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Biomedical subjects

M Leahy

Publications and source records attributed to M Leahy.

At least 37 records · Page 2Linked to original sources

Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients.

The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60-78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1-37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.

Age Factors↗

Nucleotide and deduced amino acid sequences of Rhizobium meliloti 102F34 lacZ gene: comparison with prokaryotic beta-galactosidases and human beta-glucuronidase.

The nucleotide (nt) sequence of a 2.57-kb Sau3A fragment carrying the Rhizobium meliloti beta-galactosidase (beta Gal)-encoding gene (RmlacZ) was determined. An open reading frame (ORF) of 2.26 kb was identified which encoded a 755-amino-acid (aa) polypeptide with a calculated molecular mass of 84,141 Da, in fair agreement with the value of 88 kDa determined by SDS-PAGE. The deduced N-terminal aa sequence was confirmed by direct sequencing of electrophoretically purified R. meliloti beta Gal. The size of the native R. meliloti beta Gal was approx. 174 kDa. Similarities were found between the aa sequence of the R. meliloti beta Gal and those from Clostridium thermosulfurogenes EM1 and Agrobacterium radiobacter, as well as human beta-glucuronidase (beta Glu). Comparisons with beta Gal from Escherichia coli, Klebsiella pneumoniae, Lactobacillus bulgaricus and Kluyveromyces lactis found only weak similarities; however, the putative active site residues appear to be conserved. The RmlacZ sequence is flanked by two partially sequenced ORFs, which show aa sequence and organisational similarities to the previously reported lac operon in A. radiobacter.

Amino Acid Sequence↗

Patterns of survival in patients with Hodgkin's disease: long follow up in a single centre.

BACKGROUND: Prolonged remission can now be induced in the majority of patients with Hodgkin's disease with chemotherapy and/or irradiation. However, there is a significant proportion of patients in whom this approach fails, either at presentation or subsequently. Survival is the definitive endpoint to assess treatment efficacy. In this study, the survival patterns of a large group of consecutive patients treated in a single institution are presented. RESULTS: The overall median survival was 18.3 years. Clinical remission (complete remission plus good partial remission) was induced in 443 (85%); the median survival of patients in remission has not been reached. Fifty-eight patients achieved responses less than clinical remission with initial therapy (partial response) or had progressive disease, the median survival of this group being 1.4 years. With further therapy, remission was subsequently induced in 10; 5 are still alive, 5 have died between 1.9 years and 14.3 years. Twenty patients died before completion of therapy. Recurrence has been documented in 147 of the patients in remission (following initial therapy) over a median follow up period of 13 years (minimum 5 years). One hundred forty-three of these patients were retreated following recurrence (105 chemotherapy, 28 radiotherapy, 6 combined modality treatment and 4 surgery). Second remission was induced in 109/143 (76%). There was a trend towards better second remission induction in patients whose first remission was longer than 1 year (p = 0.06). The median duration of second remission was inferior to first remission duration (p < 0.001). There was no correlation between duration of first remission and survival following recurrence (p = 0.8) or with duration of second remission (p = 0.54). There was no significant difference in duration of second remission between patients who were initially treated with radiotherapy or chemotherapy (p = 0.3). The median survival following second remission was 12.0 years, being the same for patients with initially localized disease (stages I and II) treated with radiation alone and for patients with advanced Hodgkin's disease (stages III and IV) treated with chemotherapy. Survival after recurrence is significantly better for patients under 50 years at the time of recurrence (p < 0.001). Second recurrence was documented in 46 patients, third remission being reinduced in 22, the median survival of the latter being 5.1 years. CONCLUSION: These results illustrate the importance of prolonged follow up in defining the clinical course of patients with HD and are vital for planning experimental chemotherapy at the time of treatment failure or recurrence.

Adolescent↗

Mitoxantrone and cytosine arabinoside as treatment for acute myelogenous leukemia (AML) at first recurrence.

A total of 107 patients with newly diagnosed acute myeloblastic leukemia (AML) were referred to the ICRF Department of Medical Oncology at St Bartholomew's Hospital between August 1986 and July 1989. Of those referred, 92 (87%) were treated with remission induction chemotherapy comprising: Adriamycin, cytosine arabinoside (ara-C) and 6-thioguanine if aged < 60 years (57 patients) or mitoxantrone (MTN) and ara-C if aged > 60 years (35 patients). Of those treated, 54 (58%) entered complete remission (CR). Recurrent AML developed in 38 out of these 54 patients (70%) of whom 25 aged 19-73 years (median 50 years) subsequently received MTN and ara-C as reinduction therapy. The 19 younger patients (under 60 years old) received MTN at 12 mg/m2, intravenously, daily for 5 days and ara-C at 100 mg/m2, intravenously, twice daily for 7 days. The six older patients received the same ara-C schedule but the dose of MTN was reduced to 10 mg/m2 for 5 days. Second CR was achieved in 16 out of 25 patients (64%) [12/19 (63%) and 4/6 (67%) for patients aged under or over 60 years, respectively]. Eight of the patients in whom second CR was achieved were aged under 50 years and were thus eligible for additional consolidation comprising myeloablative therapy with autologous bone marrow transplantation (ABMT). Four patients actually received the latter treatment: two remain in second CR at 21 and 46 months. Three of the remaining eight patients aged > 50 years in whom second CR was achieved remain in second CR 8 to 43 months later. Censored for myeloablative therapy + ABMT, the overall median duration of second CR was 5 months. Although remissions tended to be short, in younger patients the possibility of proceeding to myeloablative therapy with autologous bone marrow support makes the regimen worthwhile and, even in older patients, it was sometimes possible to achieve prolonged second remissions.

Adolescent↗

Effects of recombinant human interleukin-1 alpha on clonogenic growth of primary human tumors in vitro.

Interleukin-1 alpha (IL-1 alpha) is a low-molecular-weight cytokine that regulates proliferation and differentiation of lymphatic and myeloid cells. It also has pleiotropic activity on a variety of other target cells and acts as an important mediator of inflammation and septic shock. Recombinant human IL-1 alpha (rhIL-1 alpha) is undergoing clinical evaluation of its potential as an anticancer agent. We have studied the growth modulating effects of rhIL-1 alpha on a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.01-100 ng/ml were used in continuous incubation experiments. Of 139 specimens tested, 56 (40%) were evaluable for determination of tumor growth modulating activity. The most common tumor types examined included breast, nonsmall cell lung, ovarian, colorectal cancer, and melanoma. Stimulation of tumor colony-forming units (colony formation greater than or equal to 1.5 x controls) was observed in only 1/56 (2%) tumors. No evidence was found for increased size of individual colonies after incubation with rhIL-1 alpha. At a concentration of 100 ng/ml, colony formation of 9/56 (16%) tumor specimens was significantly inhibited (colony formation less than or equal to 0.5 x controls). We conclude that rhIL-1 alpha is not a major modulator of tumor colony formation in vitro. However, some antitumor effects may be observed at high concentrations.

Humans↗

An experimental evaluation of a prototype public access nutrition information system for supermarkets.

Located the Nutrition for a Lifetime System (NLS-1), a prototype interactive information system, in a large supermarket to help users decrease high-fat food purchases and increase high-fiber food purchases. Study participants were randomly assigned to control (n = 23; used the NLS-1 to enter food purchases only) or experimental (n = 26; viewed videodisc instructional programs, received prompts, made commitments, received feedback from the NLS-1) conditions. According to data entered in the NLS-1 and actual food shopping receipts, experimental participants significantly reduced higher fat purchases. Increases in higher fiber purchases favored the experimental group but were not significant.

Adult↗

Altering shoppers' supermarket purchases to fit nutritional guidelines: an interactive information system.

This study reports the results of one effort to help supermarket shoppers alter food purchases to make purchases (and meals) that are lower in fat and higher in fiber. A prototype interactive information system using instructional video programs, feedback on purchases with specific goals for change, weekly programs, and the ability to track user interactions and intended purchases was evaluated. The major dependent measure was users' actual food purchases as derived from participants' highly detailed supermarket receipts. After a 5- to 7-week baseline phase, participants were randomly assigned to an experimental or control condition for the 7- to 8-week intervention phase. A follow-up phase began 5 to 8 weeks after participants completed the intervention and discontinued use of the system. The results indicated that experimental participants, when compared to control participants, decreased high fat purchases and increased high fiber purchases during intervention, with evidence for some maintenance of effect in follow-up. Plans for increasing the use and impact of the system are discussed.

Dietary Fats↗

Seroepidemiology of hepatitis B virus infection in the United States. 1976 to 1980.

The prevalence of hepatitis B virus (HBV) infection was determined using sera from persons participating in the second National Health and Nutrition Examination Survey, conducted from 1976 to 1980. Of 14,488 scientifically selected participants aged 12 to 74, 821 had evidence of past or present infection with HBV. In the white population, the weighted estimate of hepatitis B infection was 3.2 percent (95 percent confidence interval, 3.1 to 4.2). A steady increase with age was seen; by ages 65 to 74, the prevalence was 6.9 percent (95 percent confidence interval, 5.2 to 8.5). In the black population, the overall weighted estimate of prevalence was 13.7 percent (95 percent confidence interval, 11.6 to 15.8). In this racial group, there was a dramatic increase with age, with the oldest age groups having a prevalence of 39.6 percent (95 percent confidence interval, 29.1 to 50.0). In both racial groups, there was a low prevalence of infection in young children that began to rise between ages 12 and 18. In a multivariate analysis of factors associated with infection, there was an interaction of race with age; therefore, the odds ratio for race is presented for four ages. This ratio ranged from 3.0 (95 percent confidence interval, 1.8 to 4.2) for a 15-year-old to 8.2 (95 percent confidence interval, 6.5 to 10.3) for a 70-year-old. These relative odds estimates were not substantially affected by adjustment for the available information on risk factors for HBV infection. The results of this study in a representative sample of the United States population show that adult black Americans are at high risk for hepatitis B infection. Other independent predictors of HBV positivity include male sex; residing in the South, Northeast, or West; residing in a city of 250,000 or more people; serving in the armed forces; living below the poverty level; and having a positive treponemal test for syphilis. These data suggest that the immunization practices for controlling this disease should be re-examined.

Adolescent↗

Sparing of the flexor carpi ulnaris in ulnar neuropathy at the elbow.

A common misconception attributes sparing of the flexor carpi ulnaris (FCU) in ulnar neuropathy at the elbow (UNE) to its innervating branch arising "at or above the elbow." We examined the relationship of FCU branches to the medial epicondyle (ME) and humeroulnar aponeurotic arcade (HUA) in 30 cadaver elbows. In only three did the first FCU branch arise at or proximal to the ME. In 36 UNE cases with fibrillations in the first dorsal interosseous, the FCU was normal in 10, mildly abnormal in 11, and severely abnormal in 15. FCU involvement correlated with the severity of the neuropathy and with whether compression was retroepicondylar or at the HUA. We conclude that sparing of the FCU in UNE is unrelated to the level of origin of its innervating branch, but rather is related to the internal neural topography and to the severity and level of compression.

Elbow↗

Vitamin B12 deficiency in a breast fed infant.

We report the case of a 5 month old breast fed infant who presented with a history of vomiting, pallor, and failure to thrive. Investigations showed severe nutritional vitamin B12 deficiency with a megaloblastic pancytopenia. This deficiency was due to low vitamin B12 concentrations in the maternal breast milk, and subsequent investigations showed maternal pernicious anaemia. Treatment of the infant with vitamin B12 resulted in a rapid clinical and haematological improvement. This case represents an unusual presentation of pernicious anaemia.

Anemia, Pernicious↗

An analysis of physicians' reasons for prescribing long-term digitalis therapy in outpatients.

We examined by medical-record review why long-term digitalis therapy was prescribed in 150 outpatients, the reasons were: supraventricular tachyarrhythmias (35): supraventricular tachyarrhythmias and heart failure (33); and heart failure with sinus rhythm (82). In the patients without supraventricular tachyarrhythmias we scrutinized the diagnosis of heart failure using a clinicoradiographic scoring system and found the diagnosis unlikely in 32 patients. When these 32 patients are combined with the 31 patients who had only one occurrence of supraventricular tachyarrhythmias or heart failure, 42% of the patients were on long-term digitalis therapy for a questionable reason. We conclude that a substantial fraction of general medical outpatients might benefit from digitalis withdrawal, if evidence for heart failure is lacking or if the reason prompting digitalis therapy is isolated to the distant past.

Aged↗

Elevated growth hormone levels in sera from breast cancer patients.

The concentrations of growth hormone (GH) and prolactin (PRL) in the serum of 42 breast cancer patients were determined by radioimmunoassay (RIA). Forty percent of the patients had elevated GH levels while only 17% had elevated PRL levels. These findings suggest a relationship between GH and breast cancer; a weaker correlation exists between PRL and this malignancy. In addition, total lactogens in the serum were measured by a bioassay (BA). The BA/RIA (GH + PRL) ratio was greater in the breast cancer patients than the controls, indicating that variant forms of the hormones with higher than normal biological activity might be present.

Adult↗

Pheromone-induced aggregation of ixodid ticks before host contact.

The presence of a pre-feeding aggregation pheromone was demonstrated in the species Dermacentor variabilis, Dermacentor andersoni, Dermacentor parumapertus, Amblyomma americanum and Haemaphysalis leporispalustris by assay within a petri dish. However, Amblyomma maculatum and Amblyomma cajennense did not aggregate in the sector containing discs of presumed pheromone within the hour period. D. andersoni and A. americanum recognized each other's pheromone and A. americanum recognized that of H. leporispalustris. Preliminary experiments with guanine and hemin as possible aggregating factors have thus far given inconsistent results.

Aggression↗