Cobalamin (vitamin B12) deficiency detection by urinary methylmalonic acid quantitation

A study was made to assess the value of cobalamin deficiency detection through quantitation of urinary methylmalonic acid (MMA). Urinary MMA was measured in 1118 patients suffering from megaloblastic anemia, other anemias, elevated red cell mean corpuscular volume, or unexplained neurologic disorders. Patients without proven cobalamin deficiency had urinary MMA levels less than 20 micrograms/ml. All patients (n = 27) confirmed to have cobalamin deficiency showed MMA levels greater than 20 micrograms/ml. Data are presented showing the Schilling test results, the comparison of serum cobalamin to urinary MMA levels, and other basic hematologic data. MMA levels are a good indication of cobalamin distribution and function since they are directly related to a cobalamin-dependent metabolic pathway. With rapid, reliable quantitation by mass spectrometry, urinary MMA can now be a useful clinical test.     

Neutrophil elastase produces 52-kD and 30-kD glucocorticoid receptor fragments in the cytosol of human leukemia cells

Characterization of glucocorticoid receptors in leukemia cells is important to understand mechanisms of glucocorticoid resistance but has been impeded by receptor fragmentation in cytosol extracts. We recently found that formation of 52- and 30-kilodalton (kD) glucocorticoid receptor fragments in cytosol of leukemia cells is due to proteolysis and is blocked by diisopropylfluorophosphate (DFP). In the present study, we identify a 28-kD serine protease in cytosol of leukemia cells that binds [3H]DFP and correlates with the formation of 52- and 30-kD receptor fragments. This protease is immunoprecipitated by antiserum to neutrophil elastase. Limited digestion of [3H]dexamethasone-21-mesylate- labeled receptors by purified neutrophil elastase produces 52- and 30- kD receptor fragments. Receptor fragmentation in the cytosol of leukemia cells in inhibited by methoxysuccinyl-alanyl-alanyl-prolyl- valyl-chloromethylketone, a highly specific inhibitor of neutrophil elastase. The addition of as few as 5% neutrophils to a lymphoid cell suspension provides sufficient elastase to produce receptor fragmentation. Our findings indicate that neutrophil elastase is responsible for receptor fragmentation in the cytosol of leukemia cells. The neutrophil elastase may be endogenous to the leukemia cells or may come from neutrophils that contaminate leukemia cell suspensions.     

An audit of metal stent palliation for malignant biliary obstruction

BACKGROUND AND AIMS: Endoscopic stent insertion is the optimum method of palliation for malignant biliary obstruction. Metal stents have several advantages over the polyethylene alternatives, but are significantly more expensive. It has been reported that patients need to survive beyond 6 months to make metal stents more cost-effective. The aim of this study was to audit the performance of expanding metal biliary stents in our endoscopy unit, and to identify factors that might help with patient selection. METHODS: The records of all patients who were selected for endoscopic metal stent insertion at the Royal Perth Hospital for malignant biliary obstruction between September 1994 and November 1998 were reviewed. RESULTS: Thirty-two patients (16 males, mean age 71 years (range 34-88 years) were identified and followed up for a mean 201 days (range 3-810 days). Fifteen (47%) had cholangiocarcinoma, 13 (41%) had pancreatic cancer, and four had metastatic disease as the cause of obstruction. Mortality rates after metal stent insertion were 16, 41 and 55% at 30, 90 and 180 days, respectively. In total, 24 (75%) patients died during the follow-up period. Eleven (34%) stents became obstructed during follow up with a median time to occlusion of 125 days (range 44-729 days). Patients with cholangiocarcinoma had significantly longer survival than pancreatic cancer cases (median 286 vs 58 days, P = 0.04). No other factors were found to correlate with the survival or stent complications. CONCLUSIONS: Less than half of this mixed cohort survived beyond 6 months. Metal stent palliation of malignant biliary obstruction should probably be targeted at those with cholangiocarcinoma, as these patients tend to survive longer.     

p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma

BACKGROUND: Cutaneous spindle cell squamous cell carcinoma (SCSCC) is a rare variant of SCC. This lesion is sometimes difficult to diagnose based purely on morphologic features. p63 is a member of the p53 gene family that can be identified in epithelial malignancies. METHODS: Thirteen cases of spindle SCC were stained with p63, CK34betaE12, MNF116, vimentin, and S100. Control cases included desmoplastic melanoma (eight cases), atypical fibroxanthoma (AFX) (10 cases), dermatofibrosarcoma protuberans (eight cases), and cutaneous leiomyosarcoma (LMS) (four cases). RESULTS: p63 was expressed diffusely in the nuclei of 100% (13/13) of SCSCCs. Of controls, p63 showed focal labeling of two LMS and two AFX. MNF116 and CK34betaE12 were positive in 13/13 SCSCCs. Of controls, one LMS was focally positive for MNF116. All SCSCCs and all control cases were positive for vimentin. CONCLUSIONS: In the given differential diagnosis, p63 appears relatively specific to SCSCC and adds a useful nuclear marker to the available repertoire. The findings also suggest that cytokeratins MNF116 and CK34betaE12 may be more useful than standard cytokeratins in labeling SCSCC.     

Early histopathologic changes in purple glove syndrome

An 86-year-old African-American man presented with tonic-clonic seizures. Intravenous phenytoin was urgently administered into the dorsum of the right hand. The patient developed a raised purple area of discoloration around the intravenous insertion site within 2 h and edema and vesiculobullous lesions of the distal forearm, hands, and fingers within 8 h. Microscopic sections from a biopsy at 12 h revealed epidermal necrosis, superficial ulceration, and a mild superficial and deep perivascular lymphoid infiltrate, associated with numerous thrombi of small vessels throughout the dermis. The findings were judged to be consistent with soft-tissue injury associated with intravenous administration of phenytoin, also termed purple glove syndrome. Purple glove syndrome, named for its distinctive purple discoloration and swelling of the hands in the distribution of a glove, is an uncommon complication of intravenous phenytoin administration through small dorsal veins of the hands. It is comprised by pain, discoloration, and edema in the vicinity of intravenous infusion of phenytoin through dorsal veins of the hand. The histopathologic features of fully developed lesions have been reported; however, early-stage findings have not been previously described, and the histogenesis of this lesion is controversial. The presence of thrombi in this early-stage lesion suggests that thrombosis plays a role in the initial pathogenesis of this condition.     

A meta-analysis on depression and subsequent cancer risk

Background

The authors tested the hypothesis that depression is a possible factor influencing the course of cancer by reviewing prospective epidemiological studies and calculating summary relative risks.

Methods

Studies were identified by computerized searches of Medline, Embase and PsycINFO. as well as manual searches of reference lists of selected publications. Inclusion criteria were cohort design, population-based sample, structured measurement of depression and outcome of cancer known for depressed and non-depressed subjects

Results

Thirteen eligible studies were identified. Based on eight studies with complete crude data on overall cancer, our summary relative risk (95% confidence interval) was 1.19 (1.06–1.32). After adjustment for confounders we pooled a summary relative risk of 1.12 (0.99–1.26).No significant association was found between depression and subsequent breast cancer risk, based on seven heterogeneous studies, with or without adjustment for possible confounders. Subgroup analysis of studies with a follow-up of ten years or more, however, resulted in a statistically significant summary relative risk of 2.50 (1.06–5.91).No significant associations were found for lung, colon or prostate cancer.

Conclusion

This review suggests a tendency towards a small and marginally significant association between depression and subsequent overall cancer risk and towards a stronger increase of breast cancer risk emerging many years after a previous depression.