BACKGROUND: The antiphospholipid antibody syndrome has been associated with thromboembolic events, thrombocytopenia, fetal death, fetal growth retardation, and early-onset severe preeclampsia. CASE: A postpartum woman developed fever, pulmonary infiltrates, cardiac conduction defects, and renal insufficiency following severe preeclampsia. She tested positive for lupus anticoagulant and anticardiolipin antibody, and responded to steroid therapy and plasmapheresis. CONCLUSION: The postpartum multi-system involvement suggests that a variety of clinical presentations may be associated with antiphospholipid antibodies. Treatment with plasmapheresis or corticosteroids may be of value in similar cases.

Acute Kidney Injury↗

PubMed1994

Low molecular weight heparin: a critical analysis of clinical trials.

LMWHs are an important new class of antithrombotic agents. They differ from UFH in having relatively more anti-Xa activity, greater bioavailability at low doses, longer half-life, and more predictable anticoagulant response when administered in fixed doses. These properties allow LMWHs to be administered QD or at most BID and without laboratory monitoring. The incidence of heparin-induced thrombocytopenia also appears to be lower with an LMWH than with heparin. Given their favorable pharmacological profile, it was of interest to critically appraise clinical trials of thromboprophylaxis and treatment with these new agents. In orthopedic trials, it was noted that LMWH provided safe and effective thromboprophylaxis for patients undergoing major orthopedic surgery of the lower limb. In those having hip arthroplasty, LMWH was as effective as low-intensity warfarin therapy, but its use was associated with more wound hematomas. In those having total knee arthroplasty, LMWH was more effective than warfarin and did not increase bleeding. However, the prevalence of DVTs complicating this procedure as well as acute hip fracture remains unacceptably high, and additional studies of LMWH in combination with other prophylactic methods, such as external pneumatic compression, are needed. Only one adequately designed trial found less bleeding resulted from LMWH prophylaxis administered at an equivalent antithrombotic dose to UFH. In general medical patients, LMWH appeared to be as effective as UFH and had the advantages of less frequent injections and fewer injection site hematomas. In general surgical patients, there was a lower risk of thromboembolism but a trend toward an increase in bleeding events. Subjects with strokes and spinal cord injuries benefited from fewer thrombotic events, and the latter had fewer bleeding complications. Other potential indications for LMWH, such as cardiopulmonary bypass, hemodialysis, and preservation of graft patency, are presently under study. Perhaps the most impressive benefits of LMWH will be realized when it is used for the treatment of venous thromboembolism. The meta-analysis presented in this review showed a trend toward greater efficacy with LMWH and fewer major bleeding events in comparison with adjusted-dose intravenous UFH. Also, during the months following the thrombotic event, there was significantly less mortality in patients receiving LMWH. A further advantage was the subcutaneous route of administration and lack of requirement for laboratory monitoring. Additional treatment trials are presently in progress and may establish LMWH as the treatment of choice for patients with thromboembolic disorders.

Animals↗

PubMed1993

A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies.

Thirty-one non-hemophilic patients with acquired antibodies to factor VIII were entered into a prospective, randomized, multi-institutional trial to determine the safety and efficacy of prednisone (P), cyclophosphamide (C), or the combination in the treatment of this disorder. Patients were eligible if they had antibody demonstrated by the Bethesda assay, had not received these agents previously, and gave informed consent. All patients were treated initially with P, 1 mg/kg, for 3 weeks. If the antibody persisted and there was no rise in factor VIII activity, patients were randomized to either continue P for an additional 6 weeks; taper P and begin C, 2 mg per kg; or continue P and add C. Antibody disappeared in 10 during the initial P therapy, and in three of four others randomized to continue on P; one patient was discontinued because of an herpetic infection. Antibody disappeared in three of six patients treated with C alone, and five of ten given C and P. The titer of antibody was significantly lower in responders than in non-responders (p = 0.003), but seven patients with titers of more than five Bethesda units had complete remissions. There was no difference in antibody titers between those responding to P and those responding to C. We conclude that all patients with acquired antibodies to factor VIII should receive initial management with P, and that C is effective as second-line therapy for many of those who are steroid-resistant.

Adult↗

PubMed1993

A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation.

BACKGROUND: Deep-vein thrombosis is a potentially life-threatening complication of total hip or knee replacement. There are few data on the effectiveness and safety of warfarin as compared with low-molecular-weight heparin as prophylaxis against this problem. METHODS: We therefore performed a randomized, double-blind trial in 1436 patients to evaluate the effectiveness and safety of low-molecular-weight heparin (given subcutaneously once daily) as compared with adjusted-dose warfarin to prevent venous thrombosis after hip or knee replacement. Treatment with the drugs was started postoperatively. The primary end point was deep-vein thrombosis as detected by contrast venography (performed a mean of 9.4 days after surgery in each group). RESULTS: Among the 1207 patients with interpretable venograms, 231 of 617 patients (37.4 percent) in the warfarin group and 185 of 590 patients (31.4 percent) in the low-molecular-weight-heparin group had deep-vein thrombosis (P = 0.03). The reduction in risk with low-molecular-weight heparin as compared with warfarin was 16 percent, and the absolute difference in the incidence of venous thrombosis was 6 percent in favor of low-molecular-weight heparin (95 percent confidence interval, 0.8 to 11.4 percent). The incidence of major bleeding was 1.2 percent (9 of 721 patients) in the warfarin group and 2.8 percent (20 of 715 patients) in the low-molecular-weight-heparin group (P = 0.04), and the absolute difference was 1.5 percent in favor of warfarin (95 percent confidence interval, 0.1 to 3.0 percent). CONCLUSIONS: Our data demonstrate that the small reduction in the incidence of venous thrombosis with low-molecular-weight heparin, as compared with warfarin, was offset by an increase in bleeding complications. Although the use of low-molecular-weight heparin is simpler, because it is administered subcutaneously without the need for monitoring, it may be more costly than warfarin. Warfarin is inexpensive, but the overall cost of its use is increased by the need to monitor the intensity of anticoagulation. At this time it is unclear which of these approaches is the most cost effective.

Administration, Oral↗

PubMed1993

Structure of an interleukin-1 beta mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition.

Site-specific mutagenesis was used to obtain the human interleukin-1 beta mutant protein with glycine substituted for threonine at position 9 (IL-1 beta Thr9Gly). The mutant maintains receptor binding but exhibits significantly reduced biological activity. The crystal structure of IL-1 beta Thr9Gly has been determined at 2.4-A resolution by molecular replacement techniques and refined to a crystallographic R-factor of 19.0%. IL-1 beta Thr9Gly crystallizes in a different space group (P6(5)22) than does native IL-1 beta (P4(3)); thus the molecules pack differently. Their overall structure is similar, nevertheless, with both composed of 153 amino acids which form 12 antiparallel beta-strands. However, significant conformational differences both close to and far from the site of the mutation may explain the mutant's altered properties.

Amino Acid Sequence↗

PubMed1993

Management of the severely anemic Jehovah's Witness.

Explore the source record for details and available documents.

Albumins↗

PubMed1993

Mapping of neutralizing epitopes and the receptor binding site of human interleukin 1 beta.

Antibodies to synthetic peptides of human interleukin 1 beta (IL-1 beta) and to recombinant human IL-1 beta were used to identify epitopes of IL-1 beta associated with the neutralization of its biological activity. Analysis of antisera raised to 17 synthetic peptides derived from the mature IL-1 beta sequence showed that five regions (residues 6-15, 49-80, 58-80, 92-101, and 120-133) were both immunoprecipitating and neutralizing. Using a hexamer epitope mapping method, comparison of the regions recognized by four neutralizing rabbit antisera with those recognized by a rabbit antiserum raised to denatured IL-1 beta suggested two further neutralizing epitopes, residues 39-48 and 83-95. Finally, a neutralizing monoclonal antibody was shown to bind to the peptides 6-11 and 87-95 by peptide binding and mutagenesis. All of these regions appear predominantly on one face of IL-1 beta. The effect of mutations in residues 4-11 and 88-97, which lie within this face, on receptor binding and biological activity was determined. Most of the mutations tested affected both receptor binding and activity, whereas mutations in another face of IL-1 beta (residues 74-80) had no effect. Purification of two of the mutants with reduced bioactivity and receptor binding and analysis by two-dimensional NMR indicated no gross changes in tertiary structure. A third mutant had reduced bioactivity in two different bioassays but no change in receptor binding. Although two-dimensional NMR revealed no gross changes in conformation, small changes did occur at a site distal from that mutated. The data are consistent with other epitope mapping and receptor binding mutagenesis data and suggest that the neutralizing antibodies and receptor recognize different but overlapping regions of IL-1 beta.

Amino Acid Sequence↗

PubMed1993

Up-regulation of GAP-43 and growth of axons in rat spinal cord after compression injury.

The growth-associated protein-43 (GAP-43) is an axonal phosphoprotein which is expressed at high levels during development and is reinduced by regeneration in the PNS. Consequently it is believed to be a key molecule in the regulation of axonal growth. However, injury to the CNS does not result in significant regeneration and this has been suggested to correlate with a failure of central neurons to up-regulate GAP-43 after axotomy. We have examined a model of spinal cord injury which is unique in two respects; first dural integrity is maintained by compression of the cord with smooth forceps (thus excluding connective tissue elements) and, secondly, considerable axonal growth has been reported through the resulting lesion. Our previous studies have shown that GAP-43 is extensively distributed in the rat spinal cord (see accompanying paper), but here we have used anti-GAP-43 antiserum at a dilution which did not yield any immunostaining in normal cord. However, supranormal levels of GAP-43 were detected in cell bodies and axons around the lesion within four days of compression injury. Double immunostaining with the RT97 monoclonal antibody indicated that a small subpopulation of neurons local to the site of compression were axotomized and expressed GAP-43 and phosphorylated neurofilament epitopes in their cell bodies. Although damage to long axon tracts was extensive, there was no evidence of regeneration in white matter. On the other hand cavities which formed in grey matter provided an environment for axonal elongation. Immunolabelling with markers for astrocytes and endothelial cells was used to evaluate the interaction of elongating axons with endogenous CNS cell types. Sprouting axons, identified by the presence of elevated levels of GAP-43, did not appear to grow in contact with astrocytes but preliminary evidence suggested that newly formed capillaries provided an appropriate substrate.

Animals↗

PubMed1993

An approach to the management of toxic epidermal necrolysis in a burn centre.

Toxic epidermal necrolysis syndrome, a life-threatening skin disorder, requires specialized nursing care to optimize survival. The similarity of the condition to partial skin thickness burns suggests that management on a burn unit is an effective means of therapy. A review of eight patients treated at our Burn Center emphasizes the need for aggressive team management of the condition.

Adult↗

PubMed1993

Hair replacement surgery for male pattern alopecia.

Male pattern alopecia is the most common type of hair loss encountered. Although this malady has no direct adverse consequences on physical health, physicians should be aware of the impact hair loss may have on a man's self-esteem. This type of hair loss and current hair replacement surgical techniques are discussed.

Alopecia↗

PubMed1993

Intraocular lens implantation in rural India.

We performed 379 extracapsular cataract surgeries with implantation of intraocular lenses (IOLs) in a public eye camp in Ganeshpuri, India (50 miles north of Bombay). Ninety percent (341) of the patients returned for follow up. At 8 weeks postoperatively, 48% of the patients had a visual acuity of 6/18 or better uncorrected; with correction, this figure rises to 71.5%. In general, surgical complications were neither severe nor frequent. More serious difficulties were associated with measuring initial IOL power, obtaining refractive data (including astigmatism), follow up of astigmatism (suture cutting), posterior capsule opacification, and associated preoperative pathology. On the basis of our data, we believe that IOL implantation in public eye camps, under controlled conditions of asepsis and with appropriate instrumentation, is a safe and effective way to provide visual rehabilitation to the rural populations of third-world countries.

Cataract Extraction↗

PubMed1993

Fusiform dilatations of the esophagus secondary to protracted distention and emetogenic injury.

We report the case of a 74-year-old woman who presented with a 2-year history of dysphagia, weight loss, nausea, and vomiting. She was diagnosed as having secondary achalasia due to external compression probably by a tumor of the lower part of the esophagus. At autopsy, however, no tumor was found at that site, whereas a pancreatic microcystic serous adenoma and multiple gastric leiomyomata--one of which occupied the pyloric sphincter area leading to gastric outlet obstruction--were noted. The esophagus displayed two fusiform dilatations located at the lower and midportions, the latter being associated with rupture and necrosis of the muscularis and adventitial wall layers. The lower dilatation showed only attenuation of the muscularis, without necrosis. The epithelium was intact in both dilatations. This was an unusual series of pathogenetic events, leading from gastric outlet obstruction to secondary achalasia and protracted vomiting, followed by spontaneous partial esophageal wall rupture (a variant of intramural hematoma) or atrophy of the muscularis, morphologically evident as fusiform dilatations.

Adenoma↗

PubMed1993

The role of dipyridamole in the therapy of vascular disease.

The antiplatelet agent dipyridamole is FDA-approved as an adjunct to warfarin for the prevention of thromboembolism in patients receiving prosthetic heart values. It is also prescribed in several other situations, although data supporting these uses remain equivocal. Dipyridamole does not appear to be superior to aspirin alone in the management of patients with cerebral or coronary artery disease nor in maintaining the patency of autologous grafts. Its role in the management of patients who fail aspirin or other antithrombotic therapy remains to be examined. The drug may offer long-term advantages in the prevention of atherogenesis, but this use also warrants future investigation.

Animals↗