Choledochal cyst: case reports and current concepts

Choledochal cyst is an unusual but serious condition which most commonly affects Oriental people. Recent experience of three patients with this condition in whom diagnosis was made by ultrasound examination is reported. Cholangiography (ERCP or PTC) was performed in two of the cases to define the anatomy. All three cases were successfully managed by cyst excision and biliary reconstruction by Roux-en-Y hepaticojejunostomy. The rationale for and importance of cyst excision are discussed.     

Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.     

Zinc takes the center stage: its paradoxical role in Alzheimer’s disease

There is compelling evidence that the etiology of Alzheimer’s disease (AD) involves characteristic amyloid-β (Aβ) deposition, oxidative stress, and anomalous metal–Aβ protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer’s disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-β plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Aβ, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Aβ cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer’s diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Humanized monoclonal antibody treatment in rheumatoid arthritis.

A 41-year-old woman with active, seropositive erosive rheumatoid arthritis was treated with the humanized monoclonal antibody Campath 1H. She had not responded or developed side effects to myocrisin, sulfasalazine and penicillamine, and had not responded to inpatient bedrest and physiotherapy. There was a rapid clinical improvement within 24 hours of infusion, which was maintained for about 12-14 weeks after the infusion. The lymphocyte count was suppressed for 7 months after treatment. There were no significant side effects during or after treatment. No anti-Campath 1H response was detected. This preliminary study suggests humanized monoclonal antibody therapy may be of value in the treatment of rheumatoid arthritis.     

Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress

Pretreatment of cultured hepatocytes with the ferric iron chelator deferoxamine prevents the killing of the cells by tert-butyl hydroperoxide (TBHP). Incubation of the deferoxamine-pretreated hepatocytes in a serum-free medium containing only 0.25 nM iron restored the sensitivity of the cells to TBHP within 4 to 6 hr. An amino acid-free medium accelerated the restoration of sensitivity in parallel with an enhanced rate of degradation of 14C-prelabeled protein. By contrast, inhibitors of the autophagic degradation of protein, including chymostatin, 3-methyladenine, benzyl alcohol, colchicine, oligomycin, and methylamine, inhibited the restoration of sensitivity of deferoxamine-treated hepatocytes to TBHP in parallel with their inhibition of protein degradation. With chymostatin, 3-methyladenine, benzyl alcohol, and colchicine, there was a parallel dose dependency of both the inhibition of protein turnover and the inhibition of the restoration of sensitivity to TBHP. Ascorbic acid, known to specifically retard the autophagic degradation of ferritin, inhibited the restoration of sensitivity to TBHP without effect on the general rate of protein turnover. None of the agents studied had any protective effect on the toxicity of TBHP for hepatocytes that were not pretreated with deferoxamine. These data indicate that the autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by TBHP.