The risk of alloimmunization to c (Rh4) in R1R1 patients who present with anti-E

BACKGROUND: Because the Rh antigens E (Rh3) and c (Rh4) are relatively immunogenic, it has been suggested that R1R1 (E-, c-) patients who present with anti-E alone receive prophylactic c- (Rh: -4) red cell transfusions. STUDY DESIGN AND METHODS: To determine the utility of this approach, the transfusion records of 100 consecutive R1R1 patients with anti-E identified over a 6-year period were reviewed. RESULTS: Thirty-two (32%) had anti-c concurrent with anti-E. Twenty-seven of the 68 patients who presented with anti-E alone received random (i.e., not typed for c [Rh4]) red cell transfusions. Five (18.5%) of the 27 subsequently developed anti-c 13 to 193 days (mean, 50) after transfusion of 2 to 14 (mean, 8) red cell units. None of the five had clinical evidence of hemolysis that could be attributed to a delayed hemolytic transfusion reaction. Twenty-two (81.5%) of the 27 failed to develop anti-c even after transfusion of 1 to 41 (mean, 9; median, 7) red cell units. CONCLUSION: The overall rate of immunization to c (Rh4) antigen in R1R1 patients with anti-E was 37 percent. Production of anti- c following transfusion to R1R1 patients with anti-E occurred in 18.5 percent of the cases in this series, which could have been avoided by the prophylactic use of R1R1 (E-, c-) blood for transfusion. The prophylactic use of c- (Rh: -4) blood in this patient population may be justified by the high immunization rate and the potential risk of delayed hemolytic transfusion reaction.     

Informed consent for blood transfusion: a regional hospital survey

Ninety-two hospitals in a three-state mid-Atlantic region were surveyed to determine their policy toward obtaining written informed consent for transfusion and to examine the content of written consent documents and the process by which consent is obtained. Of 81 hospitals responding, 50 (62%) required written informed consent. Hospitals with fewer than 200 beds were more likely to require written informed consent. The attending physicians had responsibility for obtaining consent in 28 (57%) of 49 institutions, most often on the day or evening before surgery. Twenty-seven of 48 forms mentioned complications: hepatitis in 80 percent, human immunodeficiency virus infection in 46 percent, nonhemolytic reactions in 32 percent, and hemolysis in 25 percent. Alternatives to allogeneic transfusion were mentioned infrequently; eight hospital forms listed autologous transfusion options and only two mentioned designated donation. The reading level required to comprehend 34 consent forms submitted was grade 14.6, which has been attained by only 23 percent of the adult United States population. Although the majority of respondent institutions require written informed consent, those forms, per se, do not document that the fundamental tenets of informed choice have been applied to the decision to transfuse blood.     

Increased rotational mobility and extractability of band 3 from protein 4.2-deficient erythrocyte membranes: evidence of a role for protein 4.2 in strengthening the band 3-cytoskeleton linkage

Band 3 (anion-exchange protein 1-[AE1]) is the major integral membrane protein of human erythrocytes and links the membrane to the underlying cytoskeleton via high-affinity binding to ankyrin. It is unclear whether other cytoskeletal proteins participate in strengthening the ankyrin-band 3 linkage, but a putative role for protein 4.2 (P4.2) has been proposed based on the increased osmotic fragility and spherocytic morphology of P4.2-deficient red blood cells (RBCs). The present study was designed to investigate the hypothesis that P4.2 has a direct role in strengthening the band 3-cytoskeleton linkage in human RBCs, by measuring independent features of this interaction in normal and P4.2- deficient RBCs. The features examined were the rotational mobility of band 3 assayed by time-resolved phosphorescence emission anisotropy (TPA), and the extractability of band 3 by octyl-beta-glucoside, the latter being a nonionic detergent that selectively extracts only band 3 that is not anchored to the cytoskeleton. We find that the amplitude of the most rapidly rotating population of band 3 (correlation time, approximately 30 to 60 microseconds) is increased 81% and 67% in P4.2- deficient ghosts (P4.2NIPPON and band 3MONTEFIORE, respectively) compared with control ghosts. The amplitude of the intermediate speed rotating population of band 3 (correlation time, approximately 200 to 500 microseconds) is increased 23% and 8% in P4.2-deficient ghosts (P4.2NIPPON and band 3MONTEFIORE, respectively) compared with control ghosts, at the expense of the slowly rotating component (correlation time, approximately 2,000 to 3,000 microseconds, amplitude decreased 43% and 39% in P4.2NIPPON and band 3MONTEFIORE, respectively) and immobile component (immobile on this experimental time scale; amplitude decreased 26% and 10% in P4.2NIPPON and band 3MONTEFIORE, respectively) of band 3. These results demonstrate that P4.2 deficiency partially removes band 3 rotational constraints, ie, it increases band 3 rotational mobility. The nonionic detergent octyl-beta-glucoside, which does not disturb band 3-cytoskeleton associations, ie, it extracts only band 3 that is not attached to the cytoskeleton, extracted 30% and 61% more band 3 from P4.2NIPPON and band 3MONTEFIORE ghost membranes, respectively, compared with control ghosts. The octyl-beta-glucoside ghost extracts from both P4.2-deficient phenotypes were enriched in band 3 oligomeric species (tetramers, higher-order oligomers, and aggregates) compared with controls. Since band 3 oligomers selectively associate with the cytoskeleton, these results are consistent with a weakened band 3-cytoskeleton linkage in P4.2-deficient RBC membranes. P4.2 deficiency does not affect band 3 anion transport activity, since uptake of radiolabeled sulfate was similar for control and P4.2- deficient RBCs. Thus, we propose that P4.2 directly participates in strengthening the band 3-cytoskeleton linkage.     

A case of sarcomatoid carcinoma of the skin

We describe the histological and immunocytochemical findings of an exophytic cutaneous tumour with mixed features of atypical fibroxanthoma (AFX) and basal cell carcinoma (BCC). A 73-year-old woman presented with a rapidly growing tumour measuring 35 mm in diameter and 10 mm in height on the left forearm. The tumour was excised and histology revealed a biphasic tumour with a pleomorphic spindle cell component and an associated tumour composed of discrete islands of atypical basaloid cells with peripheral palisading consistent with BCC. The two tumours merged into each other at one point. The spindle cell tumour showed a positive immunocytochemical reaction to fibrohistiocytic marker of KP-1 (CD68) and a negative immunocytochemical reaction to AE1/AE3, CAM5.2, S-100 and HMB-45, features consistent with AFX. Immunocytochemistry of the basaloid tumour showed a positive reaction to epithelial markers AE1/AE3 and CAM5.2, and a negative reaction to S-100, HMB-45 and KP-1 (CD68). To date, 15 cases of primary cutaneous carcinosarcoma have been reported in the literature. It has been postulated that these tumours may originate from undifferentiated progenitor cells capable of producing multiple cell lines.     

Traditional and commercial alcohols and esophageal cancer risk in Kenya

Squamous cell esophageal cancer is common throughout East Africa, but its etiology is poorly understood. We investigated the contribution of alcohol consumption to esophageal cancer in Kenya, based on a hospital-based case–control study conducted from 08/2013 to 03/2018 in Eldoret, western Kenya. Cases had an endoscopy-confirmed esophageal tumor whose histology did not rule out squamous cell carcinoma. Age and gender frequency-matched controls were recruited from hospital visitors/patients without digestive diseases. Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CI) adjusting for tobacco (type, intensity) and 6 other potential confounders. A total of 422 cases (65% male, mean at diagnosis 60 (SD 14) years) and 414 controls were included. ORs for ever-drinking were stronger in ever-tobacco users (9.0, 95% CI: 3.4, 23.8, with few tobacco users who were never drinkers) than in never-tobacco users (2.6, 95% CI: 1.6, 4.1). Risk increased linearly with number of drinks: OR for >6 compared to >0 to ≤2 drinks/day were 5.2 (2.4, 11.4) in ever-tobacco users and 2.1 (0.7, 4.4) in never-tobacco users. Although most ethanol came from low ethanol alcohols (busaa or beer), for the same ethanol intake, if a greater proportion came from the moonshine chang'aa, it was associated with a specific additional risk. The population attributable fraction for >2 drinks per day was 48% overall and highest in male tobacco users. Alcohol consumption, particularly of busaa and chang'aa, contributes to half of the esophageal cancer burden in western Kenya.