Paternal behavior is associated with central neurohormone receptor binding patterns in meadow voles (Microtus pennsylvanicus).

Paternal and nonpaternal voles (microtus) have different arginine-vasopressin (AVP) and oxytocin (OT) receptor patterns in the extended amygdala, a neural pathway associated with parental behavior. Using receptor autoradiography, the authors examined whether AVP and OT receptor patterns were associated with facultative paternal behavior in either sexually and parentally inexperienced or experienced meadow voles (Microtus pennsylvanicus). Experienced, in contrast to inexperienced, males had less AVP binding in the lateral septum (LS), more AVP binding in the anterior olfactory nucleus (AON), and more OT binding in the AON, bed nucleus of the stria terminalis, LS, and lateral amygdala. Thus, specific AVP receptor patterns, which co-occur with paternal care in consistently paternal voles, also may be associated with paternal care (when present) in typically nonpaternal species. This study also demonstrated a possible relationship between OT receptor patterns and paternal state in male mammals.

Day length and sociosexual cohabitation alter central oxytocin receptor binding in female meadow voles (Microtus pennsylvanicus).

In voles (Microtus), central oxytocin (OT) receptor patterns are associated with interspecific social organization. Social, monogamous voles have more OT receptors in the extended amygdala than asocial, nonmonogamous voles. Nonmonogamous meadow voles (Microtus pennsylvanicus), which exhibit seasonal changes in social organization (long day [LD] females are territorial, short day [SD] females live socially), provide a model for examining whether OT receptor patterns are associated with seasonal changes in intraspecific social behaviors. The authors examined whether sexually inexperienced (naive) SD females had more OT receptor binding than naive LD females. Naive SD females had greater OT receptor binding in the lateral septum (LS), lateral amygdala (LatAmyg), and central amygdala (CenAmyg) than less social, naive LD females. Because both SD and LD females acquire partner preferences, the authors assessed whether OT receptor binding was associated with partner preference onset. For LD females, partner preference onset corresponded with greater OT receptor binding in the anterior olfactory nucleus, LS, and bed nucleus of the stria terminalis, compared with naive LD females. In contrast, naive SD females and those exhibiting partner preferences did not differ. However, SD females that failed to acquire partner preferences showed less OT binding in the LatAmyg and CenAmyg. This study is the first to show that central OT receptor patterns are associated with seasonal changes in intraspecific social organization and partner preference onset in a nonmonogamous rodent.

Comparative testicular toxicity of bis(2-methoxyethyl) ether and 2-methoxyethanol in rats.

Male rats were exposed to 0, 110, 370, or 1100 ppm bis(2-methoxyethyl)ether (diglyme) 6 h/day, 5 days/week for 2 weeks. One group of male rats was exposed to 300 ppm 2-methoxyethanol (2-ME) for 2 weeks as a positive control. Exposed rats were killed after 10 days of exposure and 14, 42, or 84 days post-exposure (PE), respectively. At 110 ppm diglyme, spermatocytes in pachytene and meiotic division at spermatogenic stages XII-XIV were mainly affected. At 370 ppm diglyme, affected germ cells were similar to those seen at 110 ppm diglyme, but round spermatids at spermatogenic stages I-VII were also affected. The testes regained normal spermatogenesis by 84 days PE. At 1100 ppm diglyme or 300 ppm 2-ME, marked testicular atrophy was found affecting all spermatogenic stages. Damaged seminiferous tubules were lined with regenerating pachytene spermatocytes at 14 days PE and with spermatocytes and round spermatids after 42 days PE. Most but not all testes in rats exposed to 300 ppm 2-ME or 1100 ppm diglyme had normal morphology after 84 days PE. Based on the observation of germ cell damage, spermatozoa population in the epidymal tubules, reversibility of spermatogenesis after various PE periods, testicular toxicity induced by 300 ppm 2-ME was more severe than that seen at 370 ppm diglyme but was slightly less remarkable than that of 1100 ppm diglyme.

Interaction of nickel with UV-light in the induction of cytogenetic effects in human peripheral lymphocytes.

Chemical interaction is of major concern in the assessment of risk by regulatory agencies. In the present study, treatment of human lymphocytes with NiSO4 (1-100 microM) or UV-light (200, 1000 ergs/mm2) induced micronuclei (MN) in a dose-dependent fashion. Statistical analysis of the interaction factor (IF), showed that combined treatments of Ni(II) (1-100 microM) with UV-light (200, or 1000 ergs/mm2) interacted antagonistically for the induction of MN. Recently we reported that Ni(II) (0.5-10 microM) with UV-light (200 or 1000 ergs/mm2) or Cr(VI) or X-rays interacted antagonistically for the induction of sister chromatid exchanges (SCE), in peripheral human lymphocytes. These observations suggest that nickel present in complex mixtures may reduce the response, even in the presence of strong MN or SCE inducers, and may lead, therefore, to an underestimate of chemical exposure as assessed by these assays. Furthermore, metals affecting certain microsteps in the process of DNA replication or repair (e.g., histones, polymerases, ligases) may have similar antagonistic effects. Further studies are therefore recommended.

Effect of cued and uncued inescapable shock on voluntary alcohol consumption in rats.

Rats were given cued and uncued inescapable shock; their voluntary alcohol intake was compared to a group given a yoked cue but no shock. Results suggested that, unlike uncued inescapable shock, cued inescapable shock caused an increase in voluntary alcohol intake, although the increase was insufficient to produce overt inebriation. It was suggested that the increase which occurred was due to a combination of adjunctive drinking and a gustatory and olfactory discrimination breakdown, both occurring in direct response to shock.

A comparison of methylphenidate induced active avoidance and water maze performance facilitation.

Methylphenidate was shown to facilitate both active avoidance and water performance compared to controls. Repetitive errors on both tasks were greater in the drug than the nondrug group and were positively correlated to water maze performance. These results fail to support the view that water maze acquisition is less influenced by performance variables than active avoidance. An unanticipated enhancement of water maze performance was also noted in the control group which had been previously tested on active avoidance compared with naive controls. Moreover, this group made fewer repetitive errors than naive controls, suggesting that previous shock exposure reduced inappropriate responses.

Acute inhalation toxicity of ammonium perfluorononanoate.

Ammonium perfluorononanoate (CAS Registry No. 4149-60-4) is a white powder that can become airborne. Its acute inhalation toxicity in male rats was studied. Male rats were exposed for single 4-hr periods to dust concentrations ranging from 67 to 4600 mg/m3. The LC50 was determined to be 820 mg/m3, with the lowest concentration causing death being 590 mg/m3. Ammonium perfluorononanoate was classified as moderately toxic by the acute inhalation route. Exposure to ammonium perfluorononanoate caused a pronounced increase in liver size. The acute toxicity of ammonium perfluorononanoate appears to be similar to that of its 8-carbon homologue, ammonium perfluorooctanoate, but considerably less than that of the 10-carbon homologue, perfluoro-n-decanoic acid.

Hereditary angioedema: case report and review of management.

The classification, pathophysiology, and treatment of angioedema is reviewed. An overview of acquired and hereditary angioedema is presented with an interesting case report that illustrates the importance of recognition and perioperative management of hereditary angioedema to prevent a potentially fatal outcome.

Using the international normalized ratio to standardize prothrombin time.

The international normalized ratio, or INR, was introduced in 1983 by the World Health Organization, or WHO, Committee on Biological Standards to more accurately assess patients receiving anticoagulation therapy. The INR mandates the universal standardization of prothrombin time. This article describes the method used to calculate INR, as well as its clinical relevance to the practice of dentistry.

Clinical response of hard tissue replacement (HTR) polymer as an implant material in oral surgery patients.

This study evaluated the performance of a synthetic implant material, Hard Tissue Replacement Polymer, for: (1) ease of handling, (2) compatibility with bone and soft tissue, (3) stability of augmentation over time, and (4) development of untoward effects. HTR (a registered trademark of HTR Sciences, a division of United States Surgical Corporation, Norwalk, CT 06856) was implanted into 34 patients by means of five different surgical procedures. The material was found to be easy to manipulate during surgery. Tissue and bone compatibility, defined as absence of inflammation, was present in 32/34 surgical sites (94%). In extraction sites during the 18-month follow-up, no measurable decrease in bone height or width was seen. One patient with a large periodontal endodontic defect developed a post-operative infection necessitating extraction of the tooth. No induction of bone was seen in response to placement of HTR material.

Nightmares in Vietnam veterans.

Repetitive traumatic dreams remain a curiosity in our working with patients. If dreams have a sleep protecting or problem solving function, the dream that does not resolve but repeats and that disturbs rather than protects sleep remains an important clinical problem. We see in individual patient experiences and in civilian disasters samples of individuals who are unable to return their dream life to a condition in which it no longer repeats or disturbs their sleep. Clearly the recent experience of combat survivors of Vietnam becomes a major concern.

Effective interventions and implementation strategies to reduce adverse drug events in the Veterans Affairs (VA) system.

BACKGROUND: Adverse drug events (ADEs) account for considerable patient morbidity and mortality as well as legal, operational and patient care costs. In Veterans Affairs (VA) hospitals in the USA, all serious adverse events and "potential" adverse events are reviewed using root cause analysis (RCA). This study characterised RCA reports associated with ADEs to determine what actions VA RCA teams took to reduce the number or severity of ADEs, and to evaluate which actions were effective in doing so. METHODS: Every medication-related RCA submitted to the VA National Center for Patient Safety in the fiscal year 2004 (143 reports), and one medication-related aggregated RCA from each facility (111 reports covering 4834 ADEs) were reviewed and coded. Facilities were interviewed about specifics of their reports and the results of their interventions. RESULTS: The commonest classes of medication for which ADEs were reported were narcotics, chemotherapy, and diabetic and cardiovascular medications. The most common types of ADE were "wrong dose", "wrong medication", "failed to give medication", and "wrong patient". 993 actions were taken to address these ADEs, the majority (75.7%) of which were reported to be fully implemented. Improvements in equipment and improving clinical care at the bedside were associated with reports of improved outcomes (p = 0.018, and p = 0.017 respectively), and training and education were negatively correlated with reports of improved outcome (p = 0.005). Improving the process of medication order entry through the use of alerts or forcing functions was positively correlated with reports of improved outcomes (p = 0.022). Leadership support and involving staff were associated with higher implementation rates (p = 0.001 and p = 0.010, respectively). CONCLUSIONS: Changes at the bedside and improvement in equipment and computers are effective at reducing ADEs. Well-organised tracking and support from leadership and staff were characteristics of facilities successful at improving outcomes. Training without action was associated with worse outcomes.

Measuring patient safety climate: a review of surveys.

OBJECTIVE: Five years ago the Institute of Medicine recommended improving patient safety by addressing organizational cultural issues. Since then, surveys measuring a patient safety climate considered predictive of health outcomes have begun to emerge. This paper compares the general characteristics, dimensions covered, psychometrics performed, and uses in studies of patient safety climate surveys. METHODS: Systematic literature review. RESULTS: Nine surveys were found that measured the patient safety climate of an organization. All used Likert scales, mostly to measure attitudes of individuals. Nearly all covered five common dimensions of patient safety climate: leadership, policies and procedures, staffing, communication, and reporting. The strength of psychometric testing varied. While all had been used to compare units within or between hospitals, only one had explored the association between organizational climate and patient outcomes. CONCLUSIONS: Patient safety climate surveys vary considerably. Achievement of a culture conducive to patient safety may be an admirable goal in its own right, but more effort should be expended on understanding the relationship between measures of patient safety climate and patient outcomes.

The ultrastructure and reversibility of testicular atrophy induced by ethylene glycol monomethyl ether (EGME) in the rat.

Inhalation exposure to 300 ppm ethylene glycol monomethyl ether (EGME) for 3 days produced degenerative changes in spermatocytes of pachytene and meiotic division at spermatogenic stage XIV in rats. However, a wide range of germ cell types including spermatogonia was affected and the stage-specific damage was not discernible after 2 weeks exposure to 300 ppm EGME. The stage-specific damage was related to exposure concentration-time course. In early stages, degenerating spermatocytes showed nuclear chromatin clumping around synaptonemal complexes, cytoplasmic vesiculation with electron-dense material deposition, and disruption of the plasma membrane. Chromosomal microtubules in the meiotic division of spermatocytes were discontinued with deposition of electron-dense chromatin material. Sertoli cells showed cytoplasmic vacuolization, contact loss to germ cells, and cytoplasmic processes fragmentation with disrupted microtubules. Degenerative pachytene or meiotic spermatocytes were associated with disrupted Sertoli-germ cell relationship, chromosomal microtubules, and synaptonemal complexes. Spermatid degeneration and giant cell formation were observed after spermatocyte degeneration. Spermatid degeneration appeared to be a secondary change resulting from disrupted Sertoli-to-germ cell association. After 14 days post-exposure (PE) following 2 weeks exposure, some tubules were lined with regenerating spermatocytes with or without round spermatids. By 42 days PE, many tubules regained normal germinal epithelium, but some tubules were still atrophic even after 84 days PE. Reversibility of testicular atrophy was inversely proportional to severity of damaged stem cells.

Large-cell lymphoma of the infratemporal fossa presenting as myofacial pain.

Patients with temporomandibular joint or myofascial pain are often subjected to rigid protocols of diagnosis and treatment. This tendency to generalize patient care can result in overlooking occult pathology. A case of large-cell lymphoma of the infratemporal fossa causing facial pain is presented.

The effects of litter size on the expressiviity of the jaundice genotype in Gunn rats.

In 2 studies Gunn rats carrying 2 recessive alleles for jaundice (jj) were compared with their heterozygous littermates (Jj) under varied litter size (4 vs 12 pups) and handling conditions. Handling did not produce long-term effects. Litter size interacted with Genotype to increase the differential response of jj rats by 21, 23, and 50 days of age. A decrease in survival rates and weight gain was found in Jj and especially jj rats from large litters. For jj rats only, being reared in a large litter increased the severity of ataxia. Jaundiced rats from large litters showed less rearing and tended to enter fewer squares than those from small litters whereas Jj littermates showed an equivalent amount of rearing and number of squares entered in large as compared to small litter sizes. Differences between Jj and jj rats in frequency of pivoting were greater in those from large litters than in those from small litters.

Inhalation studies in rats exposed to dimethylacetamide (DMAc) from 3 to 12 hours per day.

Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentrations were increased in rats exposed for 12 hours/day to either 30, 100, or 300 ppm. Hepatocellular hypertrophy together with margination of hepatocellular cytoplasmic contents and lipid-like cytoplasmic vacuolation in hepatocytes were seen microscopically only in rats exposed for 12 hours/day to 300 ppm. Recovery from these liver changes was not complete after 14-day post-exposure period. No evidence of either testicular damage or irritation to the upper respiratory tract was seen.

Multiple power-density windows and their possible origin.

We have previously reported that in vitro exposure of chick forebrain tissue to 50-MHz radiofrequency (RF) electromagnetic radiation, amplitude modulated (AM) at 16 Hz, would enhance the efflux of calcium ions within only two power-density ranges: one from 1.44 to 1.67 mW/cm2, and the other including 3.64 mW/cm2. No effect on efflux occurred at 0.37, 0.72, 2.17, and 4.32 mW/cm2. We confirmed and extended these results by testing at another set of power densities, which included the range of the previous study. Forebrain tissue from 1-7-day-old chickens was labeled in vitro with radioactive calcium ions (30 min, at 37 degrees C), rinsed, placed in a physiological salt solution, and then exposed for 20 min to 50-MHz radiation, AM at 16 Hz, in a transverse electric and magnetic field (TEM) cell maintained at 37 degrees C. The solution was then assayed for radioactive calcium activity. A power-density series was tested. An enhanced efflux of calcium ions was found at 1.75, 3.85, 5.57, 6.82, 7.65, 7.77, and 8.82 mW/cm2; no change was observed at 0.75, 2.30, 4.50, 5.85, 7.08, 8.19, 8.66, 10.6, and 14.7 mW/cm2. Power density is converted to specific absorption rate (SAR) by 0.36 mW/kg per mW/cm2. Even the highest SAR tested (0.005 W/kg) is much too low to result in generalized heating of the sample and thus to be the underlying cause of the enhanced response. A hypothetical mechanism is proposed involving dynamic systems that may account for the power-density dependency as well as for part of the frequency dependency observed with both modulated RF radiation and extremely-low-frequency (ELF) fields.