Activation of adrenal adenyl cyclase by anti-thyroid plasma membrane antibodies

We have previously shown that IgG isolated from rabbit anti-bovine thyroid plasma membrane (anti-BTPM) antiserum exhibits properties similar to thyroid stimulating antibodies (TSAb) in that it activates thyroid adenyl cyclase. In this study, the organ non-specificity of this reaction was investigated. It was observed that anti-BTPM IgG stimulated not only adenyl cyclase of bovine thyroid but also that of the adrenal. The stimulatory activities on the thyroid and adrenal adenyl cyclase were abolished by absorption of the IgG with bovine adrenal plasma membrane (BAPM). These results indicate that anti-BTPM antibodies, similar to TSAb, exert both thyroidal and extra-thyroidal effects. Thus anti-BTPM antibodies may be directed against antigenic determinants that are common to both thyroid and adrenal plasma membranes. Like the anti-BTPM IgG, anti-BAPM IgG also activated both thyroid and adrenal adenyl cyclase. However, when IgG of the anti-BAPM antiserum was absorbed with thyroid plasma membranes, only the thyroid, but not the adrenal stimulating activity was abolished. It was concluded that the anti-BAPM antiserum contained antibodies directed against membrane antigens specific for the adrenal as well as common antigens shared by the thyroid.     

Bile salt metabolism in the human premature infant. Preliminary observations of pool size and synthesis rate following prenatal administration of dexamethasone and phenobarbital.

Bile salt synthesis and bile salt pool size were determined by isotope dilution in two groups of healthy premature infants, utilizing nonradioactive deuterium-labeled bile salts. All 9 infants were between 32 and 36 weeks of gestation; however, in one group (4 infants), the mothers had received either dexamethasone or phenobarbital prior to delivery. The total bile salt pool averaged 20 mg for the infants of untreated mothers and 79 mg for the infants of treated mothers; similarly, the bile salt synthesis of 8 mg per day in the untreated group was increased to 27 mg per day for the treated group. Expressed per sq m of body surface, the cholic acid pool for the treated group was 321 mg per sq m, and the cholic acid synthesis rate equaled 98 mg per sq m per day; values equal to those for full term infants and nearly 4 times those for the untreated prematures. The intraduodenal bile salt concentrations obtained during meals were also low in the untreated group, equaling 1.2 mM as compared to 5.3 mM for the treated group. The reductions of bile salt pool size, synthesis, and intestinal concentration establish that the functional maturity of the liver, and possibly the gastrointestinal tract, is reduced in premature infants. The results further suggest that this maturity may be dramatically influenced by medications administered to the mother prior to delivery.     

A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver

Several reliable and reproducible methods are available to induce oval cells in rat liver. Effective methods often involve inhibiting proliferation in hepatocytes using an alkylating agent, then subjecting the rat to partial hepatectomy (PH). The surgery is difficult to perform reproducibly in mice. Approaches that do not include partial hepatectomy, such as administration of D-galactosamine, are ineffective in mice. We found that a choline-deficient, ethionine-supplemented (CDE) diet, which is very effective in rats, leads to high morbidity and mortality when administered to mice. This article outlines an alternative protocol by which a CDE diet can be administered to mice. This diet is shown to be highly effective for oval cell induction, without causing high mortality. It takes less time and is at least as effective as other commonly used protocols for inducing oval cells in mice.     

Repair of ectopia cordis using a resorbable poly-L-lactic-polyglycolic acid plate in a patient with pentalogy of Cantrell

We present a case of a 10-month-old male infant with thoracoabdominal ectopia cordis, as part of Cantrell pentad, repaired using a poly-L-lactic-polyglycolic acid plate, a resorbable plating system widely used in craniomaxillofacial reconstruction. This is the first reported case of sternal reconstruction using a poly-L-lactic-polyglycolic acid plate. The repair was successfully carried out without cardiopulmonary compromise and good aesthetic outcome was achieved.     

Revision after total knee arthroplasty and unicompartmental knee arthroplasty in the medicare population

This study compares the relative risk of revision and associated risk factors after total or unicompartmental knee arthroplasty (TKA or UKA) in the Medicare population. A total of 61 767 TKA and 2848 UKA patients were identified. Reviewed data included type of treatment, gender, age, race, Charlson Index for comorbidity, length of stay, Medicare buy-in for socioeconomic status, region, and year. Unicompartmental knee arthroplasty patients were at increased risk for revision at 2 and 5 years. Those patients undergoing UKA were significantly more likely to require revision in the first 5 years as compared with those undergoing TKA. Risk factors contributing to TKA revision included younger male patients with higher comorbidities and lower socioeconomic status. About UKA, lower revision rates tend to favor those surgeons with higher volume.     

Deuterium nuclear magnetic resonance unambiguously quantifies pore and collagen‐bound water in cortical bone

Bone water (BW) plays a pivotal role in nutrient transport and conferring bone with its viscoelastic mechanical properties. BW is partitioned between the pore spaces of the Haversian and lacuno‐canalicular system, and water predominantly bound to the matrix proteins (essentially collagen). The general model of BW is that the former predominantly experiences fast isotropic molecular reorientation, whereas water in the bone matrix undergoes slower anisotropic rotational diffusion. Here, we provide direct evidence for the correctness of this model and show that unambiguous quantification in situ of these two functionally and dynamically different BW fractions is possible. The approach chosen relies on nuclear magnetic resonance (NMR) of deuterium (²H) that unambiguously separates and quantifies the two fractions on the basis of their distinguishing microdynamic properties. Twenty‐four specimens of the human tibial cortex from 6 donors (3 male, 3 female, ages 27–83 years) were cored and ²H spectra recorded at 62 MHz (9.4 Tesla) on a Bruker Instruments DMX 400 spectrometer after exchange of native BW with ²H₂O. Spectra consisted of a doublet signal resulting from quadrupole interaction of water bound to collagen. Doublet splittings were found to depend on the orientation of the osteonal axis with respect to the magnetic field direction (8.2 and 4.3 kHz for parallel and perpendicular orientation, respectively). In contrast, the isotropically reorienting pore‐resident water yielded a single resonance line superimposed on the doublet. Nulling of the singlet resonance allowed separation of the two fractions. The results indicate that in human cortical bone 60% to 80% of detectable BW is collagen‐bound. Porosity determined as the difference between total BW and collagen bound water fraction was found to strongly parallel micro–computed tomography (µCT)‐based measurements (R² = 0.91). Our method provides means for direct validation of emerging relaxation‐based measurements of cortical bone porosity by proton MRI. © 2012 American Society for Bone and Mineral Research © 2012 American Society for Bone and Mineral Research     

Sinonasal Tract Adenoid Cystic Carcinoma Ex-Pleomorphic Adenoma: A Clinicopathologic and Immunophenotypic Study of 9 Cases Combined with a Comprehensive Review of the Literature

Primary sinonasal tract carcinoma ex-pleomorphic adenoma (CEPA) is very uncommon, with adenoid cystic carcinoma (ACC) CEPA exceptional. These tumors are often misclassified. This is a retrospective study. Nine cases of ACC CEPA included 7 females and 2 males, aged 39–64 years (mean, 51.1 years). Patients presented most frequently with obstructive symptoms (n = 5), epistaxis (n = 3), nerve changes or pain (n = 3), present for a mean of 25 months (men: 9.5 versus women: 29.4 months; p = 0.264). The tumors involved the nasal cavity alone (n = 5), nasopharynx (n = 2), or a combination of locations (n = 2) with a mean size of 2.9 cm (females: 3.3; males: 1.7; p = 0.064). Most patients presented at a low clinical stage (n = 7, stage I), with one patient each in stage II and IV, respectively. Histologically, the tumors showed foci of PA associated with areas of ACC. Tumors showed invasion (lymph-vascular: n = 4; perineural: n = 6; bone: n = 6). The neoplastic cells were arranged in tubules, cribriform and solid patterns, with peg-shaped cells arranged around reduplicated basement membrane and glycosaminoglycan material. Mitoses ranged from 0 to 33, with a mean of 8.7 mitoses/10 HPFs. Necrosis (n = 2) and atypical mitotic figures (n = 1) were seen infrequently. Immunohistochemical studies showed positive reactions for cytokeratin, CK5/6, p63, CK7, EMA, SMA, calponin, S100 protein and CD117, several highlighting luminal versus basal cells components. GFAP, CK20 and MSA were non-reactive. p53 and Ki-67 were reactive to a variable degree. Surgery (n = 8), accompanied by radiation therapy (n = 5) was generally employed. Five patients developed a recurrence, all of whom died with disease (mean, 8.4 years), while 4 patients are either alive (n = 2) or had died (n = 2) without evidence of disease (mean, 15.9 years). In summary, ACC CEPA probably arises from the minor mucoserous glands of the upper aerodigestive tract, usually presenting in patients in middle age with obstructive symptoms in a nasal cavity based tumor. Most patients present with low stage disease (stage I and II), although invasive growth is common. Recurrences develop in about a 55 % of patients, who experience a shorter survival (mean, 8.4 years) than patients without recurrences (mean, 15.9 years). The following parameters, when present, suggest an increased incidence of recurrence or dying with disease: bone invasion, lymph-vascular invasion, and perineural invasion.     

Geographic factors are associated with increased risk for out-of hospital cardiac arrests and provision of bystander cardio-pulmonary resuscitation in Singapore

Background

Bystander Cardio-Pulmonary Resuscitation (BCPR) can improve survival for Out-of-Hospital Cardiac Arrest (OHCA). This study aimed to investigate the geographic variation of BCPR provision and survival to discharge outcomes among residential OHCA cases, evaluate this variation with individual and population characteristics and identify high-risk residential areas with low relative risk (RR) of BCPR and high RR of OHCA at the development guide plan (DGP) census tract levels in Singapore.

Methods

This was a retrospective, secondary analysis of two prospectively-collected registries in Singapore from 2001 to 2011. We used Bayesian conditional autoregressive spatial models to examine predictors at the DGP level and calculate smoothed RR to identify high-risk areas. We used multi-level mixed-effects logistic regression models to examine the independent effects of individual and neighborhood factors.

Results

We found a total of 3942 OHCA with a BCPR rate of 20.3% and a survival to discharge rate of 1.9% and 3578 cases eligible for BCPR. After adjusting for age, witnessed status, presumed cardiac etiology and longer response time, the risk of BCPR provision significantly increased by 0.02% for every 1% increase in the proportion of household size 5 and above in the DGP area (odds ratio1.02, 95%CI = 1.002–1.038, p < 0.026). We identified 10 high-risk residential areas with low RR of BCPR and high RR of OHCA.

Conclusion

This study informed that neighborhood household size could have played a significant role in the provision of BCPR and occurrence of high-risk areas. It demonstrates the public health potential of combining geospatial and epidemiological analysis for improving health.