Biomedical subjects

M P Smith

Publications and source records attributed to M P Smith.

At least 19 recordsLinked to original sources

PubMed1992

Presence of the earliest vertebrate hard tissue in conodonts.

From histological investigations into the microstructure of conodont elements, a number of tissue types characteristic of the phosphatic skeleton of vertebrates have been identified. These include cellular bone, two forms of hypermineralized enamel homologs, and globular calcified cartilage. The presence of cellular bone in conodont elements provides unequivocal evidence for their vertebrate affinities. Furthermore, the identification of vertebrate hard tissues in the oral elements of conodonts extends the earliest occurrence of vertebrate hard tissues back by around 40 million years, from the Middle Ordovician (475 million years ago) to the Late Cambrian (515 million years ago).

Animals↗

PubMed1992

Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia--a phase II study.

A group of 13 patients with acute myeloid leukaemia of differing disease status were treated with continuous intravenous infusion of high-dose recombinant interleukin-2 (rIL-2). There was up-regulation of the cellular cytotoxic functions in all these patients following the rIL-2 therapy, with increase in the natural killer (NK) activity, lectin-dependent cellular cytotoxicity, induction of cytotoxicity-linked cytoplasmic serine esterase and lymphocyte activation. However, the clinical response to rIL-2 in these patients was disappointing, especially in patients treated in frank relapse. Although 1 patient treated in early second relapse achieved a third complete remission, the duration of the remission was brief and lasted only 6 months. Adverse reactions among these patients were common. Whether or not lymphokine-activated killer cells are needed to improve the response rate over rIL-2 alone in these patients deserves further investigation.

Adult↗

PubMed1992

Focal retrograde amnesia following bilateral temporal lobe pathology. A neuropsychological and magnetic resonance study.

A patient who suffered a severe closed head injury was left with a dense retrograde amnesia for events which she had experienced prior to her injury, but she showed only mild, patchy anterograde memory impairment. Her retrograde amnesia included both public events and autobiographical material, and it extended back to her childhood. Previously learned skills such as playing a piano and driving a car were spared, even though she had no recollection at all of the original learning experience. A series of focused magnetic resonance scan images revealed major pathology in the anterior portion of both temporal lobes. No significant abnormality was found in the hippocampus, thalamus or other medial structures in the limbic-diencephalic system. Our findings indicate the independence of anterograde and retrograde memory mechanisms, and point to structures and pathways in the anterior temporal lobes as playing a critical role in memory for past events.

Adult↗

PubMed1992

Teicoplanin and prophylaxis of Hickman catheter insertions.

A total of 88 patients with haematological malignancies who required Hickman catheters for intensive chemotherapy, were randomized to receive either a single bolus intravenous injection of teicoplanin, or no teicoplanin, immediately before insertion of a double lumen Hickman catheter. There was a lower incidence of catheter-related Gram-positive sepsis in patients receiving prophylactic teicoplanin. This benefit was particularly clear in patients who were already neutropenic at the time of catheter insertion. Prophylactic teicoplanin may, therefore, be useful as a routine procedure during the insertion of Hickman catheters for this group of patients.

Adult↗

PubMed1991

Aplastic anaemia in Christchurch Hospital 1979-89.

We have reviewed the records of all patients referred to our departments with aplastic anaemia during the 11 years from 1979 to 1989. Of the 22 patients identified, 19 fulfilled the standard criteria for severe aplastic anaemia. There were 11 females and 11 males. Their mean age was 35 (range 2-85 years). Five cases followed exposure to drugs known to cause aplastic anaemia and one had a recent history of viral hepatitis. A variety of treatments were used. Four patients received an allogeneic bone marrow transplant (BMT) from matched sibling donors and two of these were alive and well 65 and 120 months post BMT. Antithymocyte globulin (ATG) treatment has been followed by lasting complete remission in two of the six patients treated and a partial response was seen in one other patient. Cyclosporin therapy was associated with unmaintained complete remission in one of the three patients given this drug after ATG had failed. The remaining 13 patients received only supportive care with or without androgens and six (46%) had early recovery of bone marrow function with lasting complete remission. These patients illustrate some of the therapeutic options available for aplastic anaemia.

Adolescent↗

PubMed1991

Structure of an isoxazole amino ester.

2'-(N-Methylamino)-2-methylpropyl 5-methyl-3-phenylisoxazole-4-carboxylate hydroiodide, C16H21N2O3+.I-, Mr = 416.26, orthorhombic, Pna21, a = 23.293 (7), b = 10.276 (3), c = 7.971 (1) A, V = 1908.0 (8) A3, Z = 4, Dx = 1.448 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 17.1 cm-1, F(000) = 832, T = 293 K, R = 0.0610 for 1846 unique observed reflections with F greater than 3 sigma. In the title compound, the isoxazole ring is distorted only slightly from planarity, with C(3) being 0.045 A out of the mean plane. Steric interactions force the isoxazole ring out of planarity with both the phenyl ring and the ester carbonyl O(2), which show dihedral angles of 34.9 (9) degrees and 47.2 (7) degrees, respectively. The N(2) amino methyl group is oriented approximately anti to the ester carbonyl O(2). The minimum iodide to nitrogen distance is from I to N(2)', 3.46 (2) A.

Isoxazoles↗

PubMed1991

Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study.

The prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease. Of the 7 evaluable patients, the maximum response observed was stable disease in 2 patients (1 with NHL and 1 with HD). The other patients' diseases progressed in the face of immune activation following the rIL-2 infusion. Adverse reactions were common but no life-threatening occurred. These results are disappointing. Whether or not lymphokine-activated killer (LAK) cells are needed to improve response rate deserve further investigations.

Adult↗

PubMed1991

A comparison of sustained release verapamil versus atenolol for 24 h protection from exercise-induced angina pectoris.

We have compared the efficacy of a once daily 360 mg sustained release preparation of verapamil (SRV) with that of once daily 100 mg atenolol in exercise-induced angina. The study was randomized, double-blind and cross-over in design involving 30 patients with chronic stable angina. A 2-week run-in placebo phase was followed by two 4-week periods of active treatment. Patients underwent exercise stress tests at 6 and 24 h post-dose at the end of each treatment phase. After the placebo phase, patients had significantly increased times to both 1 mm ST depression and angina at 6 h (afternoon stress test) compared to 24 h post-dose (morning test). The two treatments were found to be equivalent in terms of several indices of anti-anginal efficacy. The only significant differences between treatments were in relation to indices of heart rate, which were consistently lower with atenolol than with SRV. We conclude that once daily sustained release verapamil 360 mg has equivalent anti-anginal efficacy to once daily atenolol 100 mg. A lower angina threshold seems to occur in the morning in patients with ischaemic heart disease suggesting a diurnal variation.

Angina Pectoris↗

PubMed1991

A prospective randomized study of prophylactic teicoplanin to prevent early Hickman catheter-related sepsis in patients receiving intensive chemotherapy for haematological malignancies.

Eighty-eight patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin or no teicoplanin immediately before insertion of a double lumen Hickman catheter. There were lower incidences of catheter-related Gram-positive sepsis in patients receiving prophylactic teicoplanin. There were less exit site infections, tunnel infections and catheter-related Gram-positive septicaemia. The benefit of prophylactic teicoplanin was observed especially among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from the infected skin sites or from blood cultures taken from the Hickman catheters were sensitive to teicoplanin. No adverse reaction was reported in any of the patients in the prophylactic group. Prophylactic teicoplanin therefore may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy to reduce the early incidence of catheter-related sepsis, especially during the associated period of neutropenia following chemotherapy.

Adult↗

PubMed1991

Bacterial infections in lymphoma patients treated with recombinant interleukin-2.

10 lymphoma patients given a total of 26 courses of intravenous continuous infusion of recombinant interleukin-2 (rIL-2) alone without lymphokine-activated killer cells were analysed retrospectively for the frequency and pattern of bacterial infections associated with the immunotherapy. 4 episodes of septicaemia and 7 episodes of soft tissue infections resulted from the 26 courses of rIL-2 infusion. Although there was no death due to infection, all these infections were clinically significant, needing systemic antibiotic therapy and resulting in prolonged hospitalisation. Gram-positive infections occurred significantly (p less than 0.001) more often than gram-negative infections. Patients with non-Hodgkin's lymphoma had a higher incidence of infection than patients treated for Hodgkin's disease, analysed either as infection per patient treated (p less than 0.05) or infection per course of rIL-2 given (p less than 0.02).

Bacterial Infections↗

PubMed1990

Prophylactic teicoplanin during insertion of Hickman catheters.

With the extensive use of Hickman catheters in patients requiring cytotoxic chemotherapy there is now a resurgence of Gram-positive septicaemia among these patients during the neutropenic periods. We are currently running a prospective randomized study of prophylactic teicoplanin during insertion of Hickman catheters to determine if it reduces the incidence of Gram-positive septicaemia. A total of 44 patients have completed the study (23 in the teicoplanin group and 21 in the control group). The diagnoses were: acute myelogenous leukaemia (13), non-Hodgkin's lymphoma (16), Hodgkin's disease (11), chronic granulocytic leukaemia (3) and acute lymphoblastic leukaemia (1). The number of days between insertion of Hickman catheters and the development of neutropenia was: teicoplanin group: mean 14.7, median 11, range 0-53; control group: mean 11.8, median 10, range 0-37. In the treated patients, there were four episodes of line-associated Gram-positive septicaemia and a total of four organisms were isolated. In the control group, 10 organisms were isolated from a total of nine episodes of line-associated Gram-positive septicaemia. The organisms were: coagulase-negative staphylococci (8), Streptococcus B, (1), Strep. faecalis (1), Strep. mitis (1), alpha streptococcus (1), diphtheriods (1) and Staphylococcus aureus (1). All organisms were sensitive to teicoplanin. No adverse reaction was observed in any patient. Prophylactic teicoplanin during insertion of Hickman catheters may therefore reduce the incidence of line-associated Gram-positive septicaemia in neutropenic patients.

Anti-Bacterial Agents↗

PubMed1990

A randomized prospective study of ceftazidime and ciprofloxacin with or without teicoplanin as an empiric antibiotic regimen for febrile neutropenic patients.

Febrile neutropenic patients were randomized to receive ceftazidime and ciprofloxacin with the addition of teicoplanin in cases with clinical suspicion of a Hickman line-associated infection. At 48 h both clinical and bacteriological analyses were made. Patients were categorized as: success, in cases of improvement or stability in the clinical condition; failure, if there was a deterioration of the clinical condition; and non-evaluable, in cases of protocol violation or death due to other causes. A total of 86 patients have completed the study so far; 43 patients were randomized to the ceftazidime and 43 to the ciprofloxacin group. Teicoplanin was added to the monotherapy in 12 patients in the ceftazidime group and 15 in the ciprofloxacin group. The diagnoses were: acute myelogenous leukaemia (25), non-Hodgkin's lymphoma (34), Hodgkin's disease (17); acute lymphoblastic leukaemia (9) and chronic granulocytic leukaemia (1). Forty-eight hour clinical assessment showed a response rate in the ceftazidime group of: success 18/31 (58%), failure 13/31 (42%); in the ceftazidime and teicoplanin group: success 8/12 (67%), failure 4/12 (33%); in the ciprofloxacin group: success 23/28 (82%), failure 5/28 (18%); and in the ciprofloxacin and teicoplanin group: success 11/15 (73%), failure 4/15 (27%). Blood cultures were positive in 48/86 (56%) cases, with more than one organism isolated in seven of these 48 cases. Organisms isolated were: coagulase-negative staphylococci (20), Escherichia coli (13), Pseudomonas aeruginosa (4), Staphylococcus aureus (3), diphtheroids (3), Klebsiella sp. (3), Enterobacter cloacae (2), Streptococcus faecalis (2), Ent. adenocarboxylata (1), Clostridium septicum (1). Strept. B (1), alpha streptococcus (1) and P. fluorescens (1), In-vitro testing showed that all Gram-positive organisms were sensitive to teicoplanin, and Gram-negative organisms to ciprofloxacin or ceftazidime. There were seven cases of superimposed infections with eight organisms isolated, all cases occurring in patients receiving ciprofloxacin alone: coagulase-negative staphylococci (4), Strep. sangius (1), Strep. viridans (1), diphtheroids (1) and P. maltophilia (1). Both ciprofloxacin and ceftazidime are comparable in efficacy as empirical monotherapy for febrile neutropenic patients. There is, however, a significant increase in the incidence of superimposed infection in patients receiving only ciprofloxacin. In view of the very high incidence of Gram-positive septicaemia, we suggest that teicoplanin should be added as part of the initial empiric antibiotic regimen in all febrile neutropenic patients.

Anti-Bacterial Agents↗

PubMed1990

Chlorambucil lung toxicity.

A 67-year-old man, who had received intermittent courses of oral chlorambucil and prednisone as therapy for chronic lymphocytic leukaemia over a period of 3.5 years, developed fatal lung fibrosis. A case report and brief review of the current data on chlorambucil-induced lung disease are presented.

Aged↗

PubMed1990

Management of cerebrospinal fluid.

In traditional practice, doctors order tests and the laboratory performs them. A series of tests are requested before the results of any of the tests are known. The authors of this paper examine the interface between the clinicians and the laboratory. They produce a cost effective and clinically useful routine for handling spinal fluid. They bring to their practice an excellent example of quality assurance which is genuine, improves practice and is not "busy work." The editor heard Dr. Albright present this material and urged him to make it available to North Carolina doctors.

Adolescent↗

PubMed1989

Postnatal concerns of mothers: an update.

The purpose of this study was to determine the major concerns of primiparae and multiparae 1 month post-delivery and the resources used in meeting identified concerns. A mail-back questionnaire developed by Gruis (1977) was used. The sample was composed of 19 primiparae and 22 multiparae from Vancouver BC, Canada. The most frequently identified concerns of primiparae (N greater than 6) were baby feeding, fatigue, breast soreness, baby behaviour, return of the figure, limiting visitors, regulating demands, growth and development, interpreting behaviour, physical care of the baby, and labour and delivery. The most frequently identified major concerns of multiparae (N greater than 6) were fatigue, regulating demands, emotional tension, jealousy of other children, and the labour and delivery experience. The vast majority of major concerns were dealt with effectively. The women used a variety of resources, and their partners were particularly helpful. However, for 14 (64%) of the multiparae in this study, the hospital stay did not provide preparation for the first weeks at home with their new baby. It is suggested that community caregivers should see their postnatal clients as soon as possible after discharge from hospital. Teaching sessions can occur in the home, and in accordance with individual concerns.

Adolescent↗

PubMed1989

The relationship between apolipoprotein B-100 and low-density lipoprotein cholesterol after treatment with an HMG CoA reductase inhibitor.

Measurement of apolipoproteins AI and B-100 has been shown to provide at least equivalent information to measurement of lipoprotein cholesterol levels for evaluating risk of cardiovascular disease. In the present study, the authors examined the relationship between APO B-100 and low-density lipoprotein (LDL) cholesterol in a hypercholesterolemic population that was treated with 16 weeks of hydroxymethylglutaryl CoA reductase inhibitor therapy to lower plasma cholesterol levels. The average decrease in APO B-100 was -0.27 g/L (23% of baseline), which was similar to the decrease in LDL cholesterol, -1.6 mmol/L (-0.61 g/L) (30% of baseline). Correlation data (r = 0.902) indicated that the information provided by the two parameters corresponded in individual cases. Apolipoproteins assayed on automated equipment by kit methods are simpler, more straightforward, and provide more reproducible results than measurement of lipoprotein cholesterols. The authors conclude that, in addition to being more reliable for appraising risk of coronary artery disease, measurement of apolipoproteins may be equally useful for monitoring lipoprotein-lowering therapy.

Apolipoprotein A-I↗

PubMed1988

Defective catabolism and abnormal composition of low-density lipoproteins from mutant pigs with hypercholesterolemia.

Metabolic and chemical properties of low-density lipoproteins (LDLs) were studied in a strain of pigs carrying a specific apo-B allele associated with hypercholesterolemia and premature atherosclerosis. LDL mass was significantly greater in mutant than in control pigs (400 +/- 55 mg/dL vs 103 +/- 26 mg/dL), as was LDL cholesterol. When normal and mutant LDLs were injected into the bloodstream of normal pigs, the fractional catabolic rate (FCR) of mutant LDL was about 30% lower than that of control LDL. In mutant pigs, the mean FCRs of mutant and control LDL were similar, although they were much lower than the corresponding FCRs observed in normal pigs. The density profile of LDL particles differed in control and mutant pigs; the peak LDL flotation rate was shifted from S0f = 5.3 +/- 1.9 in controls to a more buoyant 7.4 +/- 0.5 in mutants. The elevation of LDL in the mutants was restricted to the most buoyant LDL subspecies. This subpopulation of mutant LDL was enriched with cholesteryl ester (47% vs 37%) and depleted of triglyceride, relative to LDL of similar density and size in controls. The lipid compositions of the denser LDL subpopulations (rho greater than 1.043 g/mL) were similar in mutants and controls. We conclude that the hypercholesterolemia of these mutant pigs is accounted for by defective catabolism of LDL. The buoyant cholesterol ester enriched LDL subspecies that accumulate in plasma may contribute to the accelerated atherogenesis that occurs in these animals.

Animals↗

PubMed1987

New assay of apolipoproteins A-I and B by rate nephelometry evaluated.

We evaluated new, commercially available reagents for assaying apolipoproteins (apo) A-I and B by rate nephelometry (INA). Our initial linearity studies for apoA-I indicated that use of the commercial diluent resulted in incomplete immunoreactivity. Subsequent revision of the calibration line by the manufacturer compensated for this and improved the linearity for the apoA-I assay. We observed good linearity for the apoB assay. The within-run CVs were less than 4.0% and the between-run CVs were less than 5.5% for both assays. Results were 109% for apoA-I and 101% for apoB as compared with those measured for IUIS-WHO reference materials from the Centers for Disease Control. Recovery averaged 103% for apoA-I and 105% for apoB, for duplicate assays of three concentrations of purified apoA-I and low-density lipoprotein (LDL). Assaying sera from 45 patients, we demonstrated a good correlation between INA and radial immunodiffusion for both apoA-I (r = 0.92) and apoB (r = 0.95). Correlations between apoA-I and high-density lipoprotein cholesterol, and between apoB and LDL cholesterol compared favorably with previous reports. We conclude that these assays are accurate, precise, and easily automated for clinical application.

Apolipoprotein A-I↗