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Biomedical subjects

H O Smith

Publications and source records attributed to H O Smith.

At least 55 records · Page 3Linked to original sources
PubMed1994

Single-use percutaneous catheters for intraperitoneal P32 therapy.

BACKGROUND: Intraperitoneal (IP) radioactive chromic phosphate (P32) remains investigational in the treatment of patients with ovarian and/or endometrial cancer. Single-use percutaneously placed catheters offer the advantage of therapy without additional surgery. METHODS: Between August, 1986 and October, 1992, 25 patients underwent bedside percutaneous catheter placement under local anesthesia without ultrasonographic or radiologic guidance, using a specialized central venous catheter. RESULTS: Catheter insertion was successful in 22 of 25 patients (88%) with good IP distribution. Of these, 18 of 22 patients (82%) underwent successful catheter placement with one attempt and 4 of 22 (18%) after one to three additional attempts. The technical failure rate was 12%. Multiple catheter placement attempts were associated with an increased incidence of complications (r = 0.63). Bowel entry occurred in 4 of 25 patients (16%) during 5 of 43 attempts at catheter placement (12%) but was without clinical sequelae. The likelihood of bowel entry significantly increased with more than two attempts (P = 0.02). A median of 39 days (range, 7-156 days) elapsed between the preceding laparotomy and catheter insertion. CONCLUSIONS: Percutaneous catheter placement is successful and well tolerated in the majority of patients and should be considered for patients receiving IP P32.

Adult↗
PubMed1994

Cecal cancer in a teenager presenting with a pelvic mass: a case report and review of the literature.

Colorectal cancer generally affects men and women in the later decades of life. Typically patients present with bowel obstruction and/or chronic anemia. The epidemiology, presentation, and prognosis of cecal carcinoma, the third most common colorectal cancer, is similar to other cancers of the large bowel. Cecal and other colorectal cancers rarely present in adolescence. In this case report, we describe a 19-year-old woman presenting with a pelvic mass and elevated tumor markers with the presumed diagnosis of ovarian cancer, who was found to have cecal carcinoma at laparotomy. This case illustrates that colorectal cancer, although rare, should be considered in the differential diagnosis of a pelvic mass in young women who present with anemia, constitutional symptoms, and elevated tumor markers.

Adult↗
PubMed1994

GM-CSF, carboplatin, doxorubicin: a phase I study.

Dose intensification has the potential to increase the response frequency of chemosensitive tumors to chemotherapy. G-CSF and GM-CSF offer the possibility of dose-intensifying chemotherapy without prohibitive myelosuppression. A phase I study was undertaken to identify the maximum tolerated dose (MTD) of carboplatin that could be administered with a fixed dose of doxorubicin, 60 mg/m2, administered every 28 days. Further escalation of the carboplatin dose was then attempted, with the concomitant addition of GM-CSF 10 mg/kg per day on days 1-21. We had 21 patients, 13 with prior therapy, who were eligible. In all, 60 courses of therapy were delivered, all with doxorubicin and with carboplatin doses of 250 mg/m2, 325 mg/m2 and 400 mg/m2. At carboplatin 400 mg/m2 and doxorubicin 60 mg/m2, thrombocytopenia was dose limiting. The addition of GM-CSF did not allow further escalation. Of the 6 patients treated with carboplatin 400 mg/m2, doxorubicin 60 mg/m2, and GM-CSF, grade 4 granulocytopenia and thrombocytopenia were seen in 4 and 5 patients, respectively. The severity of thrombocytopenia was related to the calculated carboplatin AUC and also to baseline platelet count and prior therapy. In addition, the interaction of GM-CSF and chemotherapy, especially carboplatin-based, may be more complex than originally anticipated.

Adult↗
PubMed1994

Racial matching and service utilization among seriously mentally ill consumers in the rural South.

The authors examined racial matching between case manager and client for 677 seriously mentally ill consumers served through a rural community mental health center in the southeastern United States. Nonparametric statistics indicated that client-case manager dyads were more likely to be of the same race than of different races. Same-race dyads tended to have greater service utilization as indicated by a greater number of made appointments over the study period. An interaction was found for failed appointments where African Americans in same-race dyads were more likely to fail appointments, while caucasian consumers in same-race dyads were less likely to fail appointments.

Adult↗
PubMed1994

Characterization and virulence analysis of catalase mutants of Haemophilus influenzae.

In addition to detoxifying peroxides generated by aerobic metabolism, the catalases of pathogenic bacteria have also been hypothesized to serve as virulence factors by enabling microorganisms to resist the oxidative bursts of host inflammatory cells. Using transposon mutagenesis of the hktE gene, encoding the Haemophilus influenzae structural gene for catalase, we constructed defined catalase mutants of H. influenzae strains Rd- and Eagan b+. These mutants show no detectable catalase production during exponential or stationary phases or following induction with hydrogen peroxide or ascorbic acid, indicating that hktE is the only functional hydroperoxidase gene present in these two strains of H. influenzae. Exponential-phase cultures of hktE mutants are 8- to 25-fold more sensitive to hydrogen peroxide than the wild type. Using the infant rat model, hktE mutants of strain Eagan b+ were 2.3-fold less virulent than the wild type following intraperitoneal inoculation (P = 0.07). When administered intranasally, the Eagan b+ hktE mutant produced wild-type levels of bacteremia and nasal colonization. The results of this study show that while the H. influenzae hktE gene is important for survival in the presence of peroxides, deletion of the gene produces only a modest reduction in ability to cause lethal sepsis following parenteral challenge and no change in ability to colonize following intranasal inoculation in the infant rat model of infection.

Animals↗
PubMed1994

A peroxide/ascorbate-inducible catalase from Haemophilus influenzae is homologous to the Escherichia coli katE gene product.

Bacterial catalases are induced by exposure to peroxide (e.g., Escherichia coli katG) or entry into stationary phase (e.g., E. coli katE). To study regulatory systems in Haemophilus influenzae, we complemented an E. coli rpoS mutant, which is unable to induce katE in stationary phase, with a plasmid library of H. influenzae Rd- chromosomal DNA. Nineteen complementing clones with a catalase-positive phenotype were obtained and characterized after screening about 10(5) transformants. All carried the same structural gene for an H. influenzae catalase. The DNA sequence of this gene, called hktE, encodes a 508-amino-acid polypeptide with strong homology to eukaryotic catalases and E. coli katE. However, hktE is regulated like E. coli katG, with catalase activity increasing 10-fold and hktE mRNA levels increasing 4-fold upon exposure to ascorbic acid, which serves to generate hydrogen peroxide. Mutations in the known global regulatory genes of H. influenzae--crp, cya, and sxy--do not affect the inducibility of hktE. The hktE gene maps to a 225-kb segment of the H. influenzae chromosome in a region encoding resistance to spectinomycin.

Amino Acid Sequence↗
PubMed1994

Clinical impact of chemotherapy-induced thrombocytopenia in patients with gynecologic cancer.

PURPOSE AND METHODS: This retrospective analysis of 501 patients with gynecologic cancer treated with chemotherapy evaluates the relationship between platelet count and clinical bleeding, as well as the clinical effects of platelet transfusion therapy. Thrombocytopenic patients were divided into six groups according to platelet counts, and major or minor bleeding manifestations were documented. Thrombocytopenia was defined as a platelet count less than 100,000/microL. RESULTS: Thrombocytopenia occurred in 182 (36.3%) patients over 808 of 1,546 chemotherapy cycles (52%). No intracranial or life-threatening bleeding occurred in any patient. The majority of patients (139 [76.4%]) had no clinical bleeding. Minor bleeding, such as purpura, occurred in 34 patients (18.7%) and 44 cycles (5.4%). Major bleeding occurred in nine patients (4.9%) and 10 cycles (1.3%). Five major bleeding events occurred in 49 patients with platelet counts between 0 and 10,000/microL. Forty-three of these patients received platelet transfusions. Thirty-eight of 43 transfused patients (88.3%) had no bleeding. Of the remaining five patients, two were transfused prophylactically with no effect. Three major bleeding events occurred in patients with platelet counts that ranged from 11,000 to 20,000/microL, but these were due to chronic instrumentation or trauma. In patients with platelet counts more than 20,000/microL, major bleeding occurred only from necrotic metastatic lesions. Random-donor platelet transfusions provided inconsistent increments in platelet counts. Overall, 27.5% of patients achieved the expected increase in platelet number based on units of platelet concentrate transfused. The use of single-donor or human leukocyte antigen (HLA)-matched platelets did not provide greater increments in those patients who were refractory to random-donor platelets. CONCLUSION: Platelet counts > or = 10,000/microL are not associated with spontaneous major bleeding. Prophylactic platelet transfusions in patients with gynecologic malignancies and chemotherapy-induced thrombocytopenia should be limited to those with platelet counts < or = 10,000/microL, provided they are not bleeding and have no major anatomic or pathophysiologic precursors of bleeding.

Antineoplastic Agents↗
PubMed1994

Dose escalation combination carboplatin/cyclophosphamide chemotherapy for epithelial ovarian cancer.

Dose intensification chemotherapy is currently under investigation in ovarian cancer. In order to establish an optimum dose for future colony stimulating factor trials, 16 patients with ovarian cancer were treated with dose-escalation combination carboplatin plus cyclophosphamide chemotherapy without growth factors. The initial carboplatin dose, 300 mg/m2, was increased to a maximum dose of 400 mg/m2. The initial cyclophosphamide dose, 600 mg/m2, was increased to a maximum dose of 1200 mg/m2. Of 10 patients completing 6 cycles, six patients (60%) were escalated to carboplatin 400 mg/m2 and cyclophosphamide 600-1200 mg/m2. Myelosuppression was severe, with all 6 patients requiring platelet and/or packed red blood cell transfusions. Based on these results, carboplatin 400 mg/m2 with cyclophosphamide 600 mg/m2 was selected as the starting dose with hematopoietic growth factors.

Adult↗
PubMed1993

Treatment of advanced or recurrent squamous cell carcinoma of the uterine cervix with mitomycin-C, bleomycin, and cisplatin chemotherapy.

Fifty-nine patients with recurrent/persistent, or advanced local/metastatic squamous cell cancer of the cervix were treated with combination chemotherapy consisting of mitomycin-C, bleomycin, and cisplatin. Response to therapy and survival analysis was determined for 44 of 49 patients who had previously been treated with radiation therapy and/or surgery and for 10 patients with advanced, previously untreated disease. Seven (16%) of the 44 previously treated patients experienced either complete response (CR) or partial response (PR). The median progression-free interval for responders (CR + PR) was 14.5 months, compared with 2.6 months for the nonresponders (significant, P < 0.001). The median survival time for responders (CR + PR) was 15.9 months, compared with 5.9 months for nonresponders (significant, P < 0.01). The 10 previously untreated patients were separately evaluated for response to chemotherapy. Of these, there was 1 CR, 2 PR, 1 < PR, and 6 SD. The 3 responders (CR + PR), who subsequently underwent radiation therapy, were alive and without evidence of disease 7.9, 13.7, and 27.6 months after treatment. Toxicities were mild to moderate, with no treatment-related deaths. In this study, this combination of mitomycin-C, bleomycin, and cisplatin chemotherapy was found to have activity in local, previously untreated disease and in patients with disease recurrence outside pelvic radiation fields.

Adult↗
PubMed1993

Cancer screening for women older than 40 years of age.

As women's doctors, we have a commitment and responsibility to promote effective cancer screening for cervical cancer and breast cancer. At present, the screening tests for ovarian cancer cannot be applied to the mass population. For an individual patient, however, the role of sonography, tumor markers, and physical examination need to be individualized. Clinicians need to look to the future for advances in screening for this dreaded disease. This article reviews and discusses the available cancer screening for cervical, breast, and ovarian cancer.

Adult↗
PubMed1993

Multimodality therapy in locally advanced cervical cancer.

In the past decade, neoadjuvant and concomitant multimodality therapies have been studied in patients with cervical cancer. The past year has witnessed more pilot studies confirming the feasibility of multimodality therapy. It is now time to move to prospective randomized clinical trials to determine the effects on disease-free intervals, to examine survival rates, and to define the ideal chemotherapeutic regimen and relationship to radiation therapy or surgery.

Chemotherapy, Adjuvant↗
PubMed1992

Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: a Southwest Oncology Group study.

Twenty-three patients with metastatic or recurrent Stage III or IV epithelial ovarian cancer who were refractory to or relapsed following previous chemotherapy with cisplatin or a cisplatin analog were entered into a phase II study of amonafide. The starting dose of amonafide was 300 mg/m2 delivered daily over 1 hr by intravenous infusion. In the absence of myelosuppression, the dose of amonafide was escalated by increments of 75 mg/m2 to a maximum of 450 mg/m2. There were 19 eligible and 17 fully evaluable patients. Grade 3 or 4 leukopenia occurred in 14 (74%) patients and grade 3 or 4 thrombocytopenia in 6 (32%) patients. No objective complete or partial responses were observed. Four patients had stable disease for 3, 4, 4.5, and 6 months, respectively. Therefore, amonafide in the doses used in the present trial does not have significant activity in previously treated patients with ovarian cancer.

Adenine↗
PubMed1991

Two-step affinity purification of U7 small nuclear ribonucleoprotein particles using complementary biotinylated 2'-O-methyl oligoribonucleotides.

U7 snRNP is a low-abundance small nuclear ribonucleoprotein particle essential for 3' processing of replication-dependent histone pre-mRNA. We have developed a two-step purification of the particle from TB21 mouse mastocytoma cell nuclear extracts, with about a 20% overall yield, using affinity binding to 2'-O-methyl oligoribonucleotides. The purified particle is homogeneous with respect to RNA content. SDS/PAGE of the U7 snRNP proteins revealed a full complement of the standard core proteins (B, DD', E, F, and G) found in the majority of snRNPs. In addition, two U7-specific polypeptides of 14 kDa and 50 kDa were identified. Summation of the molecular masses of the identified components of the U7 particle yields a particle mass of 249 kDa, in approximate agreement with estimates from sucrose gradient sedimentation (261 kDa) and nondenaturing gradient PAGE (217 kDa).

Animals↗
PubMed1991

Nucleotide sequence of a cluster of genes involved in the transformation of Haemophilus influenzae Rd.

A genetic locus implicated in the development of competence in Haemophilus influenzae Rd has been previously mapped to a 12.8-kb PstI region of the chromosome [Tomb et al., J. Bacteriol. 171 (1989) 3796-3802]. To define the boundaries of this locus and to identify the gene(s) involved in transformation, additional mini-Tn10kan mutagenesis was performed and the region containing all mutagenic insertions was sequenced. Three new transformation-deficient (Tfo-) mutants were found, bringing the number of distinct mutations mapped to this region up to eight. The transformation frequency of strains carrying the new insertions was 25- to 10(5)-fold less than wild type. The ends of the mini-Tn10kan element were used as starting points to sequence a 9.1-kb region. The position of the eight mutagenic insertions was determined and ten putative open reading frames (ORFs) were found. One of the mini-Tn10kan elements had inserted in an intergenic region while the rest had inserted in six of the ORFs. Based on the phenotypes of the mutant strains and the position of the insertions, we concluded that at least three of the genes should be involved in transformation. In addition, fourteen 9-11-bp uptake signal sequences (USS) were found, four of which were part of stem-loop structures and could function as attenuators of terminators of transcription.

Amino Acid Sequence↗
PubMed1991

Aggressive angiomyxoma of the female pelvis and perineum: review of the literature.

Aggressive angiomyxoma is an uncommon neoplasm which predominantly involves the pelvis and perineum of young White females. Misdiagnosis is common. Treatment typically involves surgery, and in spite of apparently complete resection, recurrences are common. Local spread into the adjacent fascia and musculature is frequently reported, and rarely, extension into intestine and bladder. The first reported case of pubic bone involvement, including its histology, radiologic features, and operative management, is discussed. Including this patient, 26 women with this tumor have been reported in the literature and are reviewed, along with 2 previously reported cases from the University of New Mexico Tumor Registry.

Adult↗
PubMed1990

Construction of an efficient overproducer clone of HinfI restriction endonuclease using the polymerase chain reaction.

We describe the use of the polymerase chain reaction (PCR) technique to alter transcriptional and translational signals surrounding a gene so as to achieve overexpression in Escherichia coli. By changing the ribosome-binding site sequence preceding the hinfIR gene to match the consensus E. coli signal and by adding a transcription terminator sequence immediately following the gene, the yield of HinfI was increased about tenfold over that obtained from the natural Haemophilus influenzae signals. The addition of the positive retroregulator stem-loop sequence derived from the crystal protein-encoding gene of Bacillus thuringiensis downstream from the hinfIR gene further increased yields by twofold to a level of 13% of the total cellular protein.

Base Sequence↗
PubMed1990

Finding sequence motifs in groups of functionally related proteins.

We have developed a method for rapidly finding patterns of conserved amino acid residues (motifs) in groups of functionally related proteins. All 3-amino acid patterns in a group of proteins of the type aa1 d1 aa2 d2 aa3, where d1 and d2 are distances that can be varied in a range up to 24 residues, are accumulated into an array. Segments of the proteins containing those patterns that occur most frequently are aligned on each other by a scoring method that obtains an average relatedness value for all the amino acids in each column of the aligned sequence block based on the Dayhoff relatedness odds matrix. The automated method successfully finds and displays nearly all of the sequence motifs that have been previously reported to occur in 33 reverse transcriptases, 18 DNA integrases, and 30 DNA methyltransferases.

Amino Acid Sequence↗