Implant stability in revision total hip arthroplasty: allograft bone packing following extended proximal femoral osteotomy

One method of revising the femoral component in revision total hip arthroplasty in the presence of compromised femoral bone stock is to pack the upper femur with particulate allograft and then to cement the femoral component into the allograft bed. This technique is being used clinically with encouraging results. Additionally, surgical exposure of the femoral canal during revision total hip arthroplasty can be greatly improved with an extended trochanteric osteotomy, which is subsequently repaired with wires or cables. To assess the feasibility of performing the allograft bone packing technique following an extended trochanteric osteotomy, the stability of this construct in a cadaver model was measured, using micromotion sensing instruments and loads applied on a materials testing machine. The stability of the cemented allograft impaction construct following extended trochanteric osteotomy was comparable to the stability of the control construct, which consisted of a similar impacted allograft construct without osteotomy. The stability of the osteotomized side was comparable to that of the control side. It is concluded that the initial in vitro stability of the allograft impaction technique following extended proximal femoral osteotomy is adequate to justify experimental in vivo use.     

Risk factors for hepatotoxicity induced by antituberculosis drugs

To evaluate the risk factors involved in antituberculosis treatment-induced hepatotoxicity. In a retrospective study we analyzed the rate of drug-induced hepatotoxicity in a sample of 456 patients. Patients received a combination of drugs including isoniazid, rifampin, pirazinamide and streptomycin or ethambutol. The association among hepatotoxicity and several risk factors (age, sex, alcoholism and HIV infection) was studied by univariate methods, stratified analysis and the multiple logistic regression model. Signs of liver injury were found in 9.86% of the treated patients. In the logistic model, the adjusted odds ratios (OR) and significance were found as follows: a) for alcoholism, OR = 17.31 (95% CI: 6.35-47.16), p < 0.001; b) for HIV infection, OR = 3.23 (95% CI: 1.47-7.11), p = 0.003 and c) for female sex, OR = 2.44 (95% CI: 1.22-4.86), p = 0.011. Age was not significantly associated with hepatotoxicity. Alcoholism, HIV infection and female sex were associated with an increased risk of hepatotoxicity in this study.     

Cryosurgery of the prostate: techniques and pitfalls

The preliminary data on prostate cryosurgery encompass reports only on local recurrence rates. The procedure is too new to report any survival figures. For localized organ-confined disease, the initial reports at 1 year of positive biopsies following cryosurgery range from 8% to 33%. With clinical stage C disease, a review of the literature also shows a range of 16% to 33% for local recurrence at one year. The largest series of patients treated after failure from radiation therapy is from the M.D. Anderson Cancer Center, which reports a positive biopsy rate of 29% at 6 months. Reports of major complications have included a 2% to 5% incidence of rectourethral fistulas, a 7% to 15% incidence of urinary retention requiring a secondary TURP or prolonged catheter drainage, 2% to 7% incidence of stress incontinence, and a 50% to 80% incidence of impotence. While these overall results may not be optimal to many, they do give us optimism. It is important to recognize that knowledge of the cryosurgical technique is evolving rapidly, and present modifications are not reflected yet in our results. Because hypothermia is a modality proven to cause lethal injury to cancer cells, it would be unfortunate if clinicians dismissed this modality without rigorous review of the surgical technique. The detailed methodology described in this article expedites the learning curve of practicing cryosurgeons and helps to standardize the way cryosurgery is performed.     

Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons

Rapid information transfer within the brain depends on chemical signalling between neurons that is mediated primarily by glutamate and GABA (gamma-aminobutyric acid), acting at ionotropic receptors to cause excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs), respectively. In addition, synaptically released glutamate acts on metabotropic receptors to excite neurons on a slower timescale through second-messenger cascades, including phosphoinositide hydrolysisl. We now report a unique IPSP mediated by the activation of metabotropic glutamate receptors. In ventral midbrain dopamine neurons, activation of metabotropic glutamate receptors (mGluR1) mobilized calcium from caffeine/ryanodine-sensitive stores and increased an apamin-sensitive potassium conductance. The underlying potassium conductance and dependence on calcium stores set this IPSP apart from the slow IPSPs described so far. The mGluR-induced hyperpolarization was dependent on brief exposure to agonist, because prolonged application of exogenous agonist desensitized the hyperpolarization and caused the more commonly reported depolarization. The rapid rise and brief duration of synaptically released glutamate in the extracellular space can therefore mediate a rapid excitation through activation of ionotropic receptors, followed by inhibition through the mGluR1 receptor. Thus the idea that glutamate is solely an excitatory neurotransmitter must be replaced with a more complex view of its dual function in synaptic transmission.     

Graduate education in clinical psychology. "We're not in Kansas anymore"

In this article, the author addresses changes impacting graduate education in clinical psychology, including those in technology, the academy, and the marketplace, and discusses implications of these changes for psychology. Significant concerns are raised concerning issues of supply and demand as well as the nature of the product of graduate education and training.     

Targeted disruption of SHIP leads to Steel factor-induced degranulation of mast cells

To investigate the role of the src homology 2 (SH2)-containing inositol 5' phosphatase (SHIP) in growth factor-mediated signalling, we compared Steel factor (SF)-induced events in bone marrow-derived mast cells (BMMCs) from SHIP-/- and SHIP+/+ littermates. We found SF alone stimulated massive degranulation from SHIP-/- but none from SHIP+/+ BMMCs. This SF-induced degranulation, which was not due to higher c-kit levels in SHIP-/- cells, correlated with higher intracellular calcium than that in SHIP+/+ cells and was dependent on the influx of extracellular calcium. Both this influx and subsequent degranulation were completely inhibited by PI-3-kinase inhibitors, indicating that SF-induced activation of PI-3-kinase was upstream of extracellular calcium entry. A comparison of phosphatidylinositol-3,4,5-trisphosphate (PIP3) levels following SF stimulation of SHIP+/+ and SHIP-/- BMMCs suggested that SHIP restricted this entry by hydrolyzing PIP3. Although PI-3-kinase inhibitors blocked the release of intracellular calcium, implicating PIP3, and PLCgamma-2 was slightly more tyrosine phosphorylated in SHIP-/- cells, the increase in inositol-1,4,5-trisphosphate (IP3) and intracellular calcium levels were identical in SHIP-/- and SHIP+/+ BMMCs. These results suggest that SHIP prevents SF from triggering degranulation of normal BMMCs, and does so by hydrolyzing PIP3, which in turn limits extracellular calcium entry at a step after the release of intracellular calcium.     

Ambulatory--not office--blood pressures decline during hormone replacement therapy in healthy postmenopausal women

Hormone replacement therapy (HRT, estrogen plus progestagen) in postmenopausal women has beneficial effects on the cardiovascular system. However, effects on blood pressure, determined with office measurements, remain controversial. We studied the effects of HRT in 29 healthy normotensive postmenopausal women (mean age 52.3 [3.8] years, median duration of amenorrhea 34.5 months), using ambulatory blood pressure monitoring at baseline and at 3 and 12 months of follow-up. Women were randomized to two groups: an HRT group (N = 14), treated with 1 mg 17beta-estradiol once daily and 5 or 10 mg dydrogesterone once daily during the third and fourth week of every 4 weeks; and a control group (C-group, N = 15), which did not receive therapy. Blood pressures did not differ between the groups at baseline (HRT group 117.1 (9.2)/74.4 (6.6) mm Hg, C-group 113.8 (11.2)/71.3 (7.4) mm Hg). During the follow-up period, changes from baseline of office blood pressures did not differ significantly between the groups. However, changes (95% CI) of mean 24-h blood pressures differed significantly between the two groups after 1 year of follow-up: a decrease of blood pressures was observed in the HRT group (delta systolic/delta diastolic = -5.54 [-8.86 to -2.21]/-4.23 [-6.66 to -1.80] mm Hg), whereas an increase was found in the C-group (+3.33 [-0.69 to +7.35]/+1.67 [-1.75 to +5.09] mm Hg; P [HRT v control group] = .001/.005). We conclude that HRT may have blood pressure lowering properties in healthy, normotensive postmenopausal women.     

Studies on the anchorage of ATP diphosphohydrolase in synaptic plasma membranes from rat brain

We examined performance in young and elderly on an implicit (lexical decision) and an explicit (recognition) memory test. The difference in lexical decision times between old and new words was equivalent in the two groups, although the elderly were slower. In both groups, recognition accuracy (lower in the elderly) was higher following semantic than nonsemantic encoding, whereas lexical decision times were unaffected. Divergent brain potentials for old and new words during lexical decisions constituted a repetition effect, which reflected greater positivity (200-800 ms) for old words, particularly over the left hemisphere; this effect was smaller and later in the elderly. An electrophysiological marker of enhanced recollection for words from the semantic encoding task took the form of a left-sided positivity (500-800 ms). The effect was smaller in the elderly than the young, providing an additional index of their impaired recognition processes.