Biomedical subjects

J Jensen

Publications and source records attributed to J Jensen.

At least 91 records · Page 5Linked to original sources

PubMed2000

Immunological effects of oral high-dose methylprednisolone in acute optic neuritis and multiple sclerosis.

The immunological effects of high-dose methylprednisolone in attacks of multiple sclerosis and acute optic neuritis have only been examined in a few randomized, controlled trials. We studied immunological changes in 50 patients with optic neuritis or multiple sclerosis who underwent lumbar puncture before and 1 week after completing a 15-day course of oral high-dose methylprednisolone treatment. Treatment resulted in a decrease in the concentration of myelin basic protein, a decrease in the serum concentration of immunoglobulin G (IgG) and intrathecal IgG synthesis, an increase in the cerebrospinal fluid concentration of transforming growth factor-beta1, and changes in the expression of CD25, CD26, and human leukocyte antigen-DR (HLA-DR) on CD4 T-cells. No effect was seen on the cerebrospinal fluid leucocyte count or the cerebrospinal fluid activity of matrix metalloproteinase-9 (MMP-9). The lack of a persistent effect on cerebrospinal fluid leucocyte recruitment and MMP-9 activity, despite changes in IgG synthesis, T-cell activation, and cytokine production, suggests that modulation of the function of inflammatory cells may contribute to the clinical efficacy of oral high-dose methylprednisolone treatment in optic neuritis and multiple sclerosis.

Acute Disease↗

PubMed2000

Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres.

The present investigation evaluates the effects of long-term, local delivery of insulin, insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF) on fat-graft survival using a poly (lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microsphere delivery system. Twelve-micrometer PLGA/PEG microspheres incorporated separately with insulin, IGF-1, and bFGF were manufactured using a double-emulsion solvent-extraction technique. Inguinal fat from Sprague Dawley rats was harvested, diced, washed, and mixed with (1) insulin microspheres, (2) insulin-like growth factor-1 microspheres, (3) basic fibroblast growth factor microspheres, (4) a combination of the insulin and IGF-1 microspheres, and (5) a combination of insulin, IGF-1, and bFGF microspheres. The treated fat grafts were implanted autologously into subdermal pockets in six animals for each group. Animals receiving untreated fat grafts and fat grafts treated with blank microspheres constituted two external control groups (six animals per external control group). At 12 weeks, all fat-graft groups were compared on the basis of weight maintenance and a histomorphometric analysis of adipocyte area percentage, indices of volume retention and cell composition, respectively. Weight maintenance was defined as the final graft weight as a percent of the implanted graft weight. All growth factor treatments significantly increased fat-graft weight maintenance objectively, and volume maintenance grossly, in comparison with the untreated and blank microsphere-treated controls. Treatment with insulin and IGF-1, alone or in combination, was found to increase the adipocyte area percentage in comparison with fat grafts treated with bFGF alone or in combination with other growth factors. In conclusion, the findings of this study indicate that long-term, local delivery of growth factors with PLGA/PEG microspheres has the potential to increase fat-graft survival rates. Further, the type of growth factor delivered may influence the cellular/stromal composition of the grafted tissue.

Adipose Tissue↗

PubMed2000

De novo adipose tissue generation through long-term, local delivery of insulin and insulin-like growth factor-1 by PLGA/PEG microspheres in an in vivo rat model: a novel concept and capability.

This study was undertaken to characterize the duration of long-term growth factor delivery by poly(lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long-term delivery of insulin and insulin-like growth factor-1 (IGF-1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF-1, separately, were produced by a double-emulsion solvent-extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin-containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF-1, insulin + IGF-1, and blank microspheres) (n = 4). Insulin and IGF-1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4-week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF-1, and insulin + IGF-1 microspheres. Such islands were not seen in the blank microsphere group. Hematoxylin and eosin-stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil-Red-O stained sections demonstrated that these cells contained lipid. Computer-aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of "ectopic" adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long-term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long-term local insulin and IGF-1 to induce adipogenic differentiation to mature lipid-containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks.

Abdominal Muscles↗

PubMed2000

Augmentation of adipofascial flaps using the long-term local delivery of insulin and insulin-like growth factor-1.

The adipofascial flaps currently described in the literature frequently lack the volume requirements for reconstructive goals. In this study, the authors examined the use of long-term local delivery of insulin and insulin-like growth factor-1 (IGF-1) using polylactic-coglycolic acid/polyethylene glycol (PLGA/PEG) microspheres to augment inguinal adipofascial flaps based on the inferior epigastric vessels in the rat. Two flap models, the island flap and the limited dissection flap, were used to demonstrate simultaneous treatment and pretreatment modalities, respectively. Experimental groups received 12.5 mg of insulin microspheres (carrying 1 IU of insulin) plus 12.5 mg of IGF-1 microspheres (carrying 2.5 microg of IGF-1). A group undergoing the operation only (no treatment with microspheres) and a group treated with blank microspheres (no growth factor) served as external controls for the surgical procedure and the drug delivery device, respectively. In all groups (n = 5 animals in each), the contralateral flap served as an internal control. Upon harvest on postoperative day 28, the insulin and IGF-1-treated flaps in both models weighed statistically more than the internal control flaps and the two external control flaps. Likewise, on gross inspection, the adipogenic growth factor-treated flaps had greater volumes than the internal control flap groups and both of the external control flap groups (operation only and blank microspheres). Other intergroup comparisons suggested the absence of a systemic insulin and IGF-1 effect on adiposity. A histomorphometric analysis suggested (1) that insulin and IGF-1 treatment does not alter flap cell composition and (2) that flap augmentation is secondary to the stimulation of cell proliferation and adipocytic differentiation rather than the hypertrophy of mature adipocytes. Further evidence in favor of cell proliferation and differentiation was the discovery of nonanatomic, ectopic fat islands on the pedicle sheath of the treated flaps and the lack of variation in cell size distribution among groups. The authors concluded that the long-term local delivery of insulin and IGF-1 with PLGA/PEG microspheres is an effective method of adipofascial flap augmentation; this method increases the number of mature adipocytes rather than increasing the size of preexisting cells.

Adipose Tissue↗

PubMed2000

On-line vectorcardiography during elective coronary angioplasty indicates procedure-related myocardial infarction.

BACKGROUND: Increased creatine kinase concentrations after elective percutaneous transluminal coronary angioplasty (PTCA) have been shown to be associated with increased late cardiac mortality. OBJECTIVE: To evaluate the potential of continuous on-line vectorcardiography during elective PTCA to identify procedure-related myocardial infarction. METHODS: Patients (n = 192, ages 58 +/- 10 years), treated with elective and initially successful PTCA, were studied using vectorcardiogram (VCG) recordings. VCG monitoring was started 5 min before start of the PTCA and was carried out during the entire procedure, for at least 30 min after the first balloon inflation. ST-segment vector magnitude (ST-VM) and ST-segment change vector magnitude (STC-VM) were monitored. RESULTS: Fifteen (7.8%) procedure-related myocardial infarctions occurred. Indicators of procedure-related myocardial infarction were maximum value of ST-VM (P < 0.001) and STC-VM (P < 0.001), total ischemic time of all ST-VM episodes (P < 0.001) and STC-VM episodes (P < 0.001). The variable most closely related to a procedure-related myocardial infarction was the maximum STC-VM value during the procedure. With an optimized cutoff value, maximum STC-VM predicts a procedure-related myocardial infarction with a sensitivity of 93%, a specificity of 59% and a negative predictive value of 99%. Patients who had a stent implanted had significantly greater VCG values (P < 0.05-P < 0.001) than the group without a stent. There was a trend (P < 0.06) to a relation between increased creatine kinase concentration and stent implantation. In patients both with and without an implanted stent, greater STC-VM values were associated with procedure-related myocardial infarction (P < 0.01). CONCLUSION: Continuous VCG monitoring during elective PTCA is a promising method for immediate detection of patients at increased risk of procedure-related myocardial infarction.

Adult↗

PubMed2000

Women react with more myocardial ischemia and angina pectoris during elective percutaneous transluminal coronary angioplasty.

BACKGROUND: Women have been considered to be at higher risk of complications relating to percutaneous transluminal coronary angioplasty (PTCA) than are men. One reason for this sex-related difference could be the ischemic response of myocardium during the procedure. OBJECTIVE: To investigate whether there are sex-related differences in ischemic response of myocardium during elective PTCA. METHODS: Consecutive patients (n = 192, of whom 48 were women), were subjected to vectorcardiography during the PTCA procedure. Vectorcardiographic variables, magnitude of ST-segment vector (ST-VM), and magnitude of ST-segment vector change (STC-VM) were studied. RESULTS: Women were older (63 +/- 10 versus 56 +/- 10 years, P< 0.001) than men in our study and more often had diabetes mellitus and hypertension. Women less often had stents implanted (24 versus 50%, P < 0.01) and they were subjected to fewer balloon inflations (P < 0.001), with a total inflation time shorter than that for men (P< 0.001). Maximum STC-VM was 25% greater for women (P < 0.05). Women reported greater maximum pain (P < 0.05) and nitroglycerine was more frequently used for them during PTCA (P < 0.05). Occurrence of episodes of residual ischemic STC-VM (the difference between total number of episodes and number of balloon inflations) was more common for women (3 +/- 5 versus 1 +/- 3, P< 0.01). Duration of residual ischemic STC-VM episodes (the difference between total duration of episodes and duration of balloon inflations) was longer for women than it was for men (242 +/- 275 versus 148 +/- 233 s, P < 0.05). In a stepwise multivariate analysis and for a matched case-control group, episodes of residual STC-VM and duration of residual STC-VM episodes still indicated that there was an independent sex-related difference (P < 0.01 and P < 0.01, respectively). CONCLUSIONS: Women more commonly develop vectorcardiographic signs of severe myocardial ischemia, more frequently experience episodes of ischemia and report more severe angina pectoris during elective PTCA than do men.

Angina Pectoris↗

PubMed2000

Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3.

Hepatocyte nuclear factor 6 (HNF-6) is the prototype of a new class of cut homeodomain transcription factors. During mouse development, HNF-6 is expressed in the epithelial cells that are precursors of the exocrine and endocrine pancreatic cells. We have investigated the role of HNF-6 in pancreas differentiation by inactivating its gene in the mouse. In hnf6(-/-) embryos, the exocrine pancreas appeared to be normal but endocrine cell differentiation was impaired. The expression of neurogenin 3 (Ngn-3), a transcription factor that is essential for determination of endocrine cell precursors, was almost abolished. Consistent with this, we demonstrated that HNF-6 binds to and stimulates the ngn3 gene promoter. At birth, only a few endocrine cells were found and the islets of Langerhans were missing. Later, the number of endocrine cells increased and islets appeared. However, the architecture of the islets was perturbed, and their beta cells were deficient in glucose transporter 2 expression. Adult hnf6(-/-) mice were diabetic. Taken together, our data demonstrate that HNF-6 controls pancreatic endocrine differentiation at the precursor stage and identify HNF-6 as the first positive regulator of the proendocrine gene ngn3 in the pancreas. They also suggest that HNF-6 is a candidate gene for diabetes mellitus in humans.

Animals↗

PubMed2000

Cardiovascular actions of centrally and peripherally administered trout urotensin-I in the trout.

The cardiovascular effects of centrally and peripherally administered synthetic trout urotensin (U)-I, a member of the corticotropin-releasing hormone family of neuroendocrine peptides, were investigated in unanesthetized rainbow trout Oncorhynchus mykiss. Intracerebroventricular injections of U-I (5.0 and 12.5 pmol) produced a sustained increase in mean dorsal aortic blood pressure (P(DA)) without significant change in heart rate (HR). This elevation in P(DA) was associated with an increase in cardiac output, but systemic vascular resistance did not change. Intra-arterial injection of U-I (12.5-500 pmol) evoked a dose-dependent increase in P(DA), but in contrast to the hemodynamic effects of centrally administered U-I, the hypertensive effect was associated with an increase in systemic vascular resistance and an initial fall in cardiac output. HR did not change or underwent a delayed increase. Pretreatment of trout with prazosin, an alpha-adrenoreceptor antagonist, completely abolished the rise in arterial blood pressure after intra-arterial administration of U-I, which was replaced by a sustained hypotension and tachycardia. Trout U-I produced a dose-dependent (pD(2) = 7.74 +/- 0.08) relaxation of preconstricted rings of isolated trout arterial vascular smooth muscle, suggesting that the primary action of the peptide in the periphery is vasorelaxation that is rapidly reversed by release of catecholamines. Our results suggest that U-I may regulate blood pressure in trout by acting centrally as a neurotransmitter and/or neuromodulator and peripherally as a neurohormone functioning either as a locally acting vasodilator or as a potent secretagogue of catecholamines.

Adrenergic alpha-Antagonists↗

PubMed2000

Cardiovascular actions of python bradykinin and substance P in the anesthetized python, Python regius.

The cardiovascular actions of python bradykinin (BK) and substance P (SP) have been investigated in the anesthetized ball python, Python regius. Bolus intra-arterial injections of python BK (0.03-3 nmol/kg) produced concentration-dependent increases in arterial blood pressure, heart rate (HR), and cardiac output concomitant with small decreases in systemic resistance and stroke volume. Intra-arterial injection of 3 nmol/kg python BK produced a tenfold increase in circulating concentration of norepinephrine, but epinephrine levels did not change. BK-induced tachycardia was attenuated (>90%) by the beta-adrenergic receptor antagonist sotalol, and the hypertensive response was attenuated (>70%) by the alpha-adrenergic receptor antagonist prazosin, indicating that effects of python BK are mediated at least in part by activation of the extensive network of adrenergic neurons present in vascular tissues. Bolus intra-arterial injections of python SP in the range 0. 01-30 pmol/kg produced concentration-dependent decreases in arterial blood pressure and systemic peripheral resistance concomitant with increases in cardiac output and stroke volume but with only minor effects on HR. The data suggest that kinins play a physiologically important role in cardiovascular regulation in the python.

Adrenergic alpha-Antagonists↗

PubMed2000

Prognostic role of on-line vectorcardiography as regards repeat revascularization after successful coronary angioplasty.

This study evaluated the prognostic significance of continuous on-line vectorcardiography (VCG) during elective coronary angioplasty (percutaneous transluminal coronary angioplasty, PTCA). Patients (n = 192, mean age 58 +/- 10), treated with elective and initially successful PTCA, were included. VCG monitoring was started before start of the PTCA procedure and was carried out during the entire procedure. ST vector magnitude (ST-VM) was monitored. A 6-month follow-up was obtained. Main outcome measures were the frequency of cardiac events and revascularization during follow-up. During follow-up, 1 patient died, 6 suffered a nonfatal myocardial infarction and 50 were revascularized. Angiography revealed restenosis in 88% of the patients who had a revascularization. In the total patient group, the VCG predictor of revascularization was the total ischemic time of all ST-VM episodes (p = 0.05). Clinical predictors of revascularization were diabetes mellitus (p < 0.01), a more severe type of lesion (type B; p < 0.01), percent post-PTCA stenosis (p < 0.05), nominal balloon size (p < 0.01), maximum balloon pressure (p < 0.05) and no stent implanted (p < 0.001). In a multivariate analysis all the above significant univariate variables of revascularization were entered. Total ischemic time of ST-VM (p < 0.01) was the best variable giving independent prognostic information. In the nonstent group, total ischemic time of ST-VM (p < 0.01) was the only independent predictor of a further revascularization. In conclusion, VCG monitoring during elective PTCA gives on-line information that identifies patients at an increased risk of a revascularization during 6 months after the initial procedure.

Angioplasty, Balloon, Coronary↗

PubMed2000

Prognostic value of ischemia monitoring with on-line vectorcardiography in patients with unstable coronary artery disease.

AIM: The aim of this study was to determine whether on-line vectorcardiography (VCG) gives independent prognostic information, regarding death, myocardial infarction (MI), and revascularization in patients with unstable coronary artery disease, i.e. unstable angina or non-Q-wave MI. METHODS AND RESULTS: One hundred and fifty patients (mean age 69 +/- 10), participating in a randomized study of low-molecular-weight heparin in unstable coronary artery disease, were studied with on-line VCG recordings for 24 h. During a 5-6-month follow-up, 11 patients died, 14 suffered a nonfatal MI and 31 were revascularized. Univariate predictors of death were diabetes mellitus (p < 0.01), maximum ST vector magnitude (ST-VM; p < 0.001), maximum ST change vector magnitude (STC-VM; p < 0.001), number of ST-VM (p < 0.01) and STC-VM episodes (p < 0.001). In multivariate analysis, the number of STC-VM episodes (p < 0.01) and diabetes mellitus (p < 0.02) each gave independent prognostic information regarding death. When all cardiovascular events were combined, the inability to perform an exercise test (p < 0.05), maximum value of ST-VM (p < 0.01) and STC-VM (p < 0.001), the number of episodes of STC-VM (p < 0.001) and ST-VM (p < 0.001) all gave prognostic information. In multivariate analysis, the inability to perform an exercise test and the number of STC-VM episodes were independent predictors. CONCLUSION: VCG monitoring during the first 24 h of hospitalization for unstable coronary artery disease gives independent prognostic information.

Adult↗

PubMed2000

Cognitive intervention in unemployed individuals with reading and writing disabilities.

Sixty native-born Swedish unemployed participants with reading and writing disabilities (R&WD) participated in a 20-week educational program aimed at improving reading and writing, verbal memory, self-confidence, and flexibility of perspectives. They were tested with a comprehensive battery (interviews, questionnaires, neuropsychological tests, and tests of academic achievement) before and after the intervention. Sixteen controls, matched for sex, age, education, and nonverbal IQ, participated in the pre- and posttest sessions but received only standard unemployment interventions. The educational program participants' performance in tests assessing spelling, decoding of letters, self-confidence, and flexibility improved significantly in comparison with the controls after the intervention. A significantly larger number of the participants had obtained work or started a regular education than expected. A substantial proportion of unemployed participants have R&WD and it appears that an intensive but fairly short educational program can improve their accessibility to the labor market and their motivation for study.

Aged↗

PubMed2000

Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.

Whereas nitric oxide (NO) production is associated with the toxic effect of cytokines on rodent pancreatic beta-cells, cytokine-induced apoptosis in human islets may occur independently of NO. The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase. Our aim was therefore to analyze the effect of cytokines on ICE expression in human, rat, and mouse islets and rat insulinoma cells. ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma. Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors. Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression. ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets. In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.

Adult↗

PubMed2000

Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation.

The nature and identity of the pancreatic beta-cell precursor has remained elusive for many years. One model envisions an early multihormonal precursor that gives rise to both alpha- and beta-cells and the other endocrine cell types. Alternatively, beta-cells have been suggested to arise late, directly from the GLUT2- and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage. In this study, we have identified a subset of the PDX1+ epithelial cells that are marked by expression of Neurogenin3 (Ngn3). Ngn3, a member of the basic helix-loop-helix (bHLH) family of transcription factors, is suggested to act upstream of NeuroD in a bHLH cascade. Detailed analysis of Ngn3/paired box factor 6 (PAX6) and NeuroD/PAX6 co-expression shows that the two bHLH factors are expressed in a largely nonoverlapping set of cells, but such analysis also suggests that the NeuroD+ cells arise from cells expressing Ngn3 transiently. NeuroD+ cells do not express Ki-67, a marker of proliferating cells, which shows that these cells are postmitotic. In contrast, Ki-67 is readily detected in Ngn3+ cells. Thus, Ngn3+ cells fulfill the criteria for an endocrine precursor cell. These expression patterns support the notion that both alpha- and beta-cells develop independently from PDX1+/Ngn3+ epithelial cells, rather than from GLU+/INS+ intermediate stages. The earliest sign of alpha-cell development appears to be Brain4 expression, which apparently precedes Islet-1 (ISL1) expression. Based on our expression analysis, we propose a temporal sequence of gene activation and inactivation for developing alpha- and beta-cells beginning with activation of NeuroD expression. Endocrine cells leave the cell cycle before NeuroD activation, but re-enter the cell cycle at perinatal stages. Dynamic expression of Notch1 in PDX+ epithelial cells suggests that Notch signaling could inhibit a Ngn-NeuroD cascade as seen in the nervous system and thus prevent premature differentiation of endocrine cells.

Animals↗

PubMed2000

Relationships between mastitis and functional longevity in Danish Black and White dairy cattle estimated using survival analysis.

The relationship between mastitis and functional longevity was assessed with survival analysis on data of Danish Black and White dairy cows. Different methods of including the effect of mastitis treatment on the culling decision by a farmer in the model were compared. The model in which mastitis treatment was assumed to have an effect on functional longevity until the end of the lactation had the highest likelihood, and the model in which mastitis treatment had an effect for only a short period had the lowest likelihood. A cow with mastitis had 1.69 times greater risk of being culled than did a healthy herdmate with all other effects being the same. A model without mastitis treatment was used to predict transmitting abilities of bulls for risk of being culled, based on longevity records of their daughters, and was expressed in terms of risk of being culled. The correlation between the risk of being culled and the national evaluations of the bulls for mastitis resistance was approximately -0.4, indicating that resistance against mastitis was genetically correlated with a lower risk of being culled and, thus, a longer functional length of productive life.

Animals↗

PubMed2000

Treatment of spit tobacco users with transdermal nicotine system and mint snuff.

The purpose of this study was to examine the effects of nicotine patch and mint snuff (a nonnicotine product) on craving, withdrawal symptoms, and treatment outcome. This study involved a 2 x 2 factorial design, with Active Nicotine Versus Placebo Patch as one of the factors and Mint Snuff Versus No Mint Snuff as the other factor. Spit tobacco users (N = 402, n = 100-101 in each condition) were randomly assigned to 1 of the 4 treatment conditions for a period of 10 weeks. Treatment outcome was measured up to 62 weeks. The results showed that the nicotine patch was effective in increasing short-term abstinence over the placebo patch and in reducing craving and withdrawal signs and symptoms from spit tobacco. Although mint snuff was not effective in enhancing treatment outcome, it reduced craving and withdrawal symptoms. No interaction effects were observed. At this time, the use of the nicotine patch and mint snuff should be primarily considered for the reduction of craving and withdrawal symptoms.

Administration, Cutaneous↗

PubMed2000

The waiting game.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

PubMed2000

Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial.

Bowman-Birk inhibitor is a protease inhibitor derived from soybeans that has demonstrated chemopreventive activity in a number of in vitro and animal systems. We conducted a 1-month phase IIa clinical trial of Bowman-Birk inhibitor concentrate (BBIC) in patients with oral leukoplakia. BBIC was administered to 32 subjects with oral leukoplakia for 1 month. We assessed toxicity and clinical and histological response of the lesions, and oral mucosal cell protease activity (PA) and serum micronutrient levels were measured. Clinical response was determined by measurement of pre- and posttreatment individual and total lesion areas and analysis of blinded clinical judgments of photographs. On the basis of prespecified response criteria, 31% of patients achieved a clinical response (two with complete and eight with partial responses). BBIC was nontoxic in doses up to 1066 chymotrypsin inhibitory units. The mean pretreatment total lesion area decreased from 615 to 438 mm2 after BBIC treatment (P < 0.004). A linear fit of the dose-response relationship between dose of BBIC and decrease in total lesion area was suggested (P < 0.08), and analysis of blinded clinical impression from lesion photographs confirmed this relationship (P < 0.01). Overall, at all doses tested, a 24.2% decrease in total lesion area was observed following treatment (sign rank = -142; P < 0.004). High pretreatment PA was associated with greater decreases in PA after BBIC administration (P < 0.02). BBIC demonstrated clinical activity after oral administration to patients with oral leukoplakia. These results indicate that BBIC should be investigated for chemopreventive activity in a randomized clinical trial.

Adult↗