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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 271 records · Page 15Linked to original sources

An immunocytochemical study of lymphocyte and macrophage populations in the bone marrow of patients with non-Hodgkin's lymphoma.

Pairs of bone marrow trephine samples from 67 patients with known or suspected non-Hodgkin's lymphoma (NHL) were collected. One sample was processed for morphological examination, the other for frozen section immunohistology, using a panel of monoclonal antibodies (MAB) reacting with lymphocyte and macrophage determinants, detected by the immuno-alkaline-phosphatase (APAAP) method. Forty-one cases showed definite (36) or suspected (5) involvement of the marrow by NHL. Most were examples of lymphocytic or centroblastic/centrocytic NHL. The pattern of immunostaining confirmed the presence of NHL in these cases: the phenotype of the neoplastic cells was broadly consistent with nodal histology, where available. In ten cases, the marrow showed no evidence of involvement by NHL, and in 15, the eventual diagnosis was an abnormality of the myeloid series. These two groups of marrows not involved by NHL both showed a 'reactive' pattern of immunostaining, comprising polyclonal B-cells, T-helper and suppressor/cytotoxic cells and macrophages. We conclude that immunohistological examination of the bone marrow is useful in cases where the specimen shows morphological evidence of NHL, including those that are only 'suspect', but does not detect lymphoma where there is no morphological evidence of involvement.

B-Lymphocytes↗

Interstitial fluid flow in cortical bone.

After injection of ferritin into the tibial nutrient artery of adult dogs, ferritin was seen in the interstitial fluid compartment of the tibial cortex immediately and up to 25 min after injection. The pattern of movement was consistent with bulk interstitial fluid flow influenced by hydrostatic pressure. In osteons sectioned transversely, evidence was seen of centrifugal movement of ferritin in a halo pattern around the central capillary. Haloes in the superficial part of the cortex coalesced to form a ferritin front which moved toward the periosteal surface. Movement of ferritin was delayed by appositional bone of the periosteal surface. Ferritin was seen in channels in the matrix and perivascular spaces termed "matrix prelymphatics" and "perivascular prelymphatics," respectively, because they lacked an endothelial lining.

Animals↗

High-resolution alignment of action potential waveforms using cubic spline interpolation.

A cubic spline interpolation technique is applied to the problem of aligning action potential waveforms. Interpolation is an attractive alternative to sampling at many times the Nyquist rate in order to reduce errors caused by asynchronous sampling of rapidly changing waveforms. Alignment is achieved by locating the peak of the interpolated waveform, which can be found by solving a quadratic equation. The waveform is then reconstructed for comparison with existing templates. The technique was tested using simulated noisy, randomly arriving waveforms, the interpolated signal and alignment time errors being computed as functions of the signal/noise ratio. The spline technique is superior in accuracy to sampling at eight-times the Nyquist rate and is comparable to a Fourier-transform-based interpolation algorithm. It is computationally efficient, requiring approximately five multiplications per sample point. The interpolation concept is extended to the principal component technique for separation of action potential waveforms. The energy function is interpolated and used to align the waveforms, after which the interpolated coefficients can be used for high speed classification. The technique shows an improvement in both alignment error and effective signal/noise ratio in comparison with sampling or interpolation to a voltage peak.

Action Potentials↗

Amiloride prevents amphotericin B related hypokalaemia in neutropenic patients.

Twenty neutropenic patients with various haematological disorders were randomised prospectively to receive either intravenous amphotericin B alone or amphotericin B and oral amiloride 5 mg twice a day for treatment of confirmed or suspected fungal infection. Patients receiving amiloride had a significantly higher plasma potassium (p less than 0.01), a significantly lower urinary potassium loss (p less than 0.01), and required significantly less potassium chloride supplementation to maintain their plasma potassium within the normal range (p less than 0.001). Amiloride was well tolerated, had no clinically important side effects, and provided effective control of plasma potassium in patients treated with amphotericin B.

Adolescent↗

Parathyroid hormone effects on skeletal exchangeable calcium and bone blood flow.

The effects of alterations in serum calcium levels on the volume of distribution of a calcium tracer in bone and on bone blood flow were investigated in dogs by manipulation of parathyroid status. The volume of distribution increases with increasing serum calcium. This implies that there is a concentration-dependent binding mechanism in the extravascular space of bone, which is not saturated at the levels of serum calcium achieved in these experiments. The skeletal exchangeable calcium was increased in hypercalcemic dogs and decreased in hypocalcemic dogs. Cancellous bone contains proportionately more exchangeable calcium than cortical bone. Bone blood flow was decreased by 50% 15 min after injection of a bolus of parathyroid hormone (PTH) but returned to control values by 240 min. Fifty-two hours after the induction of hypercalcemia with repeated doses of PTH, there was no difference in blood flow over control animals.

Animals↗

Ranitidine versus cimetidine. A comparison of their potential to cause clinically important drug interactions.

The literature on H2-antagonist drug interactions is now extensive. The whole subject is so complicated as to make things difficult for the potential prescriber. However, it is possible to reduce most of the information contained in the literature to a few simple messages. Firstly, H2-antagonists bind to cytochrome P450 and may inhibit the metabolism of drugs eliminated by the mixed function oxygenase system. In this respect, cimetidine has a marked effect which, in most studies, has reached statistical significance. Ranitidine, on the other hand, has a much weaker effect which, even if demonstrable, is statistically non-significant. The potential benefit of ranitidine, however, has to be weighed against the relative costs of the 2 drugs. Secondly, H2-antagonists inhibit gastric acid production and may alter the rate of gastric emptying, and hence the rate of drug absorption. They may also have some effect on portal vein and hepatic artery flow. However, these effects are small and probably not clinically relevant. Thirdly, pharmacodynamic effects of H2-antagonist-drug interactions are difficult to demonstrate in planned studies, and although they are reported from time to time, adverse reactions of consequence are relatively uncommon. Fourthly, the prescriber needs to be aware that cimetidine may produce higher plasma concentrations of some drugs which have a fairly narrow therapeutic range, and this may be clinically important. Examples of drugs for which it may be undesirable to inadvertently increase plasma concentrations include warfarin, theophylline and phenytoin. Finally, for most drugs metabolised by the liver, the risk of an important interaction is small. However, if such an interaction is noted it may be helpful to refer to the other reported cases, and a number of references are included here.

Cimetidine↗

Inhibition of graft-vs-host induced immunodeficiency with immunosuppressive therapy.

The pathologic features of the acute graft-vs-host disease occurring in unirradiated (C57Bl/6 X A/J)F1 mice injected intravenously with lymphocytes from the C57Bl/6 parent are similar to those reported for other parental----F1 hybrid combinations. When stimulated in culture with concanavalin A, lipopolysaccharide or alloantigen, spleen cells from B6AF1 mice that had been injected 11 days previously with B6 lymphocytes exhibited proliferative responses that were drastically reduced in comparison to the responses of spleen cells from F1 hosts injected with syngeneic lymphocytes. IL2 production in GVH spleen cell cultures was also diminished. Proliferative responses and IL2 production were partially restored in mice given immunosuppressive therapy with azathioprine, cyclosporin A or Sch 24937 a drug whose inhibitory effects on cellular and humoral immune responses in mice have recently been described. Phenotypic analyses by flow cytometry of the GVH splenocyte population indicated that the most consistent change in the GVH spleen was the appearance of an Lyt2+ L3T4+ T cell subset which in the majority of experiments was accompanied by an increase in cells expressing only the Lyt2 antigen. Both subpopulations were reduced in mice that had recovered immunological responsiveness following immunosuppressive therapy. The results suggest that in this GVH model the development of an immunodeficient state is directly related to the induction of an active T suppressor cell population and that such cells are effectively eliminated from the splenocyte population following treatment with some immunosuppressive drugs.

Administration, Oral↗

Effects of the 'preresidency syndrome' on students' selection of fourth-year courses.

The influence of the "preresidency syndrome" on students' selection of fourth-year courses was examined. The fourth-year courses selected by the classes of 1982 and 1986 in the Brown University Program in Medicine were compared. The author considered that members of the 1982 class were less likely than those in the 1986 class to have been influenced by perceptions of increased competition for residency positions. The students in the class of 1986 were found to have deferred third-year clerkships into the fourth year more often than the class of 1982. The class of 1986 selected more courses related to their intended specialty than did the class of 1982, particularly for those intending to pursue residencies in orthopedics. Also, the class of 1986 spent a greater proportion of their fourth year in electives at hospitals where they intended to apply for residencies. These data support the contention that medical students' perception that residency positions were more difficult to obtain led to changes in selecting courses in the fourth-year of medical school.

Curriculum↗

Remotely inserted venous occlusion catheters for the control of venous haemorrhage.

This paper describes the use of venous occlusion catheters inserted via the long saphenous vein or its tribularies for control of major retroperitoneal venous haemorrhage. The technique has been applied successfully in 10 cases of trauma and aortocaval fistula. Exposure and insertion are simple and quick and a measure of control is obtained before exposure of the injury which can then be completely repaired before deflation of the balloon and withdrawal of the catheter.

Catheterization↗

The effect of propranolol on the rise in plasma ammonia during modest exercise.

Changes in plasma ammonia in response to exercise with and without pretreatment with propranolol have been studied. A standardised submaximal treadmill exercise test was used to assess the effects of placebo or propranolol 40 mg, 80 mg, or 160 mg twice daily given in random order for 3 days, the last dose being taken 90 min before exercise. After placebo the mean incremental rise in plasma ammonia in response to exercise was 16 mumol X 1(-1). The corresponding rise after propranolol 40 mg was 56 mumol X 1(-1) (p less than 0.01). All three doses of propranolol produced similar effects on plasma ammonia and exercise heart rates.

Adolescent↗

Pharmacokinetic interactions between felodipine and metoprolol.

This double-blind, cross-over study in healthy male subjects evaluated the pharmacokinetics of felodipine and metoprolol given both separately and in combination. During three, five-day study periods, felodipine 10 mg b.d., metoprolol 100 mg b.d. and a combination of the two, were given in random order. There was at least a 7-day washout period between each pharmacokinetic study day. Plasma levels of unchanged felodipine and metoprolol were measured for 24 h after the last dose, on the 5th day of each treatment period. Eight subjects, aged 19-22 years, completed the study. Both felodipine and metoprolol, given alone and in combination, were well tolerated. None of the felodipine pharmacokinetic variables (tmax, Cmax, Cmin, AUC (0-12) and t1/2) changed significantly when felodipine and metoprolol were given in combination. Cmax and AUC (0-12) for metoprolol increased significantly when metoprolol and felodipine were combined, although tmax, Cmin and t1/2 for metoprolol remained unchanged. The changes in metoprolol pharmacokinetics induced by felodipine are small and unlikely to be clinically important.

Adult↗

Community health projects as part of a core clinical clerkship: teaching research skills in a community setting.

Although medical student research has been advocated as a valuable learning experience and specific programs have been developed to offer research opportunities, only a minority of students have participated in these programs. We report a student research program that is integrated into a required six week clinical clerkship in Community Health, thus ensuring that all students participate in a research project. The program offers the additional advantage that research projects are student initiated and executed. Although the limited time frame usually results in pilot or exploratory studies, the program introduces students to all facets of a research project within a community setting and promotes independent learning. The program has been well received by students and may stimulate further research interests in some students.

Clinical Clerkship↗

Production of and responsiveness to interleukin 2 in autoimmune BXSB mice.

BXSB male mice serve as one of several murine models of human systemic lupus erythematosus. T-cell abnormalities in these mice involve decreased production of and responsiveness interleukin 2 (IL-2) and are age-related. The studies presented here investigated the mechanism of these T-cell defects. The results suggest that excessive suppressor-T-cell activity as well as soluble inhibitors of IL-2 production and activity, including PGE, are not responsible for the low levels of IL-2 observed in culture supernatants of Con A-stimulated lymphocytes from "old" (3-6 months) BXSB male mice. Supplementation of Con A-stimulated lymphocyte cultures from BXSB male mice with human IL-1 or normal murine accessory cells did not augment IL-2 production. Reduced proliferative responses were observed in bulk cultures of Con A- or alloantigen-stimulated "old" BXSB male lymphocytes, which were not enhanced by exogenous IL-2. Limiting dilution analysis revealed reduced frequencies of Con A- and alloantigen-inducible IL-2-reactive T cells in these mice. These results suggest intrinsic defects in the ability of T cells from "old" BXSB male mice to be activated to produce and respond to IL-2.

Age Factors↗