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Biomedical subjects

V Howard

Publications and source records attributed to V Howard.

At least 19 recordsLinked to original sources
PubMed1999

Identification and analysis of dihydrofolate reductase alleles from Plasmodium falciparum present at low frequency in polyclonal patient samples.

As resistance to chloroquine spreads in sub-Saharan Africa, pyrimethamine plus sulfadoxine (PSD) is increasingly used as a first-line treatment for falciparum malaria. Populations of Plasmodium falciparum (Pf) resistant to PSD have been selected quickly in other regions. The resistance is strongly correlated with point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), the two targets of the drug. It is critical to identify drug-resistant Pf-DHFR alleles that are present at a low frequency in these populations since alleles that confer drug resistance will be quickly selected by PSD use. It is difficult to identify these rare alleles by standard molecular techniques. We have designed a yeast expression system that facilitates the identification and rapid analysis of Pf-DHFR alleles that confer PSD resistance, even when they are present at very low frequency in polyclonal patient samples. We analyzed samples from patients in Kilifi, Kenya collected between 1992 and 1995. We determined the prevalence of the drug-sensitive and drug-resistant alleles in patient samples analyzed in parallel by an allele-specific enzyme digestion (ASED) assay. We identified a pyrimethamine-resistant allele (S108N) present at a frequency of < 1% in a sample that was scored as only S108 by ASED. In addition, a novel pyrimethamine-resistant allele (1164M) was isolated twice, once each from two different patient samples. This approach will allow determination of the prevalence of Pf-DHFR alleles that confer pyrimethamine resistance in particular regions, and the rapid identification of novel alleles that confer drug resistance.

Alleles↗
PubMed1998

Fatigue in children and adolescents with cancer.

Fatigue is a common symptom found in the adult oncology literature. However, little is known about its occurrence, causes, conceptual and operational definitions, and effective interventions in children and adolescents with cancer. The purpose of this study was to define and describe fatigue experienced by children and adolescents receiving treatment for cancer. A focus group approach was used to reveal the contextual understanding of fatigue through discussions. Eleven focus groups were convened during a 2-month period at two major children's cancer centers. Twenty-nine children participated in the focus groups: 14 were 7 to 12 years of age and 15 were 13 to 16 years of age. Focus groups were held separately for each age group, lasted from 30 to 45 minutes, and were audiotaped. The audiotapes were transcribed verbatim, and Ethnograph software was used to number the data to sort and code the information. Researchers at both study sites coded the data independently within the context of the unit of analyses, which, in this study, were the study questions. Codes and descriptions were developed for the definitions of fatigue, causes of fatigue, and what helps. Eight codes emerged from the children groups and 12 from the adolescent groups to define fatigue. Six codes were developed from the children groups and 12 from the adolescent groups to describe causes of fatigue. Three codes from the children groups and eight from the adolescent groups described what helps. This study is the first to evaluate fatigue as a symptom in children and adolescents with cancer. Findings from this study will provide the foundation for developing a conceptual model for cancer-related fatigue in children and adolescents.

Adolescent↗
PubMed1991

Effect of propylthiouracil treatment during prenatal and early postnatal development on the neocortex of rat pups.

The effects of a pre- and postnatal hypothyroid environment on the development of the neocortex have been determined. Rats were treated with propylthiouracil (PTU) with or without thyroid hormone supplementation during pregnancy and throughout the early development of the pups. The Cavalieri method was used to provide an estimate of the volume of the neocortex, and a combination of the Cavalieri method and the 'disector' particle-counting method provided an unbiased estimate of the numbers of glia and neurons in the neocortex. In pups from non-treated rats the mean volume of the neocortex increased from 31.3 mm3 at 5 days postnatally to 191.5 mm3 at 20 days and then remained constant to day 48. Similarly, the mean number of glial cells increased from 5.2 x 10(6) at day 5 to 12.0 x 10(6) on day 20 and then remained constant to day 48. The mean number of neurons in the neocortex in the control condition was constant at about 14.6 x 10(6) from day 5 to day 48. PTU treatment during pregnancy and postnatal development significantly decreased the mean volume of the neocortex at all of the stages studied, for example from 31.3 to 23.3 mm3 (p less than 0.001) on day 5 and from 191.5 to 155.0 mm3 (p less than 0.001) on day 20. Supplementation with thyroxine (T4) or tri-iodothyronine partially reversed this at certain stages. For example, the mean volume of the neocortex at 48 days was 197.5 mm3 in control rats, 118.1 mm3 in PTU-treated rats and 169.3 mm3 in PTU-treated rats supplemented with T4. Within the neocortex, the volume of the neuropile was more severely affected than was the volume of the neuron cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Further experience with regional radiofrequency hyperthermia and cytotoxic chemotherapy for unresectable hepatic neoplasia.

The authors report on 178 patients with unresectable hepatic tumors who have been treated with 1 to 25 (median, 6) courses of radiofrequency hyperthermia (RFHT) and chemotherapy. In 137 patients, the hepatic tumors consisted of metastases from colorectal adenocarcinomas. For patients who had no previous therapy and who had colorectal metastases with no extraheptic disease, cumulative survival at 52 weeks' follow-up was 80.5% and partial tumor regression was seen in 78.4%. Among the 69 patients who previously had conventional treatment for their hepatic disease, partial regression was seen in 43.5%. We are no longer monitoring tumor core temperature routinely, as the invasive methods currently in use yield irreproducible results; the risks to the patient cannot be justified in view of the questionable relevance of the data obtained. A prospective randomized study of systemic chemotherapy with or without RFHT in patients with colorectal hepatic metastases is in progress.

Adenocarcinoma↗
PubMed1985

Unbiased estimation of particle density in the tandem scanning reflected light microscope.

The tandem scanning reflected light microscope has the property of being able to obtain information from 'inside' solid objects by taking a thin optical section at the focal plane of the objective lens. This plane can be focused up and down through the specimen. We describe an unbiased 3-D counting rule for the TSRLM, which is applied to the estimation of osteocyte lacunar density in whole bone. This is shown to be an extremely efficient way of making such an estimate. Further possibilities for the application of the microscope in the field of stereology are discussed.

Animals↗
PubMed1984

Palliation of advanced head and neck cancer with radiofrequency hyperthermia and cytotoxic chemotherapy.

Fourteen patients with recurrent malignant tumours of the head and neck were treated with radiofrequency hyperthermia and chemotherapy after conventional therapy had failed. After 2 to 11 treatment courses and a follow-up of 30 weeks, the neoplasms in three patients had completely regressed and one had a partial response. Of eight patients who died, two had partial responses initially; a third patient died of complications relating to surgical resection of the tumour after a partial response. Three of five patients whose tumours were unresponsive to methotrexate responded when this drug was given with radiofrequency hyperthermia. There were seven minor skin burns in six patients. Further studies of radiofrequency hyperthermia and chemotherapy for palliation of head and neck cancer are planned.

Adult↗
PubMed1983

Effect of radiofrequency hyperthermia and chemotherapy on primary and secondary hepatic malignancies when used with metronidazole.

Hyperthermia is selectively toxic to neoplastic tissue. Since August 1981, 357 patients with incurable tumors in various body areas have been treated with chemotherapy and radiofrequency hyperthermia (RFHT) with adjuvant metronidazole at this center. Of this group, the cases of 102 patients with hepatic tumors are reported here. Patients received one to ten treatment courses, each course consisting of two to five daily RFHT sessions. Systemic temperature rose 0.6 +/- 0.3 degrees C during treatment, and tumor core temperature (measured by percutaneous transhepatic thermistor) reached 39.5 +/- 1.2 degrees C in 38 monitored patients. Results have been encouraging; in particular, among 15 patients with newly diagnosed colorectal metastases limited to the liver (and as yet untreated for their secondary disease), there has been objective partial tumor regression in 66.7%. Side effects have been few. Skin burns and subcutaneous fat necrosis were seen in 3.9% and 13.7% of patients, respectively. Tumor temperature is difficult to measure reliably and does not correlate with machine power or tumor response. A phase III trial is currently underway to determine the efficacy of RFHT and chemotherapy for patients with hepatic metastases from colorectal adenocarcinoma.

Adult↗
PubMed1983

The effect of radiofrequency hyperthermia and chemotherapy upon human neoplasms when used with adjuvant metronidazole.

It appears that metronidazole causes an increase in tumor core temperature above that achieved with RFHT alone, by an as yet undetermined mechanism. Furthermore, radiofrequency hyperthermia, in combination with chemotherapy, can produce objective evidence of tumor repression in 30 to 50 per cent of the patients with metastatic cancer. These results justify proceeding to a randomized prospective trial of RFHT and chemotherapy in specific human neoplasms. Such a study is currently being undertaken at this center.

Adult↗
PubMed1982

Hyperthermia as a treatment for neoplasia.

The use of hyperthermia to treat malignant neoplasms is currently a "hot" issue. It has been demonstrated that heating tumour cells to 42 degrees C or above leads to their self-destruction by decreased cellular metabolism and aerobic respiration. The selective accumulation of heat in the malignant tissue at 42 degrees to 44 degrees C, compared with the temperature of normal tissue, is probably related to the different blood supply within the tumour. The historical background and the experimental and clinical results of hyperthermia are reviewed. The advantages and disadvantages of the different thermotherapy techniques currently in use are discussed. Hyperthermia is probably more efficient if combined with other antitumour treatment modalities.

Animals↗
PubMed1981

Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association.

One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established.

Adenocarcinoma↗
PubMed1981

A randomized comparative trial of chemotherapy and irradiation therapy for stage II breast cancer.

One hundred fifty-eight evaluable patients with Stage II carcinoma of the breast with positive lymph nodes were treated either with adjuvant chemotherapy or irradiation therapy followed by chemotherapy. Patients were randomized to test the effectiveness of L-phenylalanine mustard (L-PAM) with and without postoperative irradiation therapy (R.T.) against cyclophosphamide, 5-fluorouracil, and methotrexate (CMF) with and without postoperative irradiation therapy in decreasing the frequency of recurrence. No significant difference was observed between L-PAM as compared with R.T. plus L-PAM (P = 0.85). The difference between CMF and R.T. plus CMF was significant in support of CMF alone (P = 0.04). The frequency of recurrence between R.T. plus L-PAM and R.T. plus CMF showed no difference. A comparison of the chemotherapy only regimens showed an advantage of CMF over L-PAM (P = 0.05). Both the delay in starting chemotherapy and the significant decrease in percent optimal drug dosage during the first six cycles of therapy are factors that may influence the high frequency of relapse observed in the R.T. plus chemotherapy groups. Of the four treatments, CMF has the lowest frequency of recurrence.

Adult↗
PubMed1981

Chemotherapy vs. chemoimmunotherapy with methanol extraction residue of Bacillus Calmette-Guerin (MER) in advanced breast cancer: a randomized trial by the Piedmont Oncology Association.

Effects of the addition of MER, a nonspecific, nonviable immunostimulant, to two combination chemotherapy programs were explored in patients with metastatic breast cancer. Patients were randomized to either CDVFP [cyclophosphamide (C), doxorubicin (D), vincristine (V), fluorouracil (F) and prednisone (P)] or CD alternating with methotrexate (M) and F (CD/MF). Each group was also randomized to receive MER, 0.4 mg S.C. every four weeks or no immunotherapy. The response rates were CDVFP 56%, CDVFP + MER 54%, CD/MF 43%, and CD/MF + MER 43%. No significant differences were noted in response rate. Median durations of response and survival were similar for each group: CDVFP 16.2 and 25.2 months, respectively; CDVFP + MER 14.0 and 23.3 months, CD/MF 12.1 and 26.1 months, and CD/MF + MER 15.5 and 25.6 months. Patients who achieved CR frequently had soft-tissue disease (7/17) and patients with disease in 1 or 2 metastatic sites had a significantly higher response rate than those in greater than or equal to 3 sites. MER did not enhance response rate, duration of response, or survival. Also MER did not diminish myelosuppression.

Antineoplastic Agents↗
PubMed1981

Cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil in advanced prostatic cancer: a randomized trial.

Thirty-two evaluable patients with metastatic carcinoma of the prostate were entered into a prospective randomized trial comparing cyclophosphamide (CYC) with a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF). Progressive disease after endocrine manipulation was noted in 97% (31/32) of patients before entry. Stable disease (S) was observed in 9 of 17 patients treated with CYC. One partial response (PR) and seven stable responses occurred in the 15 CMF patients. Median duration of stable response was 4.5 months for CYC and 4.5 months on CMF. Median survival of patients with PR and S receiving CYC was 10.1 and for CMF 8.8 months. Patients with progressive disease survived a median 1.7 and 2.6 months with CYC and CMF, respectively. Toxicity was moderate, and no deaths were attributable to sepsis or bleeding. Almost all patients in this study had bone lesions as the dominant site of disease; this made objective assessment of response difficult. There was no significant improvement in response conferred by the combination regimen. Although patients with metastatic prostatic cancer may benefit from chemotherapy, impressive clinical responses are uncommon.

Aged↗
PubMed1981

A prospective study of histocompatible leukocyte and platelet transfusions during induction chemotherapy of adult acute nonlymphocytic leukemia.

A prospective clinical trial was conducted to test the effectiveness of granulocyte transfusions during induction chemotherapy of patients with adult acute non-lymphocyte leukemia. Thirty-eight patients who received prophylactic granulocyte transfusions from related donors when their phagocyte counts decreased to less than 1000 microliter were compared to twenty-five controls who did not have qualified donors from which to obtain granulocyte transfusions. The frequency of complete remissions (CR) (28/38 versus 7/25) was significantly greater for the granulocyte transfusion group than for controls. Patients older than 45 responded more often in the transfused group (P less than 0.025) when compared to the similar age group in controls. Both duration of complete remission and survival were greater in the granulocyte transfused group. However, these differences were not statistically significant. Survival for all responders (complete plus partial remission) was longer for the granulocyte transfusion group (P = 0.01). No significant difference in frequency or severity of either infection or hemorrhage was noted in the two groups. The advantage noted in this study largely occurred in patients older than 45 and this suggests that this age group is more likely to respond if they have histocompatible donors from which to obtain granulocyte and platelet transfusions. Immune mechanisms may be involved in the beneficial effects observed with HLA compatible granulocyte transfusions.

Adolescent↗
PubMed1979

Serum alkaline phosphatase determination. Value in the staging of advanced breast cancer.

A retrospective study of 146 patients with metastatic disease was undertaken to verify the clinical impression that radionuclide scanning rarely, if ever, discloses hepatic metastases in breast cancer patients with normal serum alkaline phosphatase (AP) levels. Only two of 39 patients with abnormal liver scans had normal AP levels, and we conclude that liver scans are not necessary as a routine screening method for liver metastases when the AP level is normal. In contrast AP levels were not predictive of bone scan results. All patients with a twofold or greater elevation of the AP level had abnormal bone, liver, or bone and liver scans. Routine AP determinations provide accurate staging information, and their proper use can decrease the cost of initial and follow-up examination of patients with breast cancer.

Alkaline Phosphatase↗