Autoantibodies against alanyl-tRNA synthetase and tRNAAla coexist and are associated with myositis.

The sera of six patients with autoimmune disease, predominantly myositis with pulmonary fibrosis, contain antibodies of the PL-12 specificity. These autoantibodies react with both protein and RNA components of human cells. The protein has a subunit molecular mass of 110 kD, and the RNA comprises a group of bands in the tRNA size class. Aminoacylation experiments identify the antigens as alanyl-tRNA synthetase and its corresponding tRNAs, tRNAAla. Anti-tRNA antibody can be absorbed out without depleting antisynthetase activity, showing that the antigens are recognized independently by separable antibodies that coexist in these sera. The concurrence of separate antibodies to the two components suggests that the autoimmune response may be mounted against the charging enzyme-tRNA complex. However, the antisynthetase antibody fails to coprecipitate tRNA with the enzyme, suggesting that the antibody reacts with its target only when it is not complexed with tRNA.

Anti-threonyl-tRNA synthetase, a second myositis-related autoantibody.

An autoantibody known as PL-7 was found in the serum of four patients with myositis and one with a systemic lupus erythematosus-like syndrome. The PL-7 antigen is an 80,000 dalton polypeptide that coprecipitates with transfer RNA. In aminoacylation reactions, PL-7 IgG inhibited the charging of tRNA with threonine but had little or no effect on charging with other amino acids. Experimental antibodies raised against purified threonyl-tRNA synthetase recognized the same 80,000 dalton polypeptide, but tRNA was not coprecipitated. We conclude that PL-7 antibody is directed at threonyl-tRNA synthetase, and that different antigenic sites are recognized by the human and experimental autoantibodies. Our findings emphasize the link between myositis and autoimmunity to tRNA-related structures.

A human monoclonal antimelanoma single-chain Fv antibody derived from tumor-infiltrating lymphocytes.

With the development of recombinant DNA technology, it has become feasible to clone, construct, and express fully human immunoglobulin molecules. Here we report a novel methodology to make human antitumor single-chain Fv (scFv) antibodies from tumor-infiltrating B lymphocytes. We isolated and expanded tumor-infiltrating B lymphocytes from melanomas in the presence of Epstein-Barr virus. The transformed B cells secreting tumor-specific antibodies were identified and cloned by limiting dilution. From one B cell clone with specific melanoma reactivity, we captured the immunoglobulin variable region genes VH and Vk by PCR, sequenced the genes, and linked them together by PCR assembly with the use of a (Gly4Ser)3 linker. The scFv gene was then cloned into the pET21d vector and expressed. The obtained scFv protein with a M(r), of 29,000 was purified and biotinylated for further characterization. The scFv demonstrated specific tumor reactivity to 21 of 24 different melanoma cell lines and not to 14 nonmelanoma tumor cell lines, such as breast, ovarian, and colon cancer cells lines; normal human melanocytes as well as normal human leukocytes. These results were obtained in (a) a tumor cell ELISA, (b) fixed cell immunofluorescence, and (c) live cell flow cytometry. The immunoprecipitation results indicated that a protein antigen of M(r) 45,000 was recognized by the scFv. Since we reported previously that about 70% of human tumors of different histological types contain tumor-infiltrating B lymphocytes producing specific antitumor antibodies, this approach offers a rapid, effective method by combining in vitro B-cell expansion and PCR gene cloning to elucidate the repertoire of the human antitumor immune response and to make human monoclonal antitumor antibody molecules.

Use of an automated device for alternative site blood glucose monitoring.

OBJECTIVE: To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site. RESEARCH DESIGN AND METHODS: These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device. RESULTS: Blood glucose results in samples obtained from the arm with the automated device agreed well with finger-stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was "painless;" another 31% of the patients stated that it was "much less painful," and 6% of patients considered using the device "less painful" than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5. CONCLUSIONS: The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing.

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome.

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl.

The clinical and laboratory features of 32 patients with anti-PM-Scl were studied. Patients with this rare autoantibody suffered from a homogenous overlap connective tissue disease defined by Raynaud phenomenon (32/32), features of scleroderma (31/32), arthritis (31/32, erosive in 9/32), myositis (28/32), lung restriction (25/32), calcinosis (15/32), and sicca (11/32). Significant renal and neurologic involvement was uncommon. All patients examined (22/22) had HLA-DR3, and 50% of these patients were homozygous. Our patients responded favorably to moderate immunosuppression and, with therapy, the disease generally has a good prognosis; over 50% of our series (17/32) remained well on minimal or no immunosuppression after a median follow-up of 8 years.

Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.

A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.

Assessment of platelet function in patients with Raynaud's syndrome.

Platelet function was studied in 11 patients with Raynaud's syndrome and 11 healthy controls. Platelets obtained from patients with Raynaud's syndrome were significantly more responsive to adrenaline, produced more thromboxane A2, and were resistant to prostaglandin inhibitors (prostacyclin and prostaglandin E1) of platelet aggregation. Platelets from control subjects and patients with Raynaud's syndrome were more resistant to prostaglandin inhibitors when reactions were carried out at 27 degrees C rather than at 37 degrees C. Patients with Raynaud's syndrome also had significantly increased plasma concentrations of beta-thromboglobulin, fibrinogen, and circulating platelet aggregates. In an attempt to elicit local platelet responses, the forearms of control subjects and patients with Raynaud's syndrome were cooled in water tanks and platelet function tests performed before and after cooling. No significant difference in the results was observed. The potential role of platelets in the pathogenesis of Raynaud's syndrome is discussed.

Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects.

The effect of obesity on the relationship between very low density lipoprotein (VLDL)-triglyceride (TG) production rate and concentration was studied in 80 subjects whose TG concentrations ranged from 41-1315 mg/100 ml and whose relative weight varied from 0.74-1.46. There was a positive correlation between VLDL-TG production rate and plasma TG concentration in all 80 patients (r = 0.78), which was highly statistically significant (p less than 0.001). Both male and female subjects were subdivided into quartiles on the basis of relative weight; the relationship between VLDL-TG production rate and plasma TG concentration was found to be comparable in all subgroups. These observations suggest that moderate degrees of obesity do not affect VLDL-TG kinetics in patients whose plasma TG levels vary over an extremely wide range.

Acemetacin in the long-term therapy of rheumatoid arthritis.

An open label study was carried out to assess the long-term use of acemetacin in patients suffering from rheumatoid arthritis. One hundred and two patients were treated with acemetacin, some patients for up to a 12-month period. Analysis of efficacy showed that acemetacin therapy was associated with statistically significant sustained improvements in the target variables of duration of morning stiffness, Ritchie articular index and left and right grip strength. With regard to tolerability, a number of adverse events were recorded but were generally reported as either mild or moderate. In total, 28,988 patient days' treatment with acemetacin were completed and acemetacin proved an effective and well-tolerated long-term therapy in patients with rheumatoid arthritis.

A comparative trial of a controlled-release formulation of ketoprofen ('Oruvail') and a conventional capsule formulation of ketoprofen ('Orudis') in patients with osteoarthritis of the hip.

An open study was carried out in 46 patients with osteoarthritis of the hip to compare the efficacy and tolerance of treatment with ketoprofen given either as 100 mg capsules twice daily or as 2 capsules of 100 mg ketoprofen in a controlled-release formulation given once daily. The results of subjective and objective assessments before and during 3-months' treatment in the 48 patients who completed the trial showed both treatments produced improvement in all parameters, except for the time taken for inactivity stiffness to develop, and there was no significant difference between treatments in terms of efficacy. The controlled-release preparation, however, was significantly better tolerated than the ordinary capsule form. Minor haematological and biochemical changes during treatment were noted but these were not of clinical importance. Six patients, 2 receiving the controlled-release and 4 receiving the ordinary formulation of ketoprofen, were withdrawn because of lack of efficacy or unacceptable side-effects.

Injections and surgical therapy in chronic pain.

OBJECTIVE: The purpose of this review was to determine how effective surgery and injection therapy are in the management of chronic pain. METHODOLOGY: A standardized literature search identified seven systematic reviews of the literature and six randomized controlled trials to provide evidence about surgery and injection therapy for chronic pain. RESULTS: Some study subjects had highly specific diagnoses, whereas other study subject groups had nonspecific pain, including multiple conditions. The timing of treatment interventions was generally unclear, and few studies analyzed subgroups. Overall, there was a lack of methodologically sound studies of surgery and injection therapies. CONCLUSIONS: Standard discectomy compared with conservative treatment for proven disc herniation (< or = 1 year) and local triamcinolone injection for lateral epicondylitis (< or = 12 weeks) are both effective for pain relief (level 2). There was limited evidence of effectiveness (level 3) of intraoperative steroid at discectomy, epidural steroid injection for sciatica with low back pain, caudal steroid injection for low back pain, local glycosaminoglycan polyphosphate injection for lateral epicondylitis, intraarticular steroid injection for shoulder arthritis, subacromial steroid injections for rotator cuff tendinitis, nonspecific injections for painful shoulder, systemic growth hormone for fibromyalgia, and intravenous adenosine for fibromyalgia. There was limited evidence (level 3) that there is no additional benefit of adding steroid to local anesthetic in caudal epidural injections. There is limited evidence (level 3) that intravenous adenosine is ineffective for fibromyalgia. The remaining evidence was inadequate (level 4a) or contradictory (level 4b).

Urinary excretion of albumin and retinol binding protein in systemic lupus erythematosus.

We have measured the urinary excretion of total protein, albumin and retinol binding protein (RBP) in random urine specimens obtained from 40 female patients with systemic lupus erythematosus (SLE). Thirty-three of these patients had no clinical evidence of any renal impairment (non-renal SLE); seven had overt renal disease (renal SLE). RBP:creatinine ratios were significantly higher in non-renal SLE patients compared with female controls (P = 0.002). There was no significant difference between urine total protein concentrations, albumin:creatinine or total protein:creatinine ratios in non-renal SLE patients when compared with controls, despite approximately 20% of these patients having elevated excretion of total protein or albumin. All seven renal SLE patients had elevated albumin:creatinine ratios but only four of them had an increased RBP:creatinine ratio. Of 29 non-renal SLE patients who had urinary total protein concentrations below 0.2 g/L, (i.e. approximating to a negative protein dipstick), 14 had increases in either albumin or RBP:creatinine ratios. Only two patients had increases in both. In the absence of clinical evidence of renal disease, increases in urinary albumin or RBP excretion could indicate subclinical nephropathy and measurements may have a role in the early diagnosis and subsequent monitoring of renal disease in SLE.

Computed tomography in sternocostoclavicular hyperostosis.

Sternocostoclavicular hyperostosis is a rare but recognized entity characterized by new bone formation and ligamentous ossification which limits mobility of the sternoclavicular joints. Aetiology is obscure and debated. There may be considerable delay in establishing the diagnosis, even by specialists. In confirming the diagnosis plain radiography is of limited value but radionuclide bone scan and computed tomography (CT) may be helpful. Four cases are described to emphasize these points and illustrate the clinical and radiological features of the condition. High resolution CT with thin sections (5 mm or less) is the examination of choice for demonstrating the characteristic features and is essential if the condition is to be confirmed in its early stages when treatment might be more successful in delaying progression.

The logic of follicular unit transplantation.

Follicular unit transplantation is a method of hair restoration surgery where hair is transplanted exclusively in its naturally occurring, individual follicular units. The evolution and rational for follicular unit transplantation will be discussed, as well as the logic for the various techniques used in its implementation. Specifically, the logic for single strip harvesting, stereo-microscopic dissection, automated graft insertion, and large transplant sessions will be reviewed. The central role of the follicular unit constant in the surgical planning will also be discussed.

Characterization of autoantibodies directed against T cell receptors.

Recently it has been observed that administration of intravenous immunoglobulin (IVIG) can have profound effects on a wide variety of diseases related to the dysregulation of the immune system. The mechanisms which explain these activities are poorly understood. Human IVIG and various Cohn plasma fractions contain autoantibodies directed against T cell receptors (Tcr). Previous studies have shown that IVIG contains autoantibodies against T cell receptor peptides. In order to further our understanding of autoantibody specificities, a single chain Tcr (scTcr) was constructed by recombinant DNA techniques from the variable alpha and variable beta chains of the Jurkat cell line. Anti-Tcr autoantibodies were isolated from IVIG and Cohn fractions I + III using a scTcr affinity column. This scTcr affinity purified material reacted with the surfaces of T cells at 10 micrograms/ml whereas non-purified IVIG did not. Sera from patients with rheumatoid arthritis (RA) as well as serum from patients with systemic lupus erythematosus (SLE) reacted with the scTcr at levels above that of normals.

Nonunion of a Hoffa fracture in a child.

The authors report a case of a Hoffa fracture of the lateral femoral condyle that subsequently went on to nonunion in an eight-year-old child. The child presented with symptoms of knee pain and snapping five years after a motor vehicle accident. The nonunion fragment involved most of the lateral femoral condylar articular surface but spared the physis. After treatment by open reduction and limited internal fixation, the nonunion has healed, and the child has virtually full range of motion of the knee and no evidence of growth disturbance.

Hair casts or pseudonits acquired following psychological trauma.

We present an unusual case of hair casts occurring after psychological trauma. These pseudonits must be correctly differentiated from pediculosis capitis.

Solid rod short segment anterior fusion in thoracolumbar scoliosis.

Seventeen patients with adolescent idiopathic thoracolumbar scoliosis underwent short segment anterior spinal fusion with a solid rod-screw construct. Patients were evaluated radiographically and interviewed using the Scoliosis Research Society instrument. Mean radiographic follow-up was 34 months, and mean follow-up at time of interview was 62 months. Mean curve correction was 87%, declining to 67% at 2 years. Mean correction of the instrumented curve was 114%, declining to 103% at 2 years. The thoracic curve improved 24% and remained stable throughout the follow-up period. Kyphosis over the instrumented segments increased from 4 degrees preoperatively to 10 degrees postoperatively. Although there was a trend toward increasing kyphosis over time, this was not statistically significant at final follow-up. Most patients (88%) were extremely satisfied with the surgical result. We believe that a short-segment anterior fusion with a solid rod-screw construct provides excellent curve correction with minimal kyphosis over the instrumented segment. Overcorrection of the instrumented segment must be achieved for this technique to be successful.

Spontaneous rupture of the tibialis anterior tendon.

Spontaneous rupture of the tibialis anterior tendon is an uncommon occurrence that most often affects men in their fifth to seventh decades. These ruptures occur through abnormal tendons, but may cause little disability. Early repair does seem to improve the likelihood of a good result, however. The following is a case report, and the English literature is reviewed.