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PubMed1986

High beta 1-selectivity and favourable pharmacokinetics as the outstanding properties of bisoprolol.

Bisoprolol, (+/-)1-(4-[(2-isopropoxyethoxy)-methyl]-phenoxy)-3-isopropyl-amino -2- propanol-hemifumarate, is a new, highly selective beta 1-adrenoceptor blocking agent without intrinsic sympathomimetic activity and low to moderate local anaesthetic activity. As demonstrated in binding experiments, and in classical pharmacological studies using rats, guinea pigs, cats, and dogs, bisoprolol markedly differentiated between beta 1-adrenoceptors of the heart, or the renal juxtaglomerular apparatus, and the beta 2-subtype in arterial blood vessels, bronchi, liver, or skeletal muscle. Up to concentrations nearly 100-fold higher than the therapeutic plasma levels in humans, bisoprolol did not affect the functional refractory period of the heart, and was devoid of a direct suppressive effect on myocardial contractility and of calcium antagonistic properties in heart and vascular muscle. The pattern of haemodynamic effects of bisoprolol was typical of beta-blockers and included decreases in blood pressure (BP), heart rate (HR), and cardiac output, concomitant with an increase in calculated total peripheral resistance. In contrast to other beta-blockers, bisoprolol increased renal blood flow in anaesthetized dogs. Bisoprolol lowered BP in hypertensive dogs and rats, attenuated the development of spontaneous hypertension in rats, decreased plasma renin activity and protected the heart from the sequelae of transient ischemia. It did not block presynaptic beta-adrenoceptors in blood vessels. Serum lipids and the serum lipoprotein profile remained unaltered after bisoprolol. Bisoprolol was devoid of affinity for autonomic receptors other than beta-adrenoceptors or for autacoid receptors. This is probably one of the reasons why bisoprolol did not affect the function of the central nervous, respiratory, and gastrointestinal systems in an obvious way. The high beta 1-selectivity of bisoprolol is linked with extremely favourable pharmacokinetic properties. These include nearly complete enteral absorption and virtual absence of liver first-pass metabolism, both resulting in high bioavailability, long plasma half-life, pharmacokinetics that are linear over a wide dose range and independent of age, food intake and hydroxylator status, low plasma protein binding, and a 1:1 ratio of hepatic metabolization to renal elimination of the unaltered substance. This sum of favourable pharmacological and pharmacokinetic properties characterize bisoprolol as an optimized beta-blocker.

Adrenergic beta-Antagonists↗
PubMed2001

Detection of head and neck cancer with 99Tc(m) glutathione: a correlative study with tissue glutathione and glutathione S-transferase levels.

In this study glutathione (GSH), a natural tripeptide which plays an important role in detoxification reactions, protecting cells against damage from xenobiotics, has been labelled with 99Tc(m) for the demonstration of head and neck cancer. Twenty-eight patients (10 females and 18 males) with various malignancies of the head and neck were given 740 MBq of 99Tc(m)-GSH intravenously and single-photon emission computed tomography (SPECT) images were obtained at 3 h. Semiquantification was performed by drawing regions of interest on three consecutive transaxial slices and tumour to background ratios were calculated. In addition, GSH and glutathione S-transferase (GST) levels were measured in the tumour samples and in normal tissue which were obtained during surgery. Scintigraphic images showed that there was increased uptake in the tumour compared to the normal contralateral side (tumour/normal tissue (mean +/- SD) = 1.94 +/- 0.76). The tissue analyses revealed increased levels of GST in tumour tissues, but both GST and GSH levels in tumour were not statistically different from those in the normal tissue. We conclude that scintigraphic visualization of head and neck tumours can be attributed to increased demand for GSH in cancer. Protein binding might account for the prolonged retention of 99Tc(m)-GSH in the malignant tissue. Like other peptides, it is accumulated and excreted by the kidneys, which allows clear visualization of the abdomen without interference from gastrointestinal system activity.

Adult↗
PubMed1990

Endogenous endophthalmitis due to Salmonella arizonae and Hafnia alvei.

Enteric pathogens rarely involve organs other than those of the gastrointestinal system. We have reported the case of a woman with rheumatoid arthritis who had endogenous endophthalmitis due to Salmonella arizonae and Hafnia alvei. The infection probably resulted from the use of snake powder as a food seasoner. After appropriate intravenous, intraocular, subconjunctival, topical, and oral antibiotic therapy based on laboratory susceptibility studies, the patient's condition clinically improved, but complications resulted in therapeutic enucleation. Because of the ubiquitous nature of these and other potentially pathogenic organisms, great care must be taken in evaluation, management, and education of immunocompromised patients.

Anti-Bacterial Agents↗
PubMed1996

Denuded bowel after recovery from graft-versus-host disease.

Graft-versus-host disease (GVHD) is a common complication of bone marrow transplantation and often involves the gastrointestinal system. It is unclear whether there can be severe enough damage by GVHD to permanently injure the bowel and thereby prevent mucosal regeneration. We describe a patient who had successful treatment of GVHD, but who had such severe scarring of the bowel mucosa that the colonic epithelium could not regenerate even 50 days after biopsy-demonstrated resolution of GVHD. Surveillance cultures and histological analysis indicate that this denudation was not caused by infection or continued GVHD. This is an important observation with implications for monitoring response to GVHD therapy and using rectal biopsy to evaluate GVHD.

Adult↗
PubMed2002

Response-oriented preemptive therapy against cytomegalovirus disease with low-dose ganciclovir: a prospective evaluation.

BACKGROUND: Preemptive therapy against cytomegalovirus (CMV) disease has succeeded in reducing the incidence of CMV disease, but the toxicity of ganciclovir remains problematic. METHODS: We prospectively evaluated the efficacy and toxicity of a preemptive protocol with ganciclovir at a reduced initial dose in 40 patients who achieved engraftment after allogeneic hematopoietic stem cell transplantation. RESULTS: Twenty-three (58%) patients had high-risk features, including transplant from an HLA-mismatched or unrelated donor, or associated acute graft-versus-host disease. CMV antigenemia assay was performed weekly, and ganciclovir was started in a risk-adapted manner, in which the initial dose of ganciclovir was fixed at 5 mg/kg/d and then adjusted based on the results of a weekly CMV antigenemia assay. In this protocol, 23 (58%) patients demonstrated positive antigenemia, and 19 (48%) received a preemptive administration of ganciclovir. Only one patient had CMV disease in the gastrointestinal system, which was successfully treated with a regular therapeutic dose of ganciclovir. Consequently, the total dose of ganciclovir was significantly less than that in a previous protocol using the conventional double dose (5 mg/kg twice daily) of ganciclovir (134 mg/kg vs. 190 mg/kg on average, P=0.046). There were no significant toxicities attributed to ganciclovir, except for neutropenia <0.5 x 109/L, which developed in three patients for 3, 4, and 14 days, respectively, with granulocyte colony-stimulating factor support. CONCLUSION: Preemptive therapy with a low initial dose of ganciclovir appeared to be effective even in high-risk patients. Further randomized controlled trial is warranted.

Adult↗
PubMed2001

A case of multiple congenital anomalies in association with Rett syndrome confirmed by MECP2 mutation screening.

Rett syndrome (RTT) is a severe neurodevelopmental disorder. Apparently normal at birth, girls with RTT undergo developmental regression and acquire a neurological and behavioural phenotype that has been used to define clinical diagnostic criteria for the disorder. Recently mutations in the methyl-CpG binding protein 2 gene (MECP2), located on Xq28 have been identified in females with RTT. We report a girl whose clinical course was complicated by congenital abnormalities of the respiratory tract and gastrointestinal system. In addition neurological abnormalities were evident in the newborn period. By the age of 3 years she had developed a phenotype very suggestive of RTT, but had not demonstrated deceleration of head growth and the development of expressive language was prevented by the presence of the tracheostomy. The clinical impression of RTT was confirmed by the recent finding of a mutation in the MECP2 gene. This case report highlights the importance of considering the clinical diagnosis of RTT even in the presence of other conditions and emphasises that girls with RTT may not be normal from birth.

Abnormalities, Multiple↗
PubMed1990

Nonauditory injury threshold for repeated intense freefield impulse noise.

Exposure to impulse noise is an important occupational health concern. The risk of injury to auditory structures is well recognized and provides the cornerstone for present safety standards. For freefield impulse noise, nonauditory injury is dependent on peak pressure, positive phase duration (or impulse), and number of exposures. Trivial laryngeal petechiae are shown to precede nonauditory injury to more critical organs (ie, pulmonary and gastrointestinal systems). This study identifies the critical impulse noise thresholds causing trivial laryngeal petechial changes resulting from exposure to 5, 25, and 100 repetitions of specific levels of impulse noise. Because of anatomical differences, sheep should be slightly more susceptible to impulse noise laryngeal petechial changes than man; therefore, it seems reasonable to set the absolute limits for human occupational exposure levels below those causing laryngeal petechiae in sheep for persons wearing adequate hearing protection. This study does not address human auditory injury that may occur above or below these exposure limits even with proper hearing protection.

Accidents, Occupational↗
PubMedDate not supplied

Nutritional modulation of neonatal outcomes.

In humans, growth and development continues until early adulthood when bone, muscle, and nervous tissue reaches final stages of maturity. Adequate levels of nutritional intake and utilization are critical to optimize ongoing growth. The goal of nutritional therapy for premature or ill neonates has been to provide sufficient nutrients to allow growth to continue at rates seen in utero. Functional immaturity of the gut in the premature infant makes absorption and utilization of nutritional substrates difficult. Premature infants are at risk for developing necrotizing enterocolitis, a potentially lethal bowel disorder. The etiology of necrotizing enterocolitis is not well understood, and a number of theories of causation have been proposed. Breast milk, the optimal source of nutrition for the neonate, is believed to confer some protection against necrotizing enterocolitis. A number of breast milk components have been credited with antiinflammatory properties. Breast milk is recognized for its benefits, yet for preterm infants breast milk alone does not promote adequate growth. A number of breast milk supplements have been investigated to facilitate growth and development and to prevent necrotizing enterocolitis. This article addresses development of the fetal gastrointestinal system, focusing on the biological mediators for normal function and the role of human breast milk and its additives in optimizing neonatal growth. The possible etiologies of necrotizing enterocolitis are discussed in terms of the relationship between this disease and enteral feeding practices.

Amino Acids↗
PubMed2002

Bioactive components in milk.

Milk is the only biomaterial that evolved under the Darwinian selective pressure to nourish growing mammals. The purpose of this article is to review the scientific research that is using new techniques of integrating biological sequence, structure and function, to understand the innovative biology underlying the products of that evolutionary pressure. As it emerges that milk is actively communicating between the maternal mammary epithelia and the infant's gastrointestinal system, actively directing and educating the immune, metabolic and microflora systems within the infant, enhancing nutrient absorption and delivery, and conferring multiple means of protection, nutritionists are gaining a host of new molecular targets towards which to build scientific strategies for future foods and clinical applications. As new components and functions are being discovered in milk by using traditional methods and modern genomic tools, the complexities of demonstrating, and particularly in humans, the functional mechanisms behind milk's newly observed physiological benefits are becoming the next challenge of this rapidly growing field.

Animals↗
PubMed2003

Role of intestinal flora in the development of allergy.

PURPOSE OF REVIEW: The frequency of allergic diseases is increasing worldwide. Experimental and clinical studies have linked a reduced number of early infections to this trend. The gastrointestinal system, which comprises the largest lymphoid tissue and microbial reservoir of the body, has received more attention during the last few years as a potential determiner in the development of atopic disease. RECENT FINDINGS: Alterations in intestinal microbiota have been detected both in infants suffering from allergic disease and in those later developing the disorder. Delay in the compositional development of and in gut microflora was a general finding in allergic children. In a subsequent study, perinatal administration of lactobacilli halved the later development of atopic eczema during the first 2 years of life. Specific strains of the healthy gut microbiota have been shown to induce the production of IL-10 and transforming growth factor-beta, which possess an important regulative role in the development of allergic type immune response. Probiotics also strengthen gut defence barrier mechanisms and reduce antigen load in the gut. Pattern recognition receptors in intestinal epithelial and antigen-presenting cells have been demonstrated to mediate a continuing dialogue between host and gut microbiota. SUMMARY: Despite several promising findings, the exact role of gut normal microbiota in the development of allergy remains to be elucidated. For successful interventions, more data concerning a communication between host and specific microbial species are needed.

Animals↗
PubMed2007

Primary solitary cervical amyloidosis: case report and review of the literature.

STUDY DESIGN: A case report and literature review are presented. OBJECTIVE: To describe and review the clinical presentations, characteristic findings from imaging studies, types, differential diagnosis, prognosis, and treatment of amyloidoma arising within the vertebrae. SUMMARY OF BACKGROUND DATA: Amyloidoma can occur in the bone, skin, larynx, lymph nodes, urinary bladder, eye, tongue, and gastrointestinal system. However, amyloidomas affecting the vertebral bones are very rare. To our knowledge, only 3 cases of amyloidoma involving cervical spine have been reported previously. METHODS: In this report, we present a case of solitary amyloidosis of the cervical spine. RESULTS: The differential diagnosis of primary solitary spinal amyloidoma includes metastasis, infection, primary bone tumors, plasmocytoma, and Potts abscess. The correct diagnosis can be achieved only after the specific staining of tissue. The prognosis of amyloidosis is related to the specific form of amyloidosis. However, primary solitary amyloidosis has the best prognosis, although a limited number of patients without long-term follow-up studies have been reported. CONCLUSIONS: Primary solitary amyloidosis is a rare form of the amyloidosis, which is different from the other forms of amyloidosis because of excellent prognosis with surgical excision. Combined surgical excision and spinal stabilization is the best treatment.

Aged↗
PubMed2003

Fetal alcohol and drug effects.

BACKGROUND: Alcohol and drug use by pregnant women are harmful to the developing embryo and fetus. Teasing apart the specific contributions of each substance to adverse child outcome, however, proves difficult in practice. The risks to the neonate include intra-uterine growth retardation, birth defects, altered neurobehavior, and withdrawal symptoms. Subsequent behavior, development, and neurologic function may also be impaired. REVIEW SUMMARY: Maternal cigarette smoking carries the greatest risk of impaired fetal growth of any of the substances discussed herein and has been linked to subsequent externalizing behaviors. Alcohol is a well-established teratogen. Heavy exposure to alcohol in a subset of infants is associated with fetal alcohol syndrome (FAS). Mental retardation is one of the main sequelae of alcohol exposure in utero. Fetal marijuana exposure has no consistent effect on outcome. Prenatal cocaine exposure has not been shown to have any detrimental effect on cognition, except as mediated through cocaine effects on head size. Although fetal cocaine exposure has been linked to numerous abnormalities in arousal, attention, and neurologic and neurophysiological function, most such effects appear to be self-limited and restricted to early infancy and childhood. Opiate exposure elicits a well-described withdrawal syndrome affecting central nervous, autonomic, and gastrointestinal systems, which is most severe among methadone-exposed infants. CONCLUSION: Most adverse effects of prenatal drug exposure are self-limited, with catch-up growth and resolution of withdrawal and of prior neurobehavioral abnormalities noted over time. The exception is alcohol, which is linked to life-long impairments (i.e., mental retardation and microcephaly) and possibly cigarette-related behavioral effects. The absence of tangible evidence of detrimental long-term cocaine effects may reflect limitations in the methodology used to identify children at greatest risk for adverse outcome.

Cannabis↗
PubMed1999

The human vector magnetogastrogram and magnetoenterogram.

Electrical activity in the gastrointestinal system produces magnetic fields that may be measured with superconducting quantum interference device magnetometers. Although typical magnetometers have detection coils that measure a single component of the magnetic field, gastric and intestinal magnetic fields are vector quantities. We recorded gastric and intestinal magnetic fields from nine abdominal sections in nine normal human volunteers using a vector magnetometer that measures all three Cartesian components of the magnetic field vector. A vector projection technique was utilized to separate the magnetic field vectors corresponding to gastric and intestinal activity. The gastric magnetic field vector was oriented in a cephalad direction, consistent with previously observed data, and displayed oscillatory characteristics of gastric electrical activity (f = 3.03 +/- 0.18 cycles/min). Although the small bowel magnetic field vector showed no consistent orientation, the characteristic frequency gradient of the small bowel electrical activity was observed. Gastric and intestinal magnetic field vectors were oriented in different directions and were thus distinguished by the vector projection technique. The observed difference in direction of gastric and intestinal magnetic field vectors indicates that vector recordings dramatically increase the ability to separate physiological signal components from nonphysiological components and to distinguish between different physiological components.

Analog-Digital Conversion↗
PubMed1995

Mesalazine (Mesasal/Claversal) 1.5 g b.d. vs. placebo in the maintenance of remission of patients with Crohn's disease.

UNLABELLED: INVESTIGATORS: This multicentre study was conducted by 29 principal investigators in 11 countries. AIMS: To compare the safety and efficacy of oral mesalazine (Mesasal/Claversal, 5-ASA) 1.5 g b.d. in comparison with placebo in the maintenance of remission in 286 patients with Crohn's disease. MATERIALS AND METHODS: Patients had to score less than 150 in their Crohn's Disease Activity Index (CDAI), and had to have had one period of clinical activity (CDAI > 150) within 18 months of the study start. Patients were randomized to receive 5-ASA 1.5 g b.d. daily or matching placebo for 12 months. Study visits were scheduled for months 1, 3, 6, 9 and 12, or when symptoms suggested a relapse of the disease. Relapse was defined as a CDAI score greater than 150, with at least a 60-point increase from the baseline index score. None of the patients used glucocorticoids or immunosuppressants during the trial. RESULTS: In the first group, 207 patients with Crohn's colitis or ileocolitis were randomized: there were 101 females and 106 males, in age range 18-71 years. A total of 106 patients (51 in the 5-ASA group and 55 in the placebo group) were withdrawn from the study due to adverse events, insufficient therapeutic effect, or for other reasons. This left 101 patients (51 in the 5-ASA group and 50 in the placebo group) who completed the 12-month trial. In the second group, 79 patients with Crohn's ileitis were randomized to treatment. There were 53 females and 26 males, age range 18-66 years. A total of 41 patients (19 in the 5-ASA group and 22 in the placebo group) were withdrawn from the study. This left 38 patients (17 in the 5-ASA group and 21 in the placebo group) who completed the 12-month trial. The primary efficacy variable was the CDAI. A protocol-eligible analysis and an intent-to-treat analysis were performed. No statistical differences were noted between the two analyses. In patients with Crohn's colitis or ileocolitis, or in those with ileitis, no statistically significant differences were noted with respect to the relapse rates between the 5-ASA and the placebo treatment groups. Adverse events in the gastrointestinal system were the most frequently reported in both treatment groups. Many of the events such as diarrhoea or abdominal pain are symptoms of Crohn's disease. The majority of the events reported were mild or moderate in severity. In neither study was the prevalence of adverse events or the proportion of drop-outs different between patients in the treatment or in the placebo groups. The site of the Crohn's disease had no effect on the frequency of adverse events. CONCLUSION: The relapse rates of Crohn's disease were similar for up to 12 months in both the 5-ASA 1.5 g b.d. and the placebo treatment groups.

Adult↗
PubMed1982

Maternal fetal and placental gastrin concentrations.

The radioimmunoassay technique was used to measure maternal, placental and fetal serum gastrin levels. A progressive increase in gastrin levels occurred with the advance of pregnancy reaching mean peak levels of 62 (SEM 12) pg/ml during labour. Umbilical artery (74 pg/ml: SEM 7) or vein (73 pg/ml: SEM 7) gastrin concentration was higher than maternal gastrin levels. Placental gastrin concentration was 840 pg/g (SEM 96) and amniotic fluid contained 22 pg/ml (SEM 2). This study implies that one of the reasons for increased maternal gastric residue seen during pregnancy is due to an increased serum gastrin concentration. Also the advanced stage of development of gastrointestinal system of the newborn is in accord with high fetal gastrin concentration.

Adult↗
PubMed1995

Effect of tenidap sodium on digoxin pharmacokinetics in healthy young men.

1. The effects of tenidap sodium and placebo on digoxin pharmacokinetics were compared in 14 healthy young men, in a double-blind, parallel-group study lasting for 24 days. 2. Subjects were administered digoxin alone for the first 10 days and digoxin plus tenidap 120 mg day-1 or placebo for the remaining 14 days. 3. Changes in the means between day 10 (digoxin monotherapy) and day 24 (combined therapy) for renal clearance, area under the plasma concentration-time curve during the dosing interval, and the minimum and maximum plasma digoxin concentrations did not differ significantly between the tenidap and placebo groups. There was a small but statistically significant increase (0.5 h) in the time taken to reach maximum plasma digoxin concentration following 14 days' continuous tenidap co-administration compared with placebo, but this was not considered to be clinically meaningful. 4. Co-administration of tenidap and digoxin was well tolerated. No subject withdrew from the study during combination treatment. Treatment-related adverse events were of mild to moderate severity and were reported by four subjects on digoxin monotherapy, four on tenidap and digoxin, and by two on digoxin and placebo. Those reported by the tenidap group predominantly affected the gastrointestinal system and were mild in severity. There were no reports of laboratory test abnormalities or cardiovascular abnormalities related to combined digoxin and tenidap administration. 5. The results of this study indicate that, in healthy young men, co-administration of tenidap with digoxin does not have any apparent clinically significant effects on the pharmacokinetic profile of digoxin, and the treatment is well tolerated.

Adult↗
PubMed2003

Henoch-Schönlein purpura in pregnancy.

Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis which commonly involves the skin, gastrointestinal system and kidneys. Numerous HSP triggers have been identified, and pregnancy has been reported as an exacerbating factor. After a pregnant woman had been diagnosed as having new-onset HSP, we reviewed all cases of immunofluorescence-proven HSP evaluated by the Department of Dermatology at the Johns Hopkins Hospital between 1990 and 2002, and report three cases of HSP occurring during pregnancy. Two patients developed new-onset HSP, one at 16 weeks gestation and one at 22 weeks, while the third developed a recurrence of HSP at 12 weeks gestation after 19 years of remission. We conclude that pregnancy may be a trigger for HSP onset or recurrence in susceptible individuals.

Adult↗