Distal Clavicle Fracture as a Complication of Arthroscopic Distal Clavicle Resection

Arthroscopic resection of the distal clavicle has been advocated as a surgical treatment option for acromioclavicular (AC) joint pathology. To our knowledge, iatrogenic fracture of the distal clavicle during distal clavicle resection has never been reported. This report describes distal clavicle fracture as a complication of misidentification of the AC joint and subsequent aggressive burring of the distal clavicle during shoulder arthroscopy. This case is further complicated by the development of symptomatic delayed union and adhesive capsulitis. Ultimately, a revision distal clavicle resection was performed, underscoring the fact that special care must be taken to properly identify the AC joint and rule out pre-existing distal clavicle stress fracture or osteolysis before performing the arthroscopic Mumford procedure.     

Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area

OBJECTIVE: Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake. DESIGN: A prospective study performed in a maternity hospital. PATIENTS: Two hundred and thirty pregnant women were prospectively studied and their neonates assessed at birth. MEASUREMENTS: Urine iodine concentration, thyroid function tests and thyroid volume (TV) by ultrasound were determined in the mothers during pregnancy and up to 3 months postpartum and in the neonates. RESULTS: Increased urinary iodine concentration was seen from first trimester onwards and the proportion of women having urine iodine concentration of < 0.4 micromol/l decreased from 11.3% in the first trimester to 4.7% in the third trimester. There was progressive reduction in circulating fT4 and fT3 concentrations and free thyroxine index (FTI) with increasing gestation and the percentage of women having subnormal levels at term were 53.2%, 61.1% and 4.8%, respectively. The serum TSH concentration during pregnancy doubled towards term. In the first trimester, multiparous women had significantly larger TV than the nulliparous women (P < 0.001). By the third trimester, TV had increased by 30% (range 3-230%) so that the goitre incidence was 14.1%, 21.8%, 25.9% during the three trimesters of pregnancy, and 24.3% and 21.9% at 6 weeks and 3 months postpartum (ANOVA, P < 0.05). The change in thyroid volume during pregnancy correlated positively with the change in thyroglobulin (r = 0.225, P < 0.002) and negatively with urinary iodine concentration (r = - 0.149, P < 0.02). Fourteen women with excessive thyroidal stimulation in the second trimester (defined as those with thyroglobulin (Tg) concentrations in the highest tertile and FTI in the lowest tertile) were found to have lower urine iodine concentrations and larger TV (both P < 0.005) throughout pregnancy, and their neonates had higher cord TSH (P < 0.05), Tg (P < 0.05) and slightly larger TV (P = 0.06) as compared to the findings in 216 pregnant women without evidence of thyroid stimulation. Seven neonates (50%) born to these women had subnormal fT4 levels at birth. CONCLUSION: In a borderline iodine sufficient area, pregnancy posed an important stress resulting in higher rates of maternal goitrogenesis as well as neonatal hypothyroxinaemia and hyperthyro- trophinaemia. An adequate iodization program is necessary to eliminate iodine deficiency disorders during pregnancy.     

Echocardiographic features of primary cardiac sarcoma

Primary cardiac sarcoma is extremely rare and seldom causes symptoms until late in its course. Discomfort may occur only when the mass causes obstruction to the intracardiac flow. Early diagnosis is vital because it allows prompt and relevant management. We describe the history and echocardiographic features in four patients with primary cardiac sarcoma and review the current literature.     

Well-differentiated epithelial thyroid cancer management in the Asia Pacific region: a report and clinical practice guideline.

CONTEXT: Thyroid cancer is among the 10 most common malignancies in populations in the Asia Pacific region, where access to various relevant health care resources varies widely. OBJECTIVE: An expert consensus conference was held to define regional patterns of practice and guidelines for optimal management of well-differentiated epithelial thyroid carcinomas. RESULTS: Practice patterns vary from country to country, as would be anticipated form their variety of ethnic and racial populations, health care systems, economies, and cultures. Thyroid cancer care is provided by a number of medical and surgical specialists, usually including endocrinologists. The thyroid surgical skills, experience, and outcomes vary widely in the region. Radioiodine is available, to a greater or lesser extent, is almost all countries. Laboratory services for thyroid function monitoring are universally accessible; thyroglobulin assays are available in most countries. Recombinant thyrotropin is approved for use in only two countries, but can be accessed in some others on a "named patient" compassionate need basis. Access to advanced imaging, for exampke, positron emission tomography (PET) scanning, is limited to a few countries. CONCLUSIONS: In light of these realities, appropriate strategies for initial treatment and postoperative monitoring of patients with thyroid cancer have been defined, and these are presented and discussed.     

Alcohol Modulation of Human Normal T-Cell Activation, Maturation, and Migration

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4⁺ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0-endor-phin pretreatment on the activation of CD4⁺ lymphocytes endowed with the homing receptor CD62L.     

Inducer and suppressor T-cells in hepatitis B virus-induced liver disease

During acute type B hepatitis, the proportion of inducer to cytotoxic/suppressor T-cells is decreased due to an increase in the concentration of suppressor cells. Similar changes are seen in chronically infected subjects with evidence of active viral replication (HBeAg positive) and chronic hepatitis of varying severity. This imbalance of the regulatory cells returns to normal when viral replication decreases during the recovery phase of acute hepatitis and in patients who become chronic carriers with minimal liver disease (HBeAb positive patient). Patients in whom viral replication has subsided (HBeAb positive) but who continue to exhibit chronic active liver disease have increased inducer to cytotoxic/suppressor cell ratios due to a decrease in the concentration of the cytotoxic/suppressor cell population. Further studies are needed to determine whether these alterations of the regulatory cells of the immune system are a causal factor influencing the duration of active hepatitis B virus replication and the degree of inflammatory liver damage, or merely changes secondary to the presence of a replicating virus.     

ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the liver removes toxic aldehydes including acetaldehyde, an intermediate of ethanol metabolism. Nearly 40% of East Asians inherit an inactive ALDH2*2 variant, which has a lysine-for-glutamate substitution at position 487 (E487K), and show a characteristic alcohol flush reaction after drinking and a higher risk for gastrointestinal cancers. Here we report the characterization of knockin mice in which the ALDH2(E487K) mutation is inserted into the endogenous murine Aldh2 locus. These mutants recapitulate essentially all human phenotypes including impaired clearance of acetaldehyde, increased sensitivity to acute or chronic alcohol-induced toxicity, and reduced ALDH2 expression due to a dominant-negative effect of the mutation. When treated with a chemical carcinogen, these mutants exhibit increased DNA damage response in hepatocytes, pronounced liver injury, and accelerated development of hepatocellular carcinoma (HCC). Importantly, ALDH2 protein levels are also significantly lower in patient HCC than in peritumor or normal liver tissues. Our results reveal that ALDH2 functions as a tumor suppressor by maintaining genomic stability in the liver, and the common human ALDH2 variant would present a significant risk factor for hepatocarcinogenesis. Our study suggests that the ALDH2*2 allele–alcohol interaction may be an even greater human public health hazard than previously appreciated.Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is essential for alcohol detoxification. It is the second enzyme in the major oxidative pathway of alcohol metabolism, removing acetaldehyde (ACE), a toxic intermediate product from ethanol metabolism (1). More than 500 million people worldwide, mostly in East Asia, have a G-to-A point mutation in their ALDH2 gene (2, 3). This mutation results in a glutamic acid-to-lysine substitution at residue 487 (E487K) of the human ALDH2 protein (designated ALDH2*2). ALDH2*2 has significantly reduced ability to metabolize ACE (4, 5). Importantly, its activity is partially dominant-negative over that of the wild-type ALDH2*1, due to the structural alterations introduced by the mutation to the ALDH2 homotetramer complex (6). As a result, individuals with a heterozygous ALDH2*2/2*1 genotype have less than half the wild-type activity, and ALDH2*2/2*2 homozygotes have very low residual activity (7). Accumulated ACE can cause an alcohol flush reaction, commonly found in Asians with this variant after alcohol consumption (also called “Asian glow”).ACE binds to cellular proteins and DNA, leading to DNA damage and organ injury (8). Specifically, endogenous aldehydes are detrimental to hematopoietic stem cells that are defective in Fanconi anemia DNA repair (9, 10). As a result, Fanconi anemia patients with the ALDH2*2 allele exhibit accelerated disease progression (11). ALDH2*2 can also increase the risk for gastrointestinal cancers, such as gastric carcinoma (12), esophageal cancer (13), and colon cancer (14). Despite the liver being the major organ of ethanol detoxification, the relationship between ALDH2*2 and the risk for liver cancer remains unclear (15, 16).ALDH2 is highly conserved in humans and mice (17, 18), and several mouse models with modified ALDH2 activities have been developed (19). The closest model to the human ALDH2*2 polymorphism is the Aldh2 knockout (KO) mouse, which expresses no protein or enzymatic activity (20). Although Aldh2 KO mice are useful for investigating the impact of complete lack of ALDH2 activity (21), they fail to faithfully reproduce the structural and biochemical properties of ALDH2*2 in human physiology and pathology (21–23). In particular, ALDH2*2 is expressed with reduced but not loss of enzymatic activity and increased protein turnover (24).To provide better mechanistic links between the ALDH2(E487K) mutation and human disease, we generated an ALDH2*2 knockin (KI) mouse. We observed impaired clearance of ACE from hepatocytes in these mutants after acute or chronic alcohol challenges. The ALDH2(E487K) mutation reduced total liver ALDH2 protein levels via a dominant-negative effect on protein stability, as has been documented for human tissues (24, 25). We also revealed a surprising role for ALDH2 as a liver tumor suppressor, raising the concern that this common human polymorphism may expose over 500 million carriers to greater risk of liver cancer.