Neo-adjuvant chemo-(immuno-)therapy of advanced squamous-cell head and neck carcinoma: a multicenter, phase III, randomized study comparing cisplatin + 5-fluorouracil (5-FU) with cisplatin + 5-FU + recombinant interleukin 2.

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.

Clinical evaluation of two dosages and schedules of ifosfamide in combination with cisplatin in neo-adjuvant chemotherapy of patients with advanced (stage III-IV) head and neck squamous cell carcinoma: a phase II randomized study.

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.

[Etiologic, prognostic and social health aspects of urinary infections in hospitalized elderly with an indwelling urinary catheter]. / Aspetti etiologici, prognostici e riflessi socio-sanitari delle infezioni delle vie urinarie in soggetti anziani ospedalizzati portatori di catetere vescicale a permanenza.

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.

[Relationship between cholesterol levels and depression in the elderly]. / Associazione tra livelli di colesterolo e depressione nell'anziano.

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.

[Hyperuricemia and cardiac risK factors: epidemiologic study in the aged]. / Iperuricemia e rischio cardiovascolare: studio epidemiologico nell'anziano.

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.

[Electrophysiologic diagnosis of carpal tunnel syndrome in patients with diabetes mellitus]. / Diagnosi elettrofisiologica di sindrome del tunnel carpale in corso di diabete mellito.

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.

Peripheral neuropathy and multiple myeloma in aging: a case report.

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.

[Profile of thyroid hormones in aging: evaluation of a hospitalized elderly population]. / Profilo degli ormoni tiroidei nell'invecchiamento: valutazione su di una popolazione anziana ospedalizzata.

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.

[Hypercholesterolemia in the aged: rational approach to the problem]. / Ipercolesterolemia nell'anziano: razionale approccio al problema.

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.

Vasopressin, prolactin and growth hormone in Alzheimer's disease: their evaluation after metoclopramide stimulation.

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.

Isolation of multicellular complexes of follicular dendritic cells and lymphocytes: immunophenotypical characterization, electron microscopy and culture studies.

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-like cells containing lymphocytes (nurse cells) in human adenoids and tonsils.

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.

Lymphocyte subsets in human adenoids and tonsils. Rosette formation, alpha-naphthyl acetate esterase cytochemistry, monoclonal antibodies and peanut lectin reactivity.

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.