Dentomaxillofacial manifestations of Gaucher's disease: preliminary clinical and radiographic findings

Objectives

A wide variety of manifestations is presented in patients with Gaucher''s disease (GD), including bone, haematology and visceral disturbances. This study was conducted to ascertain the main maxillofacial abnormalities by means of clinical survey, panoramic and cone beam CT (CBCT); to compare the patient''s group with an age–sex matched control group; and to correlate clinical and radiological data.

Methods

Ten patients previously diagnosed with GD were submitted to clinical and radiological surveys (CBCT and panoramic radiographs). The examination consisted of anamnesis, extra- and intraoral examinations and analyses of each patient''s records. Imaging data were collected from the point of view of 3 observers, and the results compared with a healthy group (20 individuals) by means of statistical analysis (Fisher''s exact test).

Results

Gaucher patients had significantly more manifestations than otherwise healthy carriers. The most prevalent findings were enlarged marrow spaces, generalized osteopenia and effacement of jaw structures (mandibular canal, lamina dura and mental foramen). Here we describe a case in which thickening of the maxillary sinus mucosa was observed on CBCT rather than opacification of the sinus as seen on panoramic radiographs. Pathological fractures, root resorption and delay on tooth eruption were not observed.

Conclusions

A poor relationship could be observed between clinical and radiological data. Patients showed important bone manifestations, which require careful diagnostic and surgical planning whenever necessary. Although panoramic radiographs have shown significant differences, CBCT is more effective in pointing out differences between patients and a control group, thus showing it as an important tool for evaluation of Gaucher patients.     

Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B- cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.     

Determinants of patient and health care services delays for tuberculosis diagnosis in Italy: a cross-sectional observational study

Background

Prompt diagnosis of active tuberculosis (TB) has paramount importance to reduce TB morbidity and mortality and to prevent the spread of Mycobacterium tuberculosis. Few studies so far have assessed the diagnostic delay of TB and its risk factors in low-incidence countries.

Methods

We present a cross-sectional multicentre observational study enrolling all consecutive patients diagnosed with TB in seven referral centres in Italy. Information on demographic and clinical characteristics, health-seeking trajectories and patients’ knowledge and awareness of TB were collected. Diagnostic delay was assessed as patient-related (time between symptoms onset and presentation to care) and healthcare-related (time between presentation to care and TB diagnosis). Factors associated with patient-related and healthcare-related delays in the highest tertile were explored using uni- and multivariate logistic regression analyses.

Results

We enrolled 137 patients, between June 2011 and May 2012. The median diagnostic delay was 66?days (Interquartile Range [IQR] 31–146). Patient-related and healthcare-related delay were 14.5?days (IQR 0–54) and 31?days (IQR: 7.25–85), respectively. Using multivariable analysis, patients living in Italy for <?5?years were more likely to have longer patient-related delay (>?3?weeks) than those living in Italy for >?5?years (Odds Ratio [OR] 3.47; 95% Confidence Interval [CI] 1.09–11.01). The most common self-reported reasons to delay presentation to care were the mild nature of symptoms (82%) and a good self-perceived health (76%). About a quarter (26%) of patients had wrong beliefs and little knowledge of TB, although this was not associated with longer diagnostic delay. Regarding healthcare-related delay, multivariate analysis showed that extra-pulmonary TB (OR 4.3; 95% CI 1.4–13.8) and first contact with general practitioner (OR 5.1; 95% CI 1.8–14.5) were both independently associated with higher risk of healthcare-related delay >?10?weeks.

Conclusions

In this study, TB was diagnosed with a remarkable delay, mainly attributable to the healthcare services. Delay was higher in patients with extra-pulmonary disease and in those first assessed by general practitioners. We suggest the need to improve knowledge and raise awareness about TB not only in the general population but also among medical providers. Furthermore, specific programs to improve access to care should be designed for recent immigrants, at significantly high risk of patient-related delay.

Trial registration

The study protocol was registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT01390987. Study start date: June 2011.

     

Pretreatment hematocrit as an independent prognostic variable in Hodgkin's disease

Pretreatment hematocrit in 117 advanced-stage Hodgkin's disease patients treated with a combined modality therapy program was evaluated as an independent prognostic variable with regard to survival and relapse-free survival. Age greater than 40 years, and multiple extranodal sites of involvement were found to be statistically significant independent negative prognostic factors with regard to survival. Pretreatment hematocrit, however, was not an independent negative prognostic variable.     

Concomitant aortic valve replacement and surgical angioplasty of left main coronary ostium

The association of calcific aortic valve disease and isolated coronary ostial stenosis is rare. A 80-year-old woman was found to have severe aortic stenosis with critical narrowing of the ostium of the left main coronary artery. She was successfully managed by simultaneous aortic valve replacement and patch angioplasty of the left main coronary artery, using a patch of autologous pericardium fixed in glutaraldehyde. Angiographic control at 1 month coupled with intravascular echographic imaging showed adequate relief of the ostial stenosis and patency of the left main trunk.     

New England Medical Center Posterior Circulation Stroke Registry: I. Methods, Data Base, Distribution of Brain Lesions, Stroke Mechanisms, and Outcomes

Among 407 New England Medical Center Posterior Circulation Registry (NEMC-PCR) patients, 59% had strokes without transient ischemic attacks (TIAs), 24% had TIAs before strokes, and 16% had only posterior circulation TIAs. Embolism was the commonest stroke mechanism accounting for 40% of cases (24% cardiac origin, 14% arterial origin, 2% had potential cardiac and arterial sources). In 32%, large artery occlusive lesions caused hemodynamic brain infarction. Stroke mechanisms in the posterior and anterior circulation are very similar. Infarcts most often included the distal posterior circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes), while the proximal (medulla and posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Infarcts that included the distal territory were twice as common as those that included the proximal or middle territories. Most distal territory infarcts were attributable to embolism. Thirty day mortality was low (3.6%). Embolic stroke mechanism, distal territory location, and basilar artery occlusive disease conveyed the worst prognosis.     

Digital and conventional chest images: observer performance with Film Digital Radiography System

The Film Digital Radiography System (FilmDRS) is a device with a laser optical film digitizer, 2,000 X 2,000 X 12-bit memory, and a 1,000-line video display. To evaluate the adequacy of this device for general radiography of the chest, four readers independently analyzed both radiographs and the corresponding video display of the digitized chest images of 150 patients, consisting of 100 images of abnormalities and 50 normal images. The overall results indicate equal sensitivity for the two systems. The FilmDRS, with interactive windowing, proved superior in the detection of hilar and mediastinal disease. X-ray film was superior in allowing detection of hyperlucent states. There was equivalent sensitivity for other disease categories. Superior specificity was achieved with conventional radiographs.