Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas.

Although the link between the BRCA1 tumour-suppressor gene and hereditary breast and ovarian cancer is established, the role, if any, of BRCA1 in non-familial cancers is unclear. BRCA1 mutations are rare in sporadic cancers, but loss of BRCA1 resulting from reduced expression or incorrect subcellular localization is postulated to be important in non-familial breast and ovarian cancers. Epigenetic loss, however, has not received general acceptance due to controversy regarding the subcellular localization of BRCA1 proteins, reports of which have ranged from exclusively nuclear, to conditionally nuclear, to the ER/golgi, to cytoplasmic invaginations into the nucleus. In an attempt to resolve this issue, we have comprehensively characterized 19 anti-BRCA1 antibodies. These reagents detect a 220-kD protein localized in discrete nuclear foci in all epithelial cell lines, including those derived from breast malignancies. Immunohistochemical staining of human breast specimens also revealed BRCA1 nuclear foci in benign breast, invasive lobular cancers and low-grade ductal carcinomas. Conversely, BRCA1 expression was reduced or undetectable in the majority of high-grade, ductal carcinomas, suggesting that absence of BRCA1 may contribute to the pathogenesis of a significant percentage of sporadic breast cancers.

Bowel injury from rollerball ablation of the endometrium.

A woman underwent apparently uneventful rollerball endometrial ablation but presented with an acute abdomen 2 days later. At laparotomy, a large uterine serosal burn was found and a nearby loop of ileum contained two small injuries: a serosal burn and a perforation. The ileal injuries were oversewn and the patient recovered. Pathologic examination of the uterus showed full-thickness coagulative myometrial necrosis but no uterine perforation. More experience is needed to establish the incidence of this complication.

The probability of obtaining compatible blood from related directed donors.

Patients with alloantibodies may request directed blood donations from their relatives despite the lack of any scientific data suggesting that blood from these donors is safer. We have derived formulas that are applicable to any ethnic group for calculating the probability that a given class of relatives will have compatible blood for a given patient. These formulas apply to any non-X-linked blood group system (including the ABO and Rh systems) and are simple enough for routine blood bank use in advising patients as to how likely they are to obtain compatible donors. Use of these formulas may be helpful in counseling patients who may have difficulty in obtaining compatible directed donors because of antibodies or an unusual blood type. In general, the presence of an alloantibody should not automatically exclude a patient from utilizing directed donors. Moreover, for patients with antibodies to high-incidence antigens, directed donations from siblings may be the easiest way to obtain compatible blood.

Angiomatoid malignant fibrous histiocytoma. Cytology of fine-needle aspiration and its differential diagnosis.

A case of angiomatoid malignant fibrous histiocytoma was studied by fine-needle aspiration biopsy and routine histologic methods. Smears from aspirated material consisted of numerous large loose cellular aggregates with occasional single cells. Histiocytelike cells and lymphocytes were the prominent cell types with lesser numbers of spindle-shaped, fibroblastlike cells. Moderate cytologic atypia was noted. A cystic mass with the above cytologic findings occurring in the superficial soft tissue of the extremity of a young patient should suggest the diagnosis of an angiomatoid malignant fibrous histiocytoma.

Are retrospective peer-review transfusion monitoring systems effective in reducing red blood cell utilization?

OBJECTIVE: This research used a study-control group design and examined data collected from five hospitals to evaluate the effectiveness of retrospective peer-review systems on reducing utilization of red blood cells (RBCs). DESIGN: The effects of retrospective peer-review systems were studied in three parts: (1) trends of RBC utilization were compared by the slopes of linear regression lines that assessed the effect of time on RBC utilization among four study hospitals and one control hospital, (2) diagnosis-specific RBC utilization was compared between the control hospital and one matched study hospital, and (3) the effect of the retrospective review system of one study hospital was assessed by linear regression using data accumulated 1 year before and 2 years after implementation of the program. RESULTS: Three study hospitals showed no significant changes in RBC utilization during the 10-month study period. One study hospital and the control hospital demonstrated trends of reduced RBC use with negative slopes of regression lines; however, there was no difference in the degree of the two slopes, and the diagnosis-specific RBC utilization was not lower at the study hospital than at the control hospital. Furthermore, implementation of the retrospective peer-review system at one study hospital demonstrated no effect on RBC utilization. CONCLUSIONS: We conclude that the retrospective peer-review systems implemented at these four hospitals had no effect on reducing red blood cell utilization.

Expectant management of focal nodular hyperplasia during pregnancy. A case report.

A patient with unresectable focal nodular hyperplasia of the liver completed an uncomplicated pregnancy. Although there is a risk of hepatic rupture during pregnancy, expectant management may be an option for some cases of focal nodular hyperplasia.

Pleomorphic adenoma of the breast: cytology of fine-needle aspiration and its differential diagnosis.

The cytologic findings of a case of pleomorphic adenoma of the breast are presented. This rare tumor appeared identical to pleomorphic adenoma of salivary glands. It presented diagnostic difficulties, however, because of its rarity and the fact that its associated clinical findings suggested a malignancy. The cytologic differential diagnosis includes a phyllodes tumor, fibroadenoma, and metaplastic carcinoma. Awareness of this entity should permit a definitive diagnosis by aspiration biopsy.

Light and electron microscopic characteristics of signet-ring adenocarcinoma cells in serous effusions and their distinction from mesothelial cells.

Signet-ring adenocarcinoma cells in serous fluids have been classically described as possessing vacuolated cytoplasm and eccentrically placed, crescent-shaped nuclei. We studied serous fluids from six patients that contained signet-ring adenocarcinoma cells by light microscopy; one case was also studied by transmission electron microscopy. We found that the adenocarcinoma cells were more often present in a non-signet-ring configuration. The typical crescent-shaped nucleus was rarely displayed in smears and may be seen only in the cell-block preparation. Special stains (PAS, mucicarmine and Diff-Quick) showed globular cytoplasmic positivity in signet-ring adenocarcinoma cells but not in mesothelial cells. Significant characteristic electron microscopic findings in the signet-ring adenocarcinoma cells included (1) cytoplasmic lumens or invaginations or both, (2) cytoplasmic protrusions and (3) mucin granules of various sizes and densities. Singly or in combination, all of the above features were located on one side of the nucleus, which suggests that signet-ring adenocarcinoma cells retain some degree of cellular polarity.

A morphologic and morphometric study of cells from colloid carcinoma of the breast obtained by fine needle aspiration. Distinction from other breast lesions.

Morphologic and morphometric studies were carried out on eight cases of pure and mixed colloid carcinoma of the breast initially diagnosed by fine needle aspiration (FNA). Key morphologic features included (1) cellular smears, (2) single cells, loose aggregates and cohesive groups of cells bathed in a mucinous background, (3) single cells displaying nuclear eccentricity and (4) little variation in nuclear size or shape, with bland-to-accentuated chromatin and rare nucleoli. These morphologic features are compared with those observed in pregnancy adenoma, lobular carcinoma, fibroadenoma, ductal carcinoma and medullary carcinoma. A morphometric study employing the major and minor axes of the nucleus, its axis product and axis ratio was also performed. Statistical treatment confirmed that the nuclear axis product (a size factor) distinguished colloid carcinoma from the other breast lesions, except the small-cell type of ductal carcinoma. Furthermore, the nuclear axis ratio (a shape factor) discriminates pregnancy adenoma and small-cell ductal carcinoma from the other breast lesions studied. By combining morphologic and morphometric criteria, one can specifically separate colloid carcinoma from the other breast lesions when examining smears obtained by FNA. Since colloid carcinoma is usually composed of cells with a relatively benign-appearing cytomorphology, the importance of recognizing this entity in fine needle aspirates is emphasized.

Transfusion-associated graft-versus-host disease: do transfusions from second-degree relatives pose a greater risk than those from first-degree relatives?

When a patient receives blood from a closely related donor, there is the potential for transfusion-associated graft-versus-host disease (TA-GVHD). With a mathematical model, the potential risk of TA-GVHD was derived for six classes of related donors. This risk was considered to be present when an HLA-heterozygous patient received blood from a donor who was homozygous for one of the patient's haplotypes. Calculations showed that second-degree related donors present a greater risk of TA-GVHD than some (siblings) but not all (parents, children) first-degree related donors. Moreover, there is, in general, no sharp cutoff of risk among the various classes of donors. These results should be considered in the determination of a policy for the irradiation of directed-donor units.

Derivation of new mathematic formulas for determining whether a D-positive father is heterozygous or homozygous for the D antigen.

OBJECTIVES: This article derives new mathematic formulas to calculate the probability that the husband of a D-negative woman is heterozygous for the D antigen. STUDY DESIGN: Current published formulas and tables that estimate this probability are biased in that they incorrectly assume that the father is randomly selected from the general population. With Bayes' theorem, new formulas were derived to eliminate this bias. RESULTS: The probability of the husband being homozygous or heterozygous for the D antigen can be expressed as a function of the number of previous D-positive children. If he has any D-negative children, he is an obligate heterozygote. CONCLUSION: Previously published formulas and tables that estimate the likelihood of the father being heterozygous or homozygous at the D locus should no longer be used in the obstetric setting.

The transfusion audit as a tool to improve transfusion practice: a critical appraisal.

Transfusion audits have a long history and they are required by many regulatory agencies. These audits have been touted as effective in reducing unnecessary transfusions as evidenced by many published articles on the subject. Most of these studies, however, have one or more flaws in their design including the use of historical controls, disregard of the Hawthorne effect, use of multiple interventions, and publication bias. Studies differ in the baseline rate of inappropriate transfusions and have different methods of measuring these rates. There is also little data on how long the effect of implementing a transfusion audit system may last. Transfusion audits appear most successful when there is a high baseline rate of inappropriate transfusions and interventions other than the audit itself are performed. Individual institutions should critically evaluate whether or not their current system of transfusion audits is useful.

Accuracy of statistical methods in TRANSFUSION: a review of articles from July/August 1992 through June 1993.

BACKGROUND: Statistical errors have been noted in a large percentage of articles appearing in medical journals. Their incidence in a blood banking journal, however, has not been studied. STUDY DESIGN AND METHODS: Original articles appearing in the journal TRANSFUSION from July 1992 through June 1993 were analyzed for correctness of statistical methods. Each article was reviewed by both a transfusion medicine physician and a statistician. RESULTS: There were 122 original articles, of which 59 contained statistical methods and were reviewed. Of these, 23 (39%) contained an error in the statistical description of their data, 47 (80%) failed to describe clearly the statistical tests performed, and 44 (75%) involved an incorrect statistical test or contained an error in test calculation or interpretation. As a result of these errors, 13 (22%) of the 55 articles analyzed reported conclusions not supported by the data. CONCLUSION: Misuse of statistical methodology may not be uncommon in transfusion medicine research, and it would be prudent to give more attention to statistical methodology in such research.

Risk of hemolytic disease of the newborn as a result of directed donations from relatives.

Women of childbearing age are more and more often requesting directed blood donations from their husbands or other relatives. With a mathematical model, the risk was derived of such transfusions causing hemolytic disease of the newborn (HDN) in subsequent pregnancies. Calculations were performed for six classes of relatives of the recipient and her husband and for four racial groups. In general, the risk of HDN increases with the donor's degree of relatedness to the husband and decreases with the donor's degree of relatedness to the recipient in a fairly continuous manner. The relative risk for subsequent HDN was as high as 4.1 if the husband donated. The risk varied with the recipient's race as well as Rh(D) status. Although small, the risk involved in transfusing a woman of childbearing age with blood from her husband or his relatives should be considered when using directed donors.

Urinary infection in infants and preschool children. Five-year follow-up.

A group of 1,617 infants and 1,711 preschool children were studied for symptomatic and asymptomatic urinary infection and followed up for three to five years. Asymptomatic bacteriuria was found in 1.8% of female infants, 0.5% of male infants, 0.8% of preschool girls, and none of the preschool boys. Seventeen percent of the infants and 13% of the preschool children with urinary infection studied roentgenographically had upper tract damage; 46% of the infants and 9% of the preschool children had vesicoureteral reflux. Infants with normal urinary tracts and urinary infection with or without reflux tended to have recurrent infection, whereas the kidneys remained anatomically normal. The infants with high-risk lesions, such as obstructive uropathy and vesicoureteral junction ectopia and deformity, had substantial bacteriuria on screening culture.

Preoperative autologous blood donations before elective hysterectomy.

OBJECTIVE: To determine whether preoperative autologous blood donation is justified for patients undergoing elective abdominal or vaginal hysterectomy. DESIGN: Retrospective cohort study. PATIENTS AND SETTING: A total of 263 consecutive patients admitted for elective abdominal or vaginal hysterectomy to a community health maintenance organization hospital during 1993 and 1994. MAIN OUTCOME MEASURES: Evaluation of transfusion rates for patients who did and did not donate autologous blood; determination of any risk factors that would predict the need for transfusion; and evaluation of the need for transfusion based on chart review. RESULTS: Of 263 patients, 26 received a blood transfusion. The major risk factor identified for transfusion was the donation of autologous blood. Of 140 patients who donated autologous blood, 25 were transfused, whereas just 1 patient of 123 who did not donate autologous blood was transfused (P<.001). Patients who donated autologous blood had significantly lower mean admission hemoglobin level than patients who did not donate (119 g/L vs 132 g/L; P<.05); logistic regression showed that autologous donation was an independent risk factor for transfusion. CONCLUSION: For hysterectomy patients, donation of autologous blood causes anemia and is associated with a more liberal transfusion policy. These 2 factors result in a markedly increased incidence of transfusion with its associated risks. Elimination of preoperative autologous donation for these patients should not result in frequent exposure to allogeneic blood.

A study of an educational intervention to decrease inappropriate preoperative autologous blood donation: its effectiveness and the effect on subsequent transfusion rates in elective hysterectomy.

BACKGROUND: Decreasing the overcollection of preoperative autologous blood is difficult to achieve. The purpose of this study was to determine whether an educational intervention designed to outline the risks of preoperative autologous collection can decrease such donations and, if so, to determine how this decrease will affect subsequent transfusion rates. STUDY DESIGN AND METHODS: An educational intervention consisting of a didactic presentation to the Department of Gynecology staff about the risks and benefits of autologous blood was implemented. Written material with similar information was given to patients. Subsequently, the percentage of patients donating autologous blood, the number of autologous units donated, and the rates of transfusion in patients eligible for autologous donation who were admitted for elective abdominal or vaginal hysterectomy were measured. These rates were compared to those in similar patients admitted in the 2 years before the educational intervention. RESULTS: After an educational intervention, the proportion of patients donating autologous blood decreased from 53 percent to 26 percent (p<0.01), and the number of units collected per patient decreased from 0.86 to 0.31 (p<0.01); this resulted in a savings of 80 autologous donations per year. Despite no difference in estimated blood loss (p = 0.46), the overall transfusion rate decreased from 10 percent to 3.7 percent (p = 0.03), while the allogeneic transfusion rate demonstrated no significant change (1.1% vs. 2.2%; p = 0.40). CONCLUSIONS: Unnecessary preoperative autologous donations by elective hysterectomy patients can be decreased by educating physicians and patients about the risks of preoperative autologous blood donation. Decreasing such unnecessary donations can decrease the subsequent autologous transfusion rate, with its attendant risks, without increasing the risk of allogeneic transfusion.