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Biomedical subjects

C Brewer

Publications and source records attributed to C Brewer.

At least 37 records · Page 2Linked to original sources
PubMed1999

A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality--and tolerance of segmental aneuploidy--in humans.

The distribution of simple autosomal duplications associated with congenital malformations has been analyzed by means of data contained in the Human Cytogenetics Database. For each of the 47 malformations, the frequency of duplication of a given chromosome band associated with the malformation was compared with the overall frequency of duplication of that band recorded in the database. In total, there were 143 malformation-associated chromosomal regions (MACR); 21 of these contained at least one band with a highly significant (P<.001) association. The average number of bands per MACR was 3.1. Eight bands, representing 2.1% of haploid autosomal length, were not involved in any duplication, and we suggest that these are potentially triplolethal. This compares with 31 bands, representing 11% of haploid autosomal length, that were identified in the previously reported deletion map and that were not involved in any deletion and are potentially haplolethal. In both cases, approximately half of these bands are pericentromeric. The longest duplication involves 4.3% of haploid autosomal length, and the longest deletion involves 2.7%.

Chromosome Aberrations↗
PubMed1998

A chromosomal deletion map of human malformations.

Malformations are common causes of pediatric morbidity and mortality, and genetic factors are a significant component of their etiology. Autosomal deletions, in almost all cases, cause a nonspecific embryopathy that presents after birth as growth failure, mental retardation, and multiple malformations. We have constructed a chromosome map of autosomal deletions associated with 47 different congenital malformations, using detailed clinical and cytogenetic information on 1,753 patients with nonmosaic single contiguous autosomal deletions. The 1,753 deletions involved 258 (89%) of 289 possible autosomal bands (by the use of ISCN 400-band nomenclature), giving a total of 4,190 deleted autosomal bands for analysis. We compared the band distributions of deletions associated with common major malformations with the distribution of all 1,753 deletions. We noted 283 positive associations between deleted bands and specific malformations, of which 199 were significant (P<.05, P>.001) and 84 were highly significant (P<.001). These "malformation-associated bands" (MABs) were distributed among 137 malformation-associated chromosome regions (MACRs). An average of 6 MABs in 2.9 MACRs were detected per malformation studied; 18 (6%) of 283 MABs contain a locus known to be associated with the particular malformation. A further 18 (6%) of 283 are in seven recognized specific malformation-associated aneuploid regions. Therefore, 36 (26%) of 137 of the MACRs contain an MAB coinciding with a previously recognized locus or malformation-associated aneuploid region. This map should facilitate identification of genes important in human development.

Chromosome Aberrations↗
PubMed1997

Photodynamic therapy using topically applied dihematoporphyrin ether in the treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To perform a phase I study of topically applied dihematoporphyrin ether (DHE) in the photodynamic treatment (PDT) of cervical intraepithelial neoplasia (CIN) using fixed DHE doses and application schedules, and a variable dose of 630 nm red light delivered by an argon-pumped dye laser. METHODS: Between February 1993 and April 1994, 24 nonpregnant women with a histologic diagnosis of CIN were enrolled. All patients had lesions involving at least 25% of the cervix that were colposcopically visible. Using a cervical cap, 2 ml of a 1% solution of DHE (Photofrin) in a 4% Azone and isopropyl alcohol vehicle were applied to the cervix 24 hr prior to PDT. An argon-pumped dye laser providing light at 630 nm was then used to perform PDT. Light was coupled into a 400-microm silica fiber optic terminating in a microlens which focused the laser radiation onto a circular field of uniform light intensity perpendicular to the tissue. The entire ectocervix was treated in a single field including a margin of 3-5 mm of normal cervix. Using a constant power density (150 mW/cm2) to avoid thermal injury, the PDT energy was increased every 4 patients in a phase I fashion (40, 60, 80, 100, 120, and 140 J/cm2). RESULTS: Thirteen patients with CIN I, 7 patients with CIN II, and 4 patients with CIN III were treated. The maximal energy density was well tolerated. Toxicity was minimal with no patients experiencing local necrosis, sloughing, or scarring; however, a mild vaginal discharge was noted in several patients. Systemic effects were absent. After 12 months of follow-up at 3-month intervals, 22 patients are evaluable of whom 15 (68%) are disease free. One patient was lost to follow-up and in another the cervical cap was dislodged. Four of the 7 failures or recurrences occurred at energy densities of 80 J/cm2 or less, while 8 of 11 (73%) patients were treated successfully with PDT at an energy density of 100 to 140 J/cm2. CONCLUSIONS: PDT with DHE and an argon-pumped dye laser at 630-nm wavelength delivering an energy density of 140 J/cm2 is safe and effective in treating CIN. Phase II studies using PDT at the prescribed application schedule and dose are indicated.

Administration, Topical↗
PubMed1997

Advanced-stage small cell carcinoma of the ovary in pregnancy: long-term survival after surgical debulking and multiagent chemotherapy.

We report the longest disease-free survival achieved in an advanced-stage small cell carcinoma of the ovary. The patient had a stage IIIc tumor diagnosed during pregnancy. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and optimal tumor debulking. Following her immediate postoperative recovery, she was treated with a multiagent chemotherapy regimen with germ cell activity consisting of vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide. She is alive and without evidence of disease 5(1/2) years after diagnosis. This is the second reported case in pregnancy and the longest disease-free survivor of metastatic small cell ovarian carcinoma in the medical literature.

Adult↗
PubMed1995

Recent developments in maintenance prescribing and monitoring in the United Kingdom.

After a brief historical review of British drug legislation and public and governmental attitudes, this paper describes the wide range of policies and practices that have appeared since the explosion of illicit drug abuse in the 1960s. The spectrum goes from a reluctance to prescribe at all to maintenance on injectable opiates. Comparisons are made with differing attitudes to the availability of abortion in public health services. Compared with 5 years ago, about three times more methadone is being prescribed. There is a steady increase in prescriptions for injectable methadone but heroin maintenance is still rare. The "British System" permits great flexibility in the choice of opiates for maintenance. Some amphetamine-prescribing programmes also exist. Hair analysis for drugs to monitor levels of both prescribed and unprescribed drugs is a welcome and promising alternative to undignified and often misleading urine tests.

Attitude of Health Personnel↗
PubMed1995

Second-line and 'alternative' treatments for alcohol withdrawal: alpha-agonists, beta-blockers, anticonvulsants, acupuncture and neuro-electric therapy.

Drugs which reduce autonomic overactivity but have no sedative effects can be useful in alcohol withdrawal, either as the sole pharmacological intervention or in conjunction with sedative drugs. They may reduce sedative requirements, but their lack of anticonvulsant and anti-delirium effect can be a disadvantage. Beta-blockers are more effective than alpha-2 agonists. Non-sedative anticonvulsants are of questionable value. Acupuncture and neuro-electric therapy, though often popular with patients and therapists, appear to be no more than impressive placebos in this context. Non-specific treatment effects can be very prominent in withdrawal. Support, information, reassurance and good nursing can reduce the need for specific pharmacological or psychological interventions.

Acupuncture Therapy↗
PubMed1994

Loss of heterozygosity in cervical carcinoma: subchromosomal localization of a putative tumor-suppressor gene to chromosome 11q22-q24.

Infection of cervical epithelial cells with so-called "aggressive" subtypes of human papilloma virus (HPV) appears to be an important factor in the etiology of cervical carcinoma. However, mounting evidence suggests that additional genetic changes are required for progression to an invasive carcinoma. Functional studies have shown that human chromosome 11 contains a gene or genes capable of suppressing tumorigenicity in cell lines derived from different histopathological types of cervical carcinoma, suggesting that aberration of this gene(s) may represent at least one of the additional changes required for tumorigenic progression. To identify the likely chromosomal position of this gene(s), we have carried out a systematic genetic analysis of chromosome 11 in the primary tumors of 32 patients with cervical carcinoma. Sixteen highly polymorphic markers, 10 of which were based on simple sequence repeats typed by PCR, were used to compare matched DNA samples from noninvolved tissue and portions of tumor tissue highly enriched for neoplastic cells by the cryostat-sectioning technique. Of the 32 patients examined, 14 (44%) demonstrated clonal genetic alterations resulting in loss of heterozygosity for one or more markers. Seven of the clonal genetic alterations on chromosome 11 were specific to the long arm, and the overlap between these and other allelic deletions suggests that a suppressor gene(s) relevant to cervical carcinoma maps to chromosome 11q22-q24.

Alleles↗
PubMed1994

Transport, function, and sorting of lactase-phlorizin hydrolase in Madin-Darby canine kidney cells.

Lactase-phlorizin hydrolase (LPH), a small intestinal brush-border glycoprotein, is synthesized as a single chain precursor (pro-LPH, M(r) = 215,000-230,000) that undergoes cleavage to the final mature form (LPHm, M(r) = 160,000 in the human). In the human and pig small intestine as well as in the colon carcinoma cell line Caco-2, this cleavage takes place intracellularly prior to insertion into the brush-border membrane. To assess the role of proteolytic cleavage on the transport, function, and sorting of LPH a stable Madin-Darby canine kidney cell line was generated which expresses LPH (denoted as MDCK-ML). Biosynthetic labeling experiments demonstrated that the transport kinetics and posttranslational processing pattern of LPH in this cell line are similar to those in intestinal cells. Moreover, the enzymatic activity was found to be indistinguishable from that of brush-border LPH (LPHm). The sorting of LPH was studied by biosynthetic labeling of cells grown on filters followed by cell surface immunoprecipitation. Here, we could demonstrate that the cleaved LPHm molecule was predominantly found at the apical membrane, whereas complex glycosylated uncleaved pro-LPH (pro-LPHc) was targeted to both domains, the apical as well as the basolateral. In pulse-chase experiments at 20 degrees C pro-LPH was arrested in the trans-Golgi network, and cleavage to LPHm did not take place. By contrast, when the chase temperature was raised to 37 degrees C transport of pro-LPHc resumed, and cleavage to LPHm occurred. We conclude that the proteolytic cleavage of pro-LPHc to LPHm is a post-trans-Golgi network event and is most likely not implicated in the sorting of LPH by exposition of otherwise masked sorting elements.

Animals↗