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Biomedical subjects

S B Christensen

Publications and source records attributed to S B Christensen.

At least 37 records · Page 2Linked to original sources

Modifications of the alpha,beta-double bond in chalcones only marginally affect the antiprotozoal activities.

Methods for selective alkylation of chalcones in the alpha- or beta-position and for selective reduction of the alpha,beta-double bond have been developed. The antiparasitic potencies of the alpha,beta-double bond modified chalcones only differ marginally from the potencies of the parent chalcones indicating that the propenone residue only functions as a spacer between the two benzene rings, which are the true pharmacophore.

Animals↗

Rapid increase in volume of the remnant after hemithyroidectomy does not correlate with serum concentration of thyroid stimulating hormone.

OBJECTIVE: To study the effect of postoperative thyroxine on the volume of the thyroid remnant after lobectomy for benign nontoxic goitre. DESIGN: Prospective, randomised study. SETTING: University hospital, Sweden. SUBJECTS: 50 consecutive patients who underwent lobectomy for benign non-toxic goitre. INTERVENTIONS: Patients were randomised postoperatively to take thyroxine 0.1 mg or placebo daily. MAIN OUTCOME MEASURES: The median volume of the remaining thyroid lobe measured by ultrasound. Serum concentrations of thyroxine, triiodothyronine (T3) and thyroid stimulating hormone (TSH) were measured preoperatively and 1, 3, 6, 12 months postoperatively. RESULTS: The median volume of the remaining lobe had increased significantly compared with preoperatively by 1 month postoperatively by 30% in the thyroxine group and 25% in the placebo group (p < 0.01). The difference between the groups was not significant. After the first month the volume did not change significantly. In the thyroxine group, the TSH concentration was unchanged and the thyroxine concentration increased significantly throughout the study. In the placebo group there was a significant increase in TSH concentration and a significant decrease in that of thyroxine at all follow-up examinations. CONCLUSIONS: There is a significant increase in the volume of the remaining thyroid 1 month after lobectomy that persisted throughout the first year. Thyroxine given in a dose that kept the serum TSH concentration at the same level as preoperatively did not seem to influence volume changes; consequently we consider that these are caused by factors other than TSH.

Adult↗

Living with breast cancer: care givers' perceptions in a surgical ward.

Caring for women with breast cancer has potential for increasing care giver distress and anxiety. Knowledge of the threats implicit in the disease and treatment as well as overidentification with the patient form the basis for this outcome. In order to describe perceptions of breast cancer as an illness, semistructured interviews were carried out with 37 care givers at a surgical department. The interviews were tape-recorded and transcribed verbatim. An analysis was then carried out of the stories told by the care givers about breast cancer as an illness. The results indicated that breast cancer as an illness gave rise to predominantly negative and dark associations among the care givers. Their experiences of caring for women in critical stages of the illness over many years appear to have had a negative influence on them. Death itself, and even more so the process leading to the end, were very tangible in their stories. The article concludes that care givers on a surgical ward have a fragmented picture of the patients and need to be given opportunities to follow the total care process. Those care givers who were able to follow the women's stages of illness throughout more often had a positive picture.

Adult↗

Evaluation of a hospital-based palliative support service with particular regard to financial outcome measures.

The object of this study was a financial assessment of a hospital-based palliative support service, to be made by comparing the study group with a matched historical control group and a group of contemporary reference patients. The staff consisted of one full-time nurse supported by a surgeon one half-day per week. The patients in the study group utilized fewer institutional days than the control group, according to such parameters as duration of terminal hospitalization (P < 0.05), ratio of days at home to total inclusion days (P < 0.001), and days at home during last two months of life (P < 0.01). These three outcome measures all focus on the most care-intensive last months of life and appeared to be sensitive enough to identify economic advantages of palliative care intervention. The palliative support service defrayed its own costs and in excess of that saved another SK17000 per patient (US$2500).

Aged↗

SB 207499 (Ariflo), a potent and selective second-generation phosphodiesterase 4 inhibitor: in vitro anti-inflammatory actions.

First-generation phosphodiesterase 4 (PDE4) inhibitors, such as rolipram, inhibit the activation of immune and inflammatory cells. The clinical use of these compounds is limited by gastrointestinal side effects, such as increased acid secretion and nausea. Consequently, the challenge has been to design novel PDE4 inhibitors that maintain the anti-inflammatory actions of rolipram while achieving an improved side effect profile. Among the first of this new class of PDE4 inhibitors specifically designed to have an improved therapeutic index relative to earlier compounds is SB 207499 (Ariflo) [c-4-cyano-4-(3-cyclopentyloxy-4-methoxy-phenyl)-r-1-cyclohexanecarboxyl ic acid]. In this study, we compared the anti-inflammatory and gastric secretogogue activities of SB 207499 with those of rolipram. The cellular models used were (1) histamine release from human basophils, (2) tumor necrosis factor-alpha generation in human monocytes, (3) degranulation of human neutrophils, (4) antigen-driven proliferation and cytokine synthesis from human T cells and (5) acid secretion from isolated rabbit gastric glands. SB 207499 inhibited the activation of a variety of immune and inflammatory cells in a concentration-dependent manner: (1) histamine release in basophils [-log IC25 = 6.6 +/- 0.3 vs. 8.0 for (R)-rolipram], (2) lipopolysacchride-induced TNF-alpha formation in monocytes [-log IC50 = 7.0 +/- 0.1 vs. 7.2 +/- 0.1 for (R)-rolipram], (3) fMLP-induced degranulation in neutrophils [-log IC15 = 7.1 +/- 0.2 vs. 6.4 +/- 0.5 for (R)-rolipram], (4) house dust mite induced-proliferation of peripheral blood mononuclear cells [-log IC40 = 6.5 +/- 0.3 vs. 6.4 +/- 0.3 for (R)-rolipram] and (5) ragweed-induced production of interferon-gamma [-log IC50 = 5.4] and interleukin-5 [-log IC50 = 5.0]. Although SB 207499 inhibits the activation of a variety of immune and inflammatory cells with a potency equal to that of rolipram, it is > 100-fold less potent than the latter compound as an acid secretagogue [-log EC50 = 6.1 +/- 0.1 vs. 8.3 +/- 0.2 for (R)-rolipram]. Collectively, these data indicate that SB 207499 retains the anti-inflammatory activity of the prototypical PDE4 inhibitor rolipram but is substantially less likely to stimulate gastric acid secretion.

Animals↗

Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB 207499 (Ariflo) in the guinea pig.

We evaluated the airway activity of the novel phosphodiesterase type 4 inhibitor SB 207499 [Ariflo; c-4-cyano-4-(3-cyclopentyloxy-4-methoxyp henyl-r-1-cyclohexane carboxylic acid)], in the guinea pig. Ovalbumin (OA)-induced contractions of guinea pig isolated tracheal strips were inhibited by SB 207499 with an EC50 of 1 microM but had little or no effect on exogenous agonist-induced contraction, which suggests that its effect on OA-induced contraction in vitro is primarily due to inhibition of mediator release from mast cells. In anesthetized guinea pigs, SB 207499 inhibited OA-induced bronchoconstriction with i.v. and p.o. ID50 values of 1.7 and 17 mg/kg, respectively. At 1, 3 and 6 hr after SB 207499 (30 mg/kg p.o.), OA-induced bronchospasm was inhibited by 92%, 70% and 58%, respectively, corresponding to elevated plasma concentrations of 1.62 +/- 0.19, 1.65 +/- 0.29 and 0. 93 +/- 0.24 microg/ml, respectively, of SB 207499. SB 207499 also inhibited house dust mite-induced bronchoconstriction (ID50 = 0.9 mg/kg i.v. and 8.9 mg/kg p.o.). In contrast to its lack of bronchorelaxant activity in vitro, SB 207499 inhibited bronchospasm induced by i.v. leukotriene D4 (LTD4) [ID50 = 3 mg/kg i.v.]. The bronchorelaxant effect of i.v.-administered SB 207499 was at least additive with that of salbutamol in reversing infused histamine-enhanced airway tone, but it did not alter base line or enhance salbutamol-induced cardiovascular effects. In conscious guinea pigs, SB 207499 (10 or 30 mg/kg p.o.), 1 hr before antigen or LTD4 challenge, markedly reduced bronchospasm and subsequent eosinophil influx as measured by bronchoalveolar lavage 24 hr after provocation. SB 207499 administered after OA or LTD4 challenge also reduced airway eosinophilia measured at 24 hr after OA challenge or 96 hr after LTD4 challenge. These results, coupled with the broad anti-inflammatory activity of SB 207499 previously described (Barnett et al., 1998), suggest that SB 207499 will be useful in the treatment of asthma and other inflammatory disorders.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Experience with daily single dose administration of gentamicin].

The purpose of the study was to evaluate the effect and side-effects of once daily (OD) administration of gentamicin. The study was a retrospective analysis of patients treated with gentamicin OD for at least two days for proven or suspected infection. Of the 101 patients included, 60 were female, and the median age was 64 years (range: 20-90 years). Median duration of treatment was six days (2-63 days). All patients received combination therapy with two (36 patients), three (64 patients) or four (one patient) antibiotics, apart from gentamicin usually ampicillin, cefuroxime and/or metronidazole. Gentamicin doses were usually 240 mg on a fixed basis, but reduced in patients with pre-treatment impairment of serum-creatinine. Bacteriological cultures were taken in 90% of the patients, of which 59% were positive, most often with Enterobacteriaceae (57%) or other Gram-negative rods (11%). Effect of antibiotic treatment was seen in 82% of the patients. Nephrotoxicity defined as a 44 umol/l increase in serum-creatinine during treatment was found in five patients (5%). Ototoxicity, i.e. clinical signs of tinnitus, dizziness and/or impaired hearing, was reported in two patients. In conclusion, gentamicin OD with 240 mg is easy to administer, appears to be sufficient with regard to effect and has a low frequency of side-effects.

Adult↗

Medical care utilization by incurable cancer patients in a Swedish county.

A retrospective study of patients with cancer diagnoses treated at a Swedish county hospital was carried out in order to analyse medical care utilization by incurable cancer patients. All 208 patients customarily treated at the Department of General Surgery in Ostersund Hospital for cancer diagnoses during 1 year were included in the study. The main outcome measures were: number of institutional days; admissions; duration of terminal hospitalization. The Department of General Surgery supplied 7570 of all 12,276 (62%) institutional days needed throughout the disease course. The terminal hospitalization (i.e. the period of continuous institutional care ending with the death of the patient) constituted 39% of all institutional days. The duration of the terminal hospitalization seemed to be unrelated to various diagnoses and demographic variables. Patients with cancer of the breast utilized most institutional days/patient (median 80 institutional days) during the disease course. Married patients and patients living within a 40 km radius of the hospital spent significantly more days at the Department of General Surgery during the last 6 months of life than did the unmarried and those living further afield.

Adult↗

New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica.

A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit rind led to the isolation of two new lignans named termilignan (1) and thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and anolignan B (4). All four compounds possessed demonstrable anti-HIV-1, antimalarial, and antifungal activity in vitro.

Anti-HIV Agents↗

Two new antiprotozoal 5-methylcoumarins from Vernonia brachycalyx.

Two new isomeric 5-methylcoumarins, 2'-epicycloisobrachycoumarinone epoxide (1) and cycloisobrachycoumarinone epoxide (2), have been isolated from the roots of Vernonia brachycalyx by means of bioactivity-guided fractionation. The structures were elucidated by MS and NMR spectroscopic methods. Compounds 1 and 2 showed in vitro activity against Leishmania major promastigotes and against Plasmodium falciparum schizonts and demonstrated an inhibition on the proliferation of human lymphocytes, which was significantly weaker than the antiparasitic effects.

Animals↗

Antiprotozoal compounds from Asparagus africanus.

Two antiprotozoal compounds have been isolated from the roots of Asparagus africanus Lam. (Liliaceae), a new sapogenin, 2 beta, 12 alpha-dihydroxy-(25R)-spirosta-4,7-dien-3-one (1), which was named muzanzagenin, and the lignan (+)-nyasol (2), (Z)-(+)-4,4'-(3-ethenyl-1-propene-1,3-diyl)-bisphenol. The structure of the sapogenin was elucidated by MS and by 1D and 2D NMR methods and established by a single crystal X-ray analysis. (+)-Nyasol potently inhibits the growth of Leishmania major promastigotes, the IC50 being 12 microM, and moderately inhibits Plasmodium falciparum schizonts with the IC50 49 microM. These concentrations only moderately affect the proliferation of human lymphocytes. Muzanzagenin showed a moderate in vitro activity in all three tests, the IC50 against leishmania promastigotes was 70 microM, and against four different malaria schizont strains the IC50 values were 16, 163, 23, and 16 microM, respectively.

Animals↗

Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A.

1. Four glucuronic acid conjugates of licochalcone A (Lica), and their metabolites, have been synthesized using rabbit and pig liver microsomes and purified by preparative hplc. 2. The glucuronides were identified as E-Lica 4'-O-beta-glucuronide, E and Z-Lica 4-O-beta-glucuronide and a mono-glucuronide conjugate of a beta-hydroxylated Lica metabolite. The metabolites were identified by hplc-nmr (one and two-dimensional nmr) as well as hplc-ms. 3. At pH 8.5 Lica reacted with N-acetyl-L-cysteine giving the two epimeric conjugates, which were then isolated by preparative hplc and identified by one and two-dimensional nmr spectroscopic methods. 4. Only two glucuronic acid conjugates (E- and Z-Lica 4-O-beta-glucuronide) were found in the urine of rat after i.p. administration of a single dose of Lica.

Acetylcysteine↗

Association of the anti-inflammatory activity of phosphodiesterase 4 (PDE4) inhibitors with either inhibition of PDE4 catalytic activity or competition for [3H]rolipram binding.

Phosphodiesterase 4 (PDE4) inhibitors are novel anti-inflammatory compounds. Unfortunately, the archetypal PDE4 inhibitor rolipram produces central nervous system and gastrointestinal side-effects. To exploit these agents, we need to identify PDE4 inhibitors that retain the anti-inflammatory activity with a reduced potential to elicit unwanted side-effects. PDE4 possesses both cyclic AMP catalytic activity that is inhibitable by rolipram and a high affinity binding site for rolipram. The function of this high affinity rolipram binding site is unclear; however, certain pharmacological effects of PDE4 inhibitors are associated with competition for this site. Since PDE4 inhibitors suppress both monocyte and neutrophil activation, the present experiments were carried out to establish a correlation between suppression of monocyte activation [tumor necrosis factor alpha (TNF alpha) formation] or suppression of neutrophil activation (degranulation) with inhibition of either PDE4 catalytic activity or [3H] rolipram binding. Suppression of TNF alpha formation demonstrated a strong correlation with inhibition of PDE4 catalytic activity (r=0.87; P<0.01; Spearman's Rho = 0.79, P<0.05), whereas there was no correlation with inhibition of [3H]rolipram binding(r=0.21, P>0.5; Spearman's Rho=0.16, P>0.5). Suppression of neutrophil degranulation was not associated with inhibition of PDE4 catalytic activity (r=0.25, P>0.4; Spearman's Rho=0.33, P>0.2), but was associated with inhibition of [3H]rolipram binding (r=0.68, P<0.05; Spearman's Rho=0.6, P=0.06). These results indicate that anti-inflammatory effects of PDE4 inhibitors can be associated with either inhibition of PDE4 catalytic activity or high affinity rolipram binding.

3',5'-Cyclic-AMP Phosphodiesterases↗

Place of death correlated to sociodemographic factors. A study of 203 patients dying of cancer in a rural Swedish county in 1990.

The purpose of this study was to ascertain where patients with malignant disease died and to establish whether such factors as age, sex, marital status, place of residence, diagnosis and interval between diagnosis and death bore any relation to the place of death. All medical records of 203 patients who died in one particular Swedish county in 1990 of cancers of the GI tract, the urogenital organs, the breast, the skin and the thyroid were analysed. Of all 203 patients, 25 (12%) died at home, 49 (24%) in nursing homes and 129 (64%) in hospital. The proportion of home deaths was significantly smaller when the interval from diagnosis to death was less than one month. Death in a nursing home, compared with death in a hospital, was more usual among patients older than 80 years, among those living more than 40 km from the hospital and among those from areas where the local health care centre had a nursing home attached.

Adult↗

Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12.

A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.

Animals↗

Selection of fusion levels in idiopathic adolescent scoliosis treated by Harrington-DDT instrumentation: a short-term radiologic study.

Clinical records and radiographs of 106 patients treated by Harrington-dorsal transverse traction (DDT) instrumentation for idiopathic adolescent thoracolumbar scoliosis were reviewed. Our strategy was to fuse from one vertebra above the measured curve to two vertebrae below the curve, but to avoid fusions below the third lumbar vertebra. With this strategy, the lower level of fusion rarely coincided with the stable vertebra. In King type 2 and type 3 scolioses, the best results were obtained when the lower fusion level coincided with the stable vertebra. In King type 4 and in most King type 5 scolioses, the lower level of fusion was two or three vertebrae short of the stable vertebra; nevertheless, we obtained good corrections. We conclude that in King type 4 and type 5 scolioses extensive lumbar fusion can be avoided.

Adolescent↗