Biomedical subjects
Publications and source records attributed to P Daly.
Perfusionists are highly skilled professionals providing essential life support, enabling patients to undergo open heart surgery. Although this is the main function at the Royal Liverpool Children's Hospital, Alder Hey, they also manage a Homograft bank. Also known as a heart valve bank, this is a completely independent branch of the perfusion department.
We present a retrospective analysis of survival in 48 elderly (older than 65 years) and 70 young patients with small-cell lung cancer. Thirty-four elderly and 62 young patients had combination chemotherapy. Overall probability of survival with combination chemotherapy was similar for old and young patients (chi 2 = 0.79, d.f. = 1, p = 0.374). Peripheral neuropathy secondary to vincristine was more common with elderly patients. We believe that decisions about chemotherapy in elderly patients with small-cell lung cancer should be based on performance status, extent of disease and clinical condition rather than age.
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The results of treatment of cystic and antibiotic-resistant acne vulgaris in 96 consecutive patients with the oral retinoid isotretinoin (13-cis-retinoic acid; Roacentane) are reported retrospectively. The results show that the drug, while toxic in the short term, is highly effective in clearing acne.
A 60-year-old white woman had a bilateral salpingo-oophorectomy, hysterectomy, and omentectomy for serous surface papillary carcinoma. Combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide was given for 1 year, but was followed by relapse 4 months after completion. This relapse was associated with hyperamylasemia ranging from 2400 IU/liter in the early phase of relapse to 5800 IU/liter in the preterminal phase. While hyperamylasemia has been previously described in serous ovarian cystadenocarcinoma, to our knowledge this is the first report in a patient with serous surface papillary carcinoma. This marker may help in distinguishing the latter from malignant mesothelioma of the peritoneum since this is often an extremely difficult differential diagnosis.
At least one member of the TGF-beta family, TGF-beta 1, has been previously shown to inhibit the anchorage-independent growth of some human breast cancer cell lines (Knabbe et al., 1987; Arteaga et al., 1988). Members of the TGF-beta family might, therefore, provide new strategies for breast cancer therapy. We have studied the inhibitory effects of TGF-beta 1 and TGF-beta 2 on the anchorage-independent growth of the oestrogen receptor-negative cell lines MDA-MB-231, SK-BR-3, Hs578T, MDA-MB-468, and MDA-MB-468-S4 (an MDA-MB-468 clone not growth inhibited by EGF) and the estrogen receptor-positive cell lines MCF7, ZR-75-1, T-47D. TGF-beta 1 and TGF-beta 2 caused a 75-90% growth inhibition of MDA-MB-231, SK-BR-3, Hs578T, and MDA-MB-468 cells and a 50% growth inhibition of ZR-75-1 and early passage (less than 100) MCF7 cells. T-47D cells responded to TGF-beta only in serum-free conditions in the presence of IGF-1 or EGF. The growth of MDA-MB-468-S4 cells and late passage (greater than 500) MCF7 cells was not inhibited by TGF-beta 1 or TGF-beta 2. TGF-beta-sensitive MCF7 and MDA-MB-231 cells did not respond to Muellerian inhibiting substance (MIS), a TGF-beta-related polypeptide. TGF-beta 1 or TGF-beta 2 were mutually competitive for receptor binding with a similar affinity (Kd 25-130 pM, 1,000-13,000 sites per cell). To determine the time course of the TGF-beta effect, an anchorage-dependent growth assay was carried out using MDA-MB-231 cells. Growth inhibition occurred at 6 days, and cell-cycle changes were seen 12 hr after the addition of TGF-beta. Cells accumulated in the G1 phase and were thus inhibited from entering the S-phase. These data indicate that TGF-beta is a potent growth inhibitor in most breast cancer cell lines and provide a basis for studying TGF-beta effects in vivo.
Two single-shot localization techniques, STEAM and PRESS, are analyzed with regard to specifications for in vivo localized proton NMR. In particular, attention is paid to optimum signal intensity per unit volume, sensitivity to motion and diffusion, shortest attainable echo time, water suppression and editing possibilities. Experimental results are shown for cat brain at 4.7 T and human brain at 1.5 T. Both STEAM and PRESS are highly effective localization methods. For long echo times, PRESS is the method of choice, because it offers a factor of two gain in signal intensity. In addition, the method is less sensitive to motion and diffusion, and not susceptible to multiple-quantum effects. STEAM offers advantages for observation of (coupled) metabolites with short T2, because (a) shorter TEs can be attained and (b) effective water suppression sequences can be implemented without penalty in echo time. Differences relating to editing possibilities and B1 dependence, possibly important in choosing a method, are discussed.
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Coumarin (1,2-benzopyrone) as a daily oral dose of 50 mg was evaluated in a multicentre prospectively randomized, double-blind, placebo-controlled trial to prevent early recurrence of malignant melanoma TNM Stage IB (Breslow thickness greater than 1.70 mm) and Stage II. Intake for the trial started in 1984 and was stopped prematurely, after review, in 1987. There were two recurrences in 13 treated patients and 10 in 14 controls which was significant (P 0.01). The sites of the metastases differed in each group, being local and in bone in the treated group, and in lymph nodes, skin and lung in the control group. There were no toxic effects associated with coumarin treatment and all patients without recurrence are now receiving coumarin.
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Severe disseminated intravascular coagulation was observed in a patient with Burkitt's lymphoma/leukaemia. Immunological studies on leukaemic blasts from relapsed bone marrow revealed a B-cell phenotype (B4+, B1+, HLA-Dr+, J5+) with membrane bound IgM lambda. Cytogenetic investigation revealed a variant Burkitt's translocation t(8;22)(q24;q11) involving the lambda light chain gene region and abnormalities of chromosomes 15 and 17 with breakpoints at q22 and q12 respectively, similar to those observed in the t(15;17) in acute promyelocytic leukaemia. Transmission electron microscopy of the leukaemic blasts showed crystalline cytoplasmic inclusions which may have had a role in precipitating the disseminated intravascular coagulation.
Changes in circulating catecholamines and transmyocardial catecholamine balance associated with improved left ventricular function were studied in patients with chronic heart failure after treatment with captopril (10 patients) and hydralazine in combination with isosorbide dinitrate (eight patients). Cardiac performance improved in response to both captopril and hydralazine-nitrate treatment. The systemic haemodynamic effects were also qualitatively similar, but the hydralazine-nitrate combination caused a greater increase in cardiac index and heart rate. Captopril did not change arterial adrenaline concentrations (0.63 to 0.60 nmol/l), arterial noradrenaline (4.2 to 3.9 nmol/l), or net transmyocardial noradrenaline release (390 to 317 pmol/min), while hydralazine-nitrate increased arterial adrenaline (0.91 to 1.47 nmol/l) and transmyocardial noradrenaline release (225 to 554 pmol/min). Although both captopril and hydralazine-nitrate treatment improve left ventricular performance in patients with chronic heart failure, hydralazine-nitrate enhances cardiac sympathetic tone and captopril does not. The clinical relevance of these findings, however, is not known.
The acute effects of captopril in three groups of patients with coronary artery disease were studied: 25 patients with congestive heart failure; 8 patients with hypertension; and 14 normotensive patients with angina, and systolic arterial pressure greater than 120 mmHg, but no evidence of heart failure. Systemic haemodynamics were assessed by balloon-tipped thermodilution catheter and coronary haemodynamics were assessed by thermodilution catheter in the coronary sinus. Despite significantly different baseline haemodynamic values, captopril decrease systolic arterial pressure without increasing heart rate in all three groups, thereby decreasing double-product, a major determinant of myocardial work. Coronary blood flow and myocardial oxygen consumption decreased similarly in all groups and decreased in parallel to double-product, while coronary vascular resistance and transmyocardial oxygen difference did not change except for a slight decrease in transmyocardial oxygen difference in those patients with congestive heart failure. Transmyocardial lactate extraction increased insignificantly. These findings suggest that captopril may improve metabolic balance in various types of patients with coronary artery disease and that it does this by decreasing myocardial oxygen demand.
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Plasma free epinephrine, norepinephrine, and dopamine concentrations were determined in 48, 63, and 45 patients, respectively, with overt congestive heart failure, and compared with those in 26 patients with stable angina but without heart failure. Systemic hemodynamic values were determined to assess the severity of heart failure. Arterial epinephrine levels were not different between patients with heart failure (73 +/- 92 pg/ml) and patients without heart failure (55 +/- 73 pg/ml). In patients with congestive heart failure, norepinephrine (665 +/- 510 pg/ml, mean +/- SD) and dopamine (407 +/- 405 pg/ml) levels were significantly higher than in patients with stable angina without heart failure (norepinephrine 184 +/- 136 pg/ml, p less than 0.001, and dopamine 197 +/- 259 pg/ml, p less than 0.02). However, in patients with congestive heart failure, the plasma norepinephrine levels did not correlate with cardiac index (r = 0.21, p = NS), pulmonary capillary wedge pressure (r = 0.11, p = NS), mean arterial pressure (r = 0.11, p = NS), or systemic vascular resistance (r = 0.18, p = NS). Similarly, there was no correlation between dopamine levels and the hemodynamic abnormalities in patients with congestive heart failure. These findings suggest that although endogenous norepinephrine and dopamine levels are frequently elevated in patients with heart failure, reflecting enhanced sympathetic activity, catecholamine levels do not reflect the severity of heart failure.