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Biomedical subjects

D Howe

Publications and source records attributed to D Howe.

At least 19 recordsLinked to original sources
PubMed1992

Effectiveness of preload reserve as a determinant of clinical status in patients with left ventricular systolic dysfunction. The SOLVD Investigators.

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

The genotoxicity of the anti-cancer drug mitoxantrone in somatic and germ cells of Drosophila melanogaster.

The novel antineoplastic drug mitoxantrone was studied for its genotoxic effects in Drosophila melanogaster. In male germ cells, the clinical preparation Novantrone, the dihydrochloride salt of mitoxantrone, did not induce sex-linked recessive lethal mutations in feeding and injection experiments with adult flies, although statistically the results were inconclusive rather than truly negative. However, the free base mitoxantrone was weakly, but significantly genotoxic in this test (0.14% lethals/mM exposure concentration); this is most probably the result of prolonged exposure. On the other hand, both forms of mitoxantrone assayed were clearly genotoxic in the somatic mutation and recombination test of the wing. This test assays the cells of the proliferating imaginal wing discs of larvae. Depending on the feeding method used, the overall clone induction frequency was in the range of about 2-6 x 10(-5) per cell and cell generation and per mM exposure dose. Correction of these frequencies according to mean clone size led to slightly higher estimates (by about 5-25% higher). Although the majority of the clone induction events are due to mitotic recombination, a significant proportion can be attributed to mutational events (gene and chromosome mutations). The genotoxicity of mitoxantrone seems to depend mainly on impaired DNA synthesis in cycling cells owing to the compound's ability to inhibit topoisomerase II by intercalation into DNA.

Animals↗
PubMed1992

Molecular approaches to malaria and babesiosis diagnosis.

The development of additional methods for detecting and identifying Babesia and Plasmodium infections may be useful in disease monitoring, management and control efforts. The preliminary evaluate synthetic peptide-based serodiagnosis, a hydrophilic sequence (DDESEFDKEK) was selected from the published BabR gene of B. bovis. Immunization of rabbits and cattle with the hemocyanin-conjugated peptide elicited antibody responses that specifically detected both P. falciparum and B. bovis antigens by immunofluorescence and Western blots. Using a dot-ELISA with this peptide, antisera from immunized and naturally-infected cattle, and immunized rodents, were specifically detected. Reactivity was weak and correlated with peptide immunization or infection. DNA-based detection using repetitive DNA was species-specific in dot-blot formats for B. bovis DNA, and in both dot-blot and in situ formats for P. falciparum; a streamlined enzyme-linked synthetic DNA assay for P. falciparum detected 30 parasites/mm3 from patient blood using either colorimetric (2-15 h color development) or chemiluminescent detection (0.5-6-min exposures). Serodiagnostic and DNA hybridization methods may be complementary in the respective detection of both chronic and acute infections. However, recent improvements in the polymerase chain reaction (PCR) make feasible a more sensitive and uniform approach to the diagnosis of these and other infectious disease complexes, with appropriate primers and processing methods. An analysis of ribosomal DNA genes of Plasmodium and Toxoplasma identified Apicomplexa-conserved sequence regions. Specific and distinctive PCR profiles were obtained for primers spanning the internal transcribed spacer locus for each of several Plasmodium and Babesia species.

Amino Acid Sequence↗
PubMed1991

Initial blood pressure response to enalapril in hospitalized patients (Studies of Left Ventricular Dysfunction [SOLVD]).

Studies of Left Ventricular Dysfunction (SOLVD) is a randomized trial of enalapril versus placebo in reducing mortality in patients with cardiac dysfunction (defined as left ventricular ejection fraction less than or equal to 35%). Before randomization, patients at risk for hypotension were hospitalized for a test dose of 2.5 mg of enalapril administered orally at baseline and again 12 hours later. As of February 1989, 89 of 7,539 (1.2%) patients had been studied during hospitalization. Baseline systolic and diastolic blood pressures were 115 +/- 18 and 73 +/- 10 mm Hg, respectively. After enalapril, systolic blood pressure decreased slightly but significantly 8 to 20 hours after the initial dose (mean reduction 8 to 11 mm Hg). In this highly selected group of 89 patients, symptoms relating to decrease in blood pressure were noted in 13 (15%). It is emphasized that most patients with cardiac dysfunction readily tolerate enalapril. However, the agent should be administered with caution to patients with advanced congestive failure and diminished baseline blood pressure, owing to a significant incidence of symptomatic hypotension.

Aged↗
PubMed1991

CHLVPP chemotherapy with involved-field irradiation for Hodgkin's disease: favorable results with acceptable toxicity.

Patients with Hodgkin's disease who were previously untreated with chemotherapy received the chlorambucil, vinblastine, procarbazine, and prednisone (CHLVPP) regimen plus limited involved-field radiation therapy for treatment of Hodgkin's disease through the Nebraska Lymphoma Study Group. One hundred patients, 87 with newly diagnosed Hodgkin's disease and 13 who relapsed after receiving previous radiation therapy, were treated with this regimen between 1982 and 1989. Complete remissions (CRs) were obtained in 88 of 100 patients (88%), and there have been a total of eight relapses. The overall 3-year failure-free survival was 76%, with good-prognosis patients (ie, Karnofsky performance status greater than or equal to 80) having a 3-year failure-free survival of 87%. Toxicity with this regimen was minimal, with neutropenic fevers reported in 13% of the patient population, moderate alopecia in 5%, and mild to moderate nausea and vomiting in 11% of the patients. As primary induction therapy for Hodgkin's disease, CHLVPP is an effective regimen with a high patient acceptance profile.

Adolescent↗
PubMed1990

The effects of a range of anti-cancer drugs in the white-ivory somatic mutation test in Drosophila.

The white-ivory test is based upon the reversion of the X-linked, recessive eye-colour mutation white-ivory to wild-type. Somatic reversion of white-ivory results in clones of red facets in the white-ivory eyes of eclosing adult flies. 4 anti-cancer drugs, bleomycin, adriamycin, mitoxantrone and cyclophosphamide were found to significantly increase the white-ivory reversion frequency whereas cytosine arabinoside, methotrexate and vincristine did not give positive results.

Animals↗
PubMed1990

The white-ivory somatic mutation test in Drosophila. The effects of larval age, increasing the number of copies of wi and the response to some reference mutagens.

The white-ivory somatic mutation test is based on reversion of the X-linked, recessive eye-colour mutation white-ivory to wild-type. Somatic reversion of white-ivory leads to clones of red facets in the white-ivory eyes of eclosing adult flies. The alkylating agents MMS, EMS and ENU and the mutagen DEB all induce high levels of white-ivory reversion. The response of different larval instars has been investigated and dose-response data for MMS and EMS is reported. Strains with additional copies of the white-ivory mutation are more sensitive to reversion but the increase in reversion is not as high as might be expected given the number of white-ivory mutations present. Females, having twice the number of white-ivory copies, tend to show higher levels of reversion than males of the same strain.

Animals↗
PubMed1990

The harlequin nail. A marker for smoking cessation.

Changes in the human nail frequently serve as an indicator of local and systemic disease. Alterations in the morphology, structure and growth characteristics of the nail accompany chronic cigarette smoking; yellow pigmentation of the nail plate--referred to as the "nicotine sign"--is common. The clubbed yellow nail may indicate the presence of lung cancer. In contrast to the ominous nature of the clubbed yellow nail, we describe a sign that is more propitious: the sudden cessation of smoking due to an intercurrent disease, often a cerebrovascular accident (CVA), leads to the development of a distinct line of demarcation between the distal pigmented nail and the newly emerging proximal nonpigmented nail. We propose the term "harlequin nail" for this curious physical sign. By measurement of the distance between the proximal nail base fold and the line of demarcation, we can deduce the date smoking ceased (and, by inference, the approximate date of a CVA in a patient unable to volunteer this information). This sign also serves as a reminder that the "nicotine nail" remains discolored only because of dynamic restaining of the nail with tobacco by-products.

Aged↗
PubMed1988

The Drosophila wing test: a comparison of the sensitivity of different strains.

A range of 5 chemical mutagens were tested in the Drosophila wing test using 2 different strains and carrying out the experiments in parallel under standardised conditions. The mutagens chosen for the study were the 2 alkylating agents MMS and ENU and the anti-cancer drugs methotrexate, cytosine-arabinoside and adriamycin. As a result of the different genetic backgrounds there was a marked variation in the response of the 2 strains to the mutagens.

Alkylating Agents↗
PubMed1988

ChlVPP--an effective and well-tolerated alternative to MOPP therapy for Hodgkin's disease.

The substitution of chlorambucil for nitrogen mustard and vinblastine for vincristine has been suggested to be an equally effective and well-tolerated variation of the MOPP regimen (mechlorethamine, vincristine, procarbazine, and prednisone). We treated 76 patients with advanced (i.e., Stage III, IV, or II with bulky mediastinal mass) or recurrent Hodgkin's disease with chlorambucil 6 mg/m2, procarbazine 100 mg/m2, and prednisone 40 mg p.o. daily, all on days 1-14; plus vinblastine 6 mg/m2 i.v. on day 1 and 8 of each 28-day cycle (ChlVPP). There was no maximum dose of the myelosuppressive agents. Patients who had not previously been irradiated received from 2,300 to 4,100 cGY to sites of previously bulky diseases after completing 6 cycles of ChlVPP. ChlVPP was easy to administer (i.e., 87% of patients without previous chemotherapy received greater than or equal to 80% of the planned doses of myelosuppressive drugs) and was generally well tolerated, with only occasional vomiting from procarbazine and phlebitis from vinblastine. In patients without previous chemotherapy, 49 (76%) achieved a complete remission (CR) and 7 (11%) a stable partial remission (i.e., residual, stable radiographic abnormality). With a maximum follow-up of 4 years, only one CR has relapsed for an actuarial CR durability of 97%. ChlVPP with consolidative radiation therapy to sites of bulky disease is effective in advanced Hodgkin's disease and, compared with most other available regimens, is extremely well tolerated.

Adolescent↗
PubMed1988

Clinical value of scrotal ultrasound in the investigation of scrotal pathology.

The investigation of scrotal swelling has been aided by the advent of scrotal ultrasound. We have reviewed 100 patients in whom 112 scans were performed. One quarter of this group presented with scrotal pain without swelling. Of these patients, 33% were shown to have normal testes on scan; the remainder all had benign disease. A similar number presented with scrotal pain and swelling and the majority were diagnosed on scan as having epididymitis. Nineteen patients were thought on clinical grounds to have tumours; 6 were proven at operation and all were correctly identified pre-operatively by scanning. Scrotal ultrasound is a useful investigation in the management of both painless and painful scrotal swellings.

Adolescent↗
PubMed1988

The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) is a malignancy that occurs frequently in the elderly with a median age greater than 60 years. However, most chemotherapy trials have included predominantly patients less than 60 years of age. We treated 157 patients with diffuse aggressive NHL between September 1982 and May 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), procarbazine, bleomycin, vincristine, and prednisone (CAP/BOP). There were no treatment exclusions for age. Patients in this study ranged in age from 15 to 91 years (median, 63) with 112 patients greater than or equal to 60 years of age. The overall complete remission (CR) rate was 65% with no significant difference for age less than 60 (76%) v age greater than or equal to 60 (61%) (P = .18). With a median 36-month follow-up (range, 22 to 65 months), the overall 5-year survival was 42%. The patients less than 60 years old had a 62% 5-year survival in contrast to a 34% 5-year survival in those patients greater than or equal to age 60 (P = .01). The deaths attributed to tumor or treatment-related toxicity were similar above and below age 60. The difference in survival was due to other causes of death not obviously related to the lymphoma or its therapy-occurring in 22% of patients greater than or equal to 60 years of age but only 2% of patients less than 60 years (P = .005). Our data supports the position that aggressive NHL in elderly patients is not significantly less responsive than in younger patients; however, the inclusion of older patients in clinical trials will decrease the overall survival secondary to deaths due to apparently unrelated causes.

Adolescent↗
PubMed1988

Pulmonary emboli in patients receiving chemotherapy for non-Hodgkin's lymphoma.

Combination chemotherapy has dramatically improved the prognosis of patients with intermediate and high grade histologic subtypes of non-Hodgkin's lymphomas. Treatment-related complications, however, are considerable, and a common problem encountered is respiratory distress or respiratory insufficiency. Usually these difficulties have been attributed to infectious etiologies or to chemotherapy-induced interstitial fibrosis, most often involving bleomycin. We describe five patients presenting with respiratory problems several weeks after the initiation of chemotherapy. These patients, who represent 3 percent of all patients treated with a single bleomycin-containing regimen for intermediate or high grade non-Hodgkin's lymphoma, were all initially thought to have chemotherapy-induced interstitial fibrosis but were found on subsequent evaluation to have pulmonary emboli. Of the three patients in whom pulmonary emboli were diagnosed antemortem, two had symptoms suggestive of pulmonary emboli and all were successfully treated and remained well and free of lymphoma for over 24 months. Two additional patients were diagnosed at autopsy. We suggest that pulmonary emboli may contribute significantly to the morbidity and mortality of patients undergoing chemotherapy for non-Hodgkin's lymphoma and recommend that patients presenting with respiratory difficulties be evaluated for pulmonary emboli.

Aged↗
PubMed1986

Chemotherapy for diffuse large-cell lymphoma--rapidly responding patients have more durable remissions.

Fifty-one patients with diffuse large-cell lymphoma (DLCL) were treated with a six-drug combination chemotherapy regimen including cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The patients were restaged after three cycles of therapy, and restaging was repeated at 2-month intervals in patients who had persistent disease. Responding patients received two cycles of therapy after documentation of complete remission (CR). With all patients considered evaluable, 73% of the patients achieved a CR. Twenty-six of the 37 CRs (70%) achieved remission in the first three treatment cycles. The durability of remission in the rapidly responding patients was significantly better than for patients who required five cycles to achieve CR (80% v 40% at 2 years, P = .02) despite the latter patients having received two more cycles of therapy. Rapidly responding patients with DLCL do not require prolonged therapy and have a better prognosis than patients achieving a CR more slowly.

Actuarial Analysis↗