Total hip arthroplasty. The role of antiinflammatory medications in the prevention of heterotopic ossification

Postoperative prophylaxis with antiinflammatory medications, primarily indomethacin, is extremely effective in preventing the severest degrees of heterotopic ossification (HO) after a total hip arthroplasty (THA) and the recurrence of excised HO developed after a previous hip surgery. Prophylaxis with indomethacin should be given in 25-mg doses three times daily for at least three weeks, starting on the first postoperative morning. However, a shorter treatment period may be equally effective in preventing the severest degrees of HO, and a postoperative delay of five days before the initiation of prophylaxis does not seem to be followed by the development of severe HO. As evaluated one year after surgery, treatment with antiinflammatory medications in the immediate postoperative weeks did not increase the incidence of implant-bone interface radiolucencies, aseptic loosening, or revisions in cemented or cementless THAs when compared with cases that did not have postoperative treatment. However, although no major complications have been reported regarding the use of antiinflammatory medications in the prevention of HO after THA, orthopedic surgeons prescribing such treatment should be aware of their contraindications as well as early and late side effects. Since several antiinflammatory agents are reported to be effective in preventing HO, future reports dealing with HO after THA should always include information about the postoperative antiinflammatory treatment used.     

Intestinal parasites in a rural community in Kenya: cross-sectional surveys with emphasis on prevalence, incidence, duration of infection, and polyparasitism

A cross-sectional survey of intestinal parasitic infection in a rural community, Nderu, in Kiambu District, Kenya, was carried out in 1985 by examining 1129 individuals from 203 households (about 25% of the total population). This was followed by 3 more cross-sectional surveys, in January, May and October 1986, of 56 families comprising 461 individuals, who had also participated in the first survey. In the first survey, 81.4% of the sample was positive for at least one intestinal parasite and 78% was positive for intestinal protozoa. 72.7% of those infected had multiple infections. The prevalence of most of the protozoa increased with age but that of Giardia lamblia peaked in the 0 to 4 year class at 35.5%. Females were infected more often with several of the protozoa, but males with Ascaris. People living in larger households were more often infected with Entamoeba histolytica and Iodamoeba butschlii, while the opposite was true of H. nana and tended to be for Giardia. Significant positive associations between parasite species were common at all surveys, especially among the amoebae. The majority of negative associations were for Giardia. Unformed stools were significantly associated with Giardia, Blastocystis, and trophozoites of Trichomonas hominis and Chilomastix mesnili. Endolimax nana and Entamoeba coli were found more often in formed stools. Estimates of daily incidence, and duration of infection in days, were calculated for 11 parasites. The longest mean estimated duration of infection for any species was 237 +/- S.D. 151.4 days for H. nana and the shortest was 41.6 +/- S.D. 0.4 days for T. hominis.     

The tubulointerstitial component of chronic glomerulonephritis: its clinico-functional diagnosis

Tubulointerstitial alterations associated with chronic glomerulonephritis (CGN) are definitely dependent on the clinical type of CGN and are accompanied by a decrease of homeostatic functions (the rate of glomerular filtration, osmotic concentration and dilution of urine, hydruresis, the magnitude of CH2O, excretion of ammonium and hydrogen ions, the ratio of ammonium excretion to hydrogen ion excretion). Maximal osmotic concentration and ammonium excretion show an especially considerable decrease. The clinical type permitting one to diagnose rather than to reject the presence of alterations and the status of certain tubular functions, osmotic concentration in particular and, to a less degree, ammonium excretion, permitting to reject the presence of the tubulointerstitial component (TIC) are of known but restricted importance for TIC recognition. The TIC can be diagnosed more adequately in exploring definite pairs of renal functions, particularly osmotic concentration of urine and ammonium excretion and maximal hydruresis and excretion of hydrogen ions. This approach is both helpful in confirming and rejecting the presence of the TIC. Of special value is the combined assessment of the clinical type and maximal osmotic urine concentration data.     

Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

Cloning and characterization of Ca(2+)-dependent and Ca(2+)-independent PKCs expressed in Aplysia sensory cells

We isolated cDNA clones from an Aplysia sensory-cell library encoding two isoforms of protein kinase C (PKC). Several isozyme-specific regions are conserved in the Aplysia kinases, notably the variable regions V5 in the Ca(2+)-dependent PKC (Apl I) and V1 in the Ca(2+)-independent PKC (Apl II). Neuronal proteins with the properties expected of these two isoforms can be identified with antibodies raised against peptides synthesized from the amino acid sequences deduced from the clones. Sacktor and Schwartz (1990) measured the proportion of kinase activity that can be translocated to membrane in Aplysia sensory neurons and ganglia by stimuli that produce the presynaptic facilitation underlying behavioral sensitization. Much less Apl I and Apl II are translocated, suggesting that still other isoforms of PKC exist in these cells.     

Stable xenon does not increase intracranial pressure in primates with freeze-injury-induced intracranial hypertension

Stable xenon (Xe)-enhanced computed tomography is a potentially valuable tool for high resolution, three-dimensional measurement of CBF in patients. However, reports that Xe causes cerebrovascular dilation and increases intracranial pressure (ICP) have tempered enthusiasm for its use. The effects of 5 min of 33% Xe inhalation on ICP (right and left hemispheres) were studied in eight fentanyl-anesthetized Rhesus monkeys after right-sided cortical freeze injury. ICP, CBF, and physiological variables were monitored for up to 6 h postinsult. The preinjury (control) right hemispheric ICP was 8 +/- 5 mm Hg (mean +/- SD) and left hemispheric ICP was 5 +/- 2 mm Hg. Postinjury observations were classified into low (less than 15 mm Hg) and high ICP (greater than or equal to 15 mm Hg) groups. Both right and left ICP values averaged 9 +/- 3 mm Hg in the low ICP group. In the high ICP group, the right ICP was 20 +/- 4 mm Hg and left ICP was 21 +/- 6 mm Hg. ICP was unchanged by Xe inhalation under control conditions as well as in both low and high ICP groups postinjury. Postinjury, the MABP decreased 10-15 mm Hg in the low ICP group and 10-17 mm Hg in the high ICP group 2-3 min after the start of Xe inhalation (p less than 0.05). These results show that 33% Xe inhalation does not increase ICP in fentanyl-anesthetized monkeys but could decrease MABP in stressed states, presumably because of the anesthetic effects of Xe.     

Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil

This study compared the ability of three N-methyl-D-aspartate (NMDA) receptor antagonists to prevent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neocortex. Antagonists were administered to gerbils either before or after a 5-min bilateral carotid occlusion. The intraischemic rectal temperature was either maintained at 36-37 degrees C or allowed to fall passively to 28-32 degrees C. Antagonists and doses tested were 1 and 10 mg/kg of MK-801 (pre- or postischemia), 30 mg/kg of CGS 19755 preischemia, four 25 mg/kg doses of CGS 19755 administered between 0.5 and 6.5 h postischemia, and 40 mg/kg of MDL 27,266 (pre- or postischemia). All three NMDA receptor antagonists exhibited some degree of neuroprotective activity when the carotid occlusion was performed under normothermic conditions. Most of the treatments with antagonist markedly reduced striatal damage. CA1 hippocampal and neocortical pyramidal cells were spared by only three of the treatments, however, and the extent of neuroprotection varied widely from case to case. Toxic doses of antagonist were required to protect CA1 pyramidal cells from ischemic damage. Ischemic damage to hippocampal areas CA2-CA3a and CA4 appeared to be resistant to all of these treatments. Most CA1 pyramidal cells that were protected from degeneration by an NMDA receptor antagonist were histologically abnormal. The neuroprotective effects of MK-801 and intraischemic hypothermia appeared to be additive. MK-801 (10 mg/kg) consistently reduced the postischemic brain temperature, but only the magnitude of hypothermia produced soon after reperfusion correlated with its neuroprotective action. These results suggest that NMDA receptor antagonists are relatively poor neuroprotective agents against a moderately severe ischemic insult.     

Oscillations of cortical oxidative metabolism and microcirculation in the ischaemic brain.

A new in vivo model for studying brain metabolic and haemodynamic oscillatory phenomena during ischaemia is described. In this model acute or chronic occlusion of one or two carotid arteries in the rat is performed. Due to the partial ischaemia developed, oscillations in the level of intramitochondrial pyridine nucleotides (NADH) as well as flavoproteins (Fp) were recorded from the brain by monitoring the fluorescence of these respiratory chain components. The two fluorescent signals (NADH and Fp) were measured by using the time sharing or DC fluorometer/reflectometer. The changes in the reflected light at the excitation wavelengths (366 and 450 nm) were recorded simultaneously. Bilateral carotid artery occlusion induced immediate oscillations (6-9 waves per min) in the mitochondrial redox state as well as in tissue blood volume in both hemispheres. To verify the accuracy of the NADH monitoring system, including the correction technique for haemodynamic and other artifacts, we used the intracarotid artery saline bolus injection approach. The results could be summarized as follows: (1) unilateral carotid artery occlusion resulted in delayed development of oscillations, particularly in the ipsilateral hemisphere; (2) the oscillation phenomenon was reversible if recirculation restarted within 5 min. Occlusion for more than 30 min resulted in irreversible oscillations; (3) the oscillation appearances and intensities were affected by various physiological conditions. Vasoconstriction, induced by hyperoxia, stimulated the oscillations while vasodilation, induced by hypercapnia, depressed them. Anoxia, hypoxia and spreading depression (SD) abolished the oscillations. Glucose injection was not effective.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of maternal ethanol exposure on neurotransmission and second messenger systems: a quantitative autoradiographic study in the rat brain.

The effects of maternal ethanol exposure on neurotransmission and second messenger systems were examined in rats using histochemistry and in vitro autoradiography. Thirty % ethanol was administered to pregnant rats from gestational day 7 to the day of delivery. Quantitative autoradiography was used to map muscarinic cholinergic, dopamine D2, adenosine A1, and inositol 1,4,5-trisphosphate binding sites, as well as to localize adenylate cyclase and protein kinase C. We found no difference in the patterns of staining with acetylcholinesterase and Timm's stain between control and prenatally ethanol-exposed rats on postnatal day (PN) 30. In the ethanol-exposed rats, [3H]forskolin binding sites were increased during early development in the CA1 subfield of the hippocampus and the occipital cortex; [3H]phorbol ester binding sites were increased in the cortex, striatum, and hippocampus; hippocampal muscarinic cholinergic sites were increased on PN4 and 30; adenosine A1 binding was reduced on PN10 in most regions examined, but was increased in the CA1 subfield on PN30; dopamine D2 receptor levels were significantly reduced on PN30 in the striatum; and IP3 receptors were decreased in most regions studied, but particularly in the cerebellum. Thus, some of these changes were transient and others were long-lasting. Although histopathological abnormalities were minimal, the alterations of binding sites in the cerebellum (the coordination center) and in the hippocampus (related to memory and learning) that were detected may contribute to the behavioral and mental deterioration seen in the fetal alcohol syndrome.