Direct haplotyping at the vitamin D receptor locus improves genetic resolution.
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Chromosome Mapping↗
Biomedical subjects
L Rubin
Publications and source records attributed to L Rubin.
Protein phosphorylation and the regulation of cell-cell junctions in brain endothelial cells.
Endothelial cells lining the capillaries of the brain have two properties that distinguish them from their peripheral counterparts: (1) tight junctions of extremely low permeability; and (2) low rates of fluid-phase endocytosis. In combination, these features limit the nonspecific flux of ions, proteins, and other substances into the central nervous system environment, creating the blood-brain barrier. This barrier is not immutable. Tight junction permeability can be rapidly increased, which may play a role in the development of a variety of brain pathologies. We have therefore been interested in mechanisms regulating junctional permeability and strategies for interfering with this regulation. What is becoming increasingly apparent is that junctions are not passive mechanical entities; rather, they are targets for a variety of signaling pathways.
Animals↗
Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia.
To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.
Acute Disease↗
An epidemiological study of rheumatoid arthritis in a northern Ontario clinical practice: the role of ethnicity.
This study was designed to investigate differences between cultural groupings in rheumatoid arthritis (RA). The sample was made up of 235 individuals suffering from RA from four groupings: Canadian aboriginals, Finnish Canadians, Italian Canadians and other caucasian Canadians. The study was a retrospective chart analysis (non-randomly selected) designed to compare ethnic groupings on the following dimensions: demographic factors, clinical manifestations of RA, laboratory results, and drug therapy response. Results of the study support to some extent findings from previous research. Specifically, the following was found. The study showed a female to male predominance in sufferers of RA in all but one ethnic group. Canadian aboriginals tended to contract the disease much earlier in life than other ethnic groups. More Canadian aboriginals reported a family history of RA than other groupings. Only Canadian aboriginals and caucasian Canadians showed involvement of the C1-C2 joint with subluxation. Italian Canadians tended to have a higher mean haemoglobin than other groupings, while Canadian aboriginals tended to have a higher mean platelet count than other groupings, and an elevated anti-nuclear antibody count. While most of the drugs used to treat RA produced no significantly distinct reactions, the Italian and Canadian caucasian groups had the highest percentage of subjects with reactive dermatitis.
Adult↗
Gabapentin adjunctive therapy in neuropathic pain states.
OBJECTIVE: This is a report of a trial of the new antiepileptic agent gabapentin in patients with intractable neuropathic pain. DESIGN: A case series of patients with a diagnosis of neuropathic pain whose previous management was inadequate were given oral gabapentin in increasing doses and were followed for a minimum of 2 months, monitored for efficacy and side effects. SETTING: An outpatient pain management center located within a major university medical center. PATIENTS: Convenience sample of patients referred for management of intractable neuropathic pain. INTERVENTIONS: Simplification of existing pharmacologic management, addition of gabapentin, and attempted reduction of opiate analgesic doses. MAIN OUTCOME MEASURES: Patient self-reports and pain scores in successive office visits. RESULTS: Gabapentin provides analgesic activity for patients with neuropathic pain and has the advantage of a low side effect profile and drug toxicity.
Acetates↗
Respiratory failure from corn starch aspiration: a hazard of diaper changing.
Corn starch powder is widely used for routine infant skin care as a substitute for talcum powder, as it is believed to have fewer respiratory hazards. We describe a one-month-old infant who presented to an emergency department with respiratory failure and a severe pneumonitis from aspiration of corn starch powder. The patient recovered after five days of mechanical ventilatory support. We conclude that careless use of corn starch for infant skin care can lead to accidental aspiration of this substance and severe respiratory disease.
Anti-Bacterial Agents↗
Lymphocytosis of donor origin in cerebrospinal fluid, and marrow aplasia after donor leukocyte infusion for EBV-lymphoproliferative disease.
A 29-year-old woman underwent a T cell-depleted unrelated donor transplant for CML in chronic phase. Sixty-three days after marrow infusion, the patient developed fevers and generalized lymphadenopathy. Lymph node biopsy was consistent with monoclonal EBV-associated immunoblastic lymphoma for which the patient received 10(5) CD3-positive donor leukocytes per kilogram. Six days after leukocyte infusion the patient developed mental status changes without focal neurological deficit. MRI revealed no mass lesions. Cerebral spinal fluid revealed a white blood cell count of 1650 cells/mm3 which were shown to be T lymphocytes of donor origin. The CSF was tested and found to be PCR positive for EBV virus interval repeat 1 sequence (IR1). The lymphocytosis and mental status changes resolved without specific intervention. Subsequently she developed marrow aplasia, which was believed to be secondary to the infusion of donor leukocytes. Possible mechanisms for these two previously unreported side-effects of donor leukocyte infusion are discussed.
Adult↗
Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation.
Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.
Adolescent↗
Cataractogenesis in rats induced by in utero exposure to RG 12915, a 5-HT3 antagonist.
RG 12915, a selective 5-HT3 antagonist developed for the treatment of emesis and nausea associated with cancer chemotherapy, was administered by gavage to four groups of pregnant rats from Gestation Day 6 to 17 at doses of 0, 1, 10, and 100 mg/kg/day, as part of a Segment II (developmental toxicity) study. The 100 mg/kg/day dose was maternally toxic as indicated by decreased body weight gain and food consumption during the treatment period. A portion of the rats were allowed to deliver and rear their litters and three pups from two litters in the 100 mg/kg/day group were observed to have lens opacities (visible to the naked eye) at weaning. At a later examination, when the offspring were approximately 4 months old, four additional animals from the same two litters had cataracts. A slight growth retardation was also observed postweaning in the offspring of the 100 mg/kg/day group. To confirm the lens findings and more precisely define the no-effect dose, another study was conducted in which pregnant rats were administered daily RG 12915 doses of 0, 10, 30, 60, or 100 mg/kg/day from Gestation Day 6 to 17. There was a dose-related decrement in maternal body weight gain during the treatment period in the 30, 60, and 100 mg/kg/day groups (12, 28, and 47%, respectively) compared to the control group. A treatment-related incidence of nuclear cataract was observed in the offspring of the 60 and 100 mg/kg/day groups (litter incidence 6 and 45%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Intrauterine therapy for homozygous alpha-thalassemia.
BACKGROUND: Alpha-thalassemia is one of the most common genetic disorders in the world and is becoming more common in the United States with the increase in immigration of susceptible populations. This disease has been stated previously to be incompatible with extrauterine life. CASE: A Filipino woman with a prior loss due to hemoglobin Bart's underwent prenatal diagnosis that confirmed recurrence in the index pregnancy. Intravascular intrauterine exchange transfusions maintained appropriate fetal growth. A cesarean delivery yielded a 2190-g male infant with minor malformations. The postnatal course was characterized by mild respiratory insufficiency. Postnatal chronic transfusion therapy is underway pending consideration for bone marrow transplantation. CONCLUSION: Antenatal diagnosis and therapy of homozygous alpha-thalassemia can prevent the prenatal consequences of hydrops and fetal death. New technologies such as stem cell transplantation may help to avert both prenatal and postnatal consequences.
Abnormalities, Multiple↗
The clinical and basic pharmacology of mivacurium: a short-acting nondepolarizing benzylisoquinolinium diester neuromuscular blocking drug.
Mivacurium is a benzylisoquinolinium diester. The drug is a nondepolarizing relaxant which is hydrolysed by plasma cholinesterase at 70-88% of the rate of suxamethonium. Enzymatic hydrolysis gives the drug its short duration of action. The length of paralysis is about 2-2.5 times that of suxamethonium and one-half to one-third that of the intermediate-acting nondepolarizers. The development of mivacurium represents a collaboration between industrial pharmacologists and chemists at Burroughs Wellcome Co. (USA) and investigators at the Massachusetts General Hospital, Boston, MA, USA.
Cholinesterases↗
The Duke experience with nucleus caudalis DREZ coagulation.
The results of 46 nucleus caudalis DREZ coagulations performed at Duke in the preceding 5 years are reviewed retrospectively, with a mean follow-up of 32 months. Fifteen (38%) of 39 patients with complete data indicated that they would undergo the procedure again. Fifteen (38%) described improved quality of life. Outcome was fair or better in 18 (46%). Complications in the form of ataxia were present in 21 (54%).
Aged↗
Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin.
PURPOSE: To evaluate the infertility rate in patients with germ cell tumors receiving chemotherapy with cisplatin, etoposide (VP-16), and bleomycin (PVP16B). PATIENTS AND METHODS: Thirty patients were evaluated. All patients had undergone chemotherapy with two to four cycles of PVP16B. A single semen analysis was performed 24 to 78 months following initiation of chemotherapy. All 30 patients were continuously disease-free. Eight of these patients had also undergone nerve-sparing retroperitoneal lymph node dissection (RPLND). RESULTS: The median sperm concentration was 33.9 x 10(6), with a median volume of 3.2 mL. The median total sperm count was 86.4 x 10(6). Oligospermia (< 40 x 10(6) total sperm count) was found in 13 patients (43%), including six (20%) who were azoospermic. There was a high incidence of morphologically abnormal sperm, with only one patient having more than 50% normal spermatozoa. Only 13 patients (43%) had sperm motility greater than 50%. Five patients had positive semen antisperm immunoglobulin G (IgG). Eight patients fathered children, including three with document oligospermia. CONCLUSION: Patients with germ cell tumors successfully treated with PVP16B chemotherapy are at substantial risk for persistent semen abnormalities. However, some patients with oligospermia will slowly recover and others are still capable of reproductive capacity despite continued oligospermia.
Adult↗
[Hemodynamic effect of intrathecal clonidine].
Intrathecal administration of bupivacaine and clonidine results in a significant prolongation of both motor and sensitive blocks but side effects-hypotension and bradycardia-are observed. We compared two groups of patients allocated randomly. One group received intrathecal bupivacaine-morphine and the other one received clonidine-bupivacaine-morphine. In the group which received clonidine a blood pressure decrease was observed from 2nd to 8th hour, independently from the sympathetic block and easily corrected by i.v. ephedrine. Some possible explanations are discussed. No complications due to clonidine were observed.
Aged↗
Levels of soluble interleukin-2 receptor-alpha are elevated in serum and ascitic fluid from epithelial ovarian cancer patients.
OBJECTIVE: The purpose of the study was to determine whether ovarian cancer patients have activated lymphocytes as indicated by the presence of soluble interleukin-2 receptor-alpha and to compare soluble interleukin-2 receptor-alpha with other markers in ovarian cancer. STUDY DESIGN: Ascites and serum from patients with advanced active ovarian cancer was tested for the presence of elevated levels of soluble interleukin-2 receptor-alpha and compared with normal controls. Levels of soluble interleukin-2 receptor-alpha were also compared with levels of CA 125 and macrophage colony-stimulating factor in the same patients, to evaluate the correlation between different markers. RESULTS: Elevated levels of soluble interleukin-2 receptor-alpha were detected in 86 of 86 (100%) ascites samples and 67 of 85 (79%) serum samples from patients with advanced epithelial ovarian cancer. In contrast, only 12 of 25 (48%) benign ascites samples and one of 88 (1%) serum samples from controls had elevated levels. There was no obvious correlation between levels of soluble interleukin-2 receptor-alpha and levels of CA 125; however, levels of soluble interleukin-2 receptor-alpha did correlate with levels of macrophage colony-stimulating factor. Concurrent measurement of serum-soluble interleukin-2 alpha and CA 125 levels detected 100% of patients with epithelial ovarian cancer. CONCLUSION: The detection of elevated levels of soluble interleukin-2 receptor-alpha in serum and ascites indicates the presence of activated lymphocytes in patients with epithelial ovarian cancer. Ascites and serum levels of soluble interleukin-2 receptor-alpha are elevated in patients with advanced ovarian cancer and warrant assessment as a potential complementary marker to CA 125 for early detection of ovarian cancer and management of patients with advanced ovarian cancer.
Antigens, Tumor-Associated, Carbohydrate↗
Is there a relationship between autoantibodies and silicone-gel implants?
The present study was conducted to determine if 200 patients with silicone-gel implants demonstrated elevated levels of autoantibodies, compared with a similar group of 100 age-matched control subjects without breast implants. These results were then compared with 29 patients who had demonstrated implant rupture. Differences in the frequency of autoantibody levels were determined by the chi-squared test. Differences in autoantibody titers were determined by Wilcoxon's signed rank test. Differences were considered significant with p > 0.05. The prevalence of a positive antinuclear antibody (ANA) test (dilution 1:100) in the 200 patients with breast implants was 26.5% compared with 28% in the 100 control subjects. In 29 patients with implant rupture, only 17.2% tested ANA positive. These values were not significantly different. In addition, there were no significant differences between the ANA titers of positive patients in each group. In each of the three groups, all patients who tested ANA positive were analyzed to assess the frequency and titer of other autoantibodies, including anti-DNA, anti-cardiolipin, anti-SSA, anti-SSB, anti-SM, anti-RNP, and anti-Scl-70. There were no significant differences between the frequency or titer of any of these autoantibody levels in each of the three groups of patients. These studies strengthen the concept that there is no conclusive evidence that silicone-gel implants are related to the development of connective tissue disease.
Adult↗
Changing prevalence of iron deficiency anemia in infants of the Haifa subdistrict.
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Anemia, Hypochromic↗