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Biomedical subjects

L M Aledort

Publications and source records attributed to L M Aledort.

At least 109 records · Page 6Linked to original sources
PubMed1989

A codon 338 nonsense mutation in the factor IX gene in unrelated hemophilia B patients: factor IX338 New York.

Hemophilia B is an X-linked recessive bleeding disorder resulting from a deficiency of the coagulation factor IX (FIX) protein activity, a vitamin K-dependent serine protease active in both the intrinsic and extrinsic coagulation systems. DNA analyses of the factor IX gene in two unrelated patients with severe hemophilia B, with a IX coagulant activity less than 1% and undetectable FIX antigen, detected the loss of the second TaqI site in exon h (VIII) in both individuals. Polymerase chain reaction (PCR) amplification of 576 base pairs of exon h (VIII) with cloning and dideoxy sequencing of cloned DNA from one hemophiliac revealed a single C----T transition in codon 338 that changes an arginine residue codon CGA to a nonsense codon TGA. Allele-specific oligonucleotide probe hybridization with a mutant (C----T) and a wild-type allele confirmed the same mutation in amplified genomic DNA of the second hemophilia patient. The C----T transition represents another example of mutation at a CpG dinucleotide. DNA polymorphism analysis of the FIX gene in both individuals revealed each to be on a separate FIX haplotype; therefore, predicting each to be a separate mutation event.

Amino Acid Sequence↗
PubMed1989

Blood-product usage in cardiac surgery.

Many patients undergo cardiac surgery with preexisting congenital and acquired coagulation defects. Almost all of these can be recognized and corrected preoperatively. CPB itself induces a variety of abnormalities of coagulation, affecting plasma proteins, platelets, and the fibrinolytic system. These abnormalities do not always cause clinically significant bleeding. When they do, logical laboratory assessment and blood-component usage can usually correct the defect. The use of blood products is associated with allergic, viral, and hemolytic risks. Exciting advances have been made in the use of synthetic alternatives to blood products. Both DDAVP and aprotinin seem promising in this respect, but more investigation is needed into the mechanisms of action and possible thrombotic complications of these drugs. In the future, anesthesiologists and surgeons may look forward to more safe and effective therapy of bleeding in cardiac surgical patients.

Blood Loss, Surgical↗
PubMed1989

The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience.

The response to a highly purified concentrate of porcine factor VIII was evaluated in 45 bleeding episodes in 38 patients with high responding inhibitor antibodies to factor VIII. A total of 437 infusions were given. The patients came from 25 hemophilia centers in the United States. The majority had a life- or limb-threatening hemorrhage for which other modalities had not been successful. In 32 of 45 episodes, a good to excellent response was obtained. Adverse reactions were minimal, occurring in 17 treatment episodes, and were mostly treated with antihistamines and/or hydrocortisone. No clear predictor of clinical response to porcine factor VIII concentrate was identified, including pretreatment human and porcine inhibitor levels, percentage of cross-reactivity between the human and porcine antibodies, and the presence of measurable levels of factor VIII after the porcine factor concentrate was given. Anamnesis to porcine factor VIII did occur in some instances. Porcine factor VIII is a valuable modality in the treatment of serious hemorrhages in patients with inhibitors to factor VIII. Its use should be considered early in the course of severe hemorrhage in these patients.

Adolescent↗
PubMed1989

Cost-effectiveness and reimbursement in patient care.

The recent collapse of the previously effective coalition of the federal government, universities and medical schools, the pharmaceutical industry, and third-party payers has resulted in the current crisis in funding of clinical trials. The reduced financial support for clinical research comes at a time when a number of new investigational therapies offer the promise of better medical care for patients with life-threatening diseases. Controversy exists regarding the role of physicians in encouraging federal support for clinical research and third-party reimbursement for patient care for patients on clinical trials. Some believe the physician should take an activist role on the issues in general, while others believe that the physician should focus on protecting the interests of individual patients by acting as the patient's agent. Many difficult choices lie ahead for society as a whole in determining what percentage of its health-care budget will be allocated for clinical research, who will pay for patient-care costs of patients in clinical trials, and how this relatively limited resource should be distributed among the population at large. Case-management programs are one attempt to monitor and control health-care costs, but in many instances case management has been used to determine if patients are enrolled in clinical research trials and to disallow coverage for other than standard patient care.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1988

A consortium for purchase of blood products directed by physicians.

Clotting-factor therapy is a costly part of comprehensive hemophilia treatment. Physicians treating patients with hemophilia in New York formed a consortium for the purchasing and regional distribution of clotting-factor concentrates. Concentrates are centrally purchased based on a bidding formula aimed at obtaining the lowest price for quality product while guaranteeing all suppliers continued involvement in a large market area. The consortium has successfully maintained, and, in instances, lowered prices each year. Estimated regional savings this year are more than $750,000 for an anticipated purchase of approximately 60,00,000 units of clotting-factors VIII and IX. Central distribution has additionally lowered costs to participating hospitals. The consortium is able to provide patients and third-party payers with some of the lowest prices for clotting-factor concentrates in the United States. A physician-directed regional approach to purchasing costly medical products might be applied to other areas of clinical medicine.

Blood Coagulation Factors↗
PubMed1988

A second BamHI DNA polymorphism and haplotype association in the factor IX gene.

A second BamHI DNA polymorphism has been identified in the factor IX gene in an American black population at an allelic frequency of 0.13. This site has been localized within 500 basepairs (bp) 5' to the XmnI intron 3 polymorphic site and increases the heterozygosity of black females at the factor IX gene locus. In addition, haplotype analysis of factor IX genes at five polymorphic loci indicates that although there is conservation of sequences between the races, factor IX genes show more heterogeneity in an American black population and thus more heterozygosity is observed in black females compared with whites. This increased heterogeneity is due to DNA polymorphisms unique to black populations and to linkage equilibrium between the most 5' and 3' polymorphic sites in factor IX genes in blacks.

Alleles↗
PubMed1987

Reproductive choices in hemophilic men and carriers.

We have examined reproduction patterns in hemophilic men and carrier women seen at a hemophilia treatment center. The study group included 309 patients with hemophilia A or B: 194 adults and 115 children from 246 pedigrees; 93% of affected men and 96% of parents of affected children had received genetic counseling. In the collected pedigrees, 65% of affected males were born to women with family history of hemophilia. An additional 23% of mothers were later shown to be carriers. Fewer than 12% of cases could be due to a new mutation in the child. Among 209 hemophilia A carrier tests, 95% of obligate carriers were detectable, 87% of mothers of sporadic cases, 53% of sisters of hemophiliacs, and 24% of other relatives had a high risk of carriership. Of 49 high-risk women seen during or prior to pregnancy, one-half elected prenatal diagnosis. Amniocentesis was performed in 24 cases and 8 were referred for fetoscopy, resulting in 18 normal offspring. Among 25 pregnancies not tested, 14 continued and produced 3 affected males and 11 normal offspring. Of hemophilic men over age 25, 66% have married and 41% (62% of those married) have had children. These observations will serve as a baseline for assessing any change in reproductive patterns occurring with the introduction of new genetic techniques.

Adult↗
PubMed1987

Histologic patterns of liver disease in hemophiliacs, with special reference to morphologic characteristics of non-A, non-B hepatitis.

In a retrospective study 157 liver specimens from hemophiliac patients (105 percutaneous needle and 12 wedge biopsies, 40 autopsy specimens) were read blindly and independently by four pathologists on the basis of a computer codable questionnaire asking for evaluation of individual histologic features, classification of the liver disease, and speculation on etiology. The majority of cases had histologic evidence of mild chronic viral hepatitis; 7.6% of all cases were classified as CAH, and an additional 7.6% as CPH by all four interpreters. A large number (40.8%) were on the borderline of CAH and CPH or CLH. These were classified as "possible CAH" because of a diagnosis of CAH by one to three of the pathologists. Although there was therefore some interobserver variability in the diagnostic labels applied to these cases, all four pathologists were strikingly similar in their identification of individual histologic features. Furthermore, on blind rereadings, each pathologist made the same diagnosis in more than 90% of readings. In this retrospective study, serologic data were not available in many cases. Thus, etiologic considerations were based purely on speculation from the histologic appearance. One case was identified as "definite" and 28 of 157 (18%) as "possible" HBV infection. Based on the assumption that some of the individual histologic criteria indeed might be in favor of NANB hepatitis, 21 cases (13%) were considered "definite" NANB, and "possible" NANB was suspected in 107 additional cases (68%). The addition of these figures makes clear that within the limitations of histologic assessment, double infections appear to be frequent in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗
PubMed1986

A comparison of the availability and content of genetic counseling as perceived by hemophilic men and carriers in the U.S.A., Canada, Scotland, and Greece.

A survey study was carried out with 211 hemophilic men and 205 carriers of hemophilia at four hemophilia centers in New York; London, Ontario; the West of Scotland; and Athens, Greece. The participants responded to a questionnaire exploring socio-demographic and medical information, attitudes toward hemophilia, and experience of and attitudes toward genetic counseling. The study shows differences between attitudes of hemophilic men and carriers, differences in perceived problems among patients and carriers in the four centers, and differences in opinions between consumers and professionals. Comprehensive services for hemophilic families available in the New York center facilitate both patient education and satisfaction.

Attitude to Health↗