Toxic smoke inhalation in fire victim dogs.

Fifteen dogs were found dead in a house that was on fire. Several of these dogs were partially burned. Four dogs were submitted for postmortem examination, 2 of which were determined to have died prior to the fire. Of the 2 submitted fire fatalities, only 1 dog had burns on its body (dorsum and right side of body). Internally, both dogs had soot deposits mixed with mucus in the larynx, trachea, and primary bronchi. Microscopically, soot was identified within both airways and alveolar spaces. There were no macroscopic or microscopic indications of vital heat exposure. High levels of carboxyhemoglobin were detected in the 2 dogs tested. The findings in this case support the use of postmortem examination and toxicology testing to allow for determination of vital reaction to heat and fire fumes.

Homeless mentally ill or mentally ill homeless?

Mainstream psychiatry conceptualizes people who are homeless and mentally ill as distinct from other homeless persons because it is thought that their status stems from their mental disorder and the poor implementation of deinstitutionalization. The authors believe this dichotomy is illusory. They present data indicating that recent socioeconomic and political shifts contributed greatly to homelessness among all groups, regardless of mental illness; that those with and without mental illness have similar biographical and demographic profiles; that high levels of mental distress are common to all homeless persons; and that few mentally ill homeless persons require involuntary hospitalization. This perspective suggests novel responses that de-emphasize clinical solutions and focus on empowerment, consumerism, entitlement, community-level interventions, and closer alliances with other advocates for the homeless.

Specificity of filiform hair afferent synapses onto giant interneurons in Periplaneta americana: anatomy is not a sufficient determinant.

The synapses between the filiform hair sensory afferents and giant interneurons (GIs) 1-6 of embryonic and first instar cockroaches, Periplaneta americana, were used to investigate the role of neuronal anatomy in determining synaptic specificity. The pattern of afferent-to-GI synapses was first determined by intracellular recording of excitatory postsynaptic potentials (EPSPs). The lateral (L) axon synapses only with GIs 3, 4, and 6, while the medial (M) axon synapses with the contralateral dendrites of all six GIs but with the ipsilateral dendrites only of GIs 1, 2, and 4. The three-dimensional anatomy of the filiform afferents and GIs was determined by injection of cobalt. There is little anatomical segregation of the filiform afferents; consequently, there is no correlation between the anatomy of the GIs and their synaptic inputs. The M axon and ipsilateral GI3 were studied in more detail by light and electron microscopy. Despite the presence of an anterior M axon branch which loops around the ipsilateral GI3 neurite at a distance of 2 microns, no synapses are formed between them. This lack of synapses is not due to the presence of physical barriers. Investigation of filiform afferents and GIs in embryonic ganglia shows that at no stage are the afferents sufficiently separated for their anatomy to be an important factor in determining the specificity of the synaptic inputs of the GIs. It was postulated that two pairs of complementary cell surface labels would be sufficient to code for this specificity, and that, in GIs 3, 5, and 6, spatial differences in the expression of these labels allow the M axon to distinguish ipsilateral dendrites from contralateral.

Comparative anatomy of serotonin-like immunoreactive neurons in isopods: putative homologues in several species.

It is now commonly accepted that the arthropod nervous system has evolved only once, and so homologies between crustacean and insect nervous systems can be meaningfully sought. To do this, we have examined the distribution of serotonin (5-hydroxytryptamine)-like immunoreactive neurons in the central nervous system (CNS) of four common British isopods. Two species of terrestrial woodlouse, Oniscus asellus and Armadillidium vulgare, the littoral sea slater, Ligia oceanica, and the aquatic water hoglouse, Asellus meridianus, all possess approximately 40 pairs of serotonin-like immunoreactive neurons, distributed throughout the CNS in a very similar pattern. Interspecific homology is clearly suggested. Serotonin-like immunoreactive neurons in the first (T1) and fourth (T4) thoracic ganglia are particularly prominent in each of the four species studied. Whole-mount immunohistochemistry shows that the pair of T1 neurons have large dorsolateral cell bodies and prominent neurites that project medially and then anteriorly, whereas the pair of T4 neurons have ventrolateral cell bodies and neurites that bifurcate to form a thin axon projecting anteriorly to terminate in T3 and a thick medial axon that projects posteriorly into the abdominal neuromeres of the terminal ganglion. Intracellular cobalt staining of these neurons reveals more of their arborizations: the T1 neurons send three processes anteriorly, which arborize in the brain and exist from the CNS via peripheral nerves, whereas the T4 neurons contribute considerably to the extensive pattern of serotonin-like immunoreactive fibres in T3-T6 ganglia. The overall pattern of serotonin-like immunoreactive neurons in the isopods is similar to that in decapod crustacea, and a number of putative homologies can be assigned. It is more difficult to homologize the isopod serotonin-like immunoreactive neurons with those in the insect CNS, but some stained brain and thoracic neurons share common cell body positions and axon trajectories in isopods, decapods, and insects and may therefore be homologous.

Correlation of filiform hair position with sensory afferent morphology and synaptic connections in the second instar cockroach.

An attempt is made to relate the distribution of filiform hairs on the cercus of the second instar cockroach, Periplaneta americana, to the morphology and patterns of synaptic connectivity of their afferents. We studied the most distal 25 of the 39 filiform hairs which are commonly present. Filiform afferent arborizations were stained by cobalt filling from the cell body in the cercus. Three fundamental arbor types were found, two similar to those of the first instar medial (M) and lateral (L) afferents, and a third, novel type. L-type arbors could be divided into four subtypes. The most obvious correlate of arbor type is the circumferential position of the hair on the cercus. The proximodistal position of the sensillum within each cercal segment is also a determinant of its arbor. By comparison of hair positions and afferent morphologies, we were able to ascribe homologies between the second instar hairs and members of adult longitudinal hair columns. The patterns of monosynaptic connections between afferents and giant interneurons (GIs) 1, 2, 3, 5, and 6 were determined by recording synaptic potentials in GIs evoked by direct mechanical displacement of individual filiform hairs. Latency from stimulus onset to the rise phase of the first excitatory postsynaptic potential (EPSP) was used as the criterion of monosynapticity. The EPSP amplitudes of the two original L and M afferents are halved in the second instar, in the absence of a significant decrease in GI input resistance. The other afferents can be divided into two basic classes: those which input to GI5 (M-type), and those which input to GI3 and GI6 (L-type). The former is correlated with a central or medial position, while the latter is associated with a group of afferents situated laterally on the cercus. In segments 3 and 4, input to GIs 1 and 2 also correlates with a medial cercal position, however, in the more proximal segments 5 and 6, afferents at all positions input to these interneurons. The occurrence of afferents of identical morphology and similar connectivity in equivalent positions in different segments suggests that each sensory neuron is determined by its two-dimensional position within a segment. The presence of afferents with the same morphology which display proximodistal differences in synaptic connectivity, and of other afferents which have M-type connectivity despite L-type morphology, means that anatomy is generally a poor predictor of synaptic connectivity.

Morphology of the vasopressin-like immunoreactive (VPLI) neurons in many species of grasshopper.

It has previously been shown that the pair of vasopressin-like immunoreactive (VPLI) neurons of the locust, Locusta migratoria, have cell bodies on the ventral midline of the suboesophageal ganglion and extensive arborisations in all ganglia of the central nervous system. In the present study, we have stained vasopressin-like immunoreactive neurons in 16 additional species of grasshopper, and consistently find this pair of extensive neurons: we assume these to be interspecies homologues. However, the anatomy of these neurons falls into two morphological types: the first, typified by Schistocerca gregaria, has most of its processes distributed in dorsal and lateral neuropil of all ganglia; the second, typified by Locusta migratoria, is equally extensive in its arborisation, but the distribution of branches is shifted peripherally into the optic lobes and the proximal portions of peripheral nerves. It has been suggested that the peripheral fibres in Locusta migratoria are neurohaemal organs for the release of a vasopressin-like diuretic peptide. Our sample of 17 Acridoid species has deliberately selected animals from very different habitats, but our extensive survey of VPLI anatomy shows that peripheral fibres are only present in species from the subfamily Oedipodinae (of which Locusta migratoria is a member) and that no peripheral fibres are present in any of the species from the 4 other subfamilies of the Acridoidea that we have examined. The presence of peripheral fibres is therefore determined by phylogeny and not by habitat. The absence of peripheral VPLI fibres in most grasshopper species examined in this study probably means that the release of putative diuretic hormone from VPLI to control water homeostasis cannot be a conserved function of this ubiquitous neuron. In contrast, the extensive central arborisations and rare antigenicity, which are highly conserved features of the VPLI neuron in all those grasshoppers we have examined, suggests that any conserved role is more likely to be central. A central role for the VPLI neuron has yet to be determined.

Altered composition and DNA binding activity of the AP-1 transcription factor during the ageing of human fibroblasts.

We have investigated the expression of AP-1 transcription factor proteins during the in-vitro ageing of human fibroblasts. The numbers of these cells that are in the cell cycle gradually decreases up to 45 cumulative population doublings (cPD), thereafter the decline is steeper, until almost all cells enter a post-mitotic state by 60 cPD. We observed that a 34 kd junB species began to replace the 44 kd junB species after 41 cPD. This was followed, after 44 cPD, by a loss of fra1 and both junD species. After 49 cPD there was a gradual decline in the levels of fos and jun proteins, but disproportionately, so that the fos/jun protein ratio also declined. Although fos and jun proteins were still clearly present at 60 cPD, utilisation of the AP-1 DNA consensus sequence could not be demonstrated after 54 cPD. These data indicate that significant changes occur in the composition of the AP-1 transcription factor during ageing, but also that alterations in its DNA binding activity may involve other factors.

Altered composition of the AP-1 transcription factor in immortalized compared to normal proliferating cells.

We have investigated the expression of the AP-1 transcription factor proteins, fos, fosB, fra1, fra2, jun, junB, junD, using Western blot analysis, in several types of asynchronously proliferating cells. The latter included normal fibroblasts, immortalized but not tumourigenic fibroblasts, and two immortalized tumour cell lines. All cells expressed fos, fra1 and jun proteins and none expressed fosB. There were, however, interesting qualitative differences between the normal fibroblasts and the immortalized cells. Expression of fra2 was difficult to detect in normal cells, but was very evident in all of the immortalized cells. The normal cells only expressed a 44 kDa junB species, whereas the immortalized cells expressed both this and another 34 kDa species. All of the cells expressed the two junD proteins but the smaller 39 kDa species was more prominent in the normal cells, whereas the larger 44 kDa protein was more prominent in the immortalized cells. These data indicate that immortalized cells are not simply cells in which the ageing process has been prevented or reversed, but instead exhibit additional characteristics to those associated with young normal cells.

The difficult doctor-patient relationship: somatization, personality and psychopathology.

The difficult doctor-patient relationship and "difficult patients" have been the subject of considerable anecdotal study. Reliable methods for identification of difficult patients have not been available for the empirical study of their prevalence and characteristics. We developed the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ), composed of 30 Likert items, completed by physicians after encounters with patients. Adult patients and their providers in an academic, municipal hospital clinic participated in the instrument development (n = 92), reliability (n = 224), and assessment of patient characteristics phases (n = 113) of the study. The DDPRQ was shown to be a reliable, practical instrument. Factor analysis revealed 5 dimensions with face validity. The DDPRQ classified 10.3-20.6% of patient encounters as "difficult" depending on the sample. Demographic characteristics, provider characteristics and most medical diagnoses were not associated with DDPRQ score. In contrast, difficult patients were characterized by psychosomatic symptoms, at least mild personality disorder, and Axis I (major) psychopathology, and most had more than one of these characteristics. The need to identify and understand these components of difficult patient behavior and to include the doctor-patient relationship in strategies for managing the difficult patient is discussed.

Comparison of fresh-frozen plasmas thawed in a microwave oven and in a 37 degrees C water bath.

Fresh-frozen plasma can be thawed rapidly in a microwave oven without loss of function of coagulation factors and with no adverse effects to the patients. In patients receiving fresh-frozen plasma thawed in a microwave oven, the prothrombin time was decreased by an average of 2.9 sec per unit, and the activated partial thromboplastin time was decreased by an average of 9.6 sec per unit, compared with decrease of 2.6 sec and 6.3 sec for patients receiving fresh-frozen plasma thawed in a water bath at 37 degrees C.

Analysis of the peptide content of the locust vasopressin-like immunoreactive (VPLI) neurons.

Isolated cell bodies of the locust vasopressin-like immunoreactive (VPLI) neurons, analyzed by HPLC separation and radioimmune assay, contain three arginine vasopressin-like peptides: a previously identified monomer (Fl, Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2) and its antiparallel homodimer (F2), but also the previously unreported parallel homodimer (PDm). VPLI neuron activity significantly reduces the level of cAMP in the CNS. Of the three synthetic peptides, only the monomer (F1, 10(-8) and 10(-6) M) is capable of inhibiting a forskolin-stimulated increase in cAMP in isolated neural membranes. The antiparallel (F2) and parallel dimers (PDm) of this peptide have no effect on this second messenger.

Localization of Locusta-DP in locust CNS and hemolymph satisfies initial hormonal criteria.

Locusta-diuretic peptide (Locusta-DP) is a potent stimulant of fluid secretion and cyclic AMP production by locust Malpighian tubules. In this study, a polyclonal antiserum raised to the C-terminus of Locusta-DP reveals a wide distribution of immunoreactive cell bodies and processes throughout the CNS, and endings in two important neurohemal release sites: the corpora cardiaca and the perivisceral organs. HPLC fractionation of CNS, neurohemal structures, and hemolymph reveals immunoreactive material that coelutes with synthetic Locusta-DP and stimulates cyclic AMP production by locust tubules. The identity of the immunoreactive and biologically active material is confirmed as authentic Locusta-DP by mass spectrometry.

Cellular colocalization of diuretic peptides in locusts: a potent control mechanism.

Locust abdominal ganglia are shown to colocalize Locusta-diuretic peptide-, leucokinin I-, and lysine vasopressin-like immunoreactivity in posterior lateral neurosecretory cells. Extracts of abdominal ganglia were partially purified by RP-HPLC then dot immunoassay screened with the same antisera used for immunocytochemistry. Locusta-diuretic peptide-like immunoreactive material coeluted with synthetic Locusta-diuretic peptide, and leucokinin-like immunoreactive material coeluted with locustakinin. Lysine vasopressin-like material eluted in fractions that also showed Locusta-diuretic peptide and leucokinin I immunoreactivity. The diuretic activity of synthetic Locusta-diuretic peptide and locustakinin is demonstrated, and they are shown to act at least additively to promote Malpighian tubule fluid secretion. The immunoreactive neurosecretory cells are assumed to express at least these two peptides, and a model for promoting fluid secretion is proposed.

GABA-evoked depolarisations in the rat cortical wedge: involvement of GABAA receptors and HCO3- ions.

The effect of gamma-aminobutyric acid (GABA) was investigated on cortical wedges prepared from male Sprague-Dawley rats. GABA evoked concentration-dependent depolarisations (EC50: 0.8 mM), which were attenuated by up to 60% when bicarbonate-buffered aCSF was replaced with HEPES-buffered aCSF. Responses to 1 mM GABA were attenuated by (-)-bicuculline and picrotoxin and were potentiated by chlordiazepoxide and pentobarbitone. Ionotropic glutamate receptor antagonists had no effect. We conclude that GABA-evoked depolarisations are mediated via GABAA receptors, arising in part from HCO3- efflux from cells.

Weak blockade of AMPA receptor-mediated depolarisations in the rat cortical wedge by phenytoin but not lamotrigine or carbamazepine.

The effects of the anticonvulsants, lamotrigine, phenytoin and carbamazepine, were investigated on NMDA and non-NMDA receptor agonist-evoked responses and against spontaneous epileptiform discharges, in the in vitro rat cortical wedge. Lamotrigine weakly attenuated responses to (RS)-alpha-amino-3-hydroxy-5-methoxy-4-isoxazole propionic acid (AMPA) and quisqualate (IC50 values >> 100 microM), but was without effect on responses to NMDA. Phenytoin weakly, but concentration-dependently, attenuated responses to AMPA and quisqualate, but much less potently attenuated responses to NMDA (IC50 values 163, 248 and >> 300 microM, respectively). Carbamazepine (3-100 microM) significantly attenuated responses to NMDA and at 100 microM attenuated responses to AMPA and quisqualate. These effects were not concentration dependent, with the IC50 values >> 100 microM. Lamotrigine and phenytoin weakly, but concentration-dependently, reduced the frequency (IC50 values 254 and > 300 microM, respectively) and amplitude (IC50 values 141 and > 300 microM, respectively) of spontaneous epileptiform discharges, whereas carbamazepine had no effect. The results show that the anticonvulsant effects of these antiepileptics are unlikely to involve antagonism of ionotropic glutamate receptors, although blockade of non-NMDA responses may play a role in the anticonvulsant profile of phenytoin. Furthermore, the data show that clinically effective anticonvulsants do not necessarily attenuate spontaneous epileptiform discharges in the rat cortical wedge.

Studies on uptake, sub-cellular trafficking and efflux of antisense oligodeoxynucleotides in glioma cells using self-assembling cationic lipoplexes as delivery systems.

The cellular uptake of antisense oligodeoxynucleotides (ODNs) may be enhanced by the use of carriers such as cationic liposomes or lipoplexes, but little is known about the intracellular fate and subcellular trafficking of these systems in target cells. In this study, we report on the cellular uptake and biodistribution of ODNs in the presence and absence of optimised self-assembled cationic lipoplexes using the C6 glioma cell line as an in vitro model. Biotin or radiolabelled 15-mer phosphorothioate (PS) ODNs were synthesised and their cellular uptake and subcellular biodistribution characterised in the presence and absence of an optimised cationic lipoplex delivery system using studies ranging from cellular association, cellular efflux and transmission electron microscopy (TEM). Ultrastructural studies clearly showed PS ODNs in the absence of liposomal delivery to be sequestered within endosomal and lysosomal vesicular bodies indicative of endocytic uptake. ODNs were also visible, to a lesser extent, in the nucleus and cytoplasm. By employing DOSPA (2'-(1",2"-dioleoyloxypropyldimethyl-ammonium bromide)-N-ethyl-6-amidospermine tetra trifluoroacetic acid) and DOPE (dioleoylphosphatidylethanolamine) complex in a 3 : 1 ratio, as a delivery system for ODNs at a optimal lipid/DNA charge ratio of 1 : 1, the level of ODN cellular association was significantly increased by approximately 10-12 fold with a concomitant change in subcellular distribution of PS ODN. TEM studies indicated enhanced penetration of ODN within the cytosol and the cell nucleus with reduced presence in vesicular compartments. Efflux studies confirmed that cationic lipoplexes promoted entry of ODNs into 'deeper' cellular compartments, consistent with endosomal release. Optimised cationic lipoplexes improved cellular delivery of ODNs by enhancing cell association, uptake and by favourably modulating the intracellular trafficking and distribution of ODNs into non-vesicular compartments including the cytosol and nucleus.

Merkel cell tumor of the head and neck. Five new cases with literature review.

Merkel cell carcinoma (MCC) of the skin is an uncommon, but highly aggressive neoplasm with a marked propensity for local and distant metastasis. Despite the fact that more than half of the 600 cases of MCC reported in the literature involved primary sites in the head and neck, MCC has rarely been discussed in otolaryngology publications. We present five new cases of MCC of the head and neck and summarize 89 additional cases from the literature in which detailed treatment and survival data were given. Our findings again emphasize the difficulty in making the initial histopathologic diagnosis of MCC and demonstrate the necessity of early diagnosis and multimodality treatment.

Relationship between a self-reported health questionnaire and laboratory tests at initial office visits.

BACKGROUND: Dental patients routinely complete a medical questionnaire and have an oral interview during their initial visit, but may have undiagnosed systemic problems which can affect their dental treatment. METHODS: Thirty-nine consecutive patients referred for a periodontal evaluation completed a medical questionnaire and an oral interview. They were referred to a hospital laboratory for an urinalysis, complete blood count, and a standard blood chemistry panel. RESULTS: The self-reported medical history responses were compared with the laboratory data and several abnormalities were noted. Abnormal levels were found with cholesterol, (26/39 patients, 67%); triglycerides, (13/39, 33%); glucose, (6/39, 15%); eosinophils, (18/39, 46%); and monocytes, (10/39, 26%). Smokers (17/39, 44%) had a higher number of abnormal levels or percentages of cholesterol, triglycerides, basophils, lymphocytes, eosinophils, and monocytes. Gender differences were seen in elevated triglyceride levels, abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and self-reported cardiovascular disease. CONCLUSIONS: This study demonstrated that many patients are unaware of their current medical status and a significant number had undiagnosed abnormalities.

Development of a special care unit for chronically critically ill patients.

Intensive care units (ICUs) are recognized as one of the most expensive services provided by hospitals. Within these ICUs are a growing population of patients whose stays are extensively prolonged because of complications or underlying chronic health conditions that are exacerbated by a critical illness. These patients can be described as "chronically critically ill" and are costly to hospitals both in terms of actual dollars and in terms of the burden of care to nurses and physicians. This article describes the creation of a special care unit (SCU) designed specifically to meet the needs of chronically critically ill patients. The SCU environment is composed of a physical design that accommodates limited technology and care aimed at family involvement and rehabilitation, a case management practice model, and a shared governance management model. This structure is in contrast to traditional ICU environments, which include physical layouts that allow for high technology and close monitoring of patients, a primary nursing delivery system, and a bureaucratic management model. A research project to compare the effects of the SCU with the effects of the traditional ICUs on nurse and patient outcomes is described.

Assessing the value of a short-term residential drug treatment program for homeless men.

Cocaine and other substance abuse has been found to be a contributing or primary cause of homelessness in urban men. This project evaluated the effectiveness of the Grant Street Partnership (GSP), a shelter-based treatment program for homeless, cocaine-abusing men, consisting of 90 days of residential treatment and 6 months of aftercare. We tested the hypothesis that the 182 men randomized to the GSP group, as compared to the 112 men randomized to a "usual services" group, would show significantly greater improvement over time in the areas of drug use and residential and economic stability. An 80% response rate was achieved overall for the five follow-up points. Cocaine use, defined as use of cocaine at least once in the prior 30 days, declined from about 90% at baseline for both groups to 11% in the GSP group and 55% in the control group at 21 months. The GSP group was also more likely than the usual services group to have achieved residential stability by the time of the 9 month follow-up. Neither group experienced an improvement over time in employment status.