The clinical evolution of Lyme arthritis

To determine the clinical evolution of Lyme arthritis, 55 patients who did not receive antibiotic therapy for erythema chronicum migrans were followed longitudinally for a mean duration of 6 years. Of the 55 patients, 11 (20%) had no subsequent manifestations of Lyme disease. From 1 day to 8 weeks after disease onset, 10 of the patients (18%) began to have brief episodes of joint, periarticular, or musculoskeletal pain for as long as 6 years, but they never developed objective joint abnormalities. From 4 days to 2 years after disease onset, 28 (51%) had one episode or began to have intermittent attacks of frank arthritis, primarily in large joints; a few had polyarticular movement. The total number of these patients who continued to have recurrences decreased by 10% to 20% each year. The remaining 6 patients (11%) developed chronic synovitis later in the illness; of these, 2 (4%) had erosions, and 1 (2%), permanent joint disability. The spectrum of Lyme arthritis ranges from subjective joint pain, to intermittent attacks of arthritis, to chronic erosive disease.     

Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis

We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.     

Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation

Type IIB von Willebrand disease is characterized by enhanced ristocetin- induced platelet aggregation and absence of large von Willebrand factor multimers from plasma. An alteration of the von Willebrand factor molecule resulting in increased reactivity with platelets appears to be the basis for these abnormalities. We have now identified a new variant of type IIB von Willebrand disease in a family in which the four affected members also have chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro. In spite of repeatedly prolonged bleeding times and persistent thrombocytopenia, their bleeding diathesis is only moderate.     

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats

Calcification limits the long-term success of heart valve bioprostheses fabricated from glutaraldehyde cross-linked porcine aortic valves. The pathophysiology of calcification of bioprostheses has been studied experimentally with subcutaneous implants of the valve cusps in rats; in this preparation, the accumulation of calcific deposits is biochemically and morphologically identical to that occurring in clinical specimens. The objective of the present study was to determine whether mineralization of bioprosthetic valve cusps (BC) subcutaneously implanted in 3-week-old male rats could be inhibited through the use of diphosphonate compounds. Ethanehydroxydiphosphonate (EHDP), administered by daily subcutaneous injection (25 mg/kg/24 hr) for 21 days inhibited calcification (BC Ca++ = 154.9 +/- 4.1), but caused somatic growth retardation and disruption of epiphyseal development. However, local administration of EHDP by osmotic pump (5 mg/kg/24 hr) implanted in direct contact with the cuspal tissue for 14 days prevented BC calcification (BC CA++ = 4.3 +/- 0.7) without adverse effects. Furthermore, EHDP given by osmotic pump had a prolonged effect on reducing calcification, as demonstrated by implants harvested 21 days (BC CA++ = 12.2 +/- 6.4) after the drug supply was exhausted. Finally, BC preincubated in aminopropanehydroxydiphosphonate for 24 hr before 21 day implantation underwent less calcification (CA++ = 24.2 +/- 7.4) than control valves (BC CA++ 126.6 +/- 7.5) with no adverse effects. We conclude that diphosphonates inhibit BC calcification, and that adverse effects of systemic therapy can be avoided by local administration.     

Identification of components of a phosphoinositide signaling pathway in retinal rod outer segments

Phototransduction in retinal rods involves a G protein-coupled signaling cascade that leads to cGMP hydrolysis and the closure of cGMP-gated cation channels that are open in darkness, producing a membrane hyperpolarization as the light response. For many years there have also been reports of the presence of a phosphoinositide pathway in the rod outer segment, though its functions and the molecular identities of its components are still unclear. Using immunocytochemistry with antibodies against various phosphoinositide-specific phospholipase C (PLC) isozymes (β1–4, γ1–2, and δ1–2), we have found PLCβ4-like immunoreactivity in rod outer segments. Similar experiments with antibodies against the α-subunits of the G_q family of G proteins, which are known to activate PLCβ4, have also demonstrated G_α11-like immunoreactivity in this location. Immunoblots of total proteins from whole retina or partially purified rod outer segments with anti-PLCβ4 and anti-G_α11 antibodies gave, respectively, a single protein band of the expected molecular mass, suggesting specific labelings. The retinal locations of the two proteins were also supported by in situ hybridization experiments on mouse retina with probes specific for the corresponding mouse genes. These two proteins, or immunologically identical isoforms, therefore likely mediate the phosphoinositide signaling pathway in the rod outer segment. At present, G_α11 or a G_α11-like protein represents the only G protein besides transducin (which mediates phototransduction) identified so far in the rod outer segment. Although absent in the outer segment layer, other PLC isoforms as well as G_αq (another G_q family member), are present elsewhere in the retina.     

Artifacts seen during CT pelvimetry: implications for digital systems with scanning beams

During computed tomography (CT) pelvimetry of two pregnant women, bony abnormalities of the fetuses were noted on the scout images that were not confirmed at delivery. To explore the cause of these artifacts, specimen long bones were manipulated in various ways during CT scout imaging. Artifacts like those seen during in vivo imaging were found to be caused by motion of the object. The CT scout view is an example of an image produced by a digital system that uses a scanning beam. This type of digital system is being used for several types of body imaging including screening for scoliosis and chest radiography. Attention to motion artifacts should decrease diagnostic errors and aid further development of these systems.