Comparison of hydroxyapatite granules to autogenous bone graft in fusion cages in a goat model

BACKGROUND: With the increased use of fusion cages to achieve lumbar intervertebral fusion, the question arises as to the potential for bone ingrowth from the host bone through the entire cage. Is it even necessary to have an autogenous graft to achieve total bone incorporation? METHODS: Nine adult male goats had fusion cages implanted into three vertebral bodies. The design was Surgical Dynamics/Ray Fusion Cage, measuring 21 mm x 14 mm. In each animal, one fusion cage was filled with autogenous graft, one with hydroxyapatite, porous granules, and the other with nonporous granules. Amount of new bone formation was determined by backscatter electron microscopy at 3 months post implantation in all animals. RESULTS: The histologic section shows that there was total incorporation in all specimens at 3 months. There was slightly more new bone (43%) with the nonporous granules compared with the porous granules (35%). The amount of residual void space was about the same in all specimens, indicating that the amount of new bone formation was similar and not statistically different in cages filled with hydroxyapatite granules versus granules of autogenous bone. CONCLUSION: This study confirms that total incorporation by ingrowth of new bone can be expected in fusion cages. The amount of ingrowth is about the same for autogenous graft versus hydroxyapatite granules. Apparently, it is not necessary to use bone graft to achieve successful bone incorporation if an acceptable biocompatable lattice, such as hydroxyapatite granules, is used.     

Cost effectiveness of low-molecular weight heparin versus warfarin following hip replacement surgery

Little information is available on the efficacy of low-molecular-weight heparin (enoxaparin) versus warfarin for treatment of deep vein thrombosis and pulmonary embolism following hip replacement surgery. Still less is known of the comparative cost effectiveness of these two therapies. A retrospective study was done on 56 patients who underwent elective hip surgery at an urban medical center between 1991 and 1996. All patients received enoxaparin or warfarin for purposes of thromboprophylaxis. An analysis of medication cost, therapy, laboratory monitoring, and bleeding events of the two antithrombolytic agents was undertaken. Total savings with enoxaparin averaged $1253 per patient, or $137,886 over the study period. The incidence of deep vein thrombosis or pulmonary embolism was 0% with enoxaparin and 3% with warfarin. These data indicate that enoxaparin is a more cost-effective and efficacious regimen for thromboprophylaxis following hip replacement surgery than warfarin.     

Identification, cloning, and mutational analysis of the casein kinase 1 cDNA of the malaria parasite, Plasmodium falciparum. Stage-specific expression of the gene

The cDNA for casein kinase 1 (CK1) of Plasmodium falciparum was cloned, sequenced, and expressed in bacteria. The single major open reading frame of the 1.2-kilobase pair cDNA coded for a 324-amino acid polypeptide of approximately 37 kDa, the predicted sequence of which showed strong identity with known CK1 isoforms. The purified recombinant enzyme exhibited properties characteristic of CK1, such as inhibition by CK1-7, the ability to phosphorylate a highly specific peptide substrate, and a strong preference for ATP over GTP. A casein kinase activity, partially purified from soluble extracts of P. falciparum by affinity chromatography through CK1-7 columns displayed identical properties. The activity showed a stage-specific expression in the parasite, in the order trophozoite > ring > schizont. Northern analysis indicated the existence of two major CK1 mRNAs, 2.4 and 3.2 kilobase pairs long, the levels of which were in the order ring > schizont > trophozoite. Mutagenesis of recombinant CK1 defined important amino acid residues and their potential role in the conformation of the enzyme. The malarial CK1 appeared to be the one of the smallest and perhaps the most primitive CK1 enzymes known, containing little sequence information beyond the minimal catalytic domain.     

Mortality determinants in massive pediatric burns. An analysis of 103 children with > or = 80% TBSA burns (> or = 70% full-thickness)

OBJECTIVE: Survivors and nonsurvivors among 103 consecutive pediatric patients with massive burns were compared in an effort to define the predictors of mortality in massively burned children. SUMMARY BACKGROUND DATA: Predictors of mortality in burns that are used commonly are age, burn size, and inhalation injury. In the past, burns over 80% of the body surface area that are mostly full-thickness often were considered fatal, especially in children and in the elderly. In the past 15 years, advances in burn treatment have increased rates of survival in those patients treated at specialized burn centers. The purpose of this study was to document the extent of improvement and to define the current predictors of mortality to further focus burn care. METHODS: Beginning in 1982, 103 children ages 6 months to 17 years with burns covering at least 80% of the body surface (70% full-thickness), were treated in the authors' institution by early excision and grafting and have been observed to determine outcome. The authors divided collected independent variables from the time of injury into temporally related groups and analyzed the data sequentially and cumulatively through univariate statistics and through pooled, cross-sectional multivariate logistic regression to determine which variables predict the probability of mortality. RESULTS: The mortality rate for this series of massively burned children was 33%. Lower age, larger burn size, presence of inhalation injury, delayed intravenous access, lower admission hematocrit, lower base deficit on admission, higher serum osmolarity at arrival to the authors' hospital, sepsis, inotropic support requirement, platelet count < 20,000, and ventilator dependency during the hospital course significantly predict increased mortality. CONCLUSIONS: The authors conclude that mortality has decreased in massively burned children to the extent that nearly all patients should be considered as candidates for survival, regardless of age, burn size, presence of inhalation injury, delay in resuscitation, or laboratory values on initial presentation. During the course of hospitalization, the development of sepsis and multiorgan failure is a harbinger of poor outcome, but the authors have encountered futile cases only rarely. The authors found that those patients who are most apt to die are the very young, those with limited donor sites, those who have inhalation injury, those with delays in resuscitation, and those with burn-associated sepsis or multiorgan failure.     

"Candidatus phytoplasma australiense," a new phytoplasma taxon associated with Australian grapevine yellows

A phytoplasma was detected in naturally diseased 'Chardonnay' grapevines exhibiting symptoms of Australian grapevine yellows disease. The use of PCR designed to amplify phytoplasma DNA resulted in detection of phytoplasma DNA in all of the diseased plants examined; no phytoplasma DNA was detected in healthy seedling grapevines. The collective restriction fragment length polymorphism (RFLP) patterns of amplified 16S ribosomal DNA differed from the patterns described previously for other phytoplamas. On the basis of the RFLP patterns, Australian grapevine yellows phytoplasma was classified as a representative of a new subgroup, designated subgroup 16SrI-J, in phytoplasma 16S rRNA group 16SrI (aster yellows and related phytoplasmas). A phylogenetic analysis in which parsimony of 16S rRNA gene sequences from this and other group 16SrI phytoplasmas was used identified the Australian grapevine yellows phytoplasma as a member of a distinct subclade (subclade xii) in the phytoplasma clade of the class Mollicutes. A phylogenetic tree constructed on the basis of 16S rRNA gene sequences was consistent with the hypothesis that there was divergent evolution of Australian grapevine yellows phytoplasma and its closet known relative, European stolbur phytoplasma (subgroup 16SrI-G), from a common ancestor. The unique properties of the DNA from the Australian grapevine yellows phytoplasma clearly establish that it represents a new taxon, "Candidatus Phytoplasma australiense."     

Donor treatment with the lazeroid U74389G reduces ischemia-reperfusion injury in a rat lung transplant model

BACKGROUND: Antioxidant treatment with lazeroids has proven beneficial for the amelioration of reperfusion injury in experimental lung transplantation. This study compares the effect of donor versus recipient treatment on immediate postoperative graft function. METHODS: A model of acute double-lung transplantation in rats was used to assess graft function. Transplanted controls after 2 (group I) and 16 hours of ischemia (group II) were compared to a recipient (group III; 16-hour ischemia) and a donor treatment group (group IV; 16-hour ischemia) using the lazeroid U74389G (6 mg/kg). Serial assessment of alveolar-arterial oxygen difference, dynamic lung compliance, airway and pulmonary vascular resistance was obtained during a 2-hour reperfusion period. Final analysis included survival, weight gain, and histologic examination. RESULTS: Graft function was significantly better after 2 hours of ischemia than in any of the three 16-hour ischemia groups (II, III, IV). After 16 hours of ischemia, donor treatment provided superior graft function with respect to dynamic lung compliance, airway resistance, and alveolar-arterial oxygen difference when compared with groups II and III. The pulmonary vascular resistance was significantly higher in group III when compared with groups II and IV. Graft weight increase reflecting edema was highest in groups III (104%) and II (98%). CONCLUSIONS: After prolonged ischemia only donor treatment with the lazeroid U74389G was able to significantly reduce ischemia-reperfusion-related graft dysfunction.     

Test of synergistic interactions among deleterious mutations in bacteria

Identifying the forces responsible for the origin and maintenance of sexuality remains one of the greatest unsolved problems in biology. The mutational deterministic hypothesis postulates that sex is an adaptation that allows deleterious mutations to be purged from the genome; it requires synergistic interactions, which means that two mutations would be more harmful together than expected from their separate effects. We generated 225 genotypes of Escherichia coli carrying one, two or three successive mutations and measured their fitness relative to an unmutated competitor. The relationship between mutation number and average fitness is nearly log-linear. We also constructed 27 recombinant genotypes having pairs of mutations whose separate and combined effects on fitness were determined. Several pairs exhibit significant interactions for fitness, but they are antagonistic as often as they are synergistic. These results do not support the mutational deterministic hypothesis for the evolution of sex.     

Epo-induced hemoglobinization of SKT6 cells is mediated by minimal cytoplasmic domains of the Epo or prolactin receptors without modulation of GATA-1 or EKLF

The characteristics of GABAergic inhibitory modulation of respiratory bulbospinal neuronal activity and short-term potentiation (STP) of phrenic motoneuronal activity were studied. Extracellular unit recording and picoejection techniques in anesthetized dogs showed that both the spontaneous rhythmic and reflexly induced discharge patterns of inspiratory (I) and expiratory (E) premotor neurons were proportionately amplified by the localized application of picomole amounts of bicuculline (Bic), a competitive GABAA antagonist. Intracellular recording and paired-pulse stimulation techniques in anesthetized rats demonstrated an STP of phrenic motor output that appears to be mediated by NMDA receptors and is associated with facilitation of EPSPs and prolonged depolarization of individual phrenic motoneurons. We speculate that both GABAergic gain modulation of premotor neuronal activity and NMDA-mediated STP of phrenic activity may be neural substrates which are involved with the optimization of respiratory and non-respiratory behaviors, via adaptive and/or differential control of breathing.     

Stem cells: characterization and measurement

The process of blood formation is sustained throughout an individual's life by a small population of haemopoietic stem cells (HSCs). The HSC compartment represents a hierarchy of HSC subsets with decreasing proliferative ability. This heterogeneity is reflected in the varying time periods that HSCs may contribute to the initiation and maintenance of donor-type haemopoietic multilineage chimerism in vivo. The phenotype of HSC is incompletely defined rendering morphological or flow cytometric quantitation unreliable. Functional HSC assays, both in vitro (CAFC, LTC-IC) and in vivo (repopulation of NOD/SCID mice) may be superior to phenotypic analysis; however, such assays have not been truly validated in a human transplant setting. The quiescence and proliferation of HSCs is highly regulated by the stroma in haemopoietic organs. Many of the cytokines that have been cloned in recent years are actually elaborated and presented by the haemopoietic organ stroma and are supposed to serve as local regulators in order to gain specificity and avoid pleitropic and thus undesired side effects. Most probably, additional stroma-derived factors will be characterized as suggested by the observation that HSCs produce more progeny in stroma-contact than in its absence or in stroma-conditioned medium, irrespectively of the exogenous cytokines included. Stem cells are considered to possess the ability to self-renew and are therefore attractive vehicles for gene therapy. The same assumed characteristic fuels attempts to amplify their numbers ex vivo, and is expected to enable more rapid haemopoietic recovery of conditioned recipients as well as enlarge HSC grafts of insufficient size before actual transplantation.     

Morphometric study of the placental vessels and its correlation with umbilical artery Doppler flow

OBJECTIVE: To determine the changes in the vessel-wall thickness and the radius of the lumen in tertiary-stem villi of the placenta with advancing gestational duration and their relationship to umbilical artery Doppler flow studies. METHODS: Placentas from 63 miscarriages and preterm and term deliveries (between 19 and 40 weeks) were used for morphometric study of the tertiary-stem villi vessels. Each woman had undergone Doppler flow study of the umbilical artery. The resistance index (RI) was determined from the Doppler flow velocity waveform. Placental paraffin sections of 4-micron thickness were stained with hematoxylin and eosin and with periodic acid-Schiff reagents. The tertiary-stem villi and their vessels were examined microscopically and assessed morphometrically using a personal computer with math co-processor and a touch-sensitive screen overlying a video monitor. The monitor received microscopic images from a video camera that was mounted on a microscope. We determined vessel-wall thickness by tracing the outer and inner circumferences of digitized vessel-wall images. RESULTS: Wall thickness, but not lumen size, of the tertiary-stem villi vessels decreased significantly overall at a rate of 0.63micron/week (P < .001). The rate of decrease was 0.64micron/week (P < .001) during the second trimester and 0.50micron/week (P < .001) during the third trimester. There was a significant correlation between the decrease in thickness and in RI (r = 0.83 [P < .001], r = 0.78 [P < .001] in the second and third trimesters, respectively). Resistance indices were all within normal limits. CONCLUSIONS: Placental tertiary-stem villi vessel-wall thickness decreases with advancing gestational age. There is a correlation between the changes in RI of the umbilical artery Doppler flow and the changes in mean wall thickness of the placental vessels.