Adenomyomatosis of the gallbladder. A premalignant lesion?

Gallbladder cancer is the most common malignant tumor of the biliary tract, but its early diagnosis is uncommon. The use of ultrasonography has increased the detection of benign gallbladder tumors, and the premalignant potential of gallbladder adenomas is now undisputed. Adenomyomatosis of the gallbladder has recently been suggested to have malignant potential, and we report a case of adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was successfully treated by radical curative surgery. The more rigorous use of ultrasonography and a more aggressive approach to "benign" polypoid lesions of the gallbladder may represent the best way of achieving early diagnosis and cure in gallbladder cancer.     

Heterogeneity of toxicant response: sources of human variability.

While risk assessment models attempt to predict human risk to toxicant exposure, in many cases these models cannot account for the wide variety of human responses. This review addresses several primary sources of heterogeneity that may affect individual responses to drug or toxicant exposure. Consideration was given to genetic polymorphisms, age-related factors during development and senescence, gender differences associated with hormonal function, and preexisting diseases influenced by toxicant exposure. These selected examples demonstrate the need for additional steps in risk assessment that are needed to more accurately predict human responses to toxicants and drugs.     

Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses.

Glucocorticoids are the consensus treatment for the prevention of respiratory distress in preterm infants, but there is evidence for increased incidence of neurodevelopmental disorders as a result of their administration. We administered dexamethasone (Dex) to developing rats at doses below or within the range of those used clinically, evaluating the effects on forebrain development with exposure in three different stages: gestational days 17-19, postnatal days 1-3, or postnatal days 7-9. At 24 h after the last dose, we evaluated biomarkers of neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, and synaptic signaling mediated by adenylyl cyclase (AC). Dex impaired the acquisition of neural cells, with a peak effect when given in the immediate postnatal period. In association with this defect, Dex also elicited biphasic effects on cholinergic presynaptic development, promoting synaptic maturation at a dose (0.05 mg/kg) well below those used therapeutically, whereas the effect was diminished or lost when doses were increased to 0.2 or 0.8 mg/kg. Dex given postnatally also disrupted the expression of adrenergic receptors known to participate in neurotrophic modeling of the developing brain and evoked massive induction of AC activity. As a consequence, disparate receptor inputs all produced cyclic AMP overproduction, a likely contributor to disrupted patterns of cell replication, differentiation, and apoptosis. Superimposed on the heterologous AC induction, Dex impaired specific receptor-mediated cholinergic and adrenergic signals. These results indicate that, during a critical developmental period, Dex administration leads to widespread interference with forebrain development, likely contributing to eventual, adverse neurobehavioral outcomes.     

Chronic stress injuries of the elbow in young gymnasts.

The radiological changes of chronic stress injuries of the elbow in 19 adolescent elite gymnasts are reported. The principal abnormalities were avascular necrosis of the capitellar epiphysis (Panner's disease) (one patient), post-traumatic subarticular necrosis (osteochondritis dissecans) of the capitellum (six patients) and the medial articular eminence of the distal humerus (one patient). Flattening and anterior depression of the radial head epiphysis with an underlying metaphyseal notch associated with an epiphyseal cleft (three patients), which, in one patient who continued training, developed into a chronic Salter Type IV stress fracture. A further patient, post-epiphyseal fusion, showed osteochondritis dissecans of the anterior aspect of the radial head. Seven patients exhibited a spectrum of olecranon changes from fragmentation of the epiphysis to chronic Salter Type I stress fractures of the growth plate. A follow-up survey found that, of those who responded to a questionnaire, nearly all the patients with articular surface damage failed to continue with competitive gymnastics whereas those with olecranon abnormalities were able to continue gymnastics at the same level. The mechanism of injury and the pathological changes are discussed.     

Deep brain stimulation in the central nucleus of the amygdala decreases ‘wanting’ and ‘liking’ of food rewards

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever‐pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self‐stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory‐excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an ‘information lesion’ that not only decreased motivational ‘wanting’ of food rewards, but also blocked ‘liking’ of rewards.     

Endoscopic nephrectomy in children: is retro the way forward?

OBJECTIVE: To determine the benefits of nephrectomy in children performed via a retroperitoneoscopic approach compared to the laparoscopic route. MATERIALS AND METHODS: We reviewed all endoscopic nephrectomies performed at our institution from August 1998 to February 2003. RESULTS: A total of 32 endoscopic nephrectomies were undertaken: 22 laparoscopic nephrectomies with 5 conversions to open surgery, and 10 retroperitoneoscopic. The main indication for surgery was poor function secondary to either reflux or obstructive nephropathy. Intraoperative heart rate changes were less marked in patients undergoing retroperitoneoscopic nephrectomy. The median operative time for retroperitoneoscopic nephrectomy was 65 minutes and 95 minutes for laparoscopy. Epidural analgesia was not required in successful endoscopic nephrectomies. The median postoperative morphine requirement in the retroperitoneoscopic group was 110mcg/kg compared to 280mcg/kg in the laparoscopic group. The majority of patients who had successful endoscopic nephrectomies were discharged to home within 2 days of surgery. CONCLUSION: Retroperitoneoscopic nephrectomy appears to be a safe technique in children, with reduced intraoperative physiological effects compared to the laparoscopic approach. Operative time was generally shorter than the laparoscopic approach and there appeared to be an additional benefit of reduced postoperative pain.     

Colonic complications of severe acute pancreatitis

Colonic complications are rare in acute pancreatitis. Over the last 9 years at St. Mary's Hospital, London, UK, we have managed severe acute pancreatitis by intensive supportive therapy followed by sub-total pancreatic resection and/or debridement in those who fail to improve. Of the 22 patients who have undergone this form of surgery, nine were found to have colonic involvement in the form of either necrosis or perforation. In addition, one patient presenting at West Middlesex University Hospital, Isleworth, UK, had severe acute pancreatitis and almost total colonic necrosis as an unexpected finding at emergency laparotomy. These ten patients comprised seven men and three women of median age 59 years and with a median of four Ranson criteria. In seven patients, colonic involvement was discovered at the time of pancreatic surgery or laparotomy for pancreatitis and in the remainder it presented between 1 and 3 weeks later as either a faecal fistula (n = 2) or persistent abdominal sepsis (n = 1). The ascending colon was involved in one patient, the splenic flexure and descending colon in one, the transverse colon in three, the splenic flexure alone in four, and one patient had almost total colonic involvement. All patients underwent resection of the involved colon and exteriorization with either a proximal colostomy (n = 7) or ileostomy (n = 3) and a distal mucous fistula. Pathological examination of the resected colons revealed a spectrum of changes from pericolitis through to ischaemic necrosis suggesting at least two possible mechanisms. Six patients died from overwhelming sepsis between 1 day and 4 weeks (median 11 days) after colonic resection. Severe acute pancreatitis must be recognized as a cause of colonic ischaemia and necrosis; this complication is associated with a very poor prognosis despite surgical intervention.