Use of extra-oral scanner for the study of arch form in a sample of Italian adolescents with ideal occlusion.

The aim of this study was to evaluate the shape and the average size of the maxillary and mandibular arch in an Italian adolescents' sample with correct occlusion, using the digital technology. The study sample was composed, after the use of an extra-oral scanner and after the application of inclusion and exclusion criteria, by the digitized dental casts of 79 Italian adolescents (39 females and 40 males), aged 14±1 years, with correct occlusion. On each model, both upper and lower, the reference points of the dental arches (FA), of the alveolar bone (WALA ridges) and of the incisal edge of the central incisors were identified. With these points, using a software, fourteen parameters were evaluated for each cast: basal and dental intermolar and inter-canine width, basal and dental molar and canine depth, basal and dental molar and canine ratio, overjet, overbite. Finally, the shape of the arches was assessed, dividing it into ovoid, triangular or square. Chi-square test and Student's T-test for each parameter were adopted with a p<0,05 significance level. The results showed that the ovoid form was the most frequent, followed by the triangular one for the upper arch and by the rectangular one for the lower arch. On the canine level, both upper and lower, both for dental and for basal references, the triangular shape showed the lowest width and ratio values and the highest depth values in comparison with the other two groups. The square one showed the opposite situation, and the ovoid one presented in the intermediate value. On the molar level the trend is quite similar to the canine one. The results obtained maybe suggest that on a significant percentage of the patients of the sample is expected to use a preformed ovoid arch wire, and the data found could be useful to study the adequacy of the arch wires currently on the market or to design new ones. .

Immune-neuroendocrine and metabolic disorders in human and experimental T. cruzi infection: New clues for understanding Chagas disease pathology.

Studies in mice undergoing acute Trypanosoma cruzi infection and patients with Chagas disease, led to identify several immune-neuroendocrine disturbances and metabolic disorders. Here, we review relevant findings concerning such abnormalities and discuss their possible influence on disease physiopathology.

Do Akiskal & Mallya's affective temperaments belong to the domain of pathology or to that of normality?

BACKGROUND: Kraepelin and Kretschmer hypothesized a continuum between full-blown affective pathology and premorbid temperaments. More recently Akiskal proposed a putative adaptive role for the four fundamental temperaments: the hyperthymic one characterized by emotional intensity, the cyclothymic one by emotional instability, the depressive one by a low energy level, and the irritable one by an excessive response to stimuli. Today it is widely debated whether affective temperaments belong to the domain of pathology or to that of normality. PURPOSE: To make clear, by applying an integrated model, the position of affective temperaments within the continuum between normality and pathology. METHODS: We reviewed several papers that explore the distribution of affective temperaments among the general population, and their involvement both in pathological conditions (somatic and psychiatric) and in human activities (professions and other occupations). RESULTS: Far from being intrinsically pathological conditions, affective temperaments seem to represent adaptive dispositions whose dysregulation can lead to full-blown affective pathology. All the temperamental types display some impact on people's lives by influencing personal skills and professional choices over a wide field of human activities. CONCLUSIONS: Affective temperaments are not problematic when they appear in a mild form, but when they occur in extreme form we have observed a gap between the hyperthymic temperament, which represents the most functional and desirable, and the cyclothymic, depressive, irritable and phobic anxious ones, which are closer to mood, anxiety, and substance use disorders, and imply a component of somatic diseases and life stressors.

Clinical application of prismatic lenses in the rehabilitation of neglect patients. A randomized controlled trial.

BACKGROUND: Many studies reveal that neglect is a major cause of disability in stroke patients, and two months from onset neglect is still present in approximately 50% of individuals with a right brain lesion. Among the various methods of neglect rehabilitation, we have turned our attention to the prism adaptation treatment, developed by Rossetti in 1998. This treatment uses prismatic lenses, which produce a deviation of the fixation point of the visual field of 10 degrees to the right, 5 degrees below the coordinates of reference resulting from neglect. AIM: To set out the possible effectiveness of less powerful lenses, we studied the response of a group of neglect patients treated with prismatic lenses that produce a deviation of the fixation point of only 5 degrees to the right, comparing them with a group of patients receiving placebo lenses. DESIGN: Randomized controlled trial. SETTING: Outpatients. POPULATION: The study involved 29 patients with left visual neglect. METHODS: All patients were assessed with a battery of seven visual-spatial tests. All patients were randomized by the pilot center and assigned to two different groups: "A" treated with pointing exercises and prismatic lenses of 5° to the right; "B" treated with pointing exercises and neutral lenses. Each group was treated with 5 rehabilitation sessions, lasting about 30 minutes each, from Monday to Friday for one week in the morning, by the same investigator, in each center. CONCLUSION: The results showed that the prismatic lenses of only five degrees, used for the study, did not contribute to the variation in performance. Thus, this deviation of the fixation point of the visual field to the right is not sufficient to create a therapeutic effect. The improvement observed within the two groups, seems likely to be correlated with the pointing exercises, which force the subject to perform a visuomotor task with the healthy arm also in the neglected side. CLINICAL REHABILITATION IMPACT: We believe that in order to carry out an effective treatment with prismatic lenses they must have a grade of at least 20 prism diopters. Lower grades are unable to determine an effect. Finally, because of the severe impact of neglect on the work of the rehabilitation team, and since our data shows that only five sessions are sufficient to demonstrate a change in performance, we believe that it is appropriate to use this method, especially in the acute phase of the disease.

Mutations of the APC gene in human sporadic colorectal cancers.

BACKGROUND: Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis. METHODS: Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region. RESULTS: Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C). CONCLUSIONS: These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.

Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study.

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin's disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m(2), was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1, 250 mg/m(2) to 1,500 mg/m(2). RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients' main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin's disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.

A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum. Italian Co-operative Group on Bladder Cancer.

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.

Case report: sequential bilateral carotid dissection leading to Raeder's syndrome.

A 39-year-old man complained of unilateral headache, diplopia and marked anterior neck oppression "like a necklace". MRA was used to study this case of subsequent bilateral internal artery dissection (ICAD) which initially appeared as Raeder's syndrome. MRA proved to be a non-invasive alternative for studying stenosis, occlusions and dissections of the intracranial and extracranial vessels.

Antiarthritic effects of glucosamine sulfate studied in animal models.

The antireactive activity of glucosamine sulfate (GS) (CAS 29031-19-4) was tested in the rat in experimental models of subacute inflammation (sponge granuloma and croton oil granuloma), on subacute mechanical arthritis (kaolin arthritis) and in immunological-reactive arthritis and generalized inflammation (adjuvant arthritis). On these models GS was found effective in oral daily doses of 50-800 mg/kg. Tne potency of GS in comparison of that of indometacin used in the same tests as reference substance was found 50-300 times lower. Since, however, the toxicity of indometacin in chronic toxicity experiments is 1000-4000 times larger, the therapeutic margin with regard to prolonged treatments of inflammatory disorders results 10-30 times more favourable for GS than for indometacin. GS can therefore be considered as a drug of choice for prolonged oral treatment of rheumatic disorders.

Antireactive properties of glucosamine sulfate.

Glucosamine (CAS 3416-24-8) is an aminomonosaccharide naturally occurring in the human body. It was tested for antiinflammatory activities and it showed to protect against the edema provoked in the rat paw by carrageenin, dextran, formalin, but not against the edema provoked by specific inflammation mediators, such as bradykinin, serotonin, histamine. Glucosamine protected against pleurities provoked in the rat by carrageenin, but not against that provoked by bradykinin. Furthermore glucosamine protected against peritonitis provoked in the rat by formalin and in the mouse by acetic acid. Glucosamine did not show antinoceptive properties against writings provoked by i.p. phenylquinone in the mouse. Glucosamine did not show inhibiting activities on cyclooxygenase or on the proteolytic enzymes in the inflamed paw of the rat, but it was able to inhibit in vitro superoxide generation and lysosomial enzymes of the liver. The potency of glucosamine on the antiinflammatory tests was lower than that of acetylsalicylic acid and much lower than that of indomethacin. Its acute toxicity, however, and notably the toxicity on the gastrointestinal tract is very low, practically absent. The pharmacological therapeutic index of glucosamine with regard to the antiinflammatory activities seems therefore comparable or superior to that of the known non-steroidal anti-inflammatories.

Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells.

We have investigated the possible effect of substance P (SP), a main mediator of neurogenic inflammation, on the growth of capillary vessels in vivo, and on the proliferation of cultured endothelial cells in vitro. Slow release preparations of SP were implanted into the avascular cornea of New Zealand White rabbits and vessel growth was monitored daily through a slit lamp stereomicroscope. SP (1-5 micrograms/pellet) induced a marked neovascularization. A selective NK-1 receptor agonist [beta-Ala4, Sar9, Met(O2)11]-SP(4-11) also induced neovascularization. The addition of SP to serum-free cultured endothelial cells, isolated from bovine adrenals (BACE) and from human umbilical cord veins (HUVE), increased proliferation of both cell lines in a concentration-dependent manner with maximal activity at 10(-8) M (BACE) and 10(-10) M (HUVE). The selective NK-1 receptor agonist induced a similar proliferative action on both cell lines, while the selective NK-2 receptor agonist [beta-Ala8]-NKA(4-10) and the selective NK-3 receptor agonist [MePhe7]-NKB had no significant effect. Two different SP antagonists [D-Pro2, D-Trp7,9]-SP and [D-Pro4, D-Trp7,9,Phe11]-SP (4-11) blocked the response to SP. These findings indicate that SP can directly stimulate the process of neovascularization, probably through induction of endothelial cell proliferation. This hitherto unraveled activity of SP could play a key role in the trophic action produced by activation of the efferent function of peripheral endings of primary sensory neurons.

NK1-receptors mediate the proliferative response of human fibroblasts to tachykinins.

1. The effect of synthetic tachykinin selective receptor agonists was studied on the growth of cultured human skin fibroblasts (HF). 2. Human fibroblasts were grown in serum-free conditions in the presence of natural tachykinins (substance P and neurokinin A) and of three synthetic agonists, [beta-Ala4, Sar9, Met(O2)11]-SP(4-11), [beta-Ala8]-NKA(4-10) and [MePhe7]-NKB selective for NK1-, NK2- and NK3-receptors respectively. Cell proliferation was measured by percentage increase in cell number and by [3H]-thymidine uptake following 48 h exposure to agents compared to baseline condition. 3. Neurokinin A (NKA) and substance P (SP) significantly increased cell proliferation the threshold concentrations being 10(-12) and 10(-11) M, respectively. Addition of thiorphan to culture conditions enhanced the effect of SP but not of NKA. 4. The selective NK1-receptor agonist produced a dose-dependent increase in cell proliferation as judged by total cell number and [3H]-thymidine uptake. No significant effect was observed with NK2- and NK3-receptor agonists. 5. These data indicate that the effect of SP on fibroblast proliferation is mediated by interaction with a NK1-receptor type and local metabolism can interfere with the full expression of this effect of SP on cell proliferation.

Antispasmodic activity of tiropramide.

Tiropramide hydrochloride and some of its metabolites were studied in vivo for their antispasmodic activities on the following models: gastric emptying in the mouse retarded by cholecystokinin octapeptide (CCK-8) or morphine, progression of intestinal contents in the mouse, spontaneous motility of the colon in the anesthetized rabbit, diarrhea induced by castor oil in the rat, spasm of the sphincter of Oddi provoked by morphine in the guinea pig, contractions of the urinary bladder in the anesthetized rat. On these models tiropramide had an antispasmodic activity at doses of 4-40 mg/kg i.p. or i.v. and of 50-90 mg/kg orally. The potency was greater on "pathological" contractions or spasms and smaller on "physiological" movements. Tiropramide may therefore be regarded as a "eukinetic" antispasmodic agent. Tiropramide in general was more potent than reference agents such as papaverine or flavoxate and was active also after oral administration. The metabolites of tiropramide, i.e. CR 1034, CR 1098 and CR 1166 showed similar pharmacodynamic effects, but their potency was smaller than that of tiropramide. Large doses of tiropramide have depressive actions on the cardiovascular system, which can be seen especially if tiropramide is administered i.v. and are less pronounced after oral administration. The circulatory effects are therefore probably the limiting factor for increasing the parenteral doses of tiropramide in human therapy. Tiropramide was found less toxic than papaverine (LD50). The metabolites of tiropramide were less toxic than the parent compound. The toxicity of the chiralic forms of tiropramide does not differ significantly from that of the racemic substance.

Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide.

(+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel-ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity.

[A case of 9p partial monosomy caused by paternal translocation. Clinical and cytogenetic aspects]. / Un caso di monosomia parziale 9p- da traslocazione paterna. Aspetti clinici e citogenetici.

The authors describe a case of partial monosomy 9p in a newborn infant, with breakpoint in the region p221, due to a father's balanced translocation with karyotype 46 XY t(9;16)(p221;q224). The phenotypical features of our patient reproduce those reported in other 35 cases described up to now in the literature: trigonocephaly, upward slanting palpebral fistures, little and horizontal mouth, disproportionally long fingers and toes. Some peculiar clinical and cytogenetical features of the case are discussed, particularly the early closure of the sternal body ossification centers (already detected during the prenatal life), the partial agenesia of the splenium corporis callosi and the partial anomalous pulmonary venous return. The Authors point out the importance of an early diagnosis, based on the awareness to the clinical abnormalities and dysmorphisms, in order to provide for an adequate and opportune genetic counseling.

[A new case of fronto-nasal dysplasia associated with craniosynostosis]. / Una nuova osservazione di displasia fronto-nasale associata a craniosinostosi.

The Authors report a case of frontonasal dysplasia, a rare congenital syndrome, accompanied by multiple cranial synostosis. According to Cohen, frontonasal dysplasia associated with craniosynostosis may be considered as a separate syndrome and Cohen himself has described its occurrence in members of two families as "Craniofrontonasal Dysplasia". The Authors describe a sporadical case presenting various minor abnormality reported by Cohen, in addition to the hypoplasia of the corpus callosum, demonstrated by the Cranial Ultrasonography and by the NMR study of the brain.