Maternal deaths from neurological complications of hypertensive crises in pregnancy

Fourteen maternal deaths from eclampsia or severe pre-eclampsia where disturbed cerebral function, as evidenced by prolonged unconsciousness, was given as the main cause of death are reviewed. Prolonged duration of seizures, hypotensive/hypoxic episodes, cerebral oedema and intracranial haematomas were most frequently identified as causative agents in the development of cerebral dysfunction. Failure to maintain an airway and iatrogenically induced hypotension were the two most important contributory factors to the patients' deaths. Management recommendations to prevent this type of maternal death are given.     

A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery

In this study, 417 patients undergoing "clean" elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis--a statistically significant difference (p less than 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.     

Evolution of inflammatory response and cellular immune responses in a murine model of disseminated blastomycosis.

A reproducible model of disseminated blastomycosis was established in C57BL/6 mice by intravenous injection of 10(6) yeast-phase Blastomyces dermatiditis organisms. The infection progressed over 5 weeks to involve lungs, brains, superficial fascia, livers, and spleens of mice. By week 5, there was a greater number of organisms in lungs and brains than in livers and spleens. The tissue response in lungs, brains, and livers progressed from acute neutrophilic invasion before week 1 to pyogranuloma formation by week 5. Lymph nodes and spleens were remarkably spared. By week 5, infected mice became anergic to intradermal challenge with both specific Blastomyces antigen and a nonspecific antigen (sheep erythrocytes). At this time, the response to concanavalin A or phytohemagglutinin by splenocytes was markedly less than that of normal controls. Likewise, the plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice was diminished. In coculture studies, splenocytes from 5-week-infected mice reduced the plaque-forming cell response by normal splenocytes. The development of this murine model should prove useful for elucidating the perturbations of immunoregulation associated with disseminated blastomycosis.     

Myocardial infarction in a large colony of nonhuman primates with coronary artery atherosclerosis.

Relatively few cases of myocardial infarction associated with coronary artery atherosclerosis have been described previously in macaques. In this study the authors report the prevalence and characteristics of coronary artery atherosclerosis and myocardial infarction in 10 rhesus (Macaca mulatta) and two cynomolgus (Macaca fascicularis) macaques that were fed atherogenic diets for 16 months or longer. Our findings show clearly that myocardial infarction occurs in macaques with diet-induced atherosclerosis. The frequency seems to be related to the species, composition of the atherogenic diet, and length of time fed the atherogenic diet. The myocardial lesions are remarkably similar to those described in human beings in terms of location and gross and microscopic characteristics. The characteristics of coronary artery atherosclerosis, including the occurrence of thrombosis, severe stenosis, mineralization, atheronecrosis, and sterol clefts, especially in animals fed the atherogenic diets for longer periods of time, also closely resemble those of the arterial lesions found in human beings. The greatest prevalence of myocardial infarcts was found in rhesus monkeys fed a cholesterol-containing diet with 40% of calories supplied by peanut oil and in cynomolgus macaques from Malaya that were fed the same amount of cholesterol with 40% of calories from lard. Electrocardiographic abnormalities as well as the occurrence of unexpected and relatively sudden death in several of these nonhuman primates are also consistent with signs frequently observed in human beings.     

Effect of fluoride on movement of concanavalin A-acceptor molecules of human neutrophils

The effects of fluoride (F) on neutrophil protuberance formation and induced Con A acceptor molecule migration were assessed microscopically. Below 5 mM, F had little effect on acceptor migration, while it markedly inhibited formation of colchicine-induced protuberances. The anion also increased the rate at which preformed protuberances regressed. Since protuberance formation is enhanced by disassembly of microtubules, these data suggest that F promotes and/or stabilizes microtubule assembly. Microtubule assembly is favored by binding of GTP to tubulin subunits, while GDP binding favors disassembly of microtubules. Since F binds with GDP, forming a new complex that mimics GTP, the anion would be expected to enhance microtubule assembly. Over the same F concentration range, the anion failed to inhibit acceptor polarization, but did inhibit cytochalasin B-enhanced dispersion of prepolarized Con A acceptors, implying that, at low concentrations, F also affected microfilament cycling. Concentrations of F in excess of 5 mM inhibited acceptor migration as well as protuberance formation. At 20 mM, the anion abolished both events, yet at this same concentration F induced neutrophil superoxide generation and degranulation, suggesting that acceptor migration is not a prerequisite for these two neutrophil effector activities.This research was supported by a grant from the Medical Research Foundation of Oregon     

Modulation of cellular immune responses in mice with disseminated histoplasmosis by recombinant interleukin-2.

Depression of the cellular immune responses in mice with disseminated histoplasmosis is associated with deficient production of interleukin-2 (IL-2) by splenocytes. Therefore, we examined whether a highly purified preparation of IL-2, recombinant human IL-2 (rIL-2), could modify the cellular immune responses in infected mice and whether this lymphokine could alter the severity of histoplasmosis in animals. Exogenous rIL-2, at concentrations of up to 1,000 U/ml, failed to augment the proliferative responses to concanavalin A by unfractionated splenocytes or splenic T cells from mice infected for 1 week. In addition, rIL-2 did not modulate the plaque-forming cell response to sheep erythrocytes by splenocytes from these same mice. However, at week 3, rIL-2 in concentrations ranging from 10 to 1,000 U/ml considerably augmented the proliferative response to concanavalin A and plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice. Kinetics studies demonstrated that rIL-2 exerted maximal immunoregulatory activity when added on day 0 or 1 to cultures of splenocytes. In vivo administration of rIL-2, 200 to 20,000 U/day, for 10 days to normal and 3-week-infected mice did not alter the proliferative activity of splenocytes to concanavalin A; 200,000 U of rIL-2 per day actually depressed the proliferative responses of splenocytes from normal and infected mice. In vivo, rIL-2 did not modify delayed-type hypersensitivity responses to sheep erythrocytes or to histoplasmin by normal and infected mice. Moreover, treatment with rIL-2 in vivo did not reduce the number of Histoplasma CFU in spleens of mice. Thus, despite the immunoenhancing effect of rIL-2 in vitro, this lymphokine failed to exert similar effects in vivo.     

Endogenous component chemotactic assay (ECCA)

We have developed a chemotactic assay in which migrated cells are quantitated by measuring levels of an endogenous cellular component. The endogenous component chemotactic assay (ECCA) employs standard double-membrane, blind-well methodologies but is unique in that leukocyte migration is quantitated by measuring lactic dehydrogenase (LDH) activity endogenous to cells that have migrated. This approach avoids the tedium of microscopic counting as well as the problems associated with cell-labeling techniques. Using the ECCA technique we have shown: (1) that N-formylmethionyl-leucyl-phenylalanine (fMLP) is both chemokinetic and chemotactic for human polymorphonuclear neutrophils (PMNs); (2) that both incubation time and starting PMN density affect the proportion of cells that migrate; (3) that approximately 30% of the available PMNs eventually migrate; and (4) that PMN "fall off" from membranes, readily detectable by this assay, is affected by starting PMN density, incubation period, and nature of the attractant. The technique as presented can detect migration when a starting cell density as low as 7 x 10(4) PMNs/well is employed and can be made more sensitive by increasing the period over which LDH is allowed to act. Considerable potential exists to further apply the ECCA concept to the study of the migration of subpopulations of cells in mixtures by assaying for distinguishing endogenous cellular markers.     

Risk factors for delayed graft function and their impact on graft outcomes in live donor kidney transplantation

International Urology and Nephrology - Delayed graft function (DGF) is a manifestation of acute kidney injury uniquely framed within the transplant process and a predictor of poor long-term graft...     

Fluid percussion brain injury exacerbates glutamate-induced focal damage in the rat

The role of glutamate-mediated neuronal damage in neurotrauma remains controversial. The cerebral levels measured in patients by microdialysis are sufficient to kill neurons in culture, but not in the intact brain of the normal rat. A synergistic effect between excitatory amino acid-mediated damage and other posttrauma mechanisms must therefore be proposed, if glutamate is indeed a significant cause of posttraumatic brain damage. The presence of such a synergistic mechanism was therefore investigated by combining in vivo glutamate perfusion and fluid percussion injury (FPI). Twenty-four adult male Sprague Dawley rats were randomly assigned to three groups: (1) vehicle (n = 9): mock cerebrospinal fluid (CSF) perfusion plus FPI; (2) glutamate + FPI (n = 9): 0.1 M glutamate intracortical perfusion plus FPI; and (3) glutamate without FPI (n = 6). After preparation for central FPI, at a moderate level of injury (2 +/- 0.5 atm), glutamate or mock CSF perfusion was performed via a CMA/12 microdialysis probe (3 mm). Animals were then perfusion fixed, under deep anesthesia, after 3-h survival, for volumetric histopathology. The glutamate perfusion + FPI group (2.42 +/- 1.63 mm3) produced a significantly bigger lesion than mock CSF perfusion + FPI (0.063 +/- 0.41 mm3) and glutamate perfusion alone (1.00 +/- 0.47 mm3). Traumatic brain injury thus seems to enhance glutamate-mediated brain damage, and this may be due to qualitative changes induced in ion channels and receptors, such as the N-methyl-D-aspartate channel, after shear injury.