Correlation of serum opsonic activity in cystic fibrosis with colonization and disease state: measurement of opsonins to Pseudomonas aeruginosa by neutrophil superoxide anion generation

Serum from patients with cystic fibrosis and normal controls was used to opsonize mucoid and nonmucoid Pseudomonas aeruginosa particles. Opsonic activity was then determined by measuring the production of superoxide anion (O2-) from normal neutrophils stimulated with the opsonized particles. Without any opsonization, mucoid P. aeruginosa stimulated significantly more O2- than nonmucoid P. aeruginosa. Responses to nonmucoid P. aeruginosa observed with heat-inactivated serum from patients with cystic fibrosis were significantly higher (p = 0.008) than those observed with heat-inactivated control sera. Comparisons made between patients who were colonized with P. aeruginosa and those who were not showed that heat activated serum from colonized patients had significantly higher levels of opsonic activity than heat inactivated serum from patients who were not colonized. These differences were observed with either mucoid or nonmucoid P. aeruginosa. A negative correlation was also observed between opsonic activity and clinical status measured by Schwachman scores of colonized patients. These data indicate that in patients colonized with P. aeruginosa the deterioration of their clinical status correlated with increased opsonic activity reflected in the oxidative burst response of neutrophils.     

Increased concentrations of HbAlab in hereditary fructose intolerance and galactosemia

In patients with diabetes mellitus nonenzymatic glycosylation of hemo-globin is a result of increased blood glucose concentrations. In analogy glycosylated hemo-globin fractions were determined in 23 patients with hereditary fructose intolerance (HFI) and 8 patients with galactosemia (G) by means of hemoglobin chromatography on a column packed with Bio-Rex 70 resin. The concentrations were compared to those of 14 control patients and 43 patients with type 1 diabetes mellitus. Compared to controls, in HFI- and G-patients HbAlab was significantly increased. In contrast diabetic patients presented with a marked and significant increase of the HbAlc fraction. When purified hemoglobin was incubated with different monosaccharides respectively monosaccharide phosphates, an increase of HbAlab resulted mainly after galactose and fructose-1-phosphate. The determination of HbAlab in patients with HFI and G is considered a possible means of metabolic control.     

Primary intestinal enteropeptidase deficiency

A rare case of primary enteropeptidase deficiency is reported. Details are given of the initial clinical presentation, treatment, and response of the patient from birth to the age of 18 months. Biochemical analysis of a small intestinal biopsy and duodenal juice samples confirmed the total absence of enteropeptidase activity. Proteolytic activity was very low in native duodenal juice, but normal levels could be induced by activation in vitro with a small amount of porcine enteropeptidase.     

Cognitive development of unselected girls with complete and partial X monosomy

The cognitive development of nine girls with 45,X and 45,X variant karyotypes, seven 45,X mosaics, and nine 46,XX control subjects (ages 8 to 17 years) followed since birth was evaluated. The nonmosaic group was slightly delayed in walking, had a moderately decreased full-scale and performance IQ, demonstrated a striking deficit in perceptual organization and fine motor execution, but had generally average language skills. Three nonmosaic girls with low intelligence were identified and one subject had above average intelligence. Intelligence was not correlated with the presence of physical stigmata. No obvious developmental differences were found between the three girls with 45,X variant, two with partial Xq deletions and one with a ring X chromosome, and the six girls with 45,X genotype. The 45,X mosaic group did not experience early developmental delays and was not significantly different from control subjects on any IQ score. A large amount of variability between subjects was noted, which could be partially attributed to family characteristics and socioeconomic conditions. Whereas this study corroborates previous findings of specific intellectual deficits in 45,X populations, it emphasizes the need for caution in estimating the cognitive development of any X and partial X monosomic infant.     

The use of noncancer endpoints as a basis for establishing a reference concentration for formaldehyde

Published studies involving formaldehyde were selected for quality and relevance for determining whether noncancer endpoints could be used to derive a reference concentration for formaldehyde. Chamber studies provided the highest quality data for determining the presence of eye, nose, or throat irritation at a known level of formaldehyde. Some individuals begin to sense irritation at about 0.5 ppm, 5-20% report eye irritation at 0.5 to 1 ppm, and greater certainty for sensory irritation appears at 1 ppm or greater. These levels of formaldehyde do not appear to impact asthmatics even though these individuals are thought to be more sensitive to irritants. Mild, reversible changes in pulmonary function (forced expiratory volume at 1 s and midexpiratory flow) can occur in sensitized individuals at levels approaching 2 ppm. Studies in the manufacturing setting, while confounded by multiple exposures, provide useful information for setting boundaries for sensory irritation or changes in pulmonary function. Community surveys do not provide the specificity nor sensitivity needed to establish a reference concentration. Histological studies of the nasal mucosa suffer significant methodological and technological shortcomings in addition to issues commonly associated with the design of residential and workplace studies. Based on the review of chamber, community, and workplace studies of human exposures to formaldehyde, it is not possible to identify a specific no observed adverse effect level or lowest observed adverse effect level for formaldehyde. Ranges of exposures associated with acute sensory irritation can be derived and do include sensitive subpopulations. However, given the quality and variability of the data, human studies alone, especially those involving sensory irritation, are not adequate to serve as a reference concentration for estimating risk, or lack thereof, for a lifetime of exposure to formaldehyde. Alternative approaches, such as modeling cellular changes observed in animal studies, may be more useful for quantitative risk assessment of noncancer endpoints and should be used as an adjunct to interpreting human sensory studies.     

"Dormant basket cell" hypothesis revisited: relative vulnerabilities of dentate gyrus mossy cells and inhibitory interneurons after hippocampal status epilepticus in the rat

The "dormant basket cell" hypothesis suggests that postinjury hippocampal network hyperexcitability results from the loss of vulnerable neurons that normally excite insult-resistant inhibitory basket cells. We have reexamined the experimental basis of this hypothesis in light of reports that excitatory hilar mossy cells are not consistently vulnerable and inhibitory basket cells are not consistently seizure resistant. Prolonged afferent stimulation that reliably evoked granule cell discharges always produced extensive hilar neuron degeneration and immediate granule cell disinhibition. Conversely, kainic acid-induced status epilepticus in chronically implanted animals produced similarly extensive hilar cell loss and immediate granule cell disinhibition, but only when granule cells discharged continuously during status epilepticus. In both preparations, electron microscopy revealed degeneration of presynaptic terminals forming asymmetrical synapses in the mossy cell target zone, including some terminating on gamma-aminobutyric acid-immunoreactive elements, but no evidence of axosomatic or axoaxonic degeneration in the adjacent granule cell layer. Although parvalbumin immunocytochemistry and in situ hybridization revealed decreased staining, this apparently was due to altered parvalbumin expression rather than basket cell death, because substance P receptor-positive interneurons, some of which contained residual parvalbumin immunoreactivity, survived. These results confirm the inherent vulnerability of dendritically projecting hilar mossy cells and interneurons and the relative resistance of dentate inhibitory basket and chandelier cells that target granule cell somata. The variability of hippocampal cell loss after status epilepticus suggests that altered hippocampal structure and function cannot be assumed to cause the spontaneous seizures that develop in these animals and highlights the importance of confirming hippocampal pathology and pathophysiology in vivo in each case.     

Paget's disease

A review of the signs, symptoms, and treatment of Paget's disease is presented. Paget, or osteitis deformans, is a chronic, progressive, bone disease of viral etiology. Recent investigations about the causative agent of this disorder have implicated the measles virus of the paramyxovirus family. Additional studies have demonstrated that abnormal virus-infected osteoclasts generate interleukin (IL)-6, a resorptive cytokine from the bone marrow of patients with Paget's bone disease.     

Medical students' experiences of diseases in internal medicine in university and community hospitals

Because medical students in The Netherlands should achieve common national objectives, it is important to know whether clinical experiences in different hospitals are comparable. The research questions were: (1) Do students achieve learning experiences of the required diseases during the internship in Internal Medicine and to what extent do they achieve these experiences? (2) Are there differences between the diseases experienced at a university hospital and at community hospitals? Completed logbooks of students were analysed; the percentage of students that achieved the required diseases and the mean number of experiences of diseases were calculated. A t-test was done to test for differences. Medical students in the university and in community hospitals get broad experience (76-131%) of the required diseases. In both hospitals there are many students who are not achieving the requirements, but the mean number of experiences of students at the community hospitals is higher than those at the university hospital. To eliminate the differences between students from the university hospital and the community hospitals, the educational programmes within both hospitals should be adjusted.     

Modulation of mismatch negativity by stimulus deviance and modality of attention

We studied the effect of attention on the processing of auditory sensory inputs by means of the mismatch negativity (MMN) potential, which can be derived from event-related EEG. A series of frequent standard and rare deviant auditory stimuli were presented to 20 healthy subjects in two recording sessions about five weeks apart. Deviant stimuli were either low or highly deviant as compared to the standard stimulus. While MMN was recorded, subjects were performing a visual and, subsequently, an auditory discrimination task. Directing attention towards the auditory task was associated with increased MMN amplitude only in response to low deviant stimuli and only in the first recording session. No change of MMN amplitude was found when directing attention towards the visual task or when MMN was recorded in response to highly deviant auditory stimuli. The latter may trigger an involuntary switch of attention, thereby overwriting the effect of task-directed attention. Conversely, the effects of attention on the processing of low deviant stimuli appear to be fragile and diminish with increasing automaticity of task execution.