Fatal immunopathogenesis by SIV/HIV-1 (SHIV) containing a variant form of the HIV-1SF33 env gene in juvenile and newborn rhesus macaques.

SIV/HIV-1 (SHIV) chimeric clones, constructed by substituting portions of the pathogenic molecular clone SIVmac239 with counterpart portions from HIV-1 clones, provide a means to analyze functions of selected HIV-1 genes in vivo in nonhuman primates. Our studies focused on SHIVSF33, which contains the vpu, tat, rev, and env genes of the cytopathic, T-cell line tropic clone HIV-1sf33 (subtype-B); this clone has a premature stop codon in the vpu gene. In three juvenile macaques inoculated intravenously with SHIVSF33, low-level persistent infection was established; no disease was observed for a period of >2 years. However, at approximately 16 months p.i., one of four SHIVSF33-infected juvenile macaques exhibited an increase in virus load, depletion of CD4(+) T cells in peripheral blood and lymph nodes, and other symptoms of simian AIDS (SAIDS). Virus recovered from this animal in the symptomatic stage was designated SHIVSF33a (A, adapted); this virus displayed multiple amino acid sequence changes throughout the HIV-1 env gene compared with the input SHIVSF33 clone. Additionally, a mutation in all clones from SHIVSF33a restored the open reading frame for the vpu gene. In vitro evaluations in tissue-culture systems revealed that SHIVSF33a replicated to higher levels and exhibited greater cytopathicity than SHIVSF33. Furthermore cloned env genes for SHIVSF33a were more fusogenic in a cell-fusion assay compared with the env gene of the SHIVSF33. Intravenous inoculation of SHIVsf33a into juvenile and newborn macaques resulted in a rapid decline in CD4(+) T cells to very low levels and development of a fatal AIDS-like disease. A cell-free preparation of this pathogenic chimeric virus also established persistent infection when applied to oral mucosal membranes of juvenile macaques and produced a fatal AIDS-like disease. These studies on pathogenic SHIVSF33a establish the basis for further investigations on the role of the HIV-1 env gene in virus adaptation and in mechanism(s) of immunodeficiency in primates; moreover, the chimeric virus SHIVSF33a can play a role in elucidating mucosal membrane transmission and development of antiviral vaccines in newborns as well as juvenile and adult macaques.     

Incidence of injury in elite junior Rugby Union: a prospective descriptive study

The high incidence of injury in Rugby Union is well documented, particularly at elite levels of competition. This article describes the incidence and nature of all injuries sustained by elite Western Australian junior Rugby Union players during the 26 weeks up to and including the 1997 National Championship campaign. Informed consent was gained for each participant (n = 44) prior to completion of an extensive baseline questionnaire. Exposure and injury data were collected at each training session and game. The injury incidence rate over the 26 week period was 13.26/1000 player hours. Injury data were analysed by phase of play, position, severity and if occurred at games or training. The incidence of injury was significantly associated with the position played (chi2 = 67.49, p value = 0.008) and the phase of play in which the injury occurred (chi2 = 8.07, p value = 0.042). Tackling was the most dangerous phase of play (52% of injuries) and the most common site of injury was the lower limb (37%). Most injuries occurred during games (56%) and the flanker was the position most at risk of injury (12%). Further research is needed to identify the aetiology of injury at all levels of competition and to use these findings to develop effective injury prevention strategies in this sport. Position-specific risk factors should also be investigated, as should the mechanism of injury associated with tackling which is the phase of play in which significantly more injuries occur in rugby.     

Avascular necrosis of the femoral head presenting as trochanteric bursitis.

Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Congenital midureteral obstruction

Congenital midureteral obstruction, caused either by a ureteral valve or stricture, is an exceedingly rare entity. When encountered, it is generally misdiagnosed as either primary megaureter or ureteropelvic junction obstruction, leading to a less than optimal surgical approach. Seven children with midureteral obstruction were seen over the past 17 years. Two of the patients presented with hydronephrosis on prenatal ultrasonography, and five with urinary tract infection. In only three was the diagnosis suspected on intravenous urography and voiding cystourethrography alone. Five of the seven cases had either antegrade or retrograde pyelography, prior to or at the time of their operative procedure, and in four of these a correct diagnosis was made. Notably, in five of the seven cases, recognition of the midureteral lesion prior to the surgical incision allowed the approach to be modified and a more appropriate technique (ureteroureterostomy) to be performed. The etiology of midureteral valve and stricture has been attributed to improper recanalization, insufficient vascular supply, or persistence of ureteral folds. Three of our patients had contralateral renal dysgenesis, suggesting an underlying ureteral bud abnormality.     

Osteomyelitis of the lower extremity: pathophysiology,imaging, and classification,with an emphasis on diabetic foot infection

Osteomyelitis is inflammation of the bone caused by an infectious organism, and is a difficult clinical problem. The pathophysiology, imaging, and classification of osteomyelitis are challenging, varying with the age of the patient (child versus adult), the chronicity of the infection (acute versus chronic), and the route of spread (hematogenous versus contiguous focus), as well as the immune and vascular status of the patient and affected region. The two most common classification schemes are those of Lew and Waldvogel, and Cierny and Mader. Brodie’s abscess is seen in subacute osteomyelitis, while sequestrum, involucrum, and cloaca are inter-related entities of chronic osteomyelitis. Imaging workup of suspected osteomyelitis should begin with radiographs, although MRI is the most accurate imaging test. Three patterns of T1 signal change have been described in the setting of suspected osteomyelitis including confluent intramedullary, hazy reticular, and subcortical. The confluent intramedullary pattern is most associated with osteomyelitis, while hazy reticular is rarely associated with hematogenous osteomyelitis, and subcortical is not associated with osteomyelitis. It can be challenging to differentiate neuropathic arthropathy from osteomyelitis. Osteomyelitis tends to involve a single bone subjacent to an ulcer or sinus tract. In contrast, neuropathic arthropathy tends to involve multiple bones of the midfoot. Subchondral cystic change, thin rim enhancement of a joint effusion, and the presence of intra-articular bodies are more indicative of a neuropathic joint without infection. Biopsy can play an important role in diagnosis and treatment of osteomyelitis.     

普鲁卡因选择性涂丝电极稳定性的研究

涂丝电极的应用已很广泛,但其稳定性差限制了它的进一步推广应用。本文找出普鲁卡因涂丝电极稳定性差的原因,制备了以聚乙烯醇(含盐酸普鲁卡因)为内参的Ag-Agcl丝涂(PVC)膜电极,其稳定性大为提高,并有良好的响应性能。     

Endoscopic KTP laser excision of severe tracheotomy-associated suprastomal collapse

OBJECTIVE: The purpose of this study was to investigate the feasibility, safety, and clinical utility of potassium-titanium-phosphate (KTP) laser bronchoscopy for excision of severe, obstructing tracheotomy-associated suprastomal collapse. METHODS: A retrospective review was performed of six children at a tertiary care children's hospital with severe tracheotomy-associated collapse of the suprastomal anterior tracheal wall cartilage, precluding decannulation. All subjects had undergone KTP laser endoscopic excision of the collapsed segment of suprastomal tracheal cartilage. Medical records were assessed for: (1) endoscopic demonstration of relief of suprastomal collapse, and (2) successful tracheotomy decannulation. RESULTS: All six patients had endoscopic evidence of relief of suprastomal airway obstruction after KTP laser therapy. Five of six (83%) subsequently underwent successful decannulation. There was one case of minimal thermal airway injury associated with a laser fire during use of the KTP laser, the effects of which were fortunately transient. CONCLUSIONS: KTP laser bronchoscopic excision of severe tracheotomy-associated suprastomal collapse: (1) is a feasible technique; (2) results in relief of suprastomal obstruction with subsequent successful decannulation in selected patients; and (3) avoids the need for more extensive open neck procedures. However, risks of KTP laser therapy are not negligible and strategies must be in place to minimize the occurrence of complications.     

The Accuracy of the ADOS-2 in Identifying Autism among Adults with Complex Psychiatric Conditions

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), Module 4 is considered a “gold-standard” instrument for diagnosing autism spectrum disorder (ASD) in adults. Although the ADOS-2 shows good sensitivity and specificity in lab-based settings, it is unknown whether these results hold in community clinics that serve a more psychiatrically impaired population. This study is the first to evaluate the diagnostic accuracy of the ADOS-2 among adults in community mental health centers (n?=?75). The ADOS-2 accurately identified all adults with ASD; however, it also had a high rate of false positives among adults with psychosis (30%). Findings serve as a reminder that social communication difficulties measured by the ADOS-2 are not specific to ASD, particularly in clinically complex settings.