Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Baka) detectable only in whole platelet assays.

BACKGROUND: Maternal antibodies that cause neonatal alloimmune thrombocytopenia are commonly identified by solid-phase assays that detect the causative antibodies on the basis of their reactions with specific PLT glycoproteins. Two cases of severe neonatal alloimmune thrombocytopenia caused by maternal antibodies specific for human PLT antigen 3a (HPA-3a [Baka]) that failed to give the expected reactions in some solid-phase assays were recently encountered. STUDY DESIGN AND METHODS: PLT-reactive antibodies were characterized by three different solid-phase assays and by flow cytometry. RESULTS: The two maternal antibodies gave negative reactions in the antigen capture ELISA, modified antigen capture ELISA, and MoAb immobilization of PLT antigens tests but reacted strongly in flow cytometry with intact PLTs that were HPA-3a+. Other sera samples specific for HPA-3a reacted equally well in all assays. CONCLUSIONS: The two antibodies appear to recognize an epitope on the HPA-3a+ form of glycoprotein IIb that is lost when PLTs are solubilized in detergent, as required for solid-phase assays. The diagnosis was made in these cases because no HLA antibodies were present, allowing an HPA-3a-specific reaction to be identified with intact PLTs as targets. Such antibodies are likely to be overlooked when HLA antibodies are also present.

Chemiluminescence nitrogen detection in ion chromatography for the determination of nitrogen-containing anions.

Chemiluminescence nitrogen detection (CLND) provides equimolar response for nitrogen-containing ions such as nitrate, nitrite, cyanide, ammonium and tetradecyltrimethylammonium. Only azide yields a lower response. Nitrite, azide and nitrate are separated on a Dionex AS11 column using 5 nM NaOH as eluent with a 3 microM (1 ng N) limit of detection. Matrices, such as 1:10 diluted seawater, do not degrade these detection limits. CLND also provides equally sensitive (limit of detection 3 microM, 78 ppb) detection of weak acids such, as cyanide, which yield poor sensitivity with suppressed conductivity detection.

Hyperfractionated radiation therapy plus chemotherapy in locally advanced cervical cancer: results of two phase I dose-escalation Gynecologic Oncology Group trials.

OBJECTIVE: The aims of this study were to assess the early and late toxicities of multiple-daily-fraction whole pelvic radiation plus concurrent chemotherapy with either hydroxyurea or 5-fluorouracil (5-FU)/cisplatin and to determine the maximum tolerated external radiation dose in conjunction with brachytherapy, when given with either of these drug regimens, as treatment for locally advanced carcinoma of the cervix. METHODS: The first study (GOG 8801) of 38 patients utilized hydroxyurea as a single oral dose of 80 mg/kg to a maximum of 6 g at least 2 h prior to a radiation treatment twice every week. In the second study (GOG 8901) of 30 patients, cisplatin and 5-FU were used concomitantly with radiotherapy. Fifty milligrams per square meter of cisplatin was administered on days 1 and 17 of external radiation. 5-FU was given by continuous intravenous infusion at a dose of 1000 mg/m(2)/day for 4 consecutive days on days 2, 3, 4, 5, and 18, 19, 20, and 21 of external radiation therapy. Both studies utilized external radiation given by an accelerated hyperfractionated regimen of 1.2 Gy per fraction, two fractions per day. All patients were treated 5 days per week with a minimum of 4 h between fractions. RESULTS: Acute toxicity was manageable on both protocols but nausea, vomiting, and myelosuppression were more severe with hydroxyurea. Chronic toxicity was primarily enteric and appeared to be dose-related. There was no obvious correlation seen between pelvic failure rates and the radiation dose or between the chemotherapy regimens used. CONCLUSIONS: The defined maximal tolerated dose of whole pelvic radiation was 57.6 Gy in 48 fractions which could be delivered in a hyperfractionated setting with concomitant chemotherapy, followed by brachytherapy. Follow-up is now sufficient that further adverse events should be rare.

Antibodies to Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in patients with multiple myeloma.

Kaposi's sarcoma-associated herpesvirus (KSHV) serologic assays were used to detect specific antibodies to KSHV lytic and latent antigens in 27 patients with multiple myeloma, 27 control patients with other cancers, and 50 random blood donors. Antibodies to KSHV recombinant minor capsid antigen orf65 were found in 81% of patients with multiple myeloma, 22% of control patients with other cancers, and 6% of the blood donors. Antibodies to KSHV latent nuclear antigens were found in 52% of patients with multiple myeloma, 26% of control patients with other cancers, and 2% of the blood donors. All of the 11 patients with progressive multiple myeloma were KSHV-seropositive. Antibodies to Epstein-Barr virus nuclear antigen 1 were present in 89% of patients with multiple myeloma, 93% of control patients with other cancers, and 88% of the blood donors. These data support the possible association of KSHV infection with multiple myeloma, particularly with progressive disease.

Ureteral carcinoma presenting as a complex pelvic mass in a post menopausal patient.

This is a report of a low-grade ureteral carcinoma presenting as a pelvic mass in a postmenopausal woman with a prolonged history of lower back pain. A right complex adnexal mass and right hydroureter and hydronephrosis in an atrophic nonfunctioning right kidney was found during evaluation for the back pain. Operative evaluation revealed a normal uterus and ovaries; however, a 2 x 3-cm mass in the right ureter was found at the level of the uterine arteries. A total abdominal hysterectomy, bilateral salpingo-oophorectomy, and right nephroureterectomy were performed with pathology returning grade I papillary transitional cell carcinoma of the ureter.

Practice parameter for the use of red blood cell transfusions: developed by the Red Blood Cell Administration Practice Guideline Development Task Force of the College of American Pathologists.

A practice parameter has been developed to assist physicians in the therapeutic use of red blood cell transfusions. The developers of this parameter used the best available information from the medical literature, as well as clinical experience and the extensive reality testing required by the College of American Pathologists for approval. In acute anemia, a fall in hemoglobin values below 6 g/dL or a rapid blood volume loss of more than 30% to 40% requires red blood cell transfusions in most patients. However, tissue oxygenation provides a better indication of physiologic need in situations where invasive monitoring provides this information. When these data are not available, heart rate and blood pressure measurements and the nature of bleeding (active, controlled, uncontrolled) supplement the hemoglobin value in guiding the transfusion decision. In sickle cell disease and thalassemias, red blood cells are transfused to prevent acute or chronic complications. Red blood cell transfusions are used in chronic anemias unresponsive to pharmacologic agents based on the patient's symptoms. Guidelines must be altered for neonates who require an increase in hematocrit to above 0.30 to 0.35 when respiratory distress is present. Indications for red blood cell transfusion for the pregnant or postpartum patient are similar to those for the nonpregnant patient. Risks of transfusion, particularly transmissible disease and incompatibility, remain but have been reduced. Thus, red blood cell transfusion continues to be a powerful therapeutic tool when used judiciously and carries less risk than in the recent past.

Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans.

We have carried out two independent family studies in low-income Mexican-Americans from San Antonio, Texas. In the first study, probands were ascertained at random without regard to any medical condition (658 examined individuals from 50 families), and in the second study, probands were subjects with type II diabetes identified in a prior epidemiological survey (523 examined individuals from 29 families). Pedigrees ranging in size from 2 to 45 family members (median 11) in the first study and from 2 to 50 family members (median 12) in the second study were examined. Diabetes was diagnosed according to World Health Organization criteria. In both sets of families, segregation analyses revealed support for a major gene with an autosomal dominant mode of inheritance influencing early age of onset of diabetes. Non-Mendelian inheritance was rejected in both data sets. Individuals with the early age of onset allele had a mean age of diabetes onset of 51 years in the first data set and 60 years in the second data set. In the first data set, the major gene accounted for approximately 70% of the phenotypic variance in age of onset of diabetes, and there were no residual family effects once the major gene effect was taken into account. In the second data set, the major gene accounted for approximately 50% of the phenotypic variance, and residual family effects were statistically significant. Linkage analyses were performed with 11 candidate genes, and tight linkage with diabetes was rejected for Rh blood group, glucose transporter 2, fatty acid-binding protein, tumor necrosis factor beta, glucokinase, and lipoprotein lipase. A logarithm of odds (LOD) score of 0.92 at a recombination fraction of 0.05 was observed for insulin receptor substrate 1. This LOD score corresponds to a chi2 of 4.24 (P = 0.039).

Yersinia enterocolitica bacteremia associated with red blood cell transfusion.

A chronically ill, 80-year-old man received over three fourths of a unit of CPDA-1 red blood cells contaminated with Yersinia enterocolitica serotype 0:3. He experienced rigors, high fever, elevated blood pressure, and increased pulse rate. He was treated with antibiotics and discharged in stable condition 6 days later. The blood donor, an Air Force recruit, was asymptomatic at the time of donation but recalled having had diarrhea 4 days earlier. In addition, several other flight members were reported to have had diarrhea at the same time. Serologic evidence suggested that the donor had had a recent infection with Y enterocolitica serotype 0:3.

Evidence for linkage of postchallenge insulin levels with intestinal fatty acid-binding protein (FABP2) in Mexican-Americans.

Single genes with large effects may contribute to insulin resistance or influence susceptibility to non-insulin-dependent diabetes mellitus (NIDDM). In the Pima Indians, results from sib-pair analysis have suggested that a gene on chromosome 4q influences both fasting insulin levels and maximal insulin action. We conducted sib-pair and logarithm of odds (LOD)-score linkage analysis to seek evidence for linkage between genes influencing insulin levels and chromosome 4q loci. Analyses were conducted on nondiabetic individuals from 28 different families participating in the San Antonio Family Diabetes Study. All subjects received a 2-h oral glucose tolerance test. Fasting insulin levels were measured in 382 nondiabetic individuals, and 2-h insulin levels were measured in 366 individuals. Initial sib-pair linkage analysis revealed a possible association between 2-h post-glucose challenge insulin levels and the intestinal fatty acid-binding protein (FABP2) locus located in the region of chromosome 4q28-31 (P = 0.006). Subsequent sib-pair linkage analysis of 11 additional chromosome 4q markers supported this hypothesis. We next conducted segregation analyses to estimate allele frequencies and other model parameters for the putative locus influencing 2-h insulin levels. Results of LOD-score linkage analysis indicated possible linkage between the major gene described by the segregation model and FABP2. Using combined segregation and linkage analysis, we obtained a LOD-score of 2.80 at recombination frequency of 0.0 between FABP2 and the putative locus influencing 2-h insulin levels. The maximum likelihood estimate of the allele associated with low insulin levels was 0.21.(ABSTRACT TRUNCATED AT 250 WORDS)

Unusual intramural gastric metastasis of recurrent epithelial ovarian carcinoma.

Epithelial ovarian carcinoma regularly metastasizes to peritoneal surfaces throughout the abdomen and pelvis. Gastrointestinal involvement is usually limited to seromuscular involvement of the small and large bowel and its mesentery. Gastrointestinal invasion is most often superficial, mesentery is shortened, and intestinal lumens are narrowed. Transmural invasion is less common, as is gastrointestinal hemorrhage. We present a case of life-threatening intralumenal gastric hemorrhage from an intramural gastric metastasis of epithelial ovarian carcinoma effectively palliated with a gastric resection. Intralumenal gastric metastasis represents an unusual trophism of recurrent epithelial ovarian carcinoma. Surgical intervention for life-threatening hemorrhage, while not curative, may provide effective palliation in the otherwise fully functional patient and thereby reducing the need for medical attention and the anxiety assigned to recurrent gastrointestinal hemorrhage. Palliative maneuvers for gastric metastasis may require a multidisciplinary approach.

Ultrasound-assisted percutaneous endoscopic gastrostomy in a patient with advanced ovarian carcinoma and recurrent intestinal obstruction.

We report a case of recurrent bowel obstruction in a 56-yr-old woman secondary to progressive ovarian carcinoma. Due to a history of multiple prior surgeries, intraperitoneal chemotherapy, radiotherapy, and progressive intra-abdominal disease, placement of a percutaneous endoscopic gastrostomy (PEG) for decompression was thought to carry significant risk if standard techniques were used. We therefore used transcutaneous ultrasound imaging at the time of endoscopy, which allowed for rapid localization of an appropriate area for PEG placement, thereby minimizing the risk of inadvertently entering adjacent organs or metastatic foci. To our knowledge, this is the first such case in which ultrasound-assisted PEG placement has been utilized.

Role of proficiency survey in blood bank quality control.

The College of American Pathologists' blood bank proficiency survey program began in 1964 and has expanded to a variety of surveys addressing the needs of transfusion services, blood centers and physician office laboratories. Its role has evolved from a purely voluntary educational tool for self-improvement to fulfilling the regulatory requirement of CLIA '88. Its educational component will persist through an ungraded technical portion in association with a supplemental questionnaire and a survey critique.

Special issues in transfusion medicine.

This article reviews four controversial aspects of transfusion practices: the clinical circumstances, survival, and complications of massive transfusion; specific problems related to neonatal transfusion practices and the surgical support of the small child, including the appropriate age for red cells to be transfused, cytomegalovirus transmission, and the reduction in homologous donor exposures; the clinical presentation, incidence, and prevention of transfusion-associated graft-versus-host disease; and the biochemistry, function, genetics, and clinical indication for replacement therapy of antithrombin III.

The 1989 Comprehensive Blood Bank Survey of the College of American Pathologists.

The 1989 Comprehensive Blood Bank Survey included four additional samples for a total of eight antibody detection and identification challenges. The remainder of the survey was unchanged from prior years. Performance on the graded portions has remained good, with only occasional "problem" samples. For this survey year, the discrepant results were as follows: (1) a D-positive sample not reaching 95% consensus of D typing due to a strong positive direct antiglobulin test; (2) failure of 7% of extent 3 laboratories to identify anti-K in the presence of anti-c; and (3) continued, but lessened "identification" of anti-E, which was not present. The ungraded samples continued to provide educational challenges, and supplemental questions were used to survey current practices.

Massive transfusion in adults. Diagnoses, survival and blood bank support.

In a retrospective study covering a 2-year period (1986-1987), 125 patients received massive blood transfusion. Trauma accounted for only 29% of the cases. The larger nontrauma diagnostic categories were: gastrointestinal hemorrhage, 31%; cardiovascular surgery, 12%, and oncology cases, 9%. The overall survival rate was 60%; survival rates ranged from 38% for patients with hepatic failure to 100% for obstetric cases. Clinically important alloantibodies were present in 4%, and transfusion reactions occurred in 9%. Massive transfusions accounted for a significant proportion of total blood component usage: at least 12% of the yearly total red cell units, 20% of plasma, and 14% of platelets transfused.

The 1987 Comprehensive Blood Bank Survey of the College of American Pathologists.

The 1987 Comprehensive Blood Bank Survey consisted of four shipments of samples. Each presented graded challenges in ABO and D typing, crossmatching, and antibody detection and identification and ungraded challenges for antigen typing and ungraded serum samples for educational purposes. Practice patterns were elicited through supplemental questions, generally about issues raised by the survey samples. Two of the surveys showed significant problems. Set J-C included serum with anti-Lea, which was not detected by some participants. Anti-Dia was one of two antibodies in the J-D graded sample, and this additional antibody was not detected by a significant number of participants. Although minor problems were encountered in other challenges, in general performance was good.

Relapsing Clostridium difficile toxin-associated colitis in ovarian cancer patients treated with chemotherapy.

Symptomatic relapse of Clostridium difficile toxin-associated colitis occurred in three patients with ovarian cancer. In two patients, C difficile toxin-positive diarrhea initially appeared in association with antibiotic therapy. The third patient developed diarrhea after chemotherapy, without recent antecedent antibiotic administration. Patients were initially treated with oral metronidazole and became asymptomatic and toxin-negative. A symptomatic toxin-positive recurrence then developed after the subsequent course of systemic chemotherapy. Recurrent C difficile toxin-associated colitis or pseudomembranous colitis after chemotherapy has not been reported previously in the gynecologic oncology literature. Clostridium difficile-induced diarrhea must be considered in chemotherapy patients with diarrhea because management concepts vary from those for noninfectious diarrhea.