Effect of corticosteroid therapy on the phagocytosis of antibody-coated platelets by human leukocytes

Patients with idiopathic thrombocytopenic purpura (ITP), a disorder in which antibody coated platelets are cleared from the circulation by phagocytic cells, are often treated with glucocorticoids. The effect of corticosteroids on the recognition and ingestion of sensitized platelets by phagocytes can be quantified in these patients and compared to changes in platelet levels. Six patients with ITP were treated with 96 mg daily of methylprednisolone for 5 days. This treatment raised their platelet count and simultaneously decreased the ability of their granulocytes to phagocytize antibody-coated platelets and C3-coated paraffin oil droplets. Corticosteroid treatment did not affect the binding of antibody to platelets or the quantity of antibody in the patients' serum. The ingestion defect was present in isolated, washed leukocytes and persisted for 3-5 days after the corticosteroids were discontinued. Granulocytes and purified monocytes obtained from patients with other medical disorders receiving corticosteroids also ingested paraffin oil droplets and opsonized platelets at a slower rate. These studies provide direct evidence that corticosteroids induce a generalized phagocytic defect and that this may be the mechanism by which corticosteroids raise the platelet count in patients with ITP.     

A staphylococcal slide test for detection of antineutrophil antibodies

We describe a simple test for direct or indrect detection of antineutrophil antibodies. Sensitized leukocytes adherent to glass slides and fixed with paraformaldehyde can be stored in buffer for at least 3 wk. Killed Cowan I staphylococci, containing protein A, bind to sensitized but not control cells, and binding is ascertainable by light microscopy. Indirect tests were positive for 39/41 patients suspected of having immune neutropenia and found to have antineutrophil antibodies by an indirect radiochemical opsonic method. Fifty-four control sera from healthy persons, patients with bone marrow failure, or with immune complex diseases without neutropenia, gave negative indirect tests. Direct tests for cell-bound antibody could be done even during severe neutropenia by reacting fixed autologous cells with staphylococci in the absence of added serum. In some patients only the direct test was positive.     

Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development

Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer (CRC). Variants in genes currently known to be associated with a high risk for polyposis or CRC, however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve CRC prevention, detection and treatment. We have performed genome‐wide and targeted DNA copy number profiling and resequencing in early‐onset and familial polyposis/CRC patients, and show that deletions affecting the open reading frame of the tumour suppressor gene FOCAD are recurrent and significantly enriched in CRC patients compared with unaffected controls. All patients carrying FOCAD deletions exhibited a personal or family history of polyposis. RNA in situ hybridization revealed FOCAD expression in epithelial cells in the colonic crypt, the site of tumour initiation, as well as in colonic tumours and organoids. Our data suggest that monoallelic germline deletions in the tumour suppressor gene FOCAD underlie moderate genetic predisposition to the development of polyposis and CRC. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

EFFECT OF SUBCLINICAL LEAD INTOXICATION ON LARYNGEAL CANCER

SUMMARY In this study we investigated the possible relationship of laryngeal cancer and subclinical lead intoxication, using the depression of aminolevulinic acid dehydratase (ALAD) activity in blood as indicator. Twenty-six patients with laryngeal cancer and 53 normal controls met the criteria to enter the study. Blood ALAD activity values in the patients with laryngeal cancer ranged from 27.1 to 75.3 U/l with a mean of 50.79 U/l. The respective values in the control group ranged from 36.2 to 98 U/l with a mean of 59.76 U/l. There was a statistically significant difference between the two means (0.001 <p<0.01), whereas blood lead concentrations in all patients were within normal limits. These findings support the hypothesis that low level lead intoxication (subclinical blood lead levels), from cars, industries and products, may contribute to the risk of laryngeal cancer. Further investigation is needed to clarify the exact relationship between lead and cancer of the larynx.     

Evaluation of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid in the inhibition of rouleaux formation

BACKGROUND: DIDS (4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid) inhibits the formation of serum-or plasma-induced rouleaux through its ability to bind to band 3 on red cell membranes. This property of DIDS was evaluated in the serologic testing of specimens exhibiting rouleaux. STUDY DESIGN and METHODS: Optimal test conditions for DIDS treatment of reagent red cells were determined by varying the volume and concentration of DIDS solution and the incubation temperature and duration and comparing the results of antibody screening procedures using specimens that exhibit macroscopically visible rouleaux. Blind titration studies compared untreated and DIDS-treated red cells to evaluate the maintenance of antigen integrity. The use of DIDS-treated red cells for antibody detection and identification was evaluated by comparing the results in donor specimens containing antibodies with those in untreated and DIDS-treated selected panel cells. In addition, 4-percent (wt/vol) dextran in serum was used to induce rouleaux formation as a way of determining the capability of DIDS to resolve ABO serum grouping discrepancies. RESULTS: Complete inhibition of rouleaux formation occurred when reagent red cells were treated by incubation at 37 degrees C for 10 minutes with 150 microliter (approx. 5 drops) of 0.05 mg per mL of DIDS in 0.9-percent NaCl. There were no significant differences in titration scores of untreated and DIDS-treated red cells tested with the 19 antisera used to assess antigen integrity. Antibody identification studies showed that DIDS-treated reagent red cells reacted similarly to untreated reagent red cells. In addition, DIDS resolved dextran-induced ABO serum grouping discrepancies. CONCLUSION: DIDS effectively resolved the serologic problems associated with the presence of rouleaux, without affecting the results of the test system itself. Implementation of this method to inhibit the rouleaux-forming properties of serum and plasma specimens can be useful in serologic testing.     

Population based standards for pulmonary function in non-smoking adults in Singapore

Abstract Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data ( n =406) for population-based reference values of lung function from randomly selected samples of healthy non-smoking adults of both gender (aged 20–79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), FEV₁/FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population-based reference values for assessment of pulmonary health and disease in Singapore     

小檗碱对局灶性脑缺血大鼠血小板聚集及血浆TXB2和6-keto-PGF1a水平的影响

以大鼠可逆性大脑中动脉梗塞(MCAO)致局灶性脑缺血为模型,观察小檗碱对大鼠MCAO24h后血小板粘附、聚集、血栓形成及血浆TXB2和PGI₂生成的影响。结果表明,小檗碱20mg·kg^-1·d^-1ipl,3或5d,明显降低MCAo24h后血小板粘附性及ADP、胶原和花生四烯酸诱导的血小板聚集率,抑制血浆TXB₂水平。同剂量ip3或5d,则抑制血栓形成。提示小檗碱可能通过其抗血小板粘附和聚集及影响花生四烯酸代谢而发挥抗脑缺血作用。     

MANAGEMENT OF NIDDM BY FAMILY DOCTORS IN HONG KONG: A QUESTIONNAIRE SURVEY

The management approach to non-insulin-dependent diabetes mellitus among family doctors in Hong Kong was studied using two case histories. In 1996, all 804 fellows, members and associate members of the Hong Kong College of Family Physicians were sent a letter and a questionnaire. Of the 512 who responded, 405 were male and 95 were female (12 were discarded) with ages ranging from 24 to 77 years (median 40). For the 48-year-old obese man who showed improvements in blood glucose and symptoms after diet for 6 weeks (Case 1), most respondents suggested adding a sulphonylurea (39.0%) or metformin (21.1%), or continuing diet (35.2%). Younger and more junior doctors tended to use metformin plus diet. Of 192 respondents who wanted to use a sulphonylurea, gliclazide (45.8%) and glibenclamide (42.7%) were chosen most often. For the 76-year-old overweight woman with symptomatic diabetes despite diet therapy (Case 2), most respondents suggested adding a sulphonylurea (41.9%), metformin (25.6%) or both (19.2%). Younger and more junior doctors tended to use metformin plus diet, whereas older doctors tended to use insulin plus diet. Older and more experienced doctors tended to use diet plus metformin and sulphonylurea. Of 208 respondents who wanted to use a sulphonylurea, gliclazide (47.8%) and glibenclamide (30.1%) were chosen most often. The management approach to NIDDM varied with the age and experience of the doctor.     

Bacteremia due to obligate anaerobes following large bowel surgery in a tertiary care hospital in South India

In view of the rising incidence of Anaerobic bacteremia(AB), the use of anaerobic blood culture bottles have been recommended in addition to the aerobic blood culture bottles. The need to perform antimicrobial susceptibility testing(AST) for anaerobes has become mandatory owing to increasing metronidazole resistance. The frequency of AB following large bowel surgery and the metronidazole susceptibility for members of the Bacteroides fragilis group were determined. The incidence of AB was found to be 16%. Seventeen obligate anaerobes were isolated in total, of which B. fragilis was the most common. Two of twelve isolates of B. fragilis were resistant to metronidazole.