Broad ligament fibroids—a radiological and surgical challenge

Currently, there is limited data on the ease of imaging of broad ligament fibroids and their safe laparoscopic management. We aimed to review all laparoscopic myomectomies over an 8-year period, focusing on intraoperative findings and corresponding pre-operative imaging. All laparoscopic myomectomies performed between 2004 and 2012 were reviewed. Cases with broad ligament fibroids were identified. Presenting symptoms, imaging, intraoperative findings, complications and 6-month follow-up were noted. Ten broad ligament fibroids were identified from 185 cases of laparoscopic myomectomies. Mean broad ligament fibroid diameter was 8.1 cm, and the largest was 15 cm. Mean combined fibroid weight was 267 g (range 30–560 g). Blood loss was associated with the total number of fibroids excised rather than the diameter of the broad ligament fibroid (range 30–400 ml). Accurate pre-operative diagnosis at imaging was made in only one of the ten broad ligament fibroids. Of the remainder, one was thought to be an ovarian mass, one fibroid was missed entirely and seven were reported non-specifically as ‘lateral’. This case series indicates the challenge posed by broad ligament fibroids at pre-operative imaging. Underreporting may reflect a lack of awareness of the surgical significance of broad ligament fibroids. There should be a high level of suspicion for location within the broad ligament if a fibroid reported is as lateral. With adequate operator experience, large fibroid size should not contraindicate laparoscopic management of broad ligament fibroids.     

Hydrogen peroxide alters sternohyoid muscle function

Upper airway (UA) dilator muscles are critical for the maintenance of airway patency. Injury or fatigue to this group of muscles, as observed in patients with obstructive sleep apnoea (OSA) and animal models of OSA, may leave the UA susceptible to collapse. Although the mechanisms underlying respiratory muscle dysfunction are not completely understood, there is strong evidence suggesting a link between increased production of reactive oxygen species and altered muscle function. The aim of this study was to examine the effects of H₂O₂ on rat sternohyoid muscle function in vitro. Sternohyoid contractile and endurance properties were examined at 35°C under control or hypoxic conditions. Studies were conducted in the presence of varying concentrations of H₂O₂ (0, 0.01, 0.1 and 1 mM). Muscle function was also examined in the presence of antioxidants [desferoxamine (DFX), catalase] and the reducing agent dithiothreitol (DTT). H₂O₂ decreased muscle endurance in a concentration‐dependent manner. This was partially reversed by catalase, DFX and DTT. Our results suggest that oxidants may contribute to UA respiratory muscle dysfunction with implications for the control of UA patency in vivo.     

Death in CHARGE syndrome after the neonatal period

Bergman JEH, Blake KD, Bakker MK, du Marchie Sarvaas GJ, Free RH, van Ravenswaaij‐Arts CMA. Death in CHARGE syndrome after the neonatal period. CHARGE syndrome is a multiple congenital anomaly syndrome that can be life‐threatening in the neonatal period. Complex heart defects, bilateral choanal atresia, esophageal atresia, severe T‐cell deficiency, and brain anomalies can cause neonatal death. As little is known about the causes of death in childhood and adolescence, we studied post‐neonatal death in patients with CHARGE syndrome. We collected medical data on three deceased children from a follow‐up cohort of 48 CHARGE patients and retrospectively on an additional four deceased patients (age at death 11 months to 22 years). We analyzed the factors that had contributed to their death. In five patients respiratory aspiration had most likely contributed to premature death, one died of post‐operative complications, and another choked during eating. From our findings and a literature review, we suggest that swallowing problems, gastro‐esophageal reflux disease, respiratory aspiration and post‐operative airway events are important contributors to post‐neonatal death in CHARGE syndrome. Cranial nerve dysfunction is proposed as the underlying pathogenic mechanism. We recommend every CHARGE patient with feeding difficulties to be assessed by a multidisciplinary team to evaluate cranial nerve function and swallowing. Timely treatment of swallowing problems and gastro‐esophageal reflux disease is important. Surgical procedures on these patients should be combined whenever possible because of their increased risk of post‐operative complications and intubation problems. Finally, we recommend performing autopsy in deceased CHARGE patients in order to gain more insight into causes of death.     

An Analysis of the Effect of a Vent Hole on Excess Cement Expressed at the Crown–Abutment Margin for Cement-Retained Implant Crowns

Purpose: The labial margins of anterior implant‐retained crowns are often positioned subgingivally for a superior esthetic appearance. One of the consequences of subgingival margins is the increased risk of leaving excess cement behind following cementation. This can lead to potential problems, including peri‐implant inflammation, soft tissue swelling, soreness, bleeding or suppuration on probing, and bone loss. The purpose of this laboratory study was to investigate the effect of placement, location, and diameter of a vent hole on the amount of cement being expressed at the margin of an anterior implant abutment‐retained crown. Materials and Methods: Three implant crown copings were fabricated to fit on the same custom abutment. Three vent diameters (0.75, 1.25, and 1.65 mm) and three locations on the palatal surface of the coping (cervico‐palatally, mid‐palatally, inciso‐palatally) were chosen for vent hole placement. For each test, the coping was cemented onto the abutment under standardized conditions. A preweighed thin coating of cement was applied to the fit surface of the coping. The amount of cement expressed at the margin and vent hole was measured by weight and calculated as a proportion of the amount of cement placed in the coping before seating. The procedure was completed 15 times for each variable. The results were statistically analyzed using univariate ANOVA with post hoc Bonferroni‐adjusted independent samples t‐tests. Results: The presence of a vent hole influenced the proportion of cement expressed at the coping margin (p < 0.05). The location of a vent hole influenced the proportion of cement expressed at the coping margin (p < 0.05), with the exception of the mid‐palatal and inciso‐palatal positioning where there was no significant difference (p= 0.61) between groups. The diameter of the vent hole did not significantly influence the proportion of cement expressed at the coping margin (p= 0.096). Conclusions: When using anterior cement‐retained implant crowns, the use of a 0.75‐mm mid‐palatal or inciso‐palatal vent hole to minimize the amount of cement expressed at the margin during cementation should be considered.     

The PI-PLC inhibitor U-73122 is a potent inhibitor of the SERCA pump in smooth muscle

In this issue MacMillan and McCarron in 2010 demonstrated that the phospholipase C (PLC) inhibitor U-73122 can potently inhibit Ca²⁺ release from isolated smooth muscle cells independent of its effect on PLC. Their data suggest that the PLC inhibitor can block the sarcoplasmic/endoplasmic reticulum calcium ATPase pump in smooth muscle and cast doubt on the reliability of U-73122 as the main pharmacological tool to assess the role of the phosphotidyl inositol-PLC pathway in cellular signalling.     

Δ4-3-oxosteroid-5β-reductase deficiency: Responses to oral bile acid therapy and long-term outcomes

BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of patients with Δ4-3-oxosteroid 5β-reductase(AKR1 D1) deficiency. We hypothesized that a retrospective analysis of the responses to oral bile acid replacement therapy with chenodeoxycholic acid(CDCA) in patients with this bile acid synthesis disorder will increase our understanding of the disease progression and permit evaluation of this treatment regimen as an alternative to the Food and Drug Administration(FDA) approved drug cholic acid, which is currently unavailable in China.AIM To evaluate the therapeutic responses of patients with AKR1 D1 deficiency to oral bile acid therapy, specifically CDCA.METHODS Twelve patients with AKR1 D1 deficiency, confirmed by fast atom bombardment ionization-mass spectrometry analysis of urine and by gene sequencing for mutations in AKR1 D1, were treated with differing doses of CDCA or ursodeoxycholic acid(UDCA). The clinical and biochemical responses to therapy were monitored over a period ranging 0.5-6.4 years. Dose adjustment, to optimize the therapeutic dose, was based on changes in serum biochemistry parameters,notably liver function tests, and suppression of the urinary levels of atypical hepatotoxic 3-oxo-Δ4-bile acids measured by mass spectrometry.RESULTS Physical examination, serum biochemistry parameters, and sonographic findings improved in all 12 patients during bile acid therapy, except one who underwent liver transplantation. Urine bile acid analysis confirmed a significant reduction in atypical hepatotoxic 3-oxo-Δ4 bile acids concomitant with clinical and biochemical improvements in those patients treated with CDCA. UDCA was ineffective in down-regulating endogenous bile acid synthesis as evidenced from the inability to suppress the urinary excretion of atypical 3-oxo-Δ4-bile acids. The dose of CDCA required for optimal clinical and biochemical responses varied from 5.5-10 mg/kg per day among patients based on maximum suppression of the atypical bile acids and improvement in serum biochemistry parameters, and careful titration of the dose was necessary to avoid side effects from CDCA.CONCLUSION The primary bile acid CDCA is effective in treating AKR1 D1 deficiency but the therapeutic dose requires individualized optimization. UDCA is not recommended for long-term management.     

S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora

BACKGROUND: The discovery of equol in human urine more than 2 decades ago and the finding that it is bacterially derived from daidzin, an isoflavone abundant in soy foods, led to the current nutritional interest in soy foods. Equol, unlike the soy isoflavones daidzein or genistein, has a chiral center and therefore can occur as 2 distinct diastereoisomers. OBJECTIVE: Because it was unclear which enantiomer was present in humans, our objectives were to characterize the exact structure of equol, to examine whether the S- and R-equol enantiomers are bioavailable, and to ascertain whether the differences in their conformational structure translate to significant differences in affinity for estrogen receptors. DESIGN: With the use of chiral-phase HPLC and mass spectrometry, equol was isolated from human urine and plasma, and its enantiomeric structure was defined. Human fecal flora were cultured in vitro and incubated with daidzein to ascertain the stereospecificity of the bacterial production of equol. The pharmacokinetics of S- and R- equol were determined in 3 healthy adults after single-bolus oral administration of both enantiomers, and the affinity of each equol enantiomer for estrogen receptors was measured. RESULTS: Our studies definitively establish S-equol as the exclusive product of human intestinal bacterial synthesis from soy isoflavones and also show that both enantiomers are bioavailable. S-equol has a high affinity for estrogen receptor beta (K(i) = 0.73 nmol/L), whereas R-equol is relatively inactive. CONCLUSIONS: Humans have acquired an ability to exclusively synthesize S-equol from the precursor soy isoflavone daidzein, and it is significant that, unlike R-equol, this enantiomer has a relatively high affinity for estrogen receptor beta.