Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in self-diagnosed individuals, dosage effect, and sibling risk

BACKGROUND: Celiac disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten. Traditionally, diagnosis is made by intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the serum also is used for diagnosis. Biopsy and serology revert to normal with adherence to a gluten-free diet. Often, after an index case is diagnosed, siblings with symptoms adhere to a gluten-free diet without biopsy or serologic confirmation. More than 90% of patients with celiac disease have the human leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have been implicated. METHODS: One hundred ninety-five individuals with confirmed or suspected celiac disease were identified in 73 families affected by the disease. IgA endomysial antibody testing was performed for all symptomatic family members who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276 and the HLA class II loci DQA and DQB. RESULTS: At the time sampling was begun in families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology) had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69) of cases self-diagnosed (adherence to gluten-free diet without confirmation) had at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is estimated that the HLA association and other unlinked genes contribute approximately equally to the sibling risk of celiac disease. CONCLUSIONS: A dosage effect of DQB1*0201 may be associated with an increased risk of celiac disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in families in the United States. Diagnosis of celiac disease on the basis of clinical response to gluten restriction is inaccurate. With long-term adherence to a gluten-free diet, serologic test results are likely to be negative. Based on HLA genotype, approximately one third of self-diagnosed individuals are unlikely to have celiac disease. However, it is not possible to determine which individuals consuming a gluten-free diet have the disease. Therefore, before starting a gluten-free diet, serologic screening and biopsy confirmation are necessary.     

Sensitivity to vecuronium in myasthenia gravis: a dose-response study

A cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle were used to determine the potency of vecuronium in 20 normal patients and in ten patients with myasthenia gravis under thiamylal, N2O, O2, fentanyl anaesthesia. The mean (+/- SEM) values for ED50, ED90, and ED95 in the normal patients were 19 +/- 1, 31 +/- 1 and 36 +/- 2 micrograms.kg-1, respectively. Myasthenic patients showed increased sensitivity to vecuronium, the mean values for ED50, ED90, and ED95 were 10 +/- 2, 17 +/- 2 and 20 +/- 3 micrograms.kg-1, being 50, 55 and 56 per cent of normal, respectively. We did not demonstrate a difference in sensitivity to vecuronium between those myasthenic patients who received pyridostigmine preoperatively and those who did not, nor among those chronically treated with corticosteroids, compared with those who were not.     

Risk Factors for Intimate Partner Violence and Associated Injury Among Urban Women

The objective of this study was to identify risk factors for abuse and IPV related injury among an urban population. This study reports an additional analysis of a case-control study conducted from 1994 to 2000 in 11 USA metropolitan cities where of 4746 women, 3637 (76.6%) agreed to participate. Control group women (N = 845) were identified through random digit dialing. Significant risk factors for abuse included women’s young age (adjusted odds ratio (AOR) 2.05 p = .011), being in fair or poor mental health (AOR 2.65 p < .001), and former partner (AOR 3.33 p < .001). Risk factors for partners perpetrating IPV included not being a high school graduate (AOR 2.06 p = .014), being in fair or poor mental health (AOR 6.61 p < .001), having a problem with drug (AOR 1.94 p = .020) or alcohol use (AOR 2.77 p = .001), or pet abuse (AOR 7.59 p = .011). College completion was observed to be protective (AOR 0.60, p < .001). Significant risk factors for injury included partner’s fair or poor mental health (AOR 2.13, p = .008), suicidality (AOR 2.11, p = .020), controlling behavior (AOR 4.31, p < .001), prior domestic violence arrest (AOR 2.66, p = .004), and relationship with victim of more than 1 year (AOR 2.30, p = .026). Through integration of partner related risk factors into routine and/or targeted screening protocols, we may identify more abused women and those at greater risk of abuse and injury.     

Urosepsis. Current therapy and diagnosis

Urosepsis is defined as sepsis caused by urinary tract infection. This occurs in 25% of all sepsis cases. Because of the increasing incidence of sepsis, this entity will be seen more frequently in medical practice and outpatient units. The immediate identification and treatment of the septic focus is crucial. Depending on severity, early reconstitution of adequate oxygen delivery has parallel priority, therefore necessitating intensive care unit treatment within the first hours. Therapy should consist of eliminating the infectious focus, antimicrobial treatment, supportive therapy, and special sepsis therapy.     

Ethical analysis of living organ donation

In 2003, the first 3-way living kidney donor-swap was performed at Johns Hopkins Hospital in Baltimore, Md. Three new donor protocols includingpaired donation now allow unrelated individuals to serve as donors. Some ethicists have suggested that emotionally unrelated individuals not be permitted to donate because they will not experience the same satisfaction that a family member who is a donor experiences. Others who frame living donation as an autonomous choice do not see emotionally unrelated or even nondirected donation as ethically problematic. This article uses an ethical framework of principlism to examine living donation. Principles salient to living donation include autonomy, beneficence, and nonmaleficence. The following criteria are used to evaluate autonomous decision making by living donors, including choices made (1) with understanding, (2) without influence that controls and determines their action, and (3) with intentionality. Empirical work in these areas is encouraged to inform the ethical analysis of the new living donor protocols.     

Removal of therapeutic anti-lymphocyte antibodies from human sera prior to anti-human leukocyte antibody testing

Both monoclonal (e.g. Orthoclone (OKT3®), rituximab) and polyclonal (e.g. ATGAM®, Thymoglobulin® (Thymo)) anti-lymphocyte Abs (ALAs) are used extensively in organ transplantation for immunosuppression induction, desensitization, and treatment of acute rejection. ALAs often interfere with post transplant immunologic monitoring. We describe a method that uses magnetic beads to selectively remove ALAs from patient serum. Rabbit anti-mouse Fc-specific (180 μg), or rabbit anti-mouse Fab-specific (180 μg), or rabbit anti-horse heavy and light chain-specific and rabbit anti-horse F(ab')₂ (200 μg) (Jackson Immunoresearch) was adsorbed to 6.7 × 10⁸ Dynabeads M-280 conjugated with sheep anti-rabbit IgG (Dynal Biotech). Fifty microliters of normal human serum (NHS) with 2 μg/ml of OKT3 or 100 μg/ml ATGAM, Thymo, or rituximab were incubated with conjugated beads for several incubations. NHS containing ALAs before and after treatment by the protocol were incubated with human lymphocytes and labeled with FITC-antibody to immunoglobulin of the species used to produce the particular ALA. Residual ALA was determined using flow cytometry. Average median channel for serum with or without ALA was 11.1 and 0.120, respectively for OKT3; 64.4 and 0.344 for ATGAM; 108.5 and 0.200 for Thymo; and 1022.5 and 11.4 for rituximab. Treatment lowered the median channel for serum with OKT3 to 0.103, 0.309 for ATGAM, 0.199 for Thymo, and 12.1 for rituximab. ALAs can be effectively removed from serum by the use of magnetic beads conjugated with Ab specific for ALA thereby permitting immunologic monitoring without interference.