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Biomedical subjects

L Mintz

Publications and source records attributed to L Mintz.

At least 19 recordsLinked to original sources

Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease.

BACKGROUND: Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment. OBJECTIVE: To assess the benefit of HAART in patients with advanced AIDS and anemia. DESIGN: Prospective, multicenter cohort study. SETTING: The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999. PATIENTS: 528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia. MEASUREMENTS: In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use. RESULTS: At baseline, patients had a median CD4(+) lymphocyte count of 0.015 x 10(9) cell/L, median plasma HIV RNA level of 4.8 log(10) copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [ P < 0.001]; adjusted rate ratio, 0.66 [ P < 0.05]). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [ P < 0.01]; adjusted rate ratio, 1.01 [ P > 0.2]). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.010 x 10(9) cells/L. CONCLUSIONS: The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.

AIDS-Related Opportunistic Infections↗

Qualitative and quantitative PCR measures of cytomegalovirus in patients with advanced HIV infection who require transfusions.

The Viral Activation Transfusion Study (VATS) was a randomized trial that compared leukocyte-reduced transfusions with unfiltered red blood cell transfusions in HIV and cytomegalovirus (CMV) antibody-positive patients with anemia who were undergoing their first blood transfusion. The relations of the baseline qualitative and quantitative polymerase chain reaction (PCR) measures of plasma CMV viremia, HIV RNA, CD4(+) cell counts, and quality of life in these study subjects were examined. The 511 study subjects had a median CD4(+) cell count equal to 15 cells/mm3, and 110 (21.5%) had CMV viremia by qualitative assay. In multivariate models, frequency of positive qualitative CMV increased with decreasing CD4(+) cell counts (p =.04 trend), higher HIV RNA (p <.001), and a history of CMV disease (p <.001). Quantitative CMV PCR were performed on the 110 qualitative assay-positive study subjects. Median CMV viral load was 1780 copies/ml. In multivariate regression models, lower CD4(+) cell count (p =.03), and a history of CMV disease (p <.001) correlated with the level of CMV load. HIV RNA load and CMV load were not correlated. A lower Karnofsky score was associated with both the presence and quantity of CMV DNA.

Adult↗

Evaluation and molecular characterization of EHD1, a candidate gene for Bardet-Biedl syndrome 1 (BBS1).

Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder characterized by developmental abnormalities including mental retardation, obesity, retinitis pigmentosa, polydactyly, short stature, and hypogenitalism. To date, five BBS loci have been identified. BBS1, located on 11q13, is reported to be the most prevalent form of BBS in the Caucasian population. A positional cloning approach is being used to identify the gene responsible for BBS1. EHD1, a new member of the EH-domain containing proteins, was identified in this study as lying within the BBS1 disease interval. RNA analysis of many tissues revealed that expression of EHD1 is ubiquitous, with elevated levels in the testis. The genomic structure of EHD1 was elucidated by direct BAC sequencing. Following identification of the intron/exon boundaries, mutational analysis was performed by single strand conformation polymorphism and direct sequencing of affected individuals from several large kindreds linked to the BBS1 locus, as well as a cohort of unrelated probands. No disease-causing mutations were identified in this analysis, but several polymorphisms were found.

Amino Acid Sequence↗

EHD1--an EH-domain-containing protein with a specific expression pattern.

A cDNA that is a member of the eps15 homology (EH)-domain-containing family and is expressed differentially in testis was isolated from mouse and human. The corresponding genes map to the centromeric region of mouse chromosome 19 and to the region of conserved synteny on human chromosome 11q13. Northern analysis revealed two RNA species in mouse. In addition to the high levels in testis, expression was noted in kidney, heart, intestine, and brain. In human, three RNA species were evident. The smaller one was predominant in testis, while the largest species was evident in other tissues as well. The predicted protein sequence has an EH domain at its C-terminus, including an EF, a Ca2+ binding motif, and a central coiled-coil structure, as well as a nucleotide binding consensus site at its N-terminus. As such, it is a member of the EH-domain-containing protein family and was designated EHD1 (EH domain-containing 1). In cells in tissue culture, we localized EHD1 as a green fluorescent protein fusion protein, in transferrin-containing, endocytic vesicles. Immunostaining of different adult mouse organs revealed major expression of EHD1 in germ cells in meiosis, in the testes, in adipocytes, and in specific retinal layers. Results of in situ hybridization to whole embryos and immunohistochemical analyses indicated that EHD1 expression was already noted at day 9.5 in the limb buds and pharyngeal arches and at day 10.5 in sclerotomes, at various elements of the branchial apparatus (mandible and hyoid), and in the occipital region. At day 15.5 EHD1 expression peaked in cartilage, preceding hypertrophy and ossification, and at day 17.5 there was no expression in the bones. The EHD1 gene is highly conserved between nematode, Drosophila, mouse, and human. Its predicted protein structure and cellular localization point to the possibility that EHD1 participates in ligand-induced endocytosis.

Amino Acid Sequence↗

Construction of a yeast artificial chromosome contig spanning the pseudoautosomal region and isolation of 25 new sequence-tagged sites.

Thirty-one yeast artificial chromosomes (YACs) from the human pseudoautosomal region were identified by a combination of sequence-tagged site (STS) screenings and colony hybridizations, using a subtelomeric interspersed repetitive element mapping predominantly to the pseudoautosomal region. Twenty-five new pseudoautosomal STSs were generated, of which 4 detected restriction fragment length polymorphisms. A total of 33 STSs were used to assemble the 31 YACs into a single contiguous set of overlapping DNA fragments spanning at least 2.3 megabases of the pseudoautosomal region. In addition, four pseudoautosomal genes including hydroxyindole O-methyltransferase have been positioned on this set of fragments.

Acetylserotonin O-Methyltransferase↗

Failure of the porous-coated anatomic prosthesis in total knee arthroplasty due to severe polyethylene wear.

Four hundred and eighty-seven total knee arthroplasties were performed by a single surgeon with use of a porous-coated anatomic prosthesis between 1982 and 1989. There were thirty-two clinical failures (7 per cent) due to severe wear of the surfaces of the tibial and patellar polyethylene components. Thirty patients had a revision. The average time to failure of the implant was four and one-half years. The initial clinical symptoms of failure by wear consisted of a painless effusion with a decreased range of motion. Subsequent pain was considered as the criterion for failure necessitating operative intervention. Increased weight and decreased age of the patient and a thinner tibial component were significant predictors of an increased risk of failure (p < 0.01). Examination of retrieved tibial components revealed extensive delamination caused by fracture of the polyethylene at a depth of about one millimeter below the surface. Cracks that had propagated in from the medial and lateral peripheries of the tibial component toward the center of the condyles were also a common finding. It appears that the design of the implant as well as clinical factors (the age and weight of the patient) contributed to the mechanical failure of the polyethylene of these implants.

Aged↗

Wear of polyethylene in total joint replacements. Observations from retrieved PCA knee implants.

Observations of wear damage were performed on 12 retrieved porous coated anatomic (PCA) tibial components, all of which were removed because of excessive polyethylene wear. Density measurements of the remaining polyethylene were obtained as a function of depth from the surface of the components. Comparison to previous results from similar studies of total condylar type knee components and total hip acetabular components revealed distinct differences between the types and severity of damage, emphasizing the influence of design factors on the corresponding wear damage. These results confirm previous conclusions that nonconforming articulating surfaces on thin polyethylene components will be at higher risk of damage than more conforming surfaces on thicker components. It also appears that the high cyclic loads to which polyethylene implants are subjected in vivo are most responsible for the degradation in properties of the material near the articulating surface, although the heat pressing of the articulating surface of the PCA components may contribute to the problem.

Aged↗

The arthroscopic evaluation and characteristics of severe polyethylene wear in total knee arthroplasty.

Four hundred eighty-seven porous-coated anatomic (PCA) total arthroplasties were performed by the same surgeon between January 1982 and December 1989. Forty-three patients developed an effusion, pain, or decreased range of motion after a period of pain-free function. Average time to onset of symptoms was 4.5 years. Joint fluid aspirations were sterile and revealed the presence of high-density polyethylene crystals, best seen under a polarizing microscope. Thirty-three of these patients were arthroscopically evaluated. Extensive polyethylene wear and delamination were identified. Wear was most extensive on the medial tibial plateau. Patellar polyethylene wear was also identified. Substantial femoral component abrasions were present in areas where exposure of the tibial and patellar base plates had occurred. Diffuse granulomatous synovial tissue revealed an extensive foreign-body giant-cell reaction to polyethylene particles. In all patients, temporary symptomatic relief was obtained after arthroscopy. Thirty-two patients have, subsequently, had revision surgery. Intraoperative findings and biopsies at the time of revision confirmed the arthroscopic observations. Arthroscopy allowed the accurate diagnosis of polyethylene wear, provided temporary symptomatic relief, and facilitated preoperative revision planning. Polyethylene wear in PCA total knee replacements was related to patient characteristics (larger, younger, more active patients), nonconforming femotibial articular surfaces, thin polyethylene, heat-pressed polyethylene, and nonrigid mechanical attachment of polyethylene to metal base plate. Younger, more active, larger patients with total knee arthroplasties should be observed closely for evidence of polyethylene wear.

Aged↗

Expressed emotion and relapse in first episodes of schizophrenia. A rejoinder to Macmillan et al (1986).

Re-analyses of data presented by Macmillan et al (1986b) challenge their conclusions that high expressed emotion is not prognostically significant for the course of schizophrenia or unrelated to the level of behavioural disturbance prior to admission. Several equally plausible models of causal relationships between EE and duration of untreated illness are presented. We conclude that our re-analyses of the Macmillan data do not warrant premature closure regarding the significance of the EE variable.

Antipsychotic Agents↗

Pharmacological interventions for motion sickness: cardiovascular effects.

Motion sickness (MS) was provoked in healthy volunteers subjected to simultaneous rotation through the vertical axis with head movements (HM). Arterial blood pressure (BP), heart rate (HR) and forearm blood flows (BF) were intermittently monitored. Forearm BF was measured by venous occluding plethysmography. Rotation at 20 rpm and cyclic HM were continued for 10 min or until the subject requested cessation of HM because of imminent emesis. There were no consistent changes in BP or HR, but marked increases in BF were observed with MS. There was an inverse correlation between duration of HM tolerance and increments in BF. Antimotion sickness medications scopolamine:d-amphetamine (0.4:5.0 mg) or promethazine:ephedrine (25:60 mg) failed to significantly increase the duration of HM; the latter mixture, however, did significantly reduce the HM-induced-hyperemic responses. Administration of naproxyn (275 or 550 mg) did not significantly alter HM duration or BF responses. These studies suggest that BF changes may be an objective index of MS susceptibility.

Adult↗

Efficacy of the condom as a barrier to the transmission of cytomegalovirus.

An in vitro model was used to determine whether latex condoms prevent the transmission of cytomegalovirus. When the condoms were submitted to stretching and trauma that simulated sexual intercourse, no transmission of cytomegalovirus across the condom barrier was detected. Condoms may therefore be used to minimize the transmission of cytomegalovirus via semen in both heterosexual and homosexual intercourse.

Coitus↗

Cytomegalovirus infections in homosexual men. An epidemiological study.

Levels of cytomegalovirus antibody (IgG and IgM) were measured and urine viral cultures were done in 237 homosexual men over a mean period of 14.1 months. The initial prevalence of cytomegalovirus IgG antibody was 86.9%. By the 9th month of follow-up, 71% of serosusceptible men had become infected with cytomegalovirus. During the study period cytomegaloviruria was noted in 32% of seropositive men. Cytomegalovirus IgM antibody was intermittently present in the serum of 95% of IgG-seropositive men, suggesting that frequent reactivation of latent infection or reexposure to exogenous virus had occurred. Of seven sexual practices investigated, only passive anal-genital intercourse correlated with the acquisition of cytomegalovirus infection (p = 0.008).

Adolescent↗

Indirect hemagglutination inhibition: a direct method for detecting cytomegalovirus antigen.

We have developed a simple and sensitive technique for detecting CMV antigen in tissue culture specimens. The IHI assay is a modification of the IHA, which is capable of reliably detecting 10(3) median TCID50 of virus. With the IHI assay, antigen is detected by its capacity to inhibit the reactivity of CMV antisera of known titer in an IHA assay. The test is specific, uses readily available reagents, and is easy to perform. The IHI assay may serve as a tool for screening tissue culture specimens for CMV.

Antigens, Viral↗

Outbreak of Burkitt's-like lymphoma in homosexual men.

Four cases of Burkitt's-like lymphoma (undifferentiated, monoclonal, B-cell tumours) in homosexual men were seen in a 9-month period in San Francisco. One tumour contained both Epstein-Barr-virus nuclear antigen (EBNA) and cytomegalovirus (CMV) antigen. Another tumour contained EBNA, and a third contained no viral antigen, but EBNA and CMV antigens were detected in the overlying epithelium. This outbreak widens the array of neoplasms affecting immunosuppressed homosexual men and provides further evidence of an oncogenic role for EBV and CMV.

Adult↗