (DR w framework) as those from thymus, and 40% of them bind fluorescein-conjugated peanut agglutinin. Some of them also react with the McAb OKT3 (pan-T), OKT9 (transferrin receptors) and OKT10 (immature hematopoietic cells). The presence of NC in adenoids and tonsils suggests that these organs may be involved in some stages of lymphocyte maturation requiring intimate contact with epithelial cells.