Systemic and luminal influences on the perinatal development of the gut

At birth, the mammalian gastrointestinal tract (GIT) must be able to support a shift from mainly parenteral nutrition in the fetus (via the placenta) to enteral nutrition in the neonate. In the perinatal period the GIT therefore undergoes enhanced growth as well as morphological and functional differentiation, and this maturational programme is influenced by a complex interplay of local, systemic and luminal factors. This review shows how systemic and luminal factors may influence GIT development in the perinatal period of the pig and sheep, two long-gestation species. Adrenocortical hormones play a pivotal role in the prepartum maturation of the GIT in addition to their better known effects on the development of many other tissues and body systems. More particularly, in the fetal pig and sheep, the prenatal development of gastric acid and gastrin secretion, and of GIT hydrolase activities (chymosin, pepsin, amylase, lactase, aminopeptidases) is influenced by cortisol. Additionally, glucocorticoids exert effects throughout the GIT by influencing morphological, cytological, and functional differentiation. Since the GIT epithelial cells comprise a renewing cell population there are also changes in cell kinetics. In addition to systemic factors, the presence of growth factors, hormones and nutrients from swallowed amniotic fluid (fetus) and colostrum (neonate) may influence GIT development. In utero, fetal fluid ingestion has been shown to modulate tissue growth, macromolecule and immunoglobulin transport, enterocyte differentiation, cell turnover and activity of brush-border hydrolases. These effects may be mediated via regulatory peptides (e.g. insulin-like growth factor I, gastrin-releasing peptides, insulin, epidermal growth factor, gastrin). A physiological role of luminally derived growth factors is supported by a number of unique structural and functional adaptations of the GIT in the fetus and neonate (low luminal proteolysis, intestinal macromolecule transport). Thus, in the pig and sheep, both systemic and luminal factors appear to play critical roles in GIT development in the perinatal period.     

ACTH-producing carcinoma of the pituitary with haematogenic metastases

Two laboratories equipped with CAS 200 (Becton Dickinson Image Cytometry Systems, San Jose, CA) instruments participated in this study of variability of DNA analysis of bladder tumor specimens. Formalin fixed paraffin embedded specimens were disaggregated and centrifuged onto microscope slides from ten bladder tumor specimens and two specimens of normal urothelium. Sources of variability considered were Specimen, Slide, Run, Laboratory, and Error. Slides were systematically scanned and 200 cells measured followed by the operator selecting 100 nuclei with abnormal morphology. DNA index (DI) and hyperdiploid fraction (HDF) were calculated from the DNA frequency distributions. For systematic sampling, 92% of the variability was due to Specimen indicating that differences in HDF values between specimens reflect biological differences. With selective sampling, only 67% of the variability in HDF is due to Specimen differences. Other factors, Laboratory, Error, and Laboratory x Specimen interaction each accounted for approximately 10% of the variability. Similarly variability of DI with selective sampling was also higher, and less specimen dependent than systematic sampling. It is important that sampling schemes and selection criteria be carefully documented in order to control variability. Enriched (or selective) sampling for abnormal cells has the potential to increase sensitivity but specimen classification based on these measurements must depend on determination of the frequency of such cells in the total population.     

Laryngeal survey in glyphosate intoxication: a pathophysiological investigation

Respiratory aspiration is a serious potential complication of glyphosate-surfactant herbicide intoxication. From October 1, 1992 to June 30, 1996, we performed laryngeal evaluations in 53 cases to investigate the possible pathophysiological mechanism of glyphosate intoxication. There were 36 cases with significant laryngeal injury. The blood WBC count were significantly higher and the hospital stays were significantly longer in patients with laryngeal injury, when compared with patients with no laryngeal injury (Student t-test, P < 0.005). Laryngeal injury was strongly correlated with aspiration pneumonitis (mean 2 = 4.449, P < 0.05). We concluded that laryngeal injury may be the major cause of aspiration that leads to some degree of morbidity and mortality, following concentrated glyphosate-surfactant herbicide intoxication. Laryngeal survey may be indicated in cases of glyphosate-surfactant intoxication, to evaluate the severity of mucosal injury, and to apply adequate supportive management as early as possible to prevent from aspiration complications and even mortality.     

Indication for surgery of asymptomatic carotid lesions

The incidence of cerebrovascular diseases with transient or persistent neurologic dysfunction has increased significantly. Although patients with symptomatic carotid artery stenosis clearly benefit from operative therapy, the indication to prophylactic surgery of asymptomatic carotid lesions however is still controversial. Based on data from a recently completed prospective randomized study and on analysis of the literature the indication and results of surgical treatment of asymptomatic stenoses of the carotid arteries are discussed. From 1970 to 1990 a total of 744 uni-or bilateral reconstructions of the internal carotid artery were performed in 631 patients. The perioperative morbidity (permanent neurologic deficiency) and mortality was 1.1% (n = 8) resp. 0.8% (n = 6). During the follow up period up to 18 years another 9 patients suffered from stroke (1.2%). The annual stroke incidence amounted to 0.2%. An important prerequisite for surgery is the so called critical internal carotid artery stenosis, implying reduced cerebral vasomotor reactivity or high embolic risk of an ulcerative plaque. Proper selection of patients (exclusion of multiple concomitant diseases) and an experienced team of vascular surgeons with operative morbidity and mortality below 1-2% validates surgical treatment of asymptomatic carotid artery stenoses.     

Severe methicillin-resistant Staphylococcus aureus infections. Emergence of resistance to fusidic acid or fosfomycin during treatment with continuous infusion of vancomycin

OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin METHODS: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01). CONCLUSIONS: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.     

Helicobacter pylori, achlorhydria and gastric atrophy: what kind of "ménage à trois"?

Cytokines play an important role in the mechanisms resulting in ultraviolet B-induced immunosuppression. They play a crucial role in the induction of local as well as systemic immunomodulatory events. Ultraviolet B irradiation directly induces the release of cytokines in the epidermis, resulting in complex and diverse interactions on epidermal cells, which results in migration out of the skin and infiltration into the skin of different cell types. Partly because of the interaction of locally produced cytokines with antigen-presenting cells, systemic effects, such as antigen-specific tolerance, can be observed. This review describes the different mechanisms whereby ultraviolet B exposure affects immune functions with special emphasis on the role of T-cell subsets and cytokines.     

Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.