Ryanodine as a trigger of tension oscillations in rat ventricular muscle

In rat ventricular muscles, ryanodine (10–30 nM) evoked tension oscillation in the relaxation phase of an isometric twitch (relaxation oscillations) and an increase of tonic tension (ryanodine contracture). Both events were more pronounced in Ca²⁺-loaded rat muscles due to the addition of 0.5 μM adrenaline, an increase in the Ca²⁺ concentration in the solution and high muscle activity. The ryanodine-induced tension oscillations were comparable to those triggered by caffeine in this species. In both cases, blockers of the release of Ca²⁺ from the sarcoplasmic reticulum, namely tetracaine and dantrolene, abolished the relaxation oscillations and the ryanodine contracture. The results suggest that the ability of low concentrations of ryanodine to facilitate the release of Ca²⁺ from the sarcoplasmic reticulum, as shown recently in biochemical experiments, makes a direct contribution to triggering the relaxation oscillations and the ryanodine contracture in intact ventricular muscles. The Ca²⁺ load of the sarcoplasmic reticulum appears to be essential for the manifistation of the ryanodine Ca²⁺-releasing activity in rat ventricular muscles.     

Anti-Inflammatory and Antishock Water-Soluble Polyesters of Glucocorticoids with Low Level Systemic Toxicity

Purpose. The objective of this study was to evaluate the pharmacological activity of glucocorticoid hormones incorporated into the structure of water-soluble carbochain polymers via the esterified 21-CH₂OH group. Methods. Polymer analogs of glucocorticoids were prepared by radical copolymerization of l-vinyl-2-pyrrolidone with cortisol or dexamethasone 21-crotonates and crotonic acid or 2-(diethylamino) ethylcrotonate which served as ionogenic comonomers. Anti-inflammatory, immuno-suppressive and catabolic activities for ionogenic tertiary copolymers and previously prepared non-ionogenic binary copolymers were evaluated in standard animal models. The antishock activity of some of the copolymers was evaluated using the declamping shock model. Results. Water-soluble tertiary copolymers with a steroid content up to 14 mol% and an intrinsic viscosity up to 0.30 dl/g in ethanol were synthesized. It was shown that the copolymers were stable in aqueous solutions at pH 5.2–7.3. All of the polymers studied suppressed inflammatory reactions at the level of free hormones when administered interperitoneally. The antishock activity was considerably higher compared to free steroids. The copolymers, unlike unmodified glucocorticoids, did not influence the physical development of young animals. They also caused much lower thymus hypotrophy than free hormones. No clear effect of the presence and nature of ionogenic units in copolymers on the pharmacological performance of the copolymers was detected. Conclusions. The water-soluble polymers bearing glucocorticoid 21-residues in the side chains retain the anti-inflammatory activity of free steroids and exhibit a higher antishock, a lower immunosuppressive and no catabolic effect.     

Survivorship of the Bernese Periacetabular Osteotomy: What Factors are Associated with Long-term Failure?

Background

The Bernese periacetabular osteotomy (PAO) continues to be a commonly performed nonarthroplasty option to treat symptomatic developmental hip dysplasia, but there are few long-term followup studies evaluating results after PAO.

Questions/purposes

(1) What is the long-term survivorship of the hip after PAO? (2) What were the validated outcomes scores among patients who had PAO more than 14 years ago? (3) What factors are associated with long-term failure?

Methods

One hundred fifty-eight dysplastic hips (133 patients) underwent PAO between May 1991 and September 1998 by a single surgeon. Of those, 37 hips (34 patients [26%]) were lost to followup; an additional seven patients (5% [eight hips]) had not been seen in the last 5 years. The 121 hips (in 99 patients) were retrospectively evaluated at a mean of 18 years (range, 14–22 years). Survivorship was assessed using Kaplan-Meier analysis with total hip arthroplasty (THA) as the endpoint. Hips were evaluated for activity, pain, and general health using the UCLA Activity Score, modified Harris hip score, WOMAC, and Hip disability and Osteoarthritis Outcome Score (HOOS). Failure was defined as a WOMAC pain subscale score ≥ 10 or having undergone THA. Hips were divided into three groups: asymptomatic (did not meet any failure criteria at any point in time), symptomatic (met WOMAC pain failure criteria at previous or most recent followup), and replaced (having undergone THA). A multinomial logistic regression model using a general estimating equations approach was used to assess factors associated with failure.

Results

Kaplan-Meier analysis with THA as the endpoint revealed a survival rate (95% confidence interval [CI]) of 74% (66%–83%) at 18 years. Twenty-six hips (21%) underwent THA at an average of 9 ± 5 years from the surgery. Sixty-four hips (53%) remained asymptomatic and did not meet any failure criteria at most recent followup. Thirty-one hips (26%) were symptomatic and considered failed based on a WOMAC pain score of ≥ 10 with a mean ± SD of 11 ± 4 out of 20 at most recent followup. Although some failed initially by pain, their most recent WOMAC score may have been < 10. Of the 16 symptomatic hips that failed early by pain (reported a WOMAC pain subscale score ≥ 10 in the prior study), two were lost to followup, two underwent THA at 16 and 17 years, four still failed because of pain at most recent followup, and the remaining eight had WOMAC pain scores < 10 at most recent followup. Asymptomatic hips reported better UCLA Activity Scores (asymptomatic: mean ± SD, 7 ± 2; symptomatic: 6 ± 2, p = 0.001), modified Harris hip scores (pain, function, and activity sections; asymptomatic: 80 ± 11; symptomatic: 50 ± 15, p < 0.001), WOMAC (asymptomatic: 2 ± 2, symptomatic: 11 ± 4, p < 0.001), and HOOS (asymptomatic: 87 ± 11, symptomatic: 52 ± 20, p < 0.001) compared with symptomatic hips at long-term followup. Age older than 25 years at the time of PAO (symptomatic: odds ratio [OR], 3.6; 95% CI, 1.3–9.8; p = 0.01; replaced: OR, 8.9; 95% CI, 2.6–30.9; p < 0.001) and a preoperative joint space width ≤ 2 mm (replaced: OR, 0.3; 95% CI, 0.12–0.71; p = 0.007) or ≥ 5 mm (replaced: OR, 0.121; 95% CI, 0.03–0.56; p = 0.007) were associated with long-term failure while controlling for poor or fair preoperative joint congruency.

Conclusions

This study demonstrates the durability of the Bernese PAO at long-term followup. In a subset of patients, there was progression to failure over time. Factors of progression to THA or more severe symptoms include age older than 25 years, poor or fair preoperative hip congruency, and a preoperative joint space width that is less than 2 mm or more than 5 mm. Future studies should focus on evaluating the two failure groups that we have identified in our study: those that failed early and went on to THA and those that are symptomatic at long-term followup.

Level of Evidence

Level III, therapeutic study.

     

Mixed epithelial/mesenchymal metaplastic carcinoma (carcinosarcoma) of the breast in BRCA1 carrier

This case report describes a 35-year-old woman who was diagnosed with mixed epithelial/mesenchymal metaplastic carcinoma (carcinosarcoma) of the breast. Genetic analysis of blood DNA revealed a common founder mutation, BRCA1 5382insC. Examination of microdissected tumor samples determined that both epithelial and mesenchymal components contained deletion of the wild-type BRCA1 allele. This report exemplifies that even very uncommon breast tumor types may develop through biallelic inactivation of BRCA1 gene, that has to be considered in the genetic testing settings.     

Long-term outcome of decompressive surgery for Lumbar spinal stenosis in octogenarians

The purpose of our prospective study is to evaluate the surgical outcome among patients aged 80 years and above, who underwent surgery for lumbar spinal stenosis. We assessed patients’ clinical and demographic data, procedures, perioperative complications, preoperative and postoperative pain intensity, basic activities of daily living (BADL), patients’ satisfaction, the need for repeated surgery, and overall mortality. Thirty-nine patients more than 80 years of age were operated in our institution in the last decade. Twenty-five of them were followed-up with a mean 36.8 months after the operation. The Barthel index was used to evaluate pre and postsurgery ADL, and the visual analogue scale (VAS) was used to evaluate pain. The satisfaction rate of the patients before and after the operation and the complication rate were also evaluated. A significant reduction in VAS (P < 0.001) and a significant increase in the Barthel index (P < 0.001) were recorded. Seventy-six percent of the patients were very satisfied or somewhat satisfied with the operative results. Fifty-two percent of the patients had complications (0.9 complications per patients), however, about half of them were minor. No operative or perioperative mortality was noticed and the overall hospital stay for these elderly patients was 3.6 days on average. Surgery in very old elderly patients is safe and effective in the treatment of spinal stenosis, who did not respond well to the conservative treatment. The surgery did not increase the associated morbidity and mortality and most of the patients benefited from the surgery in terms of reduction in pain, increase in ADL and walking ability and overall increase in the satisfaction rate. An erratum to this article can be found at     

Right heart masses in a patient with endometrial stromal sarcoma

We present the case of a 61-year-old woman with a large tumoral infiltration extending from the pelvis throughout the inferior vena cava inferior to the right atrium, protruding into the right ventricle and right ventricular outflow tract. She had been treated 10 years before for low-grade endometrial stromal sarcoma by hysterectomy and adnexectomy followed by hormone- and radio-therapy. Due to cancer recurrence, she underwent peritonectomy, appendectomy, and resection of terminal ileum.