The natural history of anterior cruciate ligament reconstruction using patellar tendon autograft

The purpose of this study was to review the results of ACL reconstruction using a patellar tendon graft placed ‘over the top’ plus a Macintosh lateral tenodesis, examining changes in knee laxity and functional status with increasing time. There were 74 patients operated on over an 11 year period, and divided into four groups for analysis according to postoperative time. There was a significant and progressive increase in side-to-side laxity difference with time, although functional status did not change significantly, indicating a lack of correlation between objective clinical tests and subjective findings. The highest Lysholm, Tegner and IKDC scores were at 4–5 years after operation, when 60% of patients were at their pre-injury level of sports activity. However, there was always a very significant difference between actual and desired Tegner activity levels for the group as a whole. While there was a significant correlation between degenerative changes and the time between injury and reconstruction, there was no correlation with postoperative time: this provides evidence that ACL reconstruction can protect the knee from later degeneration.     

Quantitation of HIV-1 by real-time PCR with a unique fluorogenic probe

Quantitation of HIV-1 specific RNA and DNA is pivotal to understanding the pathophysiology of HIV-1 diseases. A method has been developed for quantitation of HIV-1 DNA/RNA by real-time PCR using a unique fluorogenic primer-probe adduct known as scorpion. The probe hybridises to the extension of the adjoining primer intramolecularly, a process kinetically and thermodynamically more favourable than the conventional bimolecular probe-target hybridisation. Data presented in this paper indicate that the scorpion assay is extremely robust and is quite comparable to beacon-based assays. The scorpion assay is also comparable to quantitative competitive PCR (QC--PCR) assays but requires only a fraction of time and effort. Additionally, the dynamic range of the scorpion assay is several log-fold higher than the conventional end point PCR assays. As few as ten copies of vDNA can be detected in the presence of a large excess of exogenously added genomic DNA. Limiting dilution analysis indicates that the assay is capable of detecting a single copy of the viral template. Thus, the scorpion assay presents a specific and sensitive approach for quantitation of DNA/RNA templates by real-time PCR.     

Interleukin-2 diphtheria fusion protein (dab486il-2) in refractory rheumatoid arthritis a double-blind,placebo-controlled trial with open-label extension

Objective. This pilot phase II, double-blind, placebo-controlled trial of 1 month duration, with a 2–3-month open-label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin-2 diphtheria fusion protein (DAB₄₈₆IL-2) in refractory rheumatoid arthritis (RA). Methods. Forty-five RA patients were enrolled in the trial, and were randomized, after a 3–4-week diseasemodifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB₄₈₆-IL-2 or placebo (saline) for 5 days. A blinded, third-party observer evaluated arthritis activity. Clinical response was defined as ≥25% improvement in swollen and tender joints and ≥25% improvement in at least 2 of 6 additional parameters. The double-blind phase was 4 weeks; placebo patients could cross over to receive open-label treatment for a maximum of 3 monthly DAB₄₈₆IL-2 cycles. Results. In the double-blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open-label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB₄₈₆IL-2, respectively. Adverse events included transient fever/chills (45%), nause/vomiting (50%), elevated (≥13x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB₄₈₆IL-2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB₄₈₆IL-2-treated versus placebo-treated patients. Conclusion. Clinical responses were noted in patients treated with DAB₄₈₆IL-2 (18%) compared with placebo (0%) in the double-blind phase. In the open-label phase, 33% of patients completing 3 monthly DAB₄₈₆IL-2 cycles had improvement in arthritis activity. Further studies of IL-2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action.     

Use of a chimeric monoclonal anti-CD4 antibody in patients with refractory rheumatoid arthritis

Objectives. To evaluate the safety, immunogenicity, and biologic effects of chimeric monoclonal anti-CD4 (cM-T412) in patients with refractory rheumatoid arthritis (RA), and to obtain preliminary data on the clinical response to this treatment. Methods. Twenty-five patients with active refractory RA were treated with incremental doses (10 to 700 mg) of cM-T412 in an open-label, escalating-dose phase I trial. Results. Infusion with cM-T412 was followed by an immediate, rapid decline in CD4+ T cells. The level of circulating CD4+ T cells remained depressed in most patients even at 6 months posttreatment. Following antibody infusion, proliferative responses of peripheral blood lymphocytes to mitogens and antigens were determined; mitogen and antigen responses were decreased compared with pretreatment responses. Mitogen responses tended to return to baseline values more rapidly than did responses to antigen. Adverse events included fever (19 patients), which was associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self-limited and appeared to correlate with transient elevations in interleukin-6. No significant human antibody response to the cM-T412 variable region was detected; only 2 patients developed transiently low levels of antibodies reactive with cM-T412. Significant clinical improvement, defined as ≥50% decrease in tender joint counts compared with baseline, was noted in 43% of patients at 5 weeks and 33% at 6 months following cM-T412 infusion. Conclusions. Treatment of refractory RA with cM-T412 appears to be safe and is associated with sustained decreases in circulating CD4+ T cell counts and depressed in vitro T cell responses. No significant human antichimeric antibody response was detected. Nonblinded assessment of clinical end points suggests that treatment with cM-T412 may have beneficial effects in these patients with refractory RA. A double-blind clinical trial is warranted to determine its clinical efficacy in treating RA.     

Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand- 1

Leukocyte rolling, an early and important step in the inflammatory response, is mediated by the selectin family of adhesion molecules. The selectins bind with low affinity to sialylated and fucosylated glycans such as sialyl Lewisx (sLex), but bind with high affinity to only a few specific glycoproteins on cell surfaces. One such glycoprotein is P- selectin glycoprotein ligand-1 (PSGL-1). The relative contributions of low- and high-affinity ligands to leukocyte rolling in vivo are unknown. We show here that a monoclonal antibody to PSGL-1 (PL1) dramatically reduces rolling of human polymorphonuclear neutrophils (PMN) and promyelocytic HL-60 cells in venules of acutely exteriorized rat mesentery. Control PMN and HL-60 cell rolling flux fractions were 39% +/- 3% and 33% +/- 5%, which were reduced by PL1 to 7% +/- 2% and 6% +/- 2%, respectively. Similar reductions were seen with F(ab) fragments of PL1. PL1-treated PMN rolled at significantly higher mean velocities than untreated PMN owing to intermittent rather that continuous interactions. These findings show that interaction of P- selectin with PSGL-1 is required for rolling of myeloid cells in mesenteric venules at physiologic shear stress in vivo.     

Spinal extradural cyst and kyphosis dorsalis juvenilis

Kyphosis dorsalis juvenilis is a not uncommon disease, the etiology of which is entirely unknown. Extradural cysts of the spinal cord which give rise to symptoms during adolescence are almost always associated with deformities of the thoracic spine, usually a kyphosis of this type. The association of these two conditions was first drawn to our attention by the following case. The recognition of this association is of value, not only because of its aid in the diagnosis and prompt treatment of these benign cysts, but also because of the light which it throws upon the etiology of the commoner kyphosis dorsalis juvenilis not associated with such cysts.     

In-bath filming during extracorporeal shock wave lithotripsy

Extracorporeal shock wave lithotripsy (ESWL) is now the preferred method for treating most renal calculi. We designed a cassette and grid holder and a technique for filming in the water bath. The excellent film quality permits initial localization of small or faint calculi and confirmation of satisfactory fragmentation during ESWL. The technique facilitates patient treatment and throughput and should reduce the repeat treatment rate.