Identification of a long variant of mRNA encoding the NR3 subunit of the NMDA receptor: its regional distribution and developmental expression in the rat brain

A longer variant of rat mRNA encoding the NR3 subunit of the NMDA receptor has been identified. It contains a 60-bp insertion at the nucleotide position 3007 in the intracellular domain of the C-terminal of the previously cloned variant. Therefore, the NR3 mRNA exists in at least two variants--with the insert (NR3-long; NR3-l) and without the insert (NR3-short; NR3-s). The NR3-l variant is expressed throughout the adult rat brain. Moreover, this variant predominates in the occipital and entorhinal cortices, thalamus and cerebellum. Analysis of NR3-l development indicates that it is regulated in a region-specific manner.     

Right ventricular infarction during left ventricular assist system support

Clinical and pathologic findings are presented of the first reported case in the English-language medical literature of pseudomesotheliomatous adenocarcinoma (PMA) occurring in an HIV-infected patient. PMA is an uncommon variant of peripheral lung cancer which typically occurs in elderly male patients. It mimics a malignant mesothelioma in terms of its clinical presentation and gross and microscopic appearance. The occurrence of this rare tumor in a young HIV-infected patient suggests some association between HIV infection and the development of PMA.     

Can we change physicians'' practices in the delivery of cancer-preventive services?

We have evaluated the susceptibility of 199 pathogens isolated in pure culture from consecutive urine samples submitted from the community. Rates of susceptibility for all organisms were ampicillin, 48%; amoxycillin/clavulanic acid, 88%; cephalothin, 57%; cefuroxime axetil, 74%; nalidixic acid, 85%; ciprofloxacin, 99%; nitrofurantoin, 78%; and trimethoprim, 67%. Ciprofloxacin resistance and production of extended spectrum beta-lactamase enzymes were detected in Escherichia coli strains isolated from patients in the community.     

Three-dimensional reconstruction techniques applied to intracoronary images

In recent years, systems for the three-dimensional (3-D) reconstruction of intravascular ultrasound (IVUS) images have been developed. As a major advantage over conventional two-dimensional IVUS, 3-D IVUS offers longitudinal views of the reconstructed segments and provide more comprehensive insight into the spatial distribution of vascular structures. The present article is an overview of current 3-D reconstruction techniques. In particular, we discuss the sequence of basic steps required to obtain a 3-D reconstruction: IVUS image acquisition, digitization, segmentation and reconstruction. We also illustrate the different systems of 3-D reconstruction that are currently available. Some of them can be used on-line during surgical procedures, while others are more suited for off-line applications and are useful research tools.     

Radical prostatectomy for localized prostatic carcinoma in a renal transplant patient

A case of multiple pyogenic granuloma affecting the penis of a 28 year old man is reported. The lesions were arranged in a floret-like fashion around the inner aspect of the prepuce and developed after circumcision for congenital phimosis. Histopathological examination of sections from a biopsy specimen of the papillomatous growths revealed the findings of pyogenic granuloma. In this patient, the pathogenesis of the lesions is probably related to the failure in surgical wound repair that followed circumcision. Problems of clinical and histopathological differential diagnosis are discussed.     

Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation

Ninety-five patients undergoing an allogeneic bone marrow transplant (BMT) and developing acute graft-versus-host disease (aGvHD) were randomized to receive low-dose intravenous 6-methylprednisolone (6MPred; 2 mg/kg /d; n = 47) or high-dose 6MPred (10 mg/kg/d; n = 48) for 5 days, with subsequent tapering doses. On day 5 patients not responding or progressing on low-dose 6MPred could be switched to high-dose 6MPred. All patients, aged 1 to 55 years, were recipients of unmanipulated BMT from HLA identical sibling donors. Patients were stratified at randomization for age (/= 20 years), disease (acute leukemia, chronic myeloid leukemia [CML], nonneoplastic disease), disease status (early/advanced), and GvHD prophylaxis (cyclosporin/cyclosporin + methotrexate). Primary endpoints were response to treatment and evolution of aGvHD to grade III-IV. Secondary endpoints were cytomegalovirus (CMV) infections, transplant-related mortality (TRM), and relapse. The median interval between BMT and treatment was 12 days (6 to 43). Results in the two groups (2 v 10 mg/kg) were as follows: response of aGvHD 68% versus 71% (P = .9), evolution to aGvHD grade III-IV 17% versus 20% (P = . 6), CMV infections 55% versus 60% (P = .7), 3-year actuarial TRM 28% versus 32% (P = .7), relapse 17% versus 7% (P = .1). The actuarial survival at 3 years was 63% versus 62% (P = .9) with a median follow up of 580 and 778 days. On day 5 of therapy, 26 patients assigned to low-dose (2 mg/kg) 6MPred were switched to a higher dose of 6MPred because of no response or progression. Their actuarial TRM was 46%, which is significantly higher than TRM of patients who responded on 2 mg/kg and continued with tapering doses (TRM = 16%, P = .007). In conclusion, early treatment of acute GvHD with 6MPred 10 mg/kg/d does not improve the response rate as compared with 2 mg/kg/d, nor does it prevent evolution to aGvHD grade III-IV. CMV infections, TRM, and survival were also comparable. A group of patients at high risk of TRM can be identified after 5 days of treatment with 6MPred 2 mg/kg and could be eligible for alternative forms of therapy.     

Plasmin enzyme-assisted vitrectomy in traumatic pediatric macular holes

OBJECTIVE: This study aimed to evaluate the benefit of plasmin enzyme-assisted macular hole surgery on a consecutive series of pediatric patients with traumatic macular holes. DESIGN: Prospective noncomparative case series operated on at William Beaumont Hospital between July 13, 1996, and November 16, 1996, and observed for at least 6 months. PARTICIPANTS: During this interval, the authors operated on four eyes from four consecutive patients who were 14 years of age or younger with traumatic macular holes. INTERVENTION: The patients underwent plasmin enzyme-assisted pars plana vitrectomy with membrane peeling, fluid-gas exchange, and postoperative positioning. The enzyme used was 0.4 international unit (IU) of autologous plasmin enzyme. MAIN OUTCOME MEASURES: Snellen lines of improvement in visual acuity and rate of final visual acuity of 20/40 or greater, and incidence of complications and reoperations were measured. RESULTS: All four macular holes were closed successfully. Follow-up was from 6 to 12 months. There were no reoperations. Visual acuity improved from four to eight lines in all eyes. Three eyes (75%) achieved a postoperative visual acuity of 20/40 or better. Three eyes (75%) had transient, posterior, subcapsular cataracts develop: two of the eyes after surgery and one as a result of the initial injury. CONCLUSION: The treatment of pediatric traumatic macular holes with plasmin enzyme-assisted vitrectomy, membrane peeling, and gas-fluid exchange resulted in closure of the macular holes with significant visual improvement.     

Glutamate modulation of dendrite outgrowth: alterations in the distribution of dendritic microtubules

Glutamate can both facilitate and inhibit dendrite outgrowth in vitro. The major effects of low levels of glutamate occur only on the dendrites (not the axon) of pyramidal neurons and may be important for modulating dendrite outgrowth during neuronal development in vivo. Cytoskeletal changes resulting from glutamate exposure must underlie these changes in dendrite outgrowth. In the present study, hippocampal neuron cultures were used to measure the outgrowth of both axons and immature dendrites in the presence or absence of 50 microM glutamate. Subsequently, neurons were extracted and fixed for immunofluorescent labeling of microtubules and rhodamine phalloidin labeling of microfilaments. Additionally, neurons were prepared for electron microscopy to examine dendritic microtubules at the ultrastructural level. Glutamate led to increased dendrite outgrowth in the short term (4 hr) and dendrite retraction in the long term (8 hr). After short-term glutamate exposures, no obvious morphological changes occur in either the microtubules or microfilaments. However, longer glutamate exposure causes a decrease in the number of microtubules in the distal region of retracting dendrites, and causes an increase in microtubule number in the dendritic shaft of both retracting and growing dendrites. Thus, the microtubule cytoskeleton may be involved in producing the changes in dendrite outgrowth caused by glutamate exposure.     

Engraftment of HLA-matched sibling hematopoietic stem cells after immunosuppressive conditioning regimen in patients with hematologic neoplasias

BACKGROUND AND OBJECTIVE: The main objective of this pilot study was to assess the possibility of achieving engraftment of HLA-matched sibling donor mobilized hematopoietic stem cells after immunosuppressive non-myeloablative therapy. The second objective was to verify whether high-dose therapy with autologous stem cells rescue followed by allografting conditioned by only an immunosuppressive regimen, can be combined in order to achieve the reduction of tumor burden after autografting and the control of residual disease with immune-mediated effects after allografting. DESIGN AND METHODS: To enter the pilot study the patients had to fulfil the following criteria: advanced resistant disease, presence of an HLA matched sibling donor, no general contraindications to stem cell transplantation. Our data refers to 9 patients: Hodgkin's disease (n = 4), non-Hodgkin's lymphoma (n = 2), advanced chronic myelogenous leukemia (n = 2) (one patient with accelerated phase Ph-negative but p190 BCR-ABL gene positive by RT-PCR and one with Ph-positive blastic phase), refractory anemia with excess of blasts t(1;3) (p36;q21) (n = 1). All patients but one received the combined approach. At a median of 40 days (range 30-96), after high-dose therapy and autologous stem cell engraftment, the patients were treated with immunosuppressive therapy consisting of fludarabine and cyclophosphamide (Flu-Cy protocol) and then HLA matched donor mobilized stem cells were infused into the patients. GvHD prophylaxis consisted of cyclosporin and methotrexate. RESULTS: To date, with a median observation period of 4 months (range, 2-10), complete chimerism (100% donor cells) has been achieved in 6 patients. Three patients did not achieve complete chimerism: one patient died of progressive Hodgkin's disease when he reached 55% of donor cells, another patient is now in increasing phase of donor cell engraftment and the last patient (blastic phase-CML) was the only case who appears to have had autologous recovery. Two of the Hodgkin's disease patients, who were in partial remission after autografting, achieved complete remission after allografting and both are disease free 2 and 6 months after. Another Hodgkin's disease patient is alive at 10 months but she has progressive disease. One of the two patients with non-Hodgkin's lymphoma, who achieved partial remission after autografting, obtained complete remission and he is disease free 2 months after allografting. The other patient maintains partial remission obtained after autografting. The accelerated phase-CML patient obtained hematologic and molecular remission; the RAEB patient achieved hematologic and cytogenetic remission. In two patients severe aGVHD (grade II-III) was the single major complication but neither patient died of it. Mild aGVHD was seen in another patient. In only one patient did the ANC decrease to below 1 x 10(9)/L and in no case did platelets decrease below 20 x 10(9)/L. No patients required a sterile room or any red cell or platelet transfusions. INTERPRETATION AND CONCLUSIONS: Immunosuppressive therapy with a Flu-Cy protocol allowed engraftment of HLA-matched sibling donor stem cells without procedure-related deaths; moreover, we have demonstrated that this combined procedure can be pursued in safety in a serious ill population and some of these patients achieved a complete remission. This procedure is not likely to be curative, but a fascinating step along the path to curing these diseases. Of course, the follow-up is too short to document the incidence of cGvHD.