Recognition of human T-leukemia virus (HTLV-1) envelope by human CD4+ T- cell lines from HTLV-1 seronegative individuals: specificity and clonal heterogeneity

Because T-helper cells are critical for immune responses in retroviral infections, CD4+ T-cell lines specific for the human T-leukemia virus type 1 (HTLV-1) envelope have been generated from peripheral T lymphocytes of nonimmune donors to study their naive repertoire. Recombinant fragments (RE1, amino acids [aa] 26-200; RE3, aa 165-307; RE5, aa 308-401; and RE6, aa 165-401) of HTLV-1 envelope, whole envelope glycoprotein, and synthetic peptides were used to induce T- cell lines. CD4+ T-cell lines specific for one or more fragments were obtained from seven of eight individuals tested. T-cell lines generated against envelope glycoprotein from five of five donors did not cross- react with the RE fragments and vice versa. The lines specific for RE and env were mapped with overlapping peptides. The lines with single peptide (narrow) specificity contained a variety of clones that used different T-cell receptor V beta genes. These data (1) suggest that most of the normal individuals carry T-helper precursors specific for epitopes on HTLV-1 envelope; (2) indicate that heterogeneity of HTLV-1 envelope-specific T cells can be detected in the naive repertoire; and (3) define optimal antigenic preparations to be used to assess cellular immunity in HTLV-1-infected individuals.     

Idiopathic megarectum in adults

Outlet obstruction is thought to be one of the major factors responsible for idiopathic constipation. However, outlet obstruction itself may be due to several mechanisms. Among these, the presence of a megarectum is a leading one. Pathophysiological studies in adult patients with idiopathic megarectum are scarce. We studied by manometric and defecographic means 15 adult subjects with idiopathic megarectum and severe chronic constipation. Twenty-five healthy volunteers of both sexes acted as controls. Manometric variables showed significant differences between patients and controls with respect to internal anal sphincter pressure (P=0.02), minimum relaxation volume (P<0.001), defecatory sensory threshold (P<0.001), mean rectal tolerable volume (P<0.001), and rectal compliance (P<0.001). An altered response to straining was observed in 46.6% of patients and in 12% of controls (P=0.04); the ability to expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P<0.001). Although all patients opened the anorectal angle and had descent of the pelvic floor, thereby confirming an adequate expulsion effort, evacuation of contrast material appeared extremely difficult. In fact, no subject was able to expel more than 30% of the rectal contents during fluoroscopic screening. These results confirm previous hypotheses that idiopathic megarectum displays features of a neuropathic process as an underlying mechanism. Further studies are needed that also take into consideration the muscle tone component of the rectum in these patients.     

Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group

We designed a multicenter randomized trial comparing chemotherapy with daunorubicin-Ara C (chemotherapy group) and all transretinoic acid (ATRA) combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients aged 65 years or less. The major endpoint of the study was event-free survival (EFS) ("events" being defined as failure to achieve complete remission [CR], occurrence of relapse, or death in CR). Early termination of the trial was decided after the first interim analysis, as EFS was significantly higher in the ATRA group. At the time, 101 patients had been randomized (54 in the ATRA group and 47 in the chemotherapy group). In the ATRA group, 49 (91%) patients achieved CR, 5 (9%) had early death, and 0 had resistant leukemia, compared with 38 (81%), 4 (8%), and 5 (10%) patients, respectively, in the chemotherapy group. The difference in CR rate between the two groups was not significant. The duration of coagulopathy was significantly reduced in the ATRA group, compared with the chemotherapy group. In the ATRA group, six patients relapsed after 7 to 15.5 months. In the chemotherapy group, 12 patients relapsed after 1 to 16 months, and 2 died in CR. Kaplan-Meier EFS was estimated at 79% +/- 7% and 50% +/- 9% at 12 months, respectively, in the ATRA and the chemotherapy group (P = .001). Kaplan-Meier estimate of relapse was 19% +/- 8% and 40% +/- 12% at 12 months (P = .005). In conclusion, ATRA followed by chemotherapy increases EFS in newly diagnosed APL. These results strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL.     

A technique to visualize wound bed microcirculation and the acute effect of negative pressure

Although previous studies have proved that subatmospheric pressure in vacuum assisted closure therapy increased blood flow at the wound edge, no reports have presented data on blood flow in the wound bed. This study examined a technique that visualized microcirculation of the wound bed and estimated the acute effect of negative pressure. The superficial stratum of the mouse gluteal skin was microsurgically excised preserving the subdermal vascular plexus. The preserved vessels were visualized as the wound bed microcirculation using an intravital microscope–video–computer system. Three levels of negative pressure (?125 mmHg [n=12], ?500 mmHg [n=12], 0 mmHg [n=8]) were applied to the wound. Our experimental model successfully and quantitatively visualized wound bed microcirculation under negative pressure application. A negative pressure of ?125 mmHg significantly increased wound bed blood flow immediately after pressure application, maintained for 1 minute after pressure release, whereas in the ?500 mmHg group blood flow decreased with time and reached a statistically significant level 5 minutes after pressure application. These findings reinforce the hypothesis that enhanced blood flow in the wound bed as well as at the wound edge may contribute to the beneficial effects of certain levels of negative pressure therapy for wound perfusion.     

Guidelines for the management of traumatic dental injuries. I. Fractures and luxations of permanent teeth

Crown fractures and luxations occur most frequently of all dental injuries. An appropriate treatment plan after an injury is important for a good prognosis. Guidelines are useful for delivering the best care possible in an efficient manner. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the current best evidence, based on literature research and professional opinion. In this first article of three, the IADT Guidelines for management of fractures and luxations of permanent teeth will be presented.