Changes in condylar path inclination during maximum protrusion between the ages of 6 and 12 years.

The purpose of this study is to quantify the changes in sagittal condylar path inclination during mandibular protrusion between the ages of 6 and 12 years. A total of 172 children (82 males and 90 females) ranging in age from 6.5 to 12.9 years were divided according to their chronological age into five subgroups with mean ages of 7.1, 8, 9, 10 and 11.4 years respectively. The control group consisted of 41 adults with a mean age of 28 years. All subjects had a normal temporomandibular joint function and neutral occlusion. Five maximum protrusion-retrusion movements were recorded with six degrees of freedom in each subject using an ultrasound (JMA) jaw-tracking system. Initially, condylar path inclination angle (CPIA) was calculated stepwise for each millimetre distance, for the first 10 mm of protrusive tracing path on both sides. A single mean value was then assigned for the entire protrusive path. One-way analysis of variance proved to be significant among the five subgroups of children. Linear regression analysis showed that condylar path had a tendency to become steeper with age, although it was statistically weak. The data indicated that the mean CPIA is 43 degrees -44 degrees at the age of seven, increases annually by 1.2 degrees -1.3 degrees and reaches an average of 49 degrees -50 degrees by the age of 12 at which time it attains around 83-85% of its adult level. In subgroup V, the female population had significantly steeper condylar path on the left-hand side than the male population. Condylar path inclinations indicated a symmetrical growth pattern of the articular eminence.

Undertreatment of hypertension in community-dwelling older adults: a drug-utilization study in Dicomano, Italy.

OBJECTIVE: To define: (1) the prevalence of and (2) factors associated with undertreatment of hypertension in older persons; and (3) the prevalence of specific drug regimens and reasons for their selection. PARTICIPANTS: Cross-sectional survey of persons aged > or =65 years living in Dicomano, Italy. MAIN OUTCOME MEASURES: Prevalence of untreated and uncontrolled hypertension, both defined on the basis of two blood pressure (BP) cut-off points (> or =140/90 and > or =160/90 mm Hg) and of the presence of pharmacological treatment Predictors of undertreatment were analysed for the higher BP cut-off only. RESULTS: Five hundred of 692 (72.3%) and 380/692 (54.9%) participants met the 140/90 and the 160/90 mm Hg BP criterion, respectively. Of the latter, 162 (42.6%) were untreated, 119 (31.3%) had uncontrolled and 99 (26.1%) controlled hypertension. Women [odds ratio (OR), 0.4; 95% confidence interval (CI), 0.2-0.7], participants with coronary artery disease (CAD) (OR, 0.2; 95% CI, 0.1-0.6), stroke (OR, 0.3; 95% CI, 0.1-0.7), and preserved cognitive status (Mini Mental State Examination score >21: 0.3; 95% CI, 0.2-0.7) were more frequently treated. Uncontrolled hypertension was less likely in women (OR, 0.5; 95% CI, 0.3-1.0) and CAD patients (OR, 0.3; 95% CI, 0.1-0.7). Angiotensin converting enzyme (ACE)-inhibitors (55%), calcium (Ca)-antagonists (31%) and diuretics (20%) were the drugs most commonly prescribed. ACE-inhibitors were preferred, and diuretics rarely used, in diabetic subjects. Ca-antagonists were used mostly in CAD participants. CONCLUSIONS: Hypertension is undertreated in the majority of noninstitutionalized older adults, especially in men with impaired cognition and no vascular disease. Drug regimens are mostly based on ACE-inhibitors and Ca-antagonists, as a result of associated clinical conditions, requiring individualized treatment.

Serum melatonin in multiple myeloma: natural brake or epiphenomenon?

Melatonin (MEL), the main hormone produced by the pineal gland, seems to exert antineoplastic activity both in vitro and in vivo. Moreover, several studies reported increased melatonin blood levels in cancer patients. Plasma melatonin concentrations were determined in 46 patients with multiple myeloma and in 31 age matched healthy subjects (57.8 +/- 6.9 versus 55.2 +/- 8.9 years). Venous blood was drawn between 7.30 and 9.30 a.m. and melatonin was assayed using a commercially available radioimmunoassay. The data were analysed by Student's t test and results reported as mean values +/- standard deviation. The patients with multiple myeloma showed significantly higher mean melatonin serum levels than healthy subjects (21.6 +/- 13.5 versus 12.1 +/- 4.8 pg/ml; p < 0.001). This behaviour could actually represent a phenomenon secondary to an altered endocrine-metabolic balance caused by an increased demand of the developing tumor. On the other hand, the increased melatonin secretion might be considered as a compensatory mechanism due to its antimitotic action and therefore as an effort to secrete substances capable of regulating neoplastic growth.

Low-dose cytosine arabinoside in patients with acute myeloid leukemia not eligible for standard chemotherapy.

The results of treatment with low dose cytosine arabinoside (LDARA-C) in 131 AML patients ineligible for standard regimens were analyzed retrospectively. Eighty-seven were previously untreated, 25 were refractory to conventional chemotherapy and 19 were relapsed patients. The median age was 66 years (15-84). An antecedent hematological disorder (AHD) was documented in half of the patients. Overall, 22 (17%) achieved complete remission, 14 (11%) partial remission, 77 (59%) had resistant leukemia and 18 died during induction. Median disease free survival was 57 weeks and median survival, for the 87 previously untreated patients, was 22.5 weeks. The prognostic value of initial parameters was analyzed for response. Bone marrow cellularity was the only significant factor. We observed 33% vs 81% (p < 0.01) of responses in patients with normo-hypercellular and hypocellular marrow, respectively. Accordingly, there was a trend to more responses in patients with leukocyte counts of less than 10 x 10(9)/L. M4-M5 FAB subtypes were frequently resistant to LDARA-C, resulting in a lower response rate compared to M0-M2 (18% vs 32%). Other parameters, including age, sex, hemoglobin, platelet count, AHD and fever at diagnosis, had no prognostic value. Our findings suggest that LDARA-C may be an effective treatment for some patients who are not eligible for first line conventional chemotherapy. However, this schedule is not advised in patients with monocytic leukemia or those with an hypercellular marrow.

Attenuated-dose idarubicin in acute myeloid leukaemia of the elderly: pharmacokinetic study and clinical results.

AML in the elderly is characterized by intrinsic biological features implying an enhanced chemoresistance. Intensive chemotherapy should be the treatment of choice, but the standard doses could induce unacceptable rates of aplastic deaths. We evaluated the efficacy of an induction protocol with attenuated-dose idarubicin (IDA) 8 mg/m2 for 3 d plus cytarabine and etoposide in 26 AML patients aged > 60. 18 patients (69%) achieved CR, five (19%) were non-responders and three (12%) died during induction. To compare the pharmacokinetics of IDA between elderly and young patients, we assayed daily the serum level of the drug and of its metabolite (idarubicinol, IDAol) in a group of eight elderly patients who received a dose of 8 mg/m2 (group A) and in a group of nine younger AML patients treated with 12 mg/m2 (group B). The apparent terminal half-life of IDAol was significantly longer in the elderly than in the younger patients (mean half-life 59.7 h versus 41.4 h, P < 0.05). The values of the area under the serum concentration curve of IDAol indicated that the two patient groups received a very similar exposure to the drug despite the different doses. In conclusion, this protocol, based on attenuated doses of IDA, compares well with the results obtained previously in similar age-matched patient series.

CD34 expression fails to predict the outcome in adult acute myeloid leukemia.

BACKGROUND: The expression of the CD34 antigen on the blast cells of acute myeloid leukemia (AML) has been regarded as an unfavorable prognostic factor for the achievement of complete remission (CR). However, clinical reports on this issue still remain controversial. We evaluated the relationship between CD34 expression, some clinical characteristics and outcome in 80 consecutive adult AML patients. METHODS: Immunophenotyping was performed with a FACSCAN flow cytometer and CD34 was tested by HPCA-1 (My10, Becton-Dickinson). Samples were considered positive when at least 20% of cells were labeled. Promyelocytic leukemias were excluded from the study. Sixty-six patients were designed to receive intensive induction chemotherapy; 14 "low-dose" ARA-c. RESULTS AND CONCLUSIONS: Forty percent of AML were CD34 positive. In this group there was a higher incidence of less differentiated FAB subtypes (p = 0.03), but not of pre-existing myelodysplasia. No differences were found in complete remission (CR) rate, remission duration or survival. Excluding induction deaths from the analysis, the CR rate was slightly lower in CD34+ AML (55 vs 65%), without any impact on survival. We could not confirm the prognostic relevance of CD34 in adult AML, but larger studies are needed.

Continuous-infusion cyclophosphamide in combination with teniposide and dexamethasone in refractory myeloma.

Forty-three consecutive patients with refractory myeloma, median age 60, received monthly courses of teniposide 30 mg/m2 i.v. on days 1-2, dexamethasone 40 mg i.v. on days 1-7 and cyclophosphamide 200 mg/m2 by continuous i.v. infusion for seven days. Major response (decrease > 50% of M-protein) was achieved in 18 of 37 evaluable patients and minor response in 9, with an overall response rate of 73%. Response was irrespective of disease status, time from diagnosis and previous treatments, while beta 2 microglobulin > 6 mg/l was a powerful prognostic factor. All patients experienced transient granulocytopenia but extramedullary toxicity was negligible. Median survival of the whole group is 20 months, with 74% of responding patients projected to be alive at 30 months. In refractory myeloma cyclophosphamide appears to be more active when given by continuous infusion.

Continuous-infusion cyclophosphamide plus vincristine, cytosine-arabinoside and prednisone for refractory acute lymphoblastic leukemia in adults.

BACKGROUND: Despite more aggressive salvage regimens, the prognosis of refractory acute lymphoblastic leukemia (ALL) is still poor. Hence, alternative approaches are warranted in heavily pretreated patients. Some studies suggest the enhancement of cyclophosphamide (CY) activity when given by continuous infusion. METHODS: To evaluate the effectiveness of this scheduling in refractory ALL, we treated 15 adult patients (4 primary resistant, 11 relapsed and refractory to salvage regimens) with a seven-day course of CY 350 mg/m2/day by continuous i.v. infusion, associated with vincristine, cytosine-arabinoside and prednisone. RESULTS: The median time for hematologic recovery was 18 days, with negligible extramedullary toxicity. Two patients died while aplastic, 3 were non responders, 10 (66%) achieved complete remission after the first cycle. The response duration ranged from 5 to 32 (median 14) weeks, and the median survival of responders was 23 weeks. It is noteworthy that half of the responding patients had been resistant to prior CY in different schedules and other drug combinations. CONCLUSIONS: These data seem to confirm that CY exerts its best antineoplastic activity by continuous infusion.

Teniposide, dexamethasone and continuous-infusion cyclophosphamide in advanced refractory myeloma.

Twenty-one patients with advanced refractory myeloma (nine primary unresponsive to melphalan, 12 relapsed and resistant to first-line salvage therapy) received monthly 7 d courses of cyclophosphamide by continuous infusion, associated with teniposide and dexamethasone. Six patients died within 2 months from start of treatment, before receiving an adequate trial. Among the 15 evaluable patients, there were eight objective responses and three improvements (decrease of monoclonal protein greater than 50% or greater than 30%, respectively). After a median follow-up of 10 months, all responding patients are alive and none of them is still relapsed. In heavily pretreated patients, ineligible for more aggressive approaches, cyclophosphamide by continuous-infusion exerted a good antineoplastic activity without increasing toxicity.