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Biomedical subjects

P B Larsen

Publications and source records attributed to P B Larsen.

At least 37 records · Page 2Linked to original sources

Aminophylline versus caffeine citrate for apnea and bradycardia prophylaxis in premature neonates.

We investigated the efficacy and adverse effects of aminophylline and caffeine citrate in 180 premature neonates for 10 days and nights. Aminophylline (n = 98) and caffeine citrate (n = 82) were equally effective in preventing apnea and bradycardia. The caffeine citrate group had a lower median heart rate on day 3, fewer neonates with tachycardia and a smaller amount of gastric aspirate on day 7. The need for mononasal continuous positive airway pressure and respirator therapy was similar in both groups. We conclude that caffeine citrate is the drug of choice for apnea and bradycardia prophylaxis in premature neonates with a gestational age < or = 33 full weeks.

Apnea↗

Periwound skin microcirculation of venous leg ulcers.

Chronic venous ulceration has an estimated prevalence of from 0.06 to 1.3% with about 57 to 80% of patients with leg ulcers having demonstrable venous disease. The sequence of events whereby chronic venous insufficiency leads to leg skin ulceration is not yet worked out. Venous hypertension may set the stage for subsequent ulcer development via linkages to observed changes in skin microvessel metrics, morphology, rheology, permeability, hemodynamics, and the interstitium. Periulcer measurements show decreased transcutaneous oxygen and elevated carbon dioxide tensions, yet the skin blood perfusion measured with laser Doppler fluxometry (LDF) is reported to be elevated. This elevated perfusion, (Q), could be due to independent changes in blood velocity (U), and volume (V), with different mechanistic implications depending on the mode. Thus, we sought to determine the relative contributions of these two components with the aim of clarifying the mechanism responsible for the reported skin flow changes. Patients studied (n = 16) had unilateral venous ulcers, an ankle/brachial BP index > 0.8, and venous pathology demonstrated by duplex imaging. Ulcer areas ranged from 0.6 to 76.9 cm2 (mean = 13.7 cm2) and were present for 2 to 144 months, mean = 32. With the patient supine, Q (ml/min/100 g), V (%), and U (mm/sec) were measured by LDF (Vasamedics, BPM403A) at two to three sites on periulcer skin and compared with measurements at corresponding sites on the nonulcerated limb at local skin temperatures of 35 and 44. Results confirm an elevation in basal periulcer flow (7.0 vs 1.8 ml/min/100 g, P = 0.001) and show this to be due to elevations in both circulating blood volume (1.24 vs 0.62%, P < 0.001) and velocity (1.23 vs 0.65 mm/sec, P = .004). Maximal Q, V, and U were also higher on the ulcer leg, being for Q, 11.2 vs 6.42 ml/min/100 g, P = 0.03; for V, 1.49 vs 1.13%, P = .002; and for U, 1.76 vs 1.33 mm/sec, P = 0.020. Expressing each leg's basal values as a percentage of its own maximal response shows the ulcerated leg to have higher values for Q, V, and U, with (ulcer leg/control leg) ratios being 2.5, 1.8, and 1.4, respectively. These findings show that the LDF perfusion increase is due to roughly equal increases in microvessel circulating blood volume and velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Standard and near-surface laser-Doppler perfusion in foot dorsum skin of diabetic and nondiabetic subjects with and without coexisting peripheral arterial disease.

Appropriate assessment of microvascular function is now recognized as an important adjunct to the diagnostic workup and medical follow-up for a variety of conditions. Laser Doppler fluxmetry (LDF)-derived rbc perfusion (Q) and the volume (V) and velocity (U) components are useful in this regard but the fact that the sampled volume includes both nutritional and nonnutritional components may limit its specificity and range of usefulness. It was reasoned that if the depth of penetration could be reduced without significantly altering essential optical transmission features, then the detected signal would better represent the nutritional component. A 0.68-mm-thick Delrin spacer was fabricated and used to compare LDF values with (WITH) and without (WITHOUT) its use on the foot dorsum of 71 limbs of 44 diabetic (DM) and nondiabetic (NO-DM) subjects with lower extremity arterial disease (LEAD, n = 39) and without disease (NORM, n = 32). Overall LDF values WITH as compared to WITHOUT had a slightly greater U (1.01 vs 0.89 mm/sec, P < 0.01) and much lower V (0.06 vs 0.63%, P < 0.001) and Q (0.25 vs 1.88 ml/min/100 g, P < 0.001). In NO-DM subjects, WITH detected a lower Q in limbs with LEAD (0.14 vs 0.27, P < 0.05) but WITHOUT did not (1.48 vs 1.47, ns). In DM subjects, WITH measured a significantly lower U in LEAD limbs (1.05 vs 1.22 mm/sec, P < 0.05), which was not detected WITHOUT. Without the spacer, NORM limb LDF values were all greater in DM vs NO-DM subjects. With spacer use, only the DM velocity component was significantly greater. Use of a modified LDF procedure has shown both utility and promise as a method for evaluation of skin microcirculation and appears to offer some potential benefits as compared with the currently used standard method. Previously undocumented differences between LEAD and NORM limbs in DM and NO-DM patients as herein reported represent initial findings using a 0.68-mm spacer.

Arteries↗

Bilateral internal mammary artery grafts in patients with left main coronary artery disease.

The use of the internal mammary artery (IMA) in myocardial revascularization has been expanded with bilateral and sequential grafting. However, its application in the presence of left main coronary artery stenosis (LMCAS) has not been well established. From September 1983 through December 1990, 280 patients with LMCAS greater than 50% were revascularized (3.4 mean grafts per patient) with bilateral IMA and saphenous vein grafts. Eighty-one were sequential IMA grafts. There were 234 males (83.6%) and 46 females (16.4%) with a mean age of 64.4 years (range 39 to 84 years). Preoperatively, there were six patients (2.1%) in New York Heart Association (NYHA) Class I, 30 patients (10.7%) in Class II, 130 patients (46.4%) in Class III, and 114 patients (40.7%) in Class IV. Fifty-six patients (20.0%) had an ejection fraction less than 50%. Intraaortic balloon counterpulsation was used preoperatively in 26 patients (9.3%) and intraoperatively in 11 patients (3.9%). There were four hospital deaths (1.4%). Hospital complications included: reoperation for bleeding, 7 patients (2.5%); pulmonary insufficiency, 21 patients (7.5%); perioperative infarction, 14 patients (5.0%); and stroke, 4 patients (1.4%). Follow-up was obtained in 276 hospital survivors (100.0%) with a mean of 33.4 months. There were 20 late deaths (7.1%): seven cardiac related and 12 noncardiac related. Postoperative assessment reveals substantial functional improvement. These results furnish evidence that bilateral IMA grafts can be accomplished with a low operative risk and can provide excellent functional results in patients with LMCAS.

Adult↗

Coronary bypass grafting in the elderly. Single versus bilateral internal mammary artery grafts.

A surgical experience between October 1983 and December 1990, with 1467 consecutive patients 65 years of age and over, was used to compare patients receiving single internal mammary artery grafts (n = 736) with those receiving bilateral internal mammary artery grafts (n = 731). The mean age in the single-graft group was 73.2 years and 70.9 years in the bilateral-graft group (p < 0.001). Various clinical parameters were analyzed that revealed that the single-graft group had more women and more patients with unstable angina, a history of previous myocardial infarction, and emergency surgery (p < 0.05). There was no significant difference in cigarette smoking, hypertension, diabetes mellitus, hyperlipidemia, triple vessel coronary artery disease, left main coronary artery stenosis, or left ventricular function between the two groups. Hospital mortality for the single-graft group was 6.4% (47 patients) and 3.1% (23 patients) for the bilateral-graft group (p < 0.004). No significant difference was observed between the groups in the rate of reoperation for bleeding, sternal infection, respiratory failure, stroke, or perioperative infarction. Follow-up was obtained in 663 hospital survivors (96.4%) in the single-graft group and in 691 (97.7%) in the bilateral-graft group. Mean follow-up in the single-graft group was 42.5 months (range, 1 to 92.4 months) and 43.0 months (range, 1 to 90.3 months) in the bilateral-graft group. In the single-graft group, survival was 60.7% +/- 4.8% (+/- standard error of the mean) at 8 years (60 patients at risk); it was 67.9% +/- 8.1% (18 patients at risk) for the bilateral-graft group (p < 0.028). This comparative study demonstrates that bilateral internal mammary artery grafting can be accomplished in elderly patients with low operative risk and hospital morbidity. Moreover, patients in both groups had a reduction in cardiac events and significant functional improvement.

Actuarial Analysis↗

Expression of ethylene biosynthetic pathway transcripts in senescing carnation flowers.

We have examined the expression of mRNAs for S-adenosylmethionine synthetase (EC 2.5.1.6), 1-aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14), and the ethylene-forming enzyme (EFE) in various floral organs of carnation (Dianthus caryophyllus) during the increase in ethylene biosynthesis associated with petal senescence. The abundance of ACC synthase and EFE mRNAs increased and S-adenosylmethionine synthetase transcripts decreased concomitantly with the ethylene climacteric in senescing petals. The increase in abundance of ACC synthase and EFE mRNAs in aging flowers was prevented by treatment with the ethylene action inhibitor 2,5-norbornadiene. Furthermore, an increase in ACC synthase and EFE transcripts was detected in petals from presenescent flowers within 3 to 6 hours of exposure to 2 microliters per liter of ethylene. The increase in ethylene production by senescing petals was associated with a concomitant increase in ethylene biosynthesis in styles, ovary, and receptacle tissues. In all tissues, this increase was associated with increased activities of ACC synthase and EFE. The increase in EFE activities by all floral organs examined was correlated with increased abundance of EFE transcripts. In contrast, the level of ACC synthase mRNA, as detected by the cDNA probe pCARACC3, did not always reflect enzyme activity. The combined tissues of the pistil exhibited high rates of ACC synthase activity but contained low levels of ACC synthase mRNAs homologous to pCARACC3. In addition, pollinated styles exhibited a rapid increase in ethylene production and ACC synthase activity but did not accumulate detectable levels of ACC synthase mRNA until several hours after the initiation of ethylene production. These results suggest that transcripts for ACC synthase leading to the early postpollination increase in ACC synthase activity and ethylene production are substantially different from the mRNA for the ethylene-responsive gene represented by pCARACC3.

Journal Article↗

[Should athletic injuries be treated with non-steroidal anti-rheumatic agents (NSAID)? Tenoxicam, piroxicam and placebo in the treatment of acute stress-induced injuries].

A total of 212 patients with acute sports injuries were allotted at random to treatment with 20 mg tenoxicam daily, 20 piroxicam daily or a placebo for ten days. The injuries could be subdivided into six groups: Tendinitis, periostitis, sprains, tendovaginitis, epicondylitis and muscular ruptures. Treatment was well tolerated and analysis of the total material showed a slight but significantly better effect in the group treated with the active drugs. More detailed analysis revealed that this increased effect was produced by a definitely better therapeutic result in the group of patients with tendinitis treated with non-steroid anti-inflammatory drugs (NSAID) while, in the other types of injury, no definite effect could be observed. On the basis of these observations, the authors conclude that acute tendinitis may be treated with NSAID (tenoxicam) while the question is not yet solved where other acute stress-induced injuries are concerned.

Acute Disease↗

Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery.

Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Seventeen-year experience with bilateral internal mammary artery grafts.

The internal mammary artery (IMA) is being recognized as the conduit of choice for myocardial revascularization. From January 1972 through June 1988, 1,087 patients received bilateral IMA and supplemental vein grafts. There were 917 men (84.4%) and 170 women (15.6%) with a mean age of 62.4 years (range, 29 to 84 years). Three hundred ninety-four patients (36.2%) had unstable angina, and 194 (17.8%) had left main coronary artery stenosis greater than 50%. In all, 3,741 coronary grafts were performed, with a mean of 3.4 per patient. Hospital mortality was 2.7% (29 patients). Hospital complications included reoperation for bleeding, 19 patients (1.7%); sternal infection, 16 patients (1.5%); respiratory failure, 35 patients (3.2%); perioperative myocardial infarction, 22 patients (2.0%); and stroke, 20 patients (1.8%). Post-operative arteriography in 53 patients (mean postoperative time, 53.0 months) showed that 92.1% (58/63) of the left IMA and 84.9% (45/53) of the right IMA grafts were patent. Follow-up was completed on 1,058 hospital survivors. There were 82 late deaths (7.8%). The actuarial survival for patients discharged from the hospital was 80.0 +/- 3.2% (plus or minus standard error of the mean) at 10 years and 60.0% +/- 5.0% at 15 years. At follow-up, 866 patients (90.3%) were asymptomatic and in New York Heart Association class I and 68 (7.1%) were in class II. This longitudinal analysis demonstrates that bilateral IMA grafting has a low operative risk and provides excellent long-term functional improvement and survival.

Adult↗

[Body height in a population of children in Greater Copenhagen 7 to 18 years of age in 1981 and 1985. The Osterbro child study].

As part of the childrens' section of the Osterbro investigation, a quantity of standard health information concerning 736 boys and girls in 1981 and 892 in 1985 was collected. Review of these values revealed a significantly greater average height (greater than 3 cm) for boys in the age group 8-16 years and for girls aged 7-15 years than in previously published materials. The final height at about the age of 18 years for both girls and boys was not found to deviate significantly from previous results. The height/weight relationship remained unchanged. Current adjustments of the normal curves for childrens' growth should be made and/or an assessment of how well the subpopulation concerned is in agreement with the national average.

Adolescent↗

Cell-mediated immunity to Plasmodium falciparum infection: evidence against the involvement of cytotoxic lymphocytes.

Blood mononuclear cells (PBMC) recognizing soluble malaria antigens (SPag) are present in the peripheral blood of individuals clinically immune to malaria, and they proliferate after exposure to such antigens. To test whether these cells have effector activity against Plasmodium falciparum, we stimulated PBMC from malaria-immune donors by SPag and purified protein derivative (PPD) in culture for 7 days. The PBMC were then co-incubated with P. falciparum for 48 h, and parasitaemia was determined by microscopy. Parasite growth was only significantly impaired after incubation with PBMC stimulated by either SPag or PPD in the presence of immune serum. Studies on subpopulations of PBMC indicated that the inhibitory cells resided among the adherent cell fraction. Furthermore we tested PBMC for cytotoxic activity against P. falciparum-infected autologous or heterologous erythrocytes. Experiments were done both in the absence and the presence of immune serum. Neither fresh PBMC nor PBMC activated by SPag or PPD for 7 days prior to assay were cytotoxic, indicating that cytotoxic T cells, natural killer (NK) cells, and K cells did not possess cytotoxic activity directed against parasitized erythrocytes. These data support the hypothesis that activated monocytes are the most important effector cells in the peripheral blood of malaria immune individuals.

Animals↗

Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients.

Malaria infection has been shown to induce alterations in immune reactivity. This report describes the effect of serum obtained from Plasmodium falciparum infected patients on in vitro proliferation of human blood mononuclear cells (BMNC) isolated from healthy individuals. Serum obtained before initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium-derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition was seen on both autologous and heterologous BMNC. The degree of suppression was not correlated to the duration of the disease, the degree of parasitemia, or the use of chemoprophylaxis. Sera from 7 patients before and from 3 patients 30 days after initiation of treatment were pooled and fractionated. It was found that the strongest suppressive activity was in the serum fraction containing molecules from 30-100 kD.

Animals↗

Enhancement of human natural cytotoxicity by Plasmodium falciparum antigen activated lymphocytes.

Mononuclear cells (MNC) isolated from malaria immune donors and from donors never exposed to malaria were stimulated in vitro with soluble purified Plasmodium falciparum antigens (SPag) or PPD. After 7 days of culture the proliferative response and the cytotoxic activity against the natural killer cell (NK cell) sensitive cell line, K562, were measured. It was found that SPag stimulation enhanced cytotoxic activity of MNC from donors whose lymphocytes exhibited a strong proliferative response to the antigen. MNC with low proliferative responsiveness showed increased cytotoxic activity if the MNC were preincubated with interleukin 2 (IL-2) for one hour before the start of the cytotoxic assay. SPag activation did not enhance the cytotoxic activity of MNC which did not respond to the antigen in the proliferation assay, and preincubation of these cells with IL-2 did not increase the activity. PPD stimulation enhanced the cytotoxic activity and induced strong proliferative responses in all MNC preparations. The role of NK cells in the protection against malaria is unknown, but they play a role in the protection against virus infection and in the immune surveillance against cancer. Our findings indicate that malaria antigens either directly or through the activation of immunoregulatory cells enhance the NK cell activity.

Animals↗

Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals.

Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria-immune individuals, the proliferative response and the interleukin-2 (IL-2) production of SPAg-activated mononuclear cells (MNCs) from individuals unexposed, sensitized, and immune to malaria were measured. It was found that MNC isolated from malaria-immune individuals proliferated in response to SPAg and that this activation resulted in measurable IL-2 production in 5 of 10 MNC cultures. MNC isolates from most unexposed individuals did not respond to SPAg. To establish which cells responded to SPAg, different subpopulations of MNCs were tested. Only T helper cells were found to respond, and they responded only when cocultured with monocytes. The finding of parasite-specific T helper cells in the blood of malaria-immune individuals and the fact that some of these cells were able to produce IL-2 in vitro support the hypothesis that in malaria the cellular part of the protective immune response is initiated by immune T cells. These cells may activate nonspecific effector cells (i.e., macrophages) that eliminate the parasite.

Adult↗

In vitro effect of chloroquine, mefloquine and quinine on human lymphocyte proliferative responses to malaria antigens and other antigens/mitogens.

The effect of 3 antimalarial quinoline derivatives, chloroquine, mefloquine and quinine on human blood mononuclear cells in vitro was studied. High concentrations profoundly suppressed the proliferation of mitogen- and antigen-stimulated lymphocytes, as indicated by decreased 14C-thymidine incorporation. On a weight base, the most potent drug was mefloquine. At clinically relevant doses, chloroquine and mefloquine did not affect the response to malaria antigens, but mefloquine decreased the response to phytohaemagglutinin; quinine suppressed the response to all mitogens (with the exception of pokeweed mitogen) and antigens studied, including P. falciparum merozoites. The drugs' potential adverse effect on the immune system is discussed.

Adult↗