Search PubMed⌕ Search

Biomedical subjects

J Hanson

Publications and source records attributed to J Hanson.

At least 127 records · Page 7Linked to original sources

Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease.

In chronic heart failure, a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor only partially suppresses aldosterone despite the fact that aldosterone has many harmful effects independent of angiotensin II. These possible harmful effects of aldosterone are magnesium loss, increased cardiac sympathetic activity, and increased ventricular arrhythmias. We have therefore assessed whether adding the aldosterone antagonist, spironolactone, to a loop diuretic and ACE inhibitor reverses any of these potentially harmful effects of residual aldosterone. In a preliminary animal study, we found that exogenous aldosterone reduced myocardial norepinephrine uptake by 24% in anesthetized rats in vivo. In our main study, 42 patients with New York Heart Association II to III congestive heart failure were randomized to spironolactone (50 to 100 mg/day, titrated to blood pressure and plasma potassium) or placebo in a double-blind fashion. Our principal finding is that cardiac norepinephrine uptake as assessed by 123I-metaiodobenzylguanidine scintigraphy increased with spironolactone (p < 0.01). Spironolactone also elevated plasma magnesium (p < 0.05), reduced urinary magnesium excretion (p < 0.05), and caused a reduction in ventricular arrhythmias on 24-hour ambulatory electrocardiography (p < 0.05). Spironolactone increased plasma renin activity, plasma aldosterone (p < 0.01), 24-hour urinary sodium excretion (p < 0.05), and urinary sodium/potassium ratio (p < 0.01). Echocardiographic-determined measurements of left ventricular systolic and diastolic function were unaltered by spironolactone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule.

Amino Acid Sequence↗

Pre-hospital cardiac arrest: room for improvement.

OBJECTIVE: To audit the outcome from pre-hospital cardiac arrest managed by ambulance personnel, and to assess their proficiency by analysing the time to initiate basic and advanced cardiac life support, the compliance with national guidelines, and the overall success of resuscitation. DESIGN: A retrospective analysis of ambulance service report forms of pre-hospital cardiac arrests, where active resuscitation was attempted by ambulance personnel between October 1992 and May 1993. SETTING: The City of Salford. SUBJECTS: 100 consecutive patients who suffered cardiac arrest out-of-hospital and who were brought to the accident and emergency department of Hope Hospital alive, or with resuscitation still in progress. RESULTS: Only 4 of 100 patients were successfully resuscitated out of hospital, of whom 2 survived to leave hospital. Detailed analysis of pre-hospital performance was performed on 89 patients only, as 11 report forms were missing (no successful pre-hospital resuscitations in this 11). Ventricular fibrillation was the first recorded rhythm in 51.7%, but 85.7% were in asystole or electromechanical dissociation on arrival at hospital. No patient who was still in cardiac arrest on arrival at hospital was successfully resuscitated. 11 patients received 'bystander CPR'. The median time to basic life support was 6 min; the median call-to-response interval was 8 min; the median call-to-advanced cardiac life support interval was 21 min; the median on-scene time was 31 min (paramedics), or 15 min (technicians). The dose of drugs given by the intravenous route did not comply with the contemporary recommendations in 43.2%, and those doses given by the endotracheal route were inadequate in 37.9% of the cases. Endotracheal intubation was attempted in all paramedic resuscitations (91.4% success); intravenous access was attempted in 60.3% (91.7% success). CONCLUSIONS: The survival from pre-hospital cardiac arrest in this community is worse than the national average. There is no single explanation for this. Better community CPR training, greater efficiency at the scene through additional personnel, and stricter compliance with national ACLS guidelines, facilitated by extended refresher training, are all required if outcome is to be improved.

Adolescent↗

A prospective multicenter assessment of the Edmonton staging system for cancer pain.

Two hundred and seventy-seven patients were admitted to this prospective multicenter study in order to assess the accuracy of a staging system for cancer pain. The staging system (SS) was completed by a trained physician during the initial consultation. This system included the assessment of pain mechanism (PM, neuropathic versus nonneuropathic), pain characteristic (PC, continuous versus incidental), previous opioid dose (OD), cognitive function (CF), psychological distress (PD), tolerance (T), past history of alcohol or drugs (A). During day 21, a final assessment of pain control was made. Agreement for staging was observed in 96% of cases for investigators 1 and 2 (kappa 0.76, P < 0.001), and in 84% of cases between investigators 1 and 3 (kappa 0.723, P < 0.001). Of 276 evaluable patients, 86/92 Stage I (good prognosis) patients achieved good PC (93%) versus 102/184 Stage II and III (poor prognosis) patients (55%, P < 0.001). Sensitivity and specificity of the system were found to be 0.93 and 0.46, respectively. Univariate correlation found significant correlation between pain control and all variables except CF. In logistic regression, CF and OD showed no significant correlation. We, therefore, propose a more simple SS of five categories (PM, PC, PD, T, and A) and two stages (good and poor prognosis). We conclude that the SS is highly accurate in predicting patients with good prognosis, but patients with "poor prognosis" can still achieve good pain control in more than 50% of cases.

Aged↗

Comparison of two different concentrations of hyaluronidase in patients receiving one-hour infusions of hypodermoclysis.

The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per one-half liter to 150 units per one-half liter in patients receiving brief infusions for subcutaneous hydration. Twenty-five evaluable patients were randomized to receive a local injection of 300 units of hyaluronidase or 150 units of hyaluronidase immediately before two 1-hr infusions of two-thirds dextrose 5% and one-third normal saline solution (500 cc volume). The following day a crossover took place, and patients received the alternate treatment before each of the two 1-hr infusions. The intensity and swelling as reported by the patient (visual analogue scale 0-100), and the intensity of edema and rash as assessed by the investigator (score 0-4) were not significantly different between groups. The patients' and investigators' final choice was also not significantly different. Patients could not distinguish between bolus and their previous experience with overnight clysis. Our results suggest that brief infusions are well tolerated for subcutaneous hydration of patients with advanced cancer. A concentration of 150 units of hyaluronidase per one-half liter is well tolerated in this population.

Aged↗

The frequency of alcoholism among patients with pain due to terminal cancer.

The purpose of this retrospective study was to determine the prevalence of alcoholism among terminally ill cancer patients when assessed by multidisciplinary interviews and by the CAGE Questionnaire. We reviewed the charts of 100 consecutive patients assessed by a multidisciplinary team for the presence of alcoholism during 1989, and 100 consecutive patients assessed by the CAGE Questionnaire during 1992. Alcoholism was diagnosed in 28/100 patients during 1989 (28%) and 18/66 patients during 1992 (27%). Thirty-four patients were unable to complete the CAGE Questionnaire in 1992 because of sedation or cognitive impairment; six of these patients (17%) were found to be alcoholics after multidisciplinary assessment. Only 9/28 (32%) and 8/24 (33%) patients diagnosed as alcoholics during 1989 and 1992, respectively, had been previously diagnosed as alcoholics according to the medical charts. The mean equivalent daily dose of morphine during admission and on Day 2 during 1992 were 153 +/- 193 mg and 183 +/- 198 for alcoholic patients, versus 58 +/- 80 and 70 +/- 79 mg for nonalcoholics (P = 0.06 and 0.03, respectively). The maximal dose of opioid and the pain intensity during admission, however, were not significantly different between alcoholics and nonalcoholics. Our results suggest that alcoholism is highly prevalent and underdiagnosed among symptomatic terminally ill cancer patients. The CAGE Questionnaire should be used for screening for alcoholism in this population. When multidimensional assessment and management of pain is applied, the outcome of alcoholic patients appears to be similar to that of nonalcoholics.

Aged↗

Erythropoietin use in pregnancy: two cases and a review of the literature.

End-stage renal disease complicates only a small percentage of pregnancies, but, of these, virtually all become anemic due to a deficiency in erythropoietin. Erythropoietin has been shown to correct anemia due to renal disease in nonpregnant patients. We report two cases of erythropoietin use during pregnancy complicated by severe anemia due to renal failure. No maternal or fetal side effects were noted. Our two cases exemplify that erythropoietin is an effective means of treating anemia due to renal disease in the gravid patient.

Adult↗

Morphogenesis of calcitic sponge spicules: a role for specialized proteins interacting with growing crystals.

Crystals formed in biological tissues often adopt remarkable morphologies that are thought to be determined mainly by the shapes of the confined spaces in which they grow. Another possible way of controlling crystal shape, demonstrated only in vitro, is by means of specialized proteins preferentially interacting with certain crystal faces. In so doing, they reduce the rate of growth in these directions and consequently change the overall crystal shape. In an X-ray diffraction study of the distribution of defects within the lattice of calcite crystals produced by certain sponges, we show that a remarkable correlation exists between the defect patterns or crystal texture and the macroscopic morphology of the spicules. This was observed in two cases in which proteins are present within the spicule crystal, but not in a third case where such intracrystalline proteins are absent. Furthermore, one of the spicules exhibited marked differences in texture even within families of structurally identical crystal planes, demonstrating that the organisms exert exquisite control over the microenvironment in which crystals grow. We conclude that highly controlled intercalation of specialized proteins inside the crystals is an additional means by which organisms control spicule growth.

Animals↗

Role of rectal route in treating cancer pain: a randomized crossover clinical trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain.

PURPOSE: The aim of this double-blind, double-dummy, crossover study was to compare the efficacy, tolerability, and time of onset of analgesia after the administration of 10 mg of morphine hydrochloride via the oral and rectal routes in opioid-naive cancer patients with pain. PATIENTS AND METHODS: Thirty-four patients with cancer pain and no previous opioid treatment were randomized to receive morphine hydrochloride 10 mg orally or rectally (in the form of a microenema) for 2 days. During days 3 and 4, a crossover took place. The scores of pain, nausea, and sedation (visual analog scale of 0 to 100) calculated as the percentage change from baseline (before opioid administration) were assessed at different intervals up to 240 minutes. The number of vomiting episodes was recorded. Parity tests and analysis of variance (ANOVA) were performed to compare the two administration routes. RESULTS: A significant difference in pain intensity was achieved 10 minutes after rectal administration compared with 60 minutes after oral administration. There was still a significant reduction in pain via the rectal route after 180 minutes versus via the oral route after 120 minutes. No significant difference was observed in the intensity of sedation, nausea, or number of vomiting episodes between the oral and rectal routes. CONCLUSION: A liquid solution of morphine is well absorbed via the rectal route. Rectal morphine is safe, effective, easy to manage, and inexpensive, with a rapid onset of action. Rectal morphine can be considered a valid alternative route for opioid administration and may also be used when rescue doses of morphine are required in patients regularly treated with oral or parenteral opioids.

Administration, Oral↗

Altered development of collagen induced arthritis in T cell receptor V beta congenic B10.RIII mice.

Analysis of the mouse T cell receptor (TCR) V beta genome has revealed the existence of two distinct genotypes which bear deletions of certain V beta genes. Mice bearing the V beta a genotype lack approximately 50% of the V beta genome while V beta c mice lack 70% of the known V beta genes. Studies of the experimental model collagen induced arthritis (CIA) have indirectly suggested that the presence of truncated V beta genotypes may influence susceptibility to this autoimmune disease. In order to confirm the influence of V beta a and V beta c genotypes on CIA, we derived mice congenic for the known V beta haplotypes in the CIA susceptible B10.RIII (H-2r) background. Flow cytometric analysis of splenic lymphocytes revealed normal T cell levels in both B10.RIII-V beta congenic lines. Expectedly, a generalized increase in the expression of some non-deleted V beta genes was detected. In addition, the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-V beta a mice showed little difference in arthritis incidence or severity versus B10.RIII, but a significant delay in the onset of CIA was seen. In contrast, B10.RIII-V beta c mice showed a marked decrease in arthritis incidence versus B10.RIII and the severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus, in the B10.RIII strain, the presence of truncated TCR V beta genotypes alters the development of CIA. These findings may shed light on the influence of TCR genotypes in the induction and development of human rheumatoid arthritis.

Animals↗

Reducing the concentration of contrast medium in dynamic computed tomography of the neck: consequences for image quality, side effects and cost.

OBJECTIVE: To determine the efficacy of two concentrations of nonionic contrast medium (320 and 240 mg iodine/mL; Optiray [ioversol], Mallinckrodt Medical) for enhanced dynamic computed tomography (CT) of the neck. PATIENTS AND METHODS: Between March 1992 and August 1993, 50 patients undergoing dynamic CT of the neck were assigned randomly to receive either the higher-strength or the lower-strength contrast agent. The amount of opacification was measured objectively, and the quality of the scans was assessed subjectively by two radiologists without knowledge of which contrast agent had been administered. Both immediate and delayed side effects were recorded. RESULTS: The higher-strength contrast medium gave greater opacification (p = 0.0006, t-test), but both concentrations yielded images of excellent quality (p = 0.125, chi 2 test). The number of patients affected by immediate minor complications was lower with Optiray 240 (11 [44%]) than with Optiray 320 (23 [92%]) (p < 0.001, chi 2 test). The number of patients affected by delayed side effects was similar in the two groups (7 [28%] with Optiray 240 and 9 [36%] with Optiray 320; p > 0.70, chi 2 test). No predictive relation between immediate and delayed complications was observed. CONCLUSIONS: Because adequate contrast can be obtained with the lower-strength contrast medium, it can be used in dynamic CT of the neck as a means of reducing the cost and the side effects associated with such imaging.

Adult↗

Role of bisphosphonates in prevention and treatment of bone metastases from breast cancer.

Clinical research over the last decade has confirmed the helpful role of bisphosphonates in the management of patients with bone metastases secondary to breast cancer and other malignancies. This role is also expanding in myeloma and in the management of osteoporosis. Current clinical research in oncology is focusing on their potential for the prevention of skeletal complications of malignant disease and the development of bone metastases while basic researchers are developing compounds of higher potency and, perhaps, higher therapeutic efficacy. One of the earliest agents to be investigated, etidronate, is effective in the management of malignant hypercalcemia and, when used orally and intermittently, results in reduced bone loss in osteoporosis. However, it does not appear to reduce pain in patients with malignant disease. Clodronate has been shown to be an effective agent in the management of hypercalcemia and can be used as a single intravenous infection for this purpose. Clodronate is also effective in some patients in reducing bone pain and improving mobility. When used orally, it can, as can pamidronate, reduce the skeletal complications of breast cancer such as hypercalcemia, bone fractures and bone pain. It may have fewer gastrointestinal side effects than oral pamidronate. There is emerging evidence that bisphosphonates may delay or prevent the clinical appearance of bone metastases as well as reduce other skeletal complications. Trials of adjuvant bisphosphonates such as clodronate and pamidronate in operable breast cancer are currently under way in Europe and North America.

Analgesics, Non-Narcotic↗

Collagen-induced arthritis and TCRs in SWR and B10.Q mice expressing an Ek alpha transgene.

B10.Ek alpha transgenic mice were mated with H2-E B10.Q and SWR mice. F1 and F1 x parental strain backcross progeny were tested for arthritis and autoimmune reactivity to mouse type II collagen (MII) after immunization with bovine, chick, deer, or human type II collagen. The results were correlated with the H-2 haplotype (b/q vs q/q) and the TCR V beta profile of peripheral blood T cells in each mouse. Hybrid progeny expressed TCR profiles different from either parent because of the TCR V beta genomic deletions of SWR mice (V beta a), the wild-type TCR allele of C57Bl/10 (B10) mice (V beta b), and the intrathymic negative selection processes resulting from cell surface expression of Ek alpha-A q beta or Eb beta-Ek alpha, together with the integrated retroviral genes Mtv-9 originating in B10 mice and Mtv-7 (Mls-1a) from SWR mice. (B10.Ek alpha x SWR)F1 mice developed higher IgG anti-MII Ab titers, but much milder arthritis than (B10.E x B10.Q)F1 mice. Expression of Ek alpha did not change the level of IgG anti-MII Ab nor the degree of susceptibility to collagen-induced arthritis (CIA) in the H-2q/q and H-2b/q progeny of (B10.Ek alpha x B10.Q)F1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR V beta 5+, and V beta 11+ T cells are not critical to CIA. Among bovine type II collagen-immunized (B10.Ek alpha x SWR)F1 x SWR backcross mice: 1) arthritis severity is associated with the presence of V beta b (p < or = 0.01) and expression of Ek alpha (p < or = 0.05), but not with the MHC haplotype (b/q vs q/q); 2) regression analysis showed a significant association (R = 0.99) between IgG anti-MII Ab titers and the level of Mtv-7-reactive V beta 6+ T cells that was detectable in the IgG1, but not the IgG2a subclass. The data prompt the speculation that Mtv-7-reactive V beta 6+ (or V beta 7+) T cells in (B10.EK alpha x SWR)F1 x SWR mice express Th2-type properties, and thus contribute to the combination of mild arthritis but high anti-MII Ab titers that characterize mice of SWR heritage.

Animals↗

Collagen-induced arthritis in T cell receptor V beta congenic B10.Q mice.

B10.Q (H-2q) mice congenic for the truncated T cell receptor (TCR) V beta a and V beta c haplotypes were derived to examine the influence of TCR V beta genomic deletions in murine collagen-induced arthritis (CIA). Previous studies using gene complementation and segregation analyses suggested that in SWR (H-2q) mice, possession of the V beta a gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR V beta congenic mice allows for direct examination of V beta genotypes in CIA control. After immunization with bovine type II collagen, B10.Q-V beta a mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.Q-V beta c mice, which lack the V beta 6, 15, 17, and 19 families in addition to the V beta a deletion, were highly resistant to CIA. In vivo depletion of V beta 6+ T cells in B10.Q-V beta a mice significantly delayed arthritis onset suggesting that, among those V beta genes present in V beta a but absent in V beta c, V beta 6+ T cells contribute to arthritogenesis. Our findings show that, in B10.Q-V beta congenic mice, while the V beta a genotype does not prevent CIA, the highly truncated V beta c genotype renders B10.Q mice resistant to CIA. Thus, deletions within the V beta TCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.

Animals↗

Hierarchy in the assembly of HLA-B27 and HLA-Cw3 molecules in transgenic mice.

Cell surface expression of human class I molecules in transgenic mice is dependent upon the available pool of beta 2-microglobulin (beta 2m) and the affinity between mouse beta 2m and human class I molecules. HLA-B27 and HLA-Cw3 transgenes can be expressed in mouse strains of the H-2 haplotypes b, f, k, and s which encode two endogenous class I genes mapping to H-2K and H-2D. The human class I genes cannot be expressed on H-2d and H-2q haplotypes which encode three endogenous class I molecules (K,D,L). This suggests that there may be only enough mouse beta 2m molecules to support three class I molecules. When both the HLA-B27 and HLA-Cw3 genes are introduced into H-2b mice, only HLA-Cw3 reaches the cell surface. This suggests that HLA-Cw3 has a higher affinity than HLA-B27 for mouse beta 2m. The possible implications of our findings regarding the assembly, transport, and expression of class I MHC molecules in vivo are discussed.

Animals↗