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Biomedical subjects

M McClure

Publications and source records attributed to M McClure.

At least 19 recordsLinked to original sources

Cystic fibrosis genotyping by direct PCR analysis of Guthrie blood spots.

In the United States the most common cystic fibrosis (CF) alleles known are F508, G551D, G542X, R553X, and N1303K. These mutations comprise approximately 85% of U.S. CF alleles, and their detection along with analysis of XV-2C and KM-19 restriction fragment length polymorphisms (RFLPs) can enable the determination of CF status. To facilitate studies for determining CF carrier status, we developed methods to detect each of these mutations and RFLPs by direct PCR amplification of dried blood spots collected on newborn screening (Guthrie) cards. Following collection, samples were protected from contamination by individual plastic bags. One-mm2 segments of filter paper were added directly to 100-microliters PCR reactions containing 1/16 mM spermidine. Three initial cycles at 96 degrees C, then 55 degrees C, for 3 min were performed to free DNA and minimize inhibition by other related materials. Next, 1 unit of Taq polymerase was added and a 2-min extension was carried out at 72 degrees C, followed by 33 amplification cycles using denaturing, annealing, and extension temperatures and times optimal for each primer set. Then, 35 microliters of each reaction was run on 8% acrylamide gels directly or 1% agarose gels following digestion; genotypes were inferred by ethidium bromide staining of gels. Guthrie blood spots of 250 CF probands and their parents were screened and the frequencies of all five mutations as well as the XV-2C KM-19 RFLP haplotypes were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles

Utility of internal markers to improve the accuracy of cystic fibrosis genotype analysis.

DNA diagnostic tests often utilize restriction endonuclease digestion of PCR-amplified portions of genes under analysis. When partial digestion occurs, the resulting patterns may lead to error in diagnosis. To overcome such potential errors in cystic fibrosis testing, we have developed internal markers that can increase the precision and reliability of genotype assignments.

Cystic Fibrosis

Mutation analysis of the cystic fibrosis transmembrane regulator gene in Native American populations of the southwest.

We report DNA and clinical analyses of cystic fibrosis (CF) in two previously unstudied, genetically isolated populations: Pueblo and Navajo Native Americans. Direct mutation analysis of six mutations of the CFTR gene--namely, delta F508, G542X, G551D, R553X, N1303K, and W1282X--was performed on PCR-amplified genomic DNA extracted from blood samples. Haplotype analyses with marker/enzyme pairs XV2c/TaqI and KM19/PstI were performed as well. Of the 12 affected individuals studied, no delta F508 mutation was detected; only one G542X mutation was found. None of the other mutations was detected. All affected individuals have either an AA, AC, or CC haplotype, except for the one carrying the G542X mutation, who has the haplotype AB. Clinically, six of the affected individuals examined exhibit growth deficiency, and five (all from the Zuni Pueblo) have a severe CF phenotype. Four of the six Zunis with CF are also microcephalic, a finding not previously noted in CF patients. Our DNA data have serious implications for risk assessment of CF carrier status for these people.

Adolescent

Management of epithelial ovarian neoplasms using a platinum-based regimen: a 10-year experience.

One-hundred and twenty-four patients with primary advanced (n = 103) and recurrent (n = 21) ovarian carcinoma completed a course of platinum-based chemotherapy (cyclophosphamide/doxorubicin/cisplatin or cyclophosphamide/cisplatin) or developed progressive disease while on therapy and were evaluated. All patients were treated between August 1, 1977 and December 31, 1987. The 5-year survival for patients with primary disease was 27% for stage III (n = 73) and 7% for stage IV (n = 30). The 5-year survival based on residual disease was 91% for microscopic disease (n = 13), 24% for disease less than 2 cm (n = 27), and 8% for disease greater than or equal to 2 cm (n = 64). The 5-year survival for the patients treated with recurrent disease was 5% (n = 21). Borderline tumors have been excluded. Long-term toxicity, including cardiac toxicity, renal toxicity, and a 5% incidence of second primary tumors, is evaluated.

Adult

Serum albumin: its relationship to marrow and renal toxicity from platinum-based combination chemotherapy.

One hundred and three patients treated with CAP chemotherapy were evaluated to determine the relationship between low prechemotherapy serum albumin (less than 3 g/dl) and low WBC nadir (less than 2000 cells/mm3). Additionally, the relationship of serum albumin to renal toxicity (delta serum creatinine) was examined. Low prechemotherapy serum albumin appears to be a marker for advanced disease, but does not appear to predict marrow or renal toxicity.

Antineoplastic Combined Chemotherapy Protocols

Child psychiatry in Japan.

Japanese society strongly influences the mode of presentation of child mental health problems, both in terms of protective factors and pressures inherent in Japanese child-rearing practices. Recent changes in society associated with Japan's rapid economic development are affecting the mental health of children and families. Currently there is concern about levels of school refusal, bullying, suicidal behavior, and delinquency.

Child

Randomized trial of megestrol acetate vs. megestrol acetate/tamoxifen for the management of progressive or recurrent epithelial ovarian carcinoma.

Thirty-three patients were randomly treated with either megestrol acetate (Mg) or megestrol acetate/tamoxifen (Mg/Tx) from November, 1983, to December, 1985. Thirty-two of 33 were previously treated with platinum-based combination chemotherapy. Ten of 32 were also treated with hexamethylmelamine-based second line therapy. Doses were 160 mg/day of Mg and 20 mg/day of Tx. All patients had measurable disease. The two groups did not differ as to progression-free interval. There were no patients who demonstrated tumor regression. Overall, 39% showed stabilization of disease from 4 to 16+ months (median 8.0 months and mean 9.0 months).

Adult

In vitro effect of a microfibrillar collagen hemostat on platelets.

Microscopic particles of microfibrillar collagen hemostat (MCH) have been shown to pass through a 40-micron blood transfusion filter. This study indicates that MCH passing through the filter retains a significant portion of its ability to aggregate platelets in vitro and the aggregating ability is dose related. The extent of platelet aggregation in the presence of the MCH filtrate or an ADP standard was measured photometrically and log dose-response curves constructed from the data. An ED50 of 3.6 micrograms protein/ml platelet-rich plasma (PRP) was calculated at a protein concentration of 7.6 mg/ml in the MCH filtrate and an ED50 of 5.9 micrograms protein/ml PRP at 12 mg/ml protein in the MCH filtrate. The platelet aggregating ability of the MCH filtrates corresponded to 18.8 and 39.6% of the maximum response produced by adenosine-5'-diphosphate. These findings support the view that blood contaminated with MCH should not be returned to a patient's circulation.

Adenosine Diphosphate

Phosphonoformate (foscarnet): a pilot study in AIDS and AIDS related complex.

Phosphonoformate (PFA; a pyrophosphate analogue) is an effective inhibitor of the reverse transcriptase enzyme in many animal retroviruses. In vitro studies have shown that PFA is also an effective inhibitor of HIV (HTLV III/LAV) at doses readily attainable in vitro. A pilot study was therefore performed with a 3-week intravenous infusion of PFA in 11 patients with AIDS and AIDS-related complex (ARC). Viral isolations were performed before and at regular intervals up to 3 months post-infusion on treated patients, as well as on four untreated control patients. Virus isolation was negative after therapy in eight patients, six of whom were negative throughout the follow-up period. Virus was isolated on 70% of attempts from the four control subjects and on 20% of attempts from treated subjects. Three patients showed an improvement in delayed hypersensitivity responses. No obvious improvement was seen in patients' OKT4 positive lymphocyte counts. Treatment was not limited by side-effects with the exception of one patient who developed an axillary vein thrombosis within 4 days of treatment via a subclavian line. Treatment was therefore discontinued following administration of only one dose and the patient was excluded from further study. A further patient had reversible renal dysfunction. Other side-effects were minor, consisting of headache or thrombophlebitis at the site of infusion. These results suggest that a further trial with PFA administered over a longer period and with a longer follow-up period in AIDS and ARC patients may be warranted, particularly if an oral preparation becomes available.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex

Hexamethylmelamine, methotrexate, 5-fluorouracil as second line chemotherapy after platinum for epithelial ovarian malignancies.

Thirty-three patients were treated with HexAF after previous treatment with cyclophosphamide (C), Adriamycin (A), and cisplatin (P). The patients had either progressed on CAP, had persistent disease after CAP, or recurred after a negative second look. Treatment schedule was hexamethylmelamine (Hex) 150 mg po qd days 1-14, methotrexate (A) 40 mg/m2 IV days 1 and 8, and 5-fluorouracil (F) 600 mg/m2 IV days 1 and 8. Courses were repeated every 4 weeks. Thirty-one of 33 patients were evaluable for response. Three of 31 patients had partial responses, 7 of 31 had stable disease, and 21 of 31 progressed. Median survival of the responders (n = 3) was 23 months and the nonresponders (n = 28) was 6 months (p = 0.027). Patients with less than 1 cm disease (n = 12) had a median survival of 20 months, and those with greater than 1 cm (n = 21) had a median survival of 6 months (p = 0.004). Toxicity was mild. Even with a statistically significant survival advantage for HexAF responders, we consider a response rate of less than 10% unacceptable.

Adult

Inherent dangers of simultaneous application of microfibrillar collagen hemostat and blood-saving devices.

Microfibrillar collagen hemostat is a topically applicable hemostatic agent that has been introduced relatively recently. Because of the possibility that this substance may pass through different blood-collecting circuits and cause organ damage if reintroduced into the patient's circulation, we performed a series of in vitro and in vivo experiments. The results of these experiments suggest that such a passage may indeed occur and could cause organ damage, either by direct or by induced embolization that cannot be completely prevented even with the application of commercially used filters. We therefore recommend that the substance should not be used if the shed blood is intended to be collected and returned into the patient's circulation.

Animals

The effect of cytoxan, adriamycin, and cis-platinum on cervical, vaginal cytology.

One hundred and thirty-four cervical and vaginal smears were obtained from 51 patients receiving cyclophosphamide, doxorubicin, and cis-platinum. These drugs do not appear to cause dysplasia or significant atypia. Additionally, the Pap smear was not useful for the diagnosis of unexpected persistent or recurrent carcinoma of the ovary.

Adenocarcinoma

Stage I carcinoma of the endometrium: a 5-year experience utilizing preoperative cesium.

A treatment protocol for the management of stage I endometrial carcinoma utilizing preoperative cesium is evaluated. One hundred and twelve consecutive patients were treated according to this protocol over a 5-year period. Based on this experience and a literature review a new protocol is recommended. The significant changes include primary surgery without preoperative cesium, primary treatment based on grade without regard to uterine size, modified radical hysterectomy for G3 tumors, pelvic radiotherapy for clear cell carcinoma confined to the pelvis regardless of depth of invasion, cytoxan, adriamycin, and cis-platinum for papillary serous tumors, and postoperative vaginal cuff cesium for G2 and G3 tumors not requiring pelvic radiotherapy.

Adenocarcinoma

Bleomycin, vincristine, mitomycin-C, and cisplatin in the management of gynecological squamous cell carcinomas.

Twenty-one patients with squamous carcinoma of the genital tract were treated with bleomycin, Oncovin, mitomycin-C, and cisplatin (BOMP). Six patients received BOMP as primary therapy. Five of six responded with one patient having an autopsy-proven complete response after treatment for a disseminated adenosquamous carcinoma. Eight patients were treated for early recurrence, none responded. Seven patients were treated for late recurrences and one responded. We believe that BOMP has significant potential for primary treatment, but not for early or late recurrent disease.

Adenocarcinoma