Changes in coping style following traumatic brain injury and their relationship to productivity status.

The use of maladaptive coping strategies following traumatic brain injury (TBI) is known to be associated with increased depression and a lower productivity status. What is not known is whether coping behaviours change following TBI and if they do change whether these changes account for significant variance in outcome. Seventy-three significant others of TBI survivors were recruited at the time their friend/family member was injured and followed prospectively. They reported on their friend/family member's pre-injury and 6-month coping behaviours using the Coping with Health Injuries and Problems Scale. The use of emotional pre-occupation coping (p = .02) increased significantly and approached significance for distraction coping(p = .08). These changes in coping also accounted for significant variance (22%, p = .02) in productivity status over and above that accounted for by demographics and injury severity. Whether maladaptive coping changes can be prevented with a view to improving outcomes is a question that now needs to be explored.

Exploring violence and abuse in gay male relationships.

The purpose of this study was to examine gay male relationships where domestic violence was present. Qualitative data for this endeavor were collected by conducting in-depth interviews over an 8-month period with 25 men who self-identified both as homosexual and as victims or perpetrators of domestic violence. Implications are made throughout this piece for further research and analysis regarding gay male domestic violence. Findings include the prominent similarities between heterosexual domestic violence and the perceptions of abuse experienced by the respondents in this study with respect to definitions of the situation, actual experiences and reasons for remaining in abusive relationships. Additionally, the need for both family-based and community-based support services are documented.

Clinical course of crack cocaine body stuffers.

STUDY OBJECTIVE: To describe the clinical course of a cohort of patients presenting to the emergency department with acute crack cocaine body-stuffer syndrome. METHODS: We conducted a retrospective cohort study in the ED of a county hospital with 75,000 visits per year. Our study cohort comprised all patients who presented between January 1993 and April 1995 and who met the definition of a crack cocaine body stuffer. We defined a crack cocaine body stuffer as anyone who admitted to or was strongly suspected of ingesting crack cocaine as a means of escaping detection by authorities, not for recreational purposes or as a means of transporting the drug across borders. RESULTS: We identified 98 cases; most such patients were brought to the ED by law enforcement agents. Most were male and younger than 30 years. Self-report by patients indicated that the amount of crack cocaine ingested ranged from 1 to more than 15 rocks. Most commonly the drug was unwrapped (28%) or wrapped in a plastic sandwich bag (29%). Generalized seizures developed in 4% of the patients; in all these patients seizures occurred within 2 hours of ingestion. In no patient did dysrhythmias develop. Many patients had minor signs of cocaine intoxication: 54% were tachycardic, 23% were hypertensive, 22% were agitated, and 19% required sedation. CONCLUSION: Mild cocaine intoxication is common in crack cocaine body stuffers, with seizures occurring within 2 hours of ingestion in a small percentage of patients.

Long-term functional outcome of inpatient pediatric cardiopulmonary resuscitation.

OBJECTIVE: There is limited information published regarding the long-term outcome of pediatric survivors of inpatient cardiopulmonary resuscitation (CPR). The purpose of this study was to document the long-term (i.e., > or = 1 year after the arrest) functional outcome of children surviving inpatient CPR. METHODS: We reviewed the medical records of children (i.e., less than 18 years of age) receiving advanced CPR (i.e., chest compressions, assisted ventilation, and resuscitation medications) as inpatients in a tertiary care children's hospital. Prospective telephone follow-up of the survivors a minimum of one year after the arrest was performed. A change in the survivors' Pediatric Cerebral Performance Category (PCPC) scale was determined. RESULTS: Approximately half of the 92 subjects were diagnosed with sepsis syndrome. None (0/44) of the patients with sepsis syndrome survived at one year. None (0/24) of the patients who experienced a single episode of advanced CPR > or = 30 min in duration survived one year. Although 36% (33/92) of the patients resuscitated were alive 24 h after their arrest, the proportion surviving fell steadily to 10% (9/92) at one year. Although five of the nine survivors were moderately to severely disabled at one year, the majority (8/9) had little or no change in their PCPC score at one year compared to their prearrest level of function. CONCLUSION: Survival of inpatient pediatric CPR is small. Children surviving inpatient advanced CPR may have little or no change from prearrest function. The survival of hospitalized children with sepsis syndrome requiring CPR or receiving greater than > 30 min of advanced CPR is extremely low.

Out-of-hospital treatment of opioid overdoses in an urban setting.

OBJECTIVES: To investigate clinical outcomes in a cohort of opioid overdose patients treated in an out-of-hospital urban setting noted for a high prevalence of i.v. opioid use. METHODS: A retrospective review was performed of presumed opioid overdoses that were managed in 1993 by the emergency medical services (EMS) system in a single-tiered, urban advanced life support (ALS) EMS system. Specifically, all patients administered naloxone by the country paramedics were reviewed. Those patients with at least 3 of 5 objective criteria of an opioid overdose [respiratory rate < 6/min, pinpoint pupils, evidence of i.v. drug use. Glasgow Coma Scale (GCS) score < 12, or cyanosis] were included. A response to naloxone was defined as improvement to a GCS > or = 14 and a respiratory rate > or = 10/min within 5 minutes of naloxone administration. ED dispositions of opioid-overdose patients brought to the county hospital were reviewed. All medical examiner's cases deemed to be opioid-overdose-related deaths by postmortem toxicologic levels also were reviewed. RESULTS: There were 726 patients identified with presumed opioid overdoses. Most patients (609/726, 85.4%) had an initial pulse and blood pressure (BP). Most (94%) of this group responded to naloxone and all were transported. Of the remainder, 101 (14%) had obvious signs of death and 16 (2.2%) were in cardiopulmonary arrest without obvious signs of death. Of the patients in full arrest, 2 had return of spontaneous circulation but neither survived. Of the 609 patients who had initial BPs, 487 (80%) received naloxone i.m. (plus bag-valve-mask ventilation) and 122 (20%) received the drug i.v. Responses to naloxone were similar; 94% i.m. vs 90% i.v. Of 443 patients transported to the country hospital, 12 (2.7%) were admitted. The admitted patients had noncardiogenic pulmonary edema (n = 4), pneumonia (n = 2), other infections (n = 2), persistent respiratory depression (n = 2), and persistent alteration in mental status (n = 2). The patients with pulmonary edema were clinically obvious upon ED arrival. Hypotension was never noted and bradycardia was seen in only 2% of our presumed-opioid-overdose population. CONCLUSIONS: The majority of the opioid-overdose patients who had initial BPs responded readily to naloxone, with few patients requiring admission. Noncardiogenic pulmonary edema was uncommon and when present, hypoxia was evident upon arrival to the ED. Naloxone administered i.m. in conjunction with bag-valve-mask ventilation was effective in this patient population. The opioid-overdose patients in cardiopulmonary arrest did not survive.

ABT-200, a norepinephrine uptake inhibitor, blocks Ca2+ signals in chromaffin cells.

We previously described inhibition by racemic (+/-)-(1'R*,3R*)-3-phenyl-1- [1',2',3',4'-tetrahydro-5',6'-methylenedioxy-1'- napthalenyl-methyl]-pyrrolidine methanesulfonate (ABT-200), and its two constituent enantiomers, SS,ABT-200 and RR,ABT-200, of nicotine-stimulated but not histamine-stimulated catecholamine release from bovine adrenal chromaffin cells. To test the hypothesis that this inhibition reflects a blockade of Ca2+ influx, we used fura-2 loaded chromaffin cells to investigate cytosolic Ca2+ signals. We found that SS,ABT-200 inhibited nicotine- and K(+)-stimulated Ca2+ signals, both of which depend on Ca2+ influx. However, the early phase of the histamine-stimulated Ca2+ signals, which depends on Ca2+ mobilization from intracellular stores, was unaffected. We also examined ion flux through the nicotinic receptor by measuring 86rubidium+ (86Rb+) efflux from preloaded mouse midbrain synaptosomes. We found that SS,ABT-200 partially inhibited nicotine-stimulated 86Rb+ efflux, suggesting that it blocks ion flux through the nicotinic receptor directly. These data support a model in which ABT-200 blocks nicotine-stimulated catecholamine release by inhibiting cation flux through multiple channels.

Calcium signalling in bovine adrenal chromaffin cells: additive effects of histamine and nicotine.

In a previous report, we described the ability of two secretogogues, histamine and nicotine, to stimulate additive effects on catecholamine (CA) release and synapsin II phosphorylation in bovine adrenal chromaffin cells (BACC) [Firestone and Browning (1992), J. Neurochem., 58:441-447]. We hypothesized that these results were due to the combined effects on cytosolic Ca++ of the two distinct signalling pathways. We therefore examined the intracellular Ca++ signals stimulated by histamine and nicotine, alone and together. In Ca(++)-deficient medium, nicotine-stimulated signals were abolished, whereas histamine-stimulated signals were maintained, demonstrating that nicotine depended entirely on Ca++ influx for its effects. Indeed, the nicotine-stimulated signal could also be prevented using a Ca++ channel blocker, nicardipine. Further, the observation that exposure of BACC to thapsigargin reduced histamine-stimulated Ca++ signals verified that histamine mobilizes Ca++ from intracellular stores. Thus, the two secretogogues mobilize Ca++ from distinct pools. When BACC were stimulated with the two secretogogues together, the resulting Ca++ signal was greater than that from either alone. These data are consistent with a model in which two distinct sources of Ca++ can summate within the cell, producing a greater Ca++ signal and, hence, a greater effect on neurotransmitter release.

Distributions of phytoplankton blooms in the southern ocean.

A regional pigment retrieval algorithm for the Nimbus-7 Coastal Zone Color Scanner (CZCS) has been tested for the Southern Ocean. The pigment concentrations estimated with this algorithm agree to within 5 percent with in situ values and are more than twice as high as those previously reported. The CZCS data also revealed an asymmetric distribution of enhanced pigments in the waters surrounding Antarctica; in contrast, most surface geophysical properties are symmetrically distributed. The asymmetry is coherent with circumpolar current patterns and the availability of silicic acid in surface waters. Intense blooms (>1 milligram of pigment per cubic meter) that occur downcurrent from continental masses result from dissolved trace elements such as iron derived from shelf sediments and glacial melt.

Ca2+/calmodulin-dependent protein kinase II and protein kinase C phosphorylate a synthetic peptide corresponding to a sequence that is specific for the gamma 2L subunit of the GABAA receptor.

The gamma 2 subunit of the GABA receptor (GABAA-R) is alternatively spliced. The long variant (gamma 2L) contains eight additional amino acids that possess a consensus sequence site for protein phosphorylation. Previous studies have demonstrated that a peptide or fusion protein containing these eight amino acids is a substrate for protein kinase C (PKC), but not cyclic AMP-dependent protein kinase A (PKA)-stimulated phosphorylation. We have examined the ability of PKA, PKC, and Ca2+/calmodulin-dependent protein kinase (CAM kinase II) to phosphorylate a synthetic peptide corresponding to residues 336-351 of the intracellular loop of the gamma 2L subunit and inclusive of the alternatively spliced phosphorylation consensus sequence site. PKC and CAM kinase II produced significant phosphorylation of this peptide, but PKA was ineffective. The Km values for PKC- and CAM kinase II-stimulated phosphorylation of this peptide were 102 and 35 microM, respectively. Maximal velocities of 678 and 278 nmol of phosphate/min/mg were achieved by PKC and CAM kinase II, respectively. The phosphorylation site in the eight-amino-acid insert of the gamma 2L subunit has been shown to be necessary for ethanol potentiation of the GABAA-R. Thus, our results suggest that PKC, CAM kinase II, or both may play a role in the effects of ethanol on GABAergic function.

Actions of A-75200, a novel catecholamine uptake inhibitor, on norepinephrine uptake and release from bovine adrenal chromaffin cells.

The balance between catecholamine (CA) release and reuptake is closely regulated and determines the effective level of transmitter at the synaptic cleft. Drugs that block CA uptake have potential utility as antidepressant medications. One such drug is racemic (+/-)-(1' R*,3R*)-3-phenyl-1-[1',2',3',4'-tetrahydro-5',6'- methylenedioxy-1'-naphthalenyl-methyl]-pyrrolidine methanesulfonate (A-7500), a novel polycyclic compound developed at Abbott Laboratories. This compound is known to bind to CA transporters in the central nervous system, however, its effects on an intact neurosecretory system have not been studied. In this regard, norepinephrine (NE) release from bovine adrenal chromaffin cells (BACC) is a classic model system for CA release and is an excellent system in which to examine the effects of drugs which modulate neurotransmitter release. We compared the effects of A-75200 and its two constituent enantiomers, A-74111 and A-74112, to the effects of three well-characterized uptake inhibitors, desipramine (DMI), nomifensine and cocaine. We found that the Abbott compounds inhibit [3H]norepinephrine ([3H]NE) uptake with an EC50 comparable to cocaine. In addition, unlike nomifensine and cocaine, these compounds inhibited nicotine- and K(+)-stimulated NE release, whereas histamine-stimulated release was preserved. Thus, the Abbott compounds block the effects on secretion of two agonists (nicotine and K+) which depend on a depolarization-dependent influx of extracellular calcium. We conclude that in addition to blocking NE uptake by inhibiting the NE transporter, the Abbott compounds may modulate peripheral NE release by inhibiting calcium flux through voltage-gated channels. This study demonstrates the utility of bovine adrenal chromaffin cells for preclinical trials of drugs that affect catecholaminergic neurotransmission.

Inhibition of cyclic AMP accumulation in intact NCB-20 cells as a direct result of elevation of cytosolic Ca2+.

Earlier studies established that adenylyl cyclase in NCB-20 cell plasma membranes is inhibited by concentrations of Ca2+ that are achieved in intact cells. The present studies were undertaken to prove that agents such as bradykinin and ATP, which elevate the cytosolic Ca2+ concentration ([Ca2+]i) from internal stores in NCB-20 cells, could inhibit cyclic AMP (cAMP) accumulation as a result of their mobilization of [Ca2+]i and not by other mechanisms. Both bradykinin and ATP transiently inhibited [3H]cAMP accumulation in parallel with their transient mobilization of [Ca2+]i. The [Ca2+]i rise stimulated by bradykinin could be blocked by treatment with thapsigargin; this thapsigargin treatment precluded the inhibition of cAMP accumulation mediated by bradykinin (and ATP). A rapid rise in [Ca2+]i, as elicited by bradykinin, rather than the slow rise evoked by thapsigargin was required for inhibition of [3H]cAMP accumulation. Desensitization of protein kinase C did not modify the inhibitory action of bradykinin on [3H]cAMP. Effects of Ca2+ on phosphodiesterase were also excluded in the present studies. The accumulated data are consistent with the hypothesis that hormonal mobilization of [Ca2+]i leads directly to the inhibition of cAMP accumulation in these cells and presumably in other cells that express the Ca(2+)-inhibitable form of adenylyl cyclase.

Pulmonary surfactant secretion is regulated by the physical state of extracellular phosphatidylcholine.

Pulmonary alveolar type II cells synthesize, secrete, and recycle the components of pulmonary surfactant. In this report we present evidence that dipalmitoylphosphatidylcholine is a potent inhibitor of surfactant lipid secretion by type II cells. Monoenoic and dienoic phosphatidylcholines with fatty acids of 16 or 18 carbons are ineffective as inhibitors of surfactant lipid secretion. In contrast, disaturated phosphatidylcholines, with either symmetric or asymmetric pairs of fatty acids of 14, 16, or 18 carbons, exhibit inhibition of surfactant secretion that correlates extremely well with the phase transition temperature (Tc) of the phospholipid. The inhibitory activity of dipalmitoylphosphatidylcholine is not dependent upon lipid stereochemistry. N-Methylated derivatives of dipalmitoylphosphatidylethanolamine are significantly less effective than phosphatidylcholine as inhibitors. Phosphatidylcholines below their phase transition temperature are inhibitors of surfactant secretion, whereas those above their phase transition temperature are either ineffective or weakly inhibitory. The phase transition dependence of inhibition is observed when type II cells are incubated at 37 degrees C with different species of phosphatidylcholine. In addition, if type II cells are stimulated to secrete at different temperatures the efficacy of a given phospholipid as an inhibitor is dependent on its relationship to Tc (i.e. dipalmitoylphosphatidylcholine with a Tc of 41 degrees C significantly inhibits secretion at 37 degrees C but not at 42 degrees C). Inhibition of surfactant secretion by dipalmitoylphosphatidylcholine is abrogated when it is incorporated into the same liposome with dioleoylphosphatidylcholine as a 50:50 mixture. In contrast, the simultaneous addition of two separate populations of liposomes, one composed of dipalmitoylphosphatidylcholine and the other composed of dioleoylphosphatidylcholine, does not significantly alter the inhibitory activity found with dipalmitoylphosphatidylcholine alone. These data provide compelling evidence that the physical state of phosphatidylcholine can regulate surfactant secretion from alveolar type II cells and suggest a unique mechanism for regulating exocytosis in the alveolus of the lung.

Synapsin II phosphorylation and catecholamine release in bovine adrenal chromaffin cells: additive effects of histamine and nicotine.

Primary cultures of bovine adrenal medullary chromaffin cells can be stimulated with nicotine, which mimics the cholinergic stimulus from the splanchnic nerve. Histamine also stimulates catecholamine release in a time- and dose-dependent manner. We have previously shown that nicotine stimulates incorporation of 32Pi into the vesicle-associated phosphoprotein synapsin II. We report here that histamine, too, stimulates an increase in 32Pi incorporation into synapsin II, which is blocked by the H1-histamine receptor-specific antagonist pyrilamine. The time course of histamine-stimulated synapsin II phosphorylation closely paralleled that of histamine-stimulated catecholamine release. Interestingly, histamine and nicotine produced an additive increase in both catecholamine release and synapsin II phosphorylation, suggesting that these two secretogogues stimulate the phenomena via independent mechanisms. When we investigated the dependence of these two agonists on extracellular calcium, we found that nicotine-stimulated release and synapsin II phosphorylation were reduced to basal levels at low calcium concentrations. However, the histamine-stimulated effects remained significantly elevated. This suggests that calcium arising from two separate pools can stimulate catecholamine release and synapsin II phosphorylation in bovine chromaffin cells. Taken together, these data support the hypothesis that synapsin II phosphorylation is a component of the secretory response from these cells.

Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study.

The core protein of the proteoglycan at the cell surface of NMuMG mouse mammary epithelial cells bears both heparan and chondroitin sulfate chains and is recognized by the monoclonal antibody 281-2. Using this antibody and the peroxidase-antiperoxidase staining technique in adult mouse tissues, we found that the antibody recognizes the antigen in a highly restricted distribution, staining a variety of epithelial cells but no cells derived from embryonic mesoderm or neural crest. The antibody fails to stain any stromal (mesenchymal) or neuronal cells, with the exception of plasma cells and Leydig cells. Squamous and transitional epithelia stain intensely over their entire surfaces, whereas cuboidal and columnar epithelia stain moderately and only at the lateral surface of the basal cells. Within squamous and transitional epithelial tissues that undergo physiological regeneration (e.g., epidermis), the most superficial and differentiated cell types fail to stain. Within glandular and branched epithelia (e.g., pancreas), the secretory alveolar cells fail to stain. When evaluated by electron microscopy, granular deposits of stain are seen on the plasma membrane, especially on lateral surfaces, but none are noted within the cells or the basement membrane. These results indicate that in adult tissues the core protein of this heparan sulfate-rich proteoglycan is expressed almost exclusively at epithelial cell surfaces. Expression appears to be lost as the cells become either mature or highly differentiated.

Children of methadone-treated women at five years of age.

Infants of methadone-treated and matched non-drug dependent women were found to differ in psychomotor development at one year of age. A follow-up of these groups at age five revealed no differences in cognitive or perceptual performance as assessed by the McCarthy Scales, although both groups performed below normative expectations. Groups did not differ in observed characteristics of home environments or patterns of child or caregiver behavior in a playroom observation, although children who had been transplacentally exposed to narcotics behaved less maturely and were more inappropriately active during psychological testing.