Effect of exercise on acid-base status and ventilatory kinetics

OBJECTIVES: To study the clinical spectrum of an acute severe encephalopathy occurring in 2 patients after recovery from falciparum malaria infection and to compare it with the reported clinical features of the postmalaria neurological syndrome. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: Two patients presented with acute onset of fluctuating motor aphasia, severe generalized myoclonus, and postural tremor. Additional signs were cerebellar ataxia, and in 1 patient, generalized epileptic seizures. Magnetic resonance imaging of the brain revealed patchy white matter lesions in 1 patient. Clinically, the patients' conditions continued to worsen until corticosteroids were introduced, the use of which induced a rapid, albeit incomplete, recovery. CONCLUSIONS: We describe a new, severe variant of the still poorly defined postmalaria neurological syndrome. We propose a preliminary classification of this syndrome, according to its clinical characteristics, as follows: a mild or localized form, characterized by isolated cerebellar ataxia or postural tremor; a diffuse, but relatively mild encephalopathic form, characterized by acute confusion or epileptic seizures; and a severe, corticosteroid-responsive encephalopathy that is characterized by motor aphasia, generalized myoclonus, postural tremor, and cerebellar ataxia.     

Engineering the C-terminus of firefly luciferase as an indicator of covalent modification of proteins

Ketoprofen (Ket), a non-steroidal anti-inflammatory drug, has been incorporated into polymeric micromatrices (microspheres) prepared by a spray drying process and made of cellulose acetate trimellitate (CAT)/ethylcellulose (EC) blends. Drug loaded microspheres were obtained by spray-drying organic solutions of the two polymers and the drug. Characterization of the microparticles (morphology, particle size distribution, drug content, yield of production, surface properties, solvent residues) was carried out and in-vitro release behaviour measured. The release rate of the drug diminished as the proportion of EC was raised.     

Occupational injury and illness in the United States. Estimates of costs, morbidity, and mortality

OBJECTIVE: To estimate the annual incidence, the mortality and the direct and indirect costs associated with occupational injuries and illnesses in the United States in 1992. DESIGN: Aggregation and analysis of national and large regional data sets collected by the Bureau of Labor Statistics, the National Council on Compensation Insurance, the National Center for Health Statistics, the Health Care Financing Administration, and other governmental bureaus and private firms. METHODS: To assess incidence of and mortality from occupational injuries and illnesses, we reviewed data from national surveys and applied an attributable risk proportion method. To assess costs, we used the human capital method that decomposes costs into direct categories such as medical and insurance administration expenses as well as indirect categories such as lost earnings, lost home production, and lost fringe benefits. Some cost estimates were drawn from the literature while others were generated within this study. Total costs were calculated by multiplying average costs by the number of injuries and illnesses in each diagnostic category. RESULTS: Approximately 6500 job-related deaths from injury, 13.2 million nonfatal injuries, 60,300 deaths from disease, and 862,200 illnesses are estimated to occur annually in the civilian American workforce. The total direct ($65 billion) plus indirect ($106 billion) costs were estimated to be $171 billion. Injuries cost $145 billion and illnesses $26 billion. These estimates are likely to be low, because they ignore costs associated with pain and suffering as well as those of within-home care provided by family members, and because the numbers of occupational injuries and illnesses are likely to be undercounted. CONCLUSIONS: The costs of occupational injuries and illnesses are high, in sharp contrast to the limited public attention and societal resources devoted to their prevention and amelioration. Occupational injuries and illnesses are an insufficiently appreciated contributor to the total burden of health care costs in the United States.     

The effect of 1,4-benzodiazepine derivatives on 35S-tert-butylbicyclophosphorothionate binding in the brain of inbred mice with differing emotional stress reactions]

The effect of alprazolam, cinazepam, and hydazepam on the binding of 35S-tert-butylbicyclophosphorothionate with the brain membranes of inbred Balb/c and C57B1/6 mice with a different type of emotional-stress reaction was studied. The displacement curve of 35S-TBPS bound with alprazolam and cinazepam was two-phase in character with different degree of inhibition in the nanomolar and micromolar areas. Hydazepam displaced the bound radioligand only in micromolar concentrations. Displacement of the bound radioligand in the brain membranes began with lower concentrations of the used benzodiazepins in Balb/c animals than in C57B1/6 animals. The emotional-stress effect led to shift of the displacement curves of the bound 35S-TBPS in the direction of higher acting concentrations of the benzodiazepins in the brain membranes of mice of both lines.     

Immunohistologic quantification of Pseudomonas aeruginosa in the tracheobronchial tree from patients with cystic fibrosis

Pseudomonas aeruginosa has been recognized as a pathogen of major importance in the patient with cystic fibrosis (CF). However, no information is available regarding the histologic quantification of P. aeruginosa organisms in the CF tracheobronchial tree. We retrieved all formalin-fixed paraffin-embedded lung blocks from 20 consecutive autopsies of cystic fibrosis patients. Serial histologic sections were made and stained by three methods: hematoxylin and eosin, immunoperoxidase with anti-P. aeruginosa rabbit serum as the primary antibody, and immunoperoxidase with normal rabbit serum as the primary antibody. By studying the hematoxylin and eosin section, we classified five areas in the lung as bronchi, large bronchioles, small bronchioles, bronchioloectatic areas, and abscess/airways with destroyed epithelium. The areas stained by an anti-P. aeruginosa immunoperoxidase method were examined under high-power magnification, and the bacteria within random fields were counted. Pseudomonas aeruginosa organisms were identified in 14 of 20 cases, including 13 of 16 cases in which P. aeruginosa was specifically cultured at autopsy. Quantification of organisms within the lumens of all five airway types showed that the bacterial density in cystic fibrosis airways is highest in bronchi.     

The role of nerve growth factor in a model of visceral inflammation

There is growing evidence that nerve growth factor may be an important mediator of the sensory disorders associated with inflammation. This hypothesis was tested in a rat model of cystitis. In this model, an experimental inflammation is created in anaesthetized rats with an irritant chemical. Within 1 h, bladder reflexes, activated by the sensory innervation of this viscus, become exaggerated, mimicking the disorders seen in humans with chronic cystitis. The development of this hyper-reflexia following experimental inflammation was quantified using the technique of repeated cystometrograms. By several measures, bladder reflex excitability increased about three-fold after 5 h. Firstly, the study investigated whether inflammatory changes can be prevented by pharmacological antagonism of nerve growth factor. A synthetic fusion protein was used, consisting of the extracelluar domain of the high-affinity nerve growth factor receptor, trkA, coupled to the Fc portion of an immunoglobulin. Previous work has shown that this molecule can sequester nerve growth factor and reduce its bioavailability both in vitro and in vivo. Treatment of animals with the fusion molecule at 1 mg/kg, immediately before inflammation of the bladder, largely, and very significantly, prevented the expected increases in reflex excitability of this organ. Pretreatment with a related fusion protein, capable of sequestering the neurotrophin brain-derived neurotrophic factor and neurotrophin-4/5, but not nerve growth factor, was without effect. Similarly, a control fusion molecule, without neurotrophin-sequestering capacity, did not reduce the inflammation-induced hyper-reflexia. Systemic treatment with the nerve growth factor-sequestering molecule, but not control molecules, partially and significantly reversed established inflammatory changes, by about 30-60%, depending on outcome measure. The nerve growth factor-sequestering protein had no significant effects on bladder reflex excitability in the uninflamed state. It was also without significant effect on capsaicin-induced contractions of the urinary bladder. Administration of exogenous nerve growth factor into the lumen of the urinary bladders of normal anaesthetized rats produced a rapid and marked bladder hyper-reflexia similar to that seen with experimental inflammation. These findings are consistent with other circumstantial evidence that nerve growth factor may interact with visceral sensory systems. Together, the data strongly suggest that nerve growth factor produced in inflamed tissues is a critical mediator of the sensory disorders associated with inflammation.     

Cholesterol derivative of poly(ethylene glycol) inhibits clathrin-independent, but not clathrin-dependent endocytosis

The effect of poly(ethylene glycol) cholesteryl ethers (PEG(n)-Chols) with two different numbers of units (n = 50 and 200) in the hydrophilic PEG moiety on cellular endocytic activity was studied on HT-1080 cells. The amphipathic molecules were soluble in aqueous solution. When fluorescein derivatives of PEG-Chols (one fluorescein at the distal end of PEG) were incubated with the cells in culture, the cellular fluorescence was localized at the plasma membrane level and in intracellular vesicles. Fluorescence quantification indicated that for the same external concentration, twice more FPEG(50)-Chol than FPEG(200)-Chol was associated with the cells under the same conditions. Regardless of the length of PEG moiety, PEG-Chols' interaction with cells reduced the endocytic internalization of a fluid phase marker, horseradish peroxidase (HRP) depending on the cell-associated amount. In contrast, internalization of 125I-labeled epidermal growth factor (EGF) through receptor-mediated endocytosis did not change upon incubation with PEG(50)-Chol. The effect of PEG(200)-Chol was also small, since EGF internalization showed a reduction of 10-20%, while at the same concentration as much as 80% of HRP uptake was inhibited. PEG(50)-Chol did not influence the internalization of a larger ligand, 125I-transferrin (Tfn). However, in the presence of PEG(200)-Chol, the uptake of 125I-Tfn decreased remarkably, and yet, PEG(200)-Chol has no influence on the binding and internalization of a monoclonal antibody directed toward the ectodomain of the Tfn-receptor. These results suggested that incorporation of PEG-Chols in the outer monolayer of the plasma membrane specifically inhibited clathrin-independent, but not clathrin-dependent endocytosis.     

Differential inhibition by ethanol of norepinephrine- and clonidine-induced emesis in cats

The effect of acute ethanol administration into the cerebral ventricles on the unanesthetized cat upon emesis produced by norepinephrine and clonidine injected similarly as well as upon emesis evoked by copper sulfate given orally was compared and investigated. Ethanol inhibited the norepinephrine- and clonidine-induced emesis. The inhibitory effect of ethanol occurred after a transient and inconsistent emetic action of the drug. Norepinephrine-induced emesis was about 12 times more sensitive than clonidine-induced emesis to the inhibitory effect of ethanol. In addition, norepinephrine-, but not clonidine-induced emesis was abolished after ablation of the area postrema. On the contrary, intracerebroventricular ethanol had virtually no effect on emesis caused by intragastric copper sulfate. The inhibitory effect of ethanol is ascribed to an action on alpha-2 adrenoceptors within the area postrema and on imidazoline-preferring sites and/or muscarinic cholinoceptors outside the area postrema, but not on the emetic region of the brainstem reticular formation. It follows then that ethanol can differentiate alpha-2 adrenoceptors from imidazoline-preferring sites and/or muscarinic cholinoceptors in the brain of the cat.