Investigating anti-D in an individual with the weak D type 2 genotype.

Anti-D in individuals with a weak D phenotype is an unexpected finding that may require additional investigation to determine whether the anti-D is an autoantibody or alloantibody. Further investigation may also include assessment of the patient's RHD genotype and exclusion of anti-G. We present a case of an 84-year-old man with the weak D type 2 genotype who developed an unexpected anti-D along with anti-C. Individuals with the weak D type 2 genotype are thought not to be at risk for developing alloanti-D, although the distinction between alloanti-D and autoanti-D may be difficult to ascertain. Furthermore, investigations may affect transfusion recommendations. This patient was restricted to crossmatch-compatible, D-C- red blood cells even though the clinical significance of the anti-D was uncertain. This report is one of a few reported cases of an individual with the weak D type 2 genotype with demonstrable anti-D but without evidence for alloanti-D.

Familial lissencephaly with cleft palate and severe cerebellar hypoplasia.

Lissencephaly is a brain malformation characterized by absence of gyral formation, resulting in a smooth brain surface. Histologic study shows severe anomalies of cerebral cortical development. Several lissencephaly syndromes have been described. Here we report a familial syndrome of lissencephaly, cleft palate, diffuse agyria, and severe cerebellar hypoplasia. Microscopic examination of the abnormally thick cerebral cortex showed absence of cortical layering, with preservation of the pia-glial barrier. This is the first report of recurrent lissencephaly with cleft palate and severe cerebellar hypoplasia in which these unique neuropathology findings are described. Autosomal recessive inheritance is suggested by recurrence in sibs within the same family, but germ cell mosaicism for a dominant mutation is not excluded.

Cervical teratoma: prenatal diagnosis and long-term follow-up.

Cervical teratomas are rare tumours which are the result of abnormal prenatal development. They are usually detected at birth, but can occasionally remain silent until adulthood. Obstruction of the airway is the major challenge in the neonatal period. Prenatal diagnosis allows for early consultation with paediatric surgical specialists, so that the time and place of delivery can be addressed, and planning for resuscitative efforts can be organized in advance. If the airway is quickly stabilized and resection of the tumour is not delayed, the prognosis is good. Cervical teratomas in neonates are usually benign; however, malignant transformation and metastasis can occur as a rare event, influencing long-term survival and prognosis. We present two cases of neonatal cervical teratoma detected prenatally by ultrasound. In one case, termination of the pregnancy was elected. In the other case, the child was delivered at 36 weeks' gestation, an airway was secured, and subtotal resection of the tumour was performed. No developmental or neurological deficit has been detected on long-term follow-up at 5 years of age. We present a review of the literature, with attention to outcome and potential for malignancy in neonatal cervical teratomas, in order to provide help in decision-making, once prenatal diagnosis is made.

Randomized controlled trial of pulse/synchronization cyclophosphamide/apheresis for proliferative lupus nephritis.

OBJECTIVE: To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis. METHODS: Eighteen patients with Class III or IV renal biopsies and chronicity indices <6 were prospectively randomized to receive 6 courses of parenteral cyclophosphamide over 8 months along with prednisone. Nine of these patients also received 3 daily plasmaphereses prior to each of the 6 courses of cyclophosphamide. Assessments compiled at 6 and 24 months included serum creatinine, albumin, anti DNA, 24-hour urine protein, and C3 complement along with SLAM scores. RESULTS: Two out of nine patients in each group evolved end stage renal disease and 3/9 patients in each group went into a renal remission at 24 months. Serum albumin, C3 complement, and SLAM scores improved in both groups, and anti-DNA improved in the pulse/synchronization patients (P < 0.025). No intergroup comparisons were significant. CONCLUSION: The addition of pulse/synchronization apheresis to cyclophosphamide therapy does not improve the course of patients with proliferative lupus nephritis.

Tuberous sclerosis in a 20-week gestation fetus: immunohistochemical study.

We report an autopsy case of tuberous sclerosis complex (TSC) in a 20-week gestational age female fetus. The brain showed lesions suggestive of early cortical tubers and subependymal hamartomatous nodules. The large cells within these nodular clusters were variably immunoreactive for glial fibrillary acidic protein (GFAP) and vimentin and negative for synaptophysin and neurofilament. Subependymal radial glia expressed both vimentin and GFAP, but subpial radial glia either did not express these markers (in contrast to an age-matched control) or were absent. Tuberin expression was noted in heterotopic neurons in the white matter and brain cells consistent with Cajal Retzius cells in the neocortical molecular layer, very weakly in superficial cortical neurons, neurons in the basal ganglia, Purkinje cells and external granular cells of cerebellum, cranial nerve nuclei neurons, occasional germinal matrix cells, ependymal cells, choroid plexus epithelium, and pituitary gland neuroendocrine cells; it was not seen within the cells of subependymal nodules. The pattern of tuberin immunoreactivity was similar to that which we have observed in older TSC patients. Proliferating cell labeling indexes were comparable in the germinal matrix of the TSC patient and an age-matched control. Abnormal subpial radial glia may be responsible for some of the neuronal migration abnormalities that appear to result in neocortical tubers.

A BCNU-containing Regimen, Mini-BEAM, with GM-CSF is a Safe and Effective Mobilizing Regimen Pre-stem Cell Transplantation in Lymphoma Patients.

Concern has been raised regarding the quality and engraftment potential of peripheral stem cells obtained from mobilizing regimens containing BCNU. We compared the mononuclear cell (MNC) yields and engraftment times of neutrophils and platelets in twenty-nine patients who received autologous peripheral blood stem cell transplants at our institution. Sixteen patients with either refractory or resistant Hodgkin's disease or non-Hodgkin's lymphoma, were mobilized with a BCNU-containing regimen, mini-BEAM (BCNU 60 mg/m(2) on day 1, etoposide 100 mg/m(2) on days 1-3, cytarabine 150 mg/m(2)q12h on days 1-3, and melphalan 30 mg/m(2) on day 3). Thirteen patients with various malignancies were mobilized with non-BCNU containing priming regimens. All patients received rhGM-CSF (Leukine, Immunex, Seattle, WA) 250µg/m(2) subcutaneously daily from 24 hours after completion of mobilizing chemotherapy through the completion of leukapheresis. The mean mononuclear cell yields in the BCNU versus non-BCNU containing regimens were 2.15 and 1.97 × 10(8) MNC/kg [95% CI -.32 to.68] after a median of 3 and 3 leukaphereses respectively. The median time post-stem cell infusion to an absolute neutrophil count (ANC) of ≥0.5 × 10(9)/1 were 11 days and 13 days [mean 11.7 and 12.2, p = 0.99, 95% CI -2.5, 1.6], days to an ANC of ≥1.0 x 10(9)/1 were 13 and 13 [mean 13.8 and 13.1, p = 0.47, 95% CI-1.8, 3.3], days to a platelet count of ≥20 × 10(9)/1 were 9 and 9 days [mean 11.4 and 9.8, p = 0.10, CI -0.6, 4.0], and days to a platelet count of ≥50 × 10(9)/1 were 14 and 15 days (p = 0.14) respectively. Mini-BEAM, as a mobilizing regimen, is easily administered as an outpatient. Stem cells mobilized with this regimen produces similar mononuclear cell yields as compared to non-BCNU containing regimens. There was no difference in the engraftment times for ANC or platelets from stem cells mobilized with BCNU versus non-BCNU containing regimens.

Tissue and cell-type specific expression of the tuberous sclerosis gene, TSC2, in human tissues.

TSC2 is a gene on chromosome 16p13.3 associated with the autosomal dominant neurocutaneous disorder, tuberous sclerosis complex (TSC). By using a partial nucleotide sequence from the cloned TSC2 and polymerase chain reaction methodology, we constructed a digoxigenin-labeled complementary DNA probe to examine TSC2 gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization. TSC2 messenger RNA was widely expressed in various cell types throughout the body, including epithelia, lymphocytes, and cells with endocrine functions, e.g., adrenal cortex and anterior pituitary. It was prominently and selectively (within the central nervous system) expressed in pyramidal cells of the cerebral cortex and other motor neurons, e.g., in spinal cord and brainstem nuclei. Visceral TSC2 expression was comparable in autopsy tissues from patients with and without TSC; TSC2 messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover, e.g., epithelia and lymphocytes, with central nervous system pyramidal cells and other neurons being an obvious exception, and/or in cells with important secretory/transport functions. This widespread expression of the TSC2 gene supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor.

Confirmation of the safety of autologous blood donation by patients awaiting heart or lung transplantation. A controlled study using hemodynamic monitoring.

BACKGROUND: Though earlier investigations have demonstrated the efficacy of autologous blood transfusion in reducing allogeneic blood exposure in patients undergoing heart or lung transplantation, questions remain regarding the safety of blood donation by patients with severe heart or lung disease. METHODS: Response to autologous blood donation by candidates for heart and lung transplantation and a group of age- and gender-matched control subjects was studied. Heart rate, blood pressure, oxygen saturation, and cardiac rhythm were examined before and after phlebotomy, and response to orthostatic challenge was evaluated. Patients were also questioned regarding impressions of changes in subjective sense of well being. Differences between patients and control subjects were evaluated by the paired t test and Fisher's exact test. An alpha of 0.05 was used in all testing to determine statistical significance. RESULTS: Eighteen candidates for heart transplantation, 16 candidates for lung transplantation, and their matched control subjects were studied. Though patients and control subjects differed with respect to baseline hemodynamic measurements, significant differences between the groups' responses to phlebotomy were not observed. After whole blood donation, orthostatic challenge resulted in a mean change in mean arterial pressure of -2.1 mm Hg in candidates for heart transplantation compared with a mean of +3.6 mm Hg in their control subjects (p = 0.062). In candidates for lung transplantation there was a mean change of +2.2 mm Hg after orthostatic challenge versus a mean change of +8.5 mm Hg in their control subjects (p = 0.052). Furthermore, no changes in cardiac rhythm or arterial oxygen saturation were detected. CONCLUSIONS: The hemodynamic effects of autologous blood donation in a group of patients with significant cardiac or pulmonary disease were not different from those observed in patients considered acceptable candidates for autologous blood collection. On the basis of these objective findings, we believe that patients with less severe degrees of heart or lung disease should not be excluded from participation in autologous blood donation programs.

Unrecognized human immunodeficiency virus type 1 infection in a cohort of transfused neonates: a retrospective investigation.

OBJECTIVE: To retrospectively identify unrecognized human immunodeficiency virus type 1 (HIV-1) infection among a cohort of children transfused as neonates before donated blood was routinely screened for HIV-1 antibody. METHODS: Records at a large, private, metropolitan hospital were reviewed to identify children who were transfused as neonates between January 1980 and March 1985 and discharged alive from the hospital. Multiple data sources were used to locate these children. Parents or guardians were contacted, and their children were offered HIV-1 antibody testing and physical examination. RESULTS: Of the 775 children identified as having received transfusions during the project period, 644 (83%) were located, and 443 (69%) were evaluated for HIV-1 infection. Among those evaluated, 33 (7%) had antibody to HIV-1, including 14 whose infections had not been previously diagnosed. At the time of enrollment, 13 children infected with HIV-1 were asymptomatic an average of 63 months after transfusion. CONCLUSION: HIV-1 antibody testing should be considered for all children, regardless of clinical status, who were transfused before routine blood donor screening was implemented in March 1985, particularly in areas with a high incidence of acquired immunodeficiency syndrome during those years.

Red cell autoantibody production in utero: a case report.

BACKGROUND: Autoantibody production by the fetus is thought to be extremely unlikely. Only one possible case of in utero autoantibody production against red cells by the fetus has previously been described. STUDY DESIGN AND METHODS: A case of apparent red cell IgG autoantibody production in utero is reported. RESULTS: This was established by a positive direct antiglobulin test in a newborn infant without evidence of maternal alloantibodies or autoantibodies. There was no evidence of clinically significant hemolysis at the infant's birth. After 6 weeks, his direct antiglobulin test remained strongly positive. The infant thrived without evidence of hemolysis, and after 6 months the direct antiglobulin test was negative. CONCLUSION: The production of autoantibodies to red cells in utero is possible, though rare. This did not result in apparent hemolysis in this patient.

Treatment of babesiosis by red blood cell exchange in an HIV-positive, splenectomized patient.

Babesiosis is a malaria-like parasitic disease causing subclinical or mild illness in most cases. Splenectomized patients, however, may experience a more severe course. Although generally responsive to antibiotic therapy, several cases of severe babesiosis refractory to appropriate antibiotic therapy have been reported to respond promptly and dramatically to red blood cell (RBC) exchange transfusion. Although the role of HIV coinfection in babesiosis is uncertain, two previously reported cases raise a concern that it may predispose to a more severe clinical course. We report a third case of severe babesiosis in an HIV-positive splenectomized man, following travel to an endemic area. Antibiotic therapy, though initially effective, ultimately failed to prevent severe disease. RBC exchange transfusion resulted in prompt clinical improvement, which has been sustained during 26 months of follow-up. Although the patient has since developed various sequelae of HIV infection, including disseminated Kaposi's sarcoma, CMV retinitis, and enteritis, there has been no recurrence of observable parasitemia. In severe babesiosis, RBC exchange transfusion, combined with appropriate antibiotic therapy, appears to be a rapidly effective therapeutic modality which can induce sustained remissions.

Establishment of a schedule of optimal preoperative collection of autologous blood.

Autologous blood donation prior to elective surgery can protect patients from unnecessary exposure to allogeneic blood. However, the inappropriate use of autologous blood programs, which results in the collection of excessive quantities of blood or of the collection of any blood prior to low-risk surgical procedures, can be wasteful and potentially hazardous. All patients donating autologous blood at a large institution during a period of three months were studied in an effort to develop a schedule of optimal preoperative collection of autologous blood (SOPCAB), which is similar to a maximum surgical blood order schedule. Some 461 consecutive autologous donations from 264 patients were investigated. For certain surgical procedures, primarily the cardiac and orthopedic procedures, undercollection appeared to be the most common problem. For other procedures (laminectomies, nasal surgery), overcollection was more common. A model is presented for the careful scrutiny of autologous blood collection and use to allow for the creation of a SOPCAB for patients undergoing elective surgery.

The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease.

Patients infected by the human immunodeficiency virus (HIV) as a result of blood transfusions are unique in that their dates of infection are well defined and their medical conditions before infection are known. To characterize the natural history of transfusion-associated HIV infection, we studied 694 recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of the recipients tested, 85 were seronegative, 116 were seropositive, and 19 had AIDS. Of 101 HIV-seropositive recipients followed for a median of 55 months after infection, 54 had Centers for Disease Control Class IV disease, including 43 with AIDS. Life-table analysis suggested that AIDS will develop in 49 percent of infected recipients (95 percent confidence limits, 36 to 62 percent) within seven years after infection. As compared with recipients without AIDS, the 43 recipients with AIDS had received more transfusions at the time of infection (median, 21 vs. 7; P = 0.01). HIV-infected blood donors in whom AIDS developed were grouped according to whether AIDS developed within 29 months (the median) after donation (Group 1) or 29 or more months after donation (Group 2). As compared with the 31 recipients of blood from Group 2 blood donors, the 31 recipients of blood from Group 1 donors were more likely to have AIDS four years after infection (49 percent vs. 4 percent; P = 0.005) and illnesses resembling acute retroviral syndrome (14 of 24 vs. 5 of 22; P = 0.03). We conclude that most recipients of HIV-infected blood become seropositive, that AIDS develops in about half these recipients within seven years, and that the risk may be higher when AIDS develops in the blood donor soon after donation.