Bacteria-eradicating therapy for ocular adnexal MALT lymphoma: questions for an open international prospective trial.

We read with great interest the article by Grünberger etal. on the ‘blind’ administration of doxycyclinein a retrospective series of 11 patients with ocular adnexallymphoma of MALT-type (OAL) [1]. Authors used this therapy onthe basis that, in the Italian experience [2], most cases ofOAL were shown to be related to chlamydial     

Clinical implications of hepatitis C virus infection in MALT-type lymphoma of the ocular adnexa.

BACKGROUND: A pathogenic link between hepatitis C virus (HCV) and MALT-type lymphomas has been suggested. However, studies assessing the role of HCV infection separately in different forms of MALT lymphomas are not available. PATIENTS AND METHODS: The prevalence and clinical implications of HCV seropositivity were analyzed in 55 patients with ocular adnexa lymphoma (OAL) of MALT-type. RESULTS: HCV seropositivity was detected in seven (13%) patients. At presentation, HCV infection was significantly associated with concomitant extra-orbital disease, lymph node dissemination and involvement of additional extranodal organs. HCV seropositivity was associated also with a higher relapse rate and worse progression-free survival. In fact, 16 patients experienced relapse after first-line treatment: five (71%) were HCV-seropositive and 11 (23%) were HCV-seronegative, with a median TTP of 31 and 50+ months (P = 0.01), and a 5-year progression-free survival of 43 +/- 18% and 77 +/- 7% (P = 0.005), respectively. HCV-seropositive patients experienced frequent relapses despite further lines of therapy; relapses were systemic in all cases but one; multiple subcutaneous nodules were common at relapse. CONCLUSIONS: HCV seropositivity is present in 13% of OAL of MALT-type. Concomitant HCV infection is associated with more disseminated disease and aggressive behavior in OAL, with a consequent potential negative impact in patients managed with radiotherapy alone.     

In vitro inhibition of promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) expression and leukemogenic activity by DNA/LNA chimeric antisense oligos

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by the chromosomal translocation t(15:17) that leads to the expression of promyelocytic leukemia/retinoic acid receptor-alpha (PML/ RARalpha) oncofusion protein. The block of differentiation at the promyelocytic stage of the blasts and their increased survival induced by PML/RARalpha are the principal biological features of the disease. Therapies based on pharmacological doses of retinoic acid (RA, 10(-6) M) are able to restore APL cell differentiation in most cases, but not to achieve complete hematological remission because retinoic acid resistance occurs in many patients. In order to elaborate alternative therapeutic approaches, we focused our attention on the use of antisense oligonucleotides as gene-specific drug directed to PML/RARalpha mRNA target. We used antisense molecules containing multiple locked nucleic acid (LNA) modifications. The LNAs are nucleotide analogues that are able to form duplexes with complementary DNA or RNA sequences with highly increased thermal stability and are resistant to 3'-exonuclease degradation in vitro. The DNA/LNA chimeric molecules were designed on the fusion sequence of PML and RARalpha genes to specifically target the oncofusion protein. Cell-free and in vitro experiments using U937-PR9-inducible cell line showed that DNA/LNA oligonucleotides were able to interfere with PML/RARalpha expression more efficiently than the corresponding unmodified DNA oligo. Moreover, the treatment of U937-PR9 cells with these chimeric antisense molecules was able to abrogate the block of differentiation induced by PML/RARalpha oncoprotein. These data suggest a possible application of oligonucleotides containing LNA in an antisense therapeutic strategy for APL.     

The role of 99mTc-tetrofosmin scintigraphy for staging patients with laryngeal cancer

Diagnosis and staging of laryngeal cancer is currently based on physical examination, endoscopy, and imaging techniques such as computed tomography (CT) and/or magnetic resonance (MR) and histology. While imaging techniques have a pivotal role for defining the size of the primary tumor, they are less accurate for defining metastatic involvement of regional lymph nodes, especially if lymph nodes are smaller than 10-15 mm. The aim of this study was to comparatively assess the relevance of (99m)Tc-tetrofosmin scintigraphy for the staging of laryngeal tumors versus the CT scan. We evaluated the sensitivity of imaging with (99m)Tc-tetrofosmin in 28 consecutively enrolled patients with squamous cell laryngeal carcinoma. Total-body scintigraphy with 99mTc-tetrofosmin was performed preoperatively, and the results were compared to CT images of the neck and mediastinum. CT and (99m)Tc-tetrofosmin scintigraphy were equally sensitive (96%) in identifying the primary tumor. While CT was more sensitive for detecting metastatic lymph nodes (100% versus 50%), (99m)Tc-tetrofosmin scintigraphy was more specific (100% versus 56%; p < 0.04). The overall diagnostic capabilities of the two techniques for detecting lymph node metastases were comparable (Youden Index: J = 0.56 for CT and J = 0.50 for (99m)Tc-tetrofosmin scintigraphy). (99m)Tc-tetrofosmin scintigraphy is a useful complement to CT for staging laryngeal tumors, especially for detecting metastatic lymph nodes and distant metastases.     

Mechanical comparison of two types of fixation for proximal first metatarsal crescentic osteotomy

BACKGROUND: The proximal crescentic osteotomy is an effective technique for correcting a widened 1-2 intermetatarsal angle associated with moderate to severe hallux valgus deformities. However, postoperative dorsal malunion at the osteotomy site from loss of fixation has been reported. The purpose of this study was to evaluate the biomechanical characteristics of a new custom-designed plate and compare it to the traditional screw and Kirschner wire construct. METHODS: Twenty identical Sawbone (Pacific Research Laboratories, Vashon, WA) models were used for the study. A proximal crescentic osteotomy was done on each specimen, and 10 were secured with a dorsomedial plate (group I). The remaining 10 models were fixed with a screw and Kirschner wire combination (group II). Physiologic cyclical testing was done using a mechanical testing machine to evaluate dorsal displacement of the metatarsal. Load-to-failure testing was then done on each specimen to evaluate ultimate failure and stiffness of the constructs. Groups I and II were statistically compared using paired t-testing. RESULTS: The mean dorsal displacement of the first metatarsal head after 1000 cycles was 0.19 mm (SD = 0.09 mm) for group I and 0.28 mm (SD = 0.15) for group II, and the difference was not statistically significant (p = 0.08). Group I demonstrated statistically superior ultimate failure strength (95.2 N) and stiffness (26.8 N/mm) compared to group II (73.7 N, 19.4 N/mm). CONCLUSIONS: Based on Sawbone models, dorsal plate fixation of proximal crescentic osteotomy provides a stronger construct than the traditional screw and Kirschner wire construct. The clinical use of the specially-designed plate described in this study may lower the incidence of dorsal malunions that occur postoperatively and may decrease the occurrence of transfer metatarsalgia. Its application may be particularly helpful in patients with poor bone quality.     

Intragastric nitric oxide is abolished in intubated patients and restored by nitrite

OBJECTIVE: Nitrite in saliva is reduced to nitric oxide (NO) in the acidic stomach, and this NO may serve gastroprotective functions. We studied intragastric NO levels in healthy controls and in intubated intensive care unit patients before and after supplementation with nitrite. DESIGN: Prospective observational study involving patients and controls. SETTING: A mixed intensive care unit and a university laboratory. PATIENTS AND SUBJECTS: Eight healthy volunteers and ten intubated, mechanically ventilated intensive care unit patients. INTERVENTIONS: A tonometric catheter was first evaluated in vitro and then used for all NO measurements. In fasting controls, gastric NO levels were measured repeatedly during periods of saliva depletion and after an intragastric nitrite infusion. In patients, changes in levels of intragastric NO, nitrite in plasma and gastric juice, and S-nitrosothiols in gastric juice were measured in response to an intragastric nitrite infusion. MEASUREMENTS AND MAIN RESULTS: The tonometric catheter had a recovery of 80% with a high intraclass and interclass correlation. Median baseline NO levels in healthy volunteers were 21.6 ppm (interquartile range, 11.4-22.3 ppm) and decreased by 90% to 3.3 ppm (2.0-5.2 ppm) during 25-50 mins of saliva depletion. The NO level was restored by an intragastric nitrite infusion. Baseline NO levels in patients were almost abolished (0.1 ppm [0.07-0.4 ppm]) but increased rapidly to 124 ppm (range, 65-180 ppm) during intragastric nitrite infusion. Nitrite levels in plasma increased from 0.18 +/- 0.03 to 1.3 +/- 0.2 microM (p < .01), and levels of S-nitrosothiols in gastric juice increased from 0.12 +/- 0.09 to 6.7 +/- 1.8 microM. CONCLUSIONS: Intragastric generation of NO requires continuous delivery of nitrite-containing saliva and is almost abolished in critically ill, intubated patients. Enteral supplementation with nitrite could however fully restore gastric NO levels. Future studies will reveal if low NO levels contribute to stress ulcers and gastric overgrowth of bacteria often seen in these patients and in turn if restoring gastric NO with nitrite could be a useful therapeutic approach.     

Rituximab in patients with mucosal-associated lymphoid tissue-type lymphoma of the ocular adnexa

Eight patients with ocular adnexal mucosal-associated lymphpid tissue (MALT) lymphoma were treated with rituximab, at diagnosis (n=5) or relapse (n=3). All untreated patients achieved lymphoma regression, while relapsing patients had no benefit. Four responding patients experienced early relapse. The median time to progression was 5 months. The efficacy of rituximab in ocular adnexal lymphoma is lower than that reported for gastric MALT lymphomas.     

Impaired clearance of microemboli and cerebrovascular symptoms during carotid stenting procedures

BACKGROUND: Transcranial Doppler monitoring shows a high prevalence of microemboli during carotid artery stenting (CAS); however, the occurrence of cerebrovascular symptoms (CVSs) does not seem to be related to the microembolic load. OBJECTIVE: To evaluate embolic and hemodynamic transcranial Doppler monitoring findings and their relationships with the occurrence of procedural CVSs. Patients Fifty-four patients who had carotid stenosis of more than 70% underwent a total of 57 CAS procedures during transcranial Doppler monitoring of mean blood flow velocity and microembolic signals in the middle cerebral artery. The occurrence of transient ischemic attack, transient monocular blindness, and stroke during the CAS procedure was considered CVSs. RESULTS: Nine (15.8%) of the 57 patients had CVSs during the procedure (ie, 6 patients with transient ischemic attack, 1 with transient monocular blindness, 1 with a minor stroke, and 1 with a major stroke). The mean blood flow velocity median values were statistically significantly lower (P < .001) in the group of 9 patients with CVSs (36 cm/s; interquartile range, 32.3-38.5) compared with the 48 without CVSs (48 cm/s; interquartile range, 41.5-52). The median number of isolated microembolic signals was similar in the 2 groups (72; interquartile range, 66-81 vs 75; interquartile range, 67-83.5). The median number of microembolic signal showers (clusters of too many signals to be counted separately in one cardiac cycle) presented a nonsignificant prevalence in the patients with CVSs (9; interquartile range, 7.5-11.2) compared with the ones without CVSs (8.2; interquartile range, 7-9). CONCLUSION: The low flow velocity in the middle cerebral artery may impair the clearance of the microembolic load and should be considered a precursor of CVSs during the CAS procedure.     

Staring at one side of the face increases blood flow on that side of the face

To investigate the effect of observation on blushing, an experimenter sat next to 28 participants and looked closely at one cheek while the participant sang (embarrassing) or read aloud (not embarrassing). Increases in cheek temperature were greater on the observed than the unobserved side during both tasks. Changes in cheek temperature were symmetrical when the experimenter sat next to another 23 participants and looked straight ahead, as well as when the experimenter stared at one side of the participant's face through a glass window while the participant sang. However, increases in cutaneous blood flow were greater on the observed than the unobserved side of the forehead during singing. These findings suggest that staring at one side of the face triggers an ipsilateral increase in facial blood flow.