Emesis-induced sub-periosteal haematoma: a case report.

BACKGROUND: Orbital sub-periosteal haematoma (OSH) is usually caused by orbital trauma. We present a case of spontaneous OSH and review the literature on this condition. METHODS: We present a case of sub-periosteal haematoma secondary to migraine and vigorous emesis. DISCUSSION: OSH is very rare; this case highlights the clinical features of the condition and that rapid spontaneous resolution can occur. We review the literature on emesis- or valsava-induced OSH and discuss possible mechanisms for its formation in conjunction with migraine.

Racial differences in medication use among older, long-stay Veterans Affairs nursing home care unit patients.

OBJECTIVE: To examine racial differences in medication use by older long-stay Veterans Affairs Nursing Home Care Unit (NHCU) patients. DESIGN: Longitudinal study. SETTINGS: 133 Veterans Affairs NHCUs. PARTICIPANTS: Three thousand four hundred eighty veterans 65 years of age or older admitted between January 1, 2004, and June 30, 2005, for 90 days or more. MAIN OUTCOMES MEASURES: Prevalence of those taking nine or more medications (i.e., polypharmacy) and medications from specific therapeutic medication classes. Racial differences were determined using 0.05 level chi-squared tests. RESULTS: The sample consisted of 14.3% who were black. Blacks compared with whites (all comparisons P < 0.05 except where noted) were younger (13.6% vs. 17.4%, older than 85 years of age), had less depression (22.24 vs. 29.79%), less allergies (9.82% vs. 20.36%), and a similar rate of moderate-to severe pain (22.65% vs. 24.05; P = 0.49). The percent of polypharmacy was similar by race (blacks 74.35% vs. whites 71.18%; P = 0.62), as was the prevalence of medication class use with the exceptions that blacks were less likely than whites to take central nervous system (CNS) medications (75.75% vs. 80.14%; P = 0.02) and antihistamines (13.03% vs. 16.8%; P = 0.04). Specifically, blacks were less likely than whites to receive a selective serotonin-reuptake inhibitor (SSRI) antidepressant (20.84% vs. 27.17%; P < 0.01) or a second-generation antihistamine (3.41% vs. 6.51%; P < 0.01), but more likely than whites to receive opioids (14.63% vs. 11.27%; P = 0.03). CONCLUSION: There appears to be racial differences in the overall use of antihistamines and CNS medications and some of their subclasses.

Voxel-based morphometry and diffusion-tensor MR imaging of the brain in long-term survivors of childhood leukemia.

The aims of this study were to detect morphological changes in neuroanatomical components in adult survivors of acute lymphoblastic leukemia (ALL). Voxel-based morphometry (VBM) can be used to detect subtle structural changes in brain morphology and via analysis of fractional anisotropy (FA), diffusion-tensor imaging (DTI) can non-invasively probe white matter (WM) integrity. We used VBM and DTI to examine 20 long-term survivors of ALL and 21 healthy matched controls. Ten ALL survivors received chemotherapy and irradiation; ten survivors received chemotherapy alone during childhood. Imaging was performed on a 3.0-T MRI. For VBM, group comparisons of segmented T1-weighted grey matter (GM) and WM images from controls and ALL survivors were performed separately for patients who received chemotherapy alone and who received chemotherapy and irradiation. For DTI, FA in WM was compared for the same groups. Survivors of childhood ALL who underwent cranial irradiation during childhood had smaller WM volumes and reduced GM concentration within the caudate nucleus and thalamus. The FA in WM was reduced in adult survivors of ALL but the effect was more severe after combined treatment with irradiation and chemotherapy. Our results indicate that DTI and VBM can reveal persistent long-term WM and caudate changes in children after ALL treatment, even without T2 changes in conventional imaging.

The continuous improvement for veterans in care: Mood Disorders (civic-md) Study, a VA-academic partnership.

The Department of Veterans Affairs (VA) provides an ideal opportunity to conduct mental health services research among vulnerable populations, given its extensive data sources, disproportionate number of vulnerable patients (older, often with comorbidities), and quality improvement mission. Although VA facilities are often affiliated with universities, successful VA-academic research partnerships are sometimes elusive. The Continuous Improvement for Veterans in Care: Mood Disorders (CIVIC-MD) study was a partnership with a VA facility that had not been engaged in mood disorders research. This column describes how the partnership formed, key elements of its success, and challenges and opportunities to inform future research partnerships.

Alpha-2 adrenergic regulation of pedunculopontine nucleus neurons during development.

Rapid eye movement sleep decreases between 10 and 30 days postnatally in the rat. The pedunculopontine nucleus is known to modulate waking and rapid eye movement sleep, and pedunculopontine nucleus neurons are thought to be hyperpolarized by noradrenergic input from the locus coeruleus. The goal of the study was to investigate the possibility that a change in alpha-2 adrenergic inhibition of pedunculopontine nucleus cells during this period could explain at least part of the developmental decrease in rapid eye movement sleep. We, therefore, recorded intracellularly in 12-21 day rat brainstem slices maintained in oxygenated artificial cerebrospinal fluid. Putative cholinergic vs. non-cholinergic pedunculopontine nucleus neurons were identified using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and intracellular injection of neurobiotin (Texas Red immunocytochemistry). Pedunculopontine nucleus neurons also were identified by intrinsic membrane properties, type I (low threshold spike), type II (A) and type III (A+low threshold spike), as previously described. Clonidine (20 microM) hyperpolarized most cholinergic and non-cholinergic pedunculopontine nucleus cells. This hyperpolarization decreased significantly in amplitude (mean+/-S.E.) from -6.8+/-1.0 mV at 12-13 days, to -3.0+/-0.7 mV at 20-21 days. However, much of these early effects (12-15 days) were indirect such that direct effects (tested following sodium channel blockade with tetrodotoxin (0.3 microM)) resulted in hyperpolarization averaging -3.4+/-0.5 mV, similar to that evident at 16-21 days. Non-cholinergic cells were less hyperpolarized than cholinergic cells at 12-13 days (-1.6+/-0.3 mV), but equally hyperpolarized at 20-21 days (-3.3+/-1.3 mV). In those cells tested, hyperpolarization was blocked by yohimbine, an alpha-2 adrenergic receptor antagonist (1.5 microM). These results suggest that the alpha-2 adrenergic receptor on cholinergic pedunculopontine nucleus neurons activated by clonidine may play only a modest role, if any, in the developmental decrease in rapid eye movement sleep. Clonidine blocked or reduced the hyperpolarization-activated inward cation conductance, so that its effects on the firing rate of a specific population of pedunculopontine nucleus neurons could be significant. In conclusion, the alpha-2 adrenergic input to pedunculopontine nucleus neurons appears to consistently modulate the firing rate of cholinergic and non-cholinergic pedunculopontine nucleus neurons, with important effects on the regulation of sleep-wake states.

Rates and predictors of hepatitis C virus treatment in HCV-HIV-coinfected subjects.

BACKGROUND: True treatment rates and the impact of comorbidities on treatment rates for hepatitis C virus in the HCV-HIV-coinfected subjects are unknown. AIM: To quantify the rates of treatment prescription and the effect of comorbidities on hepatitis C virus treatment rates in HCV-HIV-coinfected veterans. METHODS: The Veterans Affairs National Patient Care Database was used to identify all hepatitis C virus-infected subjects between 1999 and 2003 using ICD-9 codes. Demographics, comorbidities and pharmacy data were retrieved. We used logistic regression to compare the predictors of hepatitis C virus treatment in hepatitis C virus-monoinfected and HCV-HIV-coinfected subjects. FINDINGS: We identified 120 507 hepatitis C virus-infected subjects, of which 6502 were HIV coinfected. 12% of the hepatitis C virus-monoinfected and 7% of the -coinfected subjects were prescribed hepatitis C virus treatment (P < 0.0001). Those not prescribed treatment were older (48.6 years vs. 47.7 years, P = 0.007) and more likely to be black (52% vs. 32%, P < 0.0001). HIV coinfected was less likely to be prescribed hepatitis C virus treatment (OR 0.74, 95% CI: 0.67-0.82). Among the coinfected subjects, the following were associated with non-treatment (OR, 95% CI): black race (0.45, 0.35-0.57); Hispanic race (0.56, 0.38-0.82); drug use (0.68, 0.53-0.88); anaemia (0.17, 0.11-0.26); bipolar disorder (0.63, 0.40-0.99); major depression (0.72, 0.53-0.99); mild depression (0.47, 0.35-0.62). CONCLUSIONS: A small number of HCV-HIV-coinfected veterans are prescribed treatment for hepatitis C virus. Non-treatment is associated with increasing age, minority race, drug use and psychiatric illness. Further studies are needed to determine the eligibility for treatment and reasons for non-treatment for hepatitis C virus.

Prenatal exposure to cigarette smoke affects the physiology of pedunculopontine nucleus (PPN) neurons in development.

Prenatal exposure to cigarette smoke is known to produce lasting arousal, attentional and cognitive deficits in humans. The pedunculopontine nucleus (PPN), as the cholinergic arm of the reticular activating system (RAS), is known to modulate arousal, waking and rapid eye movement (REM) sleep. REM sleep decreases between 10 and 30 days postnatally in the rat, especially at 12-21 days. Pregnant dams were exposed to 350 ml of cigarette smoke for 15 min, 3 times per day, from day E14 until birth, and the pups allowed to mature. Intracellularly recorded PPN neurons in 12-21 day rat brainstem slices were tested for intrinsic membrane properties, including the hyperpolarization-activated cation current Ih, which is known to drive oscillatory activity. Type II (A-current) PPN cells from 12-16 day old offspring of treated animals had a 1/2max Ih amplitude of (mean +/- SE) 4.1 +/- 0.9 mV, while 17-21 day cells had a higher 1/2max Ih of 9.9 +/- 1.1 mV (p < 0.0001). Cells from 12-16 day old control brainstems had a 1/2max Ih of 1.3 +/- 0.1 mV, which was lower (p < 0.05) than in cells from prenatally treated offspring; while 17-21 day old cells from controls had a 1/2max Ih of 3.3 +/- 0.3 mV, which was also lower (p < 0.01) than in cells from prenatally treated offspring. In addition, changes in resting membrane potential [control -65. +/- 0.9 mV (n=32); exposed -55.0 +/- 1.4 mV (n = 27) (p < 0.0001)], and action potential (AP) threshold [control -56.5 +/- 0.7 mV (n = 32), exposed -47.0 +/- 1.4 mV (n = 27) (p < 0.0001)], suggest that prenatal exposure to cigarette smoke induced marked changes in cells in the cholinergic arm of the RAS, rendering them more excitable. Such data could partially explain the differences seen in individuals whose parents smoked during pregnancy, especially in terms of their hypervigilance and increased propensity for attentional deficits and cognitive/behavioral disorders.

Inability of low- or high-fat diet to modulate late stages of colon carcinogenesis in Sprague-Dawley rats.

The main objective of the present proposal was to investigate the effect of feeding a low- or high-fat diet in the early and late stages of colon carcinogenesis. Sprague-Dawley male rats were injected with azoxymethane (20 mg/kg/week) for 2 weeks. One week later they were randomly allocated to eat a low-fat (4% beef tallow + 1% corn oil) or a high-fat (18.6% beef tallow + 4.7% corn oil) diet (LF or HF). After 10 weeks of feeding, 10 animals per group were killed, and their colons were evaluated for tumors. The remaining animals in each group were divided further into LF and HF groups. The four experimental groups consisted of groups receiving LF or HF diet throughout the study (LF-LF or HF-HF) and the groups fed LF or HF diet for the first 10 weeks, then assigned the alternate diet for the remainder of the duration (LF-HF or HF-LF). By week 26, the remaining animals were killed, and their colons were evaluated for the number, location and size of tumors. The tumor incidence in the HF-HF and HF-LF groups were higher than the LF-LF and LF-HF groups (81.6 and 84.8% versus 71.4 and 60.0%). Tumor multiplicity ranged from 1.86 +/- 0.26 to 2.54 +/- 0.33 in all groups. The average size of tumors and total tumor area/rat were affected significantly by the time at which the diet was fed. Average size and total tumor area in the animals fed HF diet during early stages (HF-HF and HF-LF) were significantly higher than those fed the LF diet during the early stages. Late intervention by specific diets did not affect tumor outcome. Sequential enumeration of aberrant crypt foci of different growth features representing early preneoplastic stages corroborated the findings of the tumor outcome. It was concluded that early preneoplastic stages were more sensitive than their advanced counterparts to the dietary interventions of the present study.

Understanding racial variation in the use of coronary revascularization procedures: the role of clinical factors.

BACKGROUND: Black patients undergo coronary artery bypass grafting and percutaneous transluminal coronary angioplasty less often than white patients. It is unclear how racial differences in clinical factors contribute to this variation. METHODS: A retrospective cohort study was performed of 666 male patients (326 blacks and 340 whites), admitted to 1 of 6 Veterans Affairs hospitals from October 1, 1989, to September 30, 1995, with acute myocardial infarction or unstable angina who underwent cardiac catheterization. The primary comparison was whether racial differences in percutaneous transluminal coronary angioplasty and coronary artery bypass grafting rates persisted after stratifying by clinical appropriateness of the procedure, measured by the appropriateness scale developed by the RAND Corporation, Santa Monica, Calif. RESULTS: Whites more often than blacks underwent a revascularization procedure (47% vs 28%). There was substantial variation in black-white odds ratios within different appropriateness categories. Blacks were significantly less likely to undergo percutaneous transluminal coronary angioplasty (odds ratio, 0.30; 95% confidence interval, 0.14-0.63 [P<.01]) when the indication was rated "equivocal." Similarly, blacks were less likely to undergo coronary artery bypass grafting (odds ratio, 0.44; 95% confidence interval, 0.23-0.86 [P<.01]) when only coronary artery bypass grafting was indicated as "appropriate and necessary." Differences in comorbidity or use of cigarettes or alcohol did not explain these variations. Using administrative data from the Veterans Health Administration, we found no differences in 1-year (5.2% vs 7.4%) and 5-year (23.3% vs 26.2%) mortality for blacks vs whites. CONCLUSION: Among patients with acute myocardial infarction or unstable angina, variation in clinical factors using RAND appropriateness criteria for procedures explained some, but not all, racial differences in coronary revascularization use.

Differentiation of atypical parkinsonian syndromes with routine MRI.

OBJECTIVE: To evaluate the use of routine MRI in differentiating between patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD) and control subjects. METHODS: Two neuroradiologists rated blindly and independently axial T2-weighted and proton density MR images of 54 patients with MSA, 35 patients with PSP, 5 patients with CBD, and 44 control subjects. RESULTS: More than 70% of patients with PSP and more than 80% of patients with cerebellar predominant MSA could be classified correctly with 0.5-T or 1.5-T scans, and no patient in these groups was misclassified. In the remaining patients an unequivocal differentiation could not be made. However, only approximately 50% of patients with parkinsonism-predominant MSA could be classified correctly, and 19% of them (all of whom had had 0.5-T scans) were misclassified. CONCLUSIONS: Characteristic findings on routine MRI, either 1.5 T or 0.5 T, can contribute to the identification of MSA and PSP. However, in a minority of patients no unequivocal diagnosis can be made using MRI findings alone.

A novel methodological approach to study the level of specific protein and gene expression in aberrant crypt foci putative preneoplastic colonic lesions by Western blotting and RT-PCR.

Aberrant crypt foci (ACF) represent microscopic preneoplastic lesions, present in the carcinogen-treated rodent colons. The cellular and molecular changes occurring within these lesions may provide important clues to the sequence of events leading to advanced preneoplastic or neoplastic lesions. The main objective of this investigation was to determine whether intact mRNA and protein can be isolated from fixed tissue and studied. A pure population of ACF was harvested from colonic tissue that had been preserved in 70% ethanol or 10% buffered formalin, by using a dissecting microscope and plucking the ACF out using fine forceps. The standard procedure of isolating RNA was performed successfully on ACF and normal tissue preserved in 70% ethanol. The expression of a housekeeping gene, beta-actin was demonstrated. Analysis of ethanol-preserved ACF for phosphorylated proteins was carried out by immunoblotting. The present study demonstrated that ACF are easily harvested from fixed tissues and that intact RNA and protein can be isolated from ACF or normal epithelium which can be used in techniques such as immunoblotting and RT-PCR.

Pericardial effusion and tamponade due to Kaposi's sarcoma in acquired immunodeficiency syndrome.

We describe a 29-year-old homosexual man with acquired immunodeficiency syndrome who developed pericardial effusion and tamponade. Pericardiocentesis resulted in clinical improvement. All diagnostic tests on pericardial fluid were negative. At autopsy, extensive plaques and nodules of Kaposi's sarcoma were found studding the epicardium, and no other cause of effusion was found. To our knowledge there has been no previous case of Kaposi's sarcoma associated with pericardial effusion and tamponade reported in patients with AIDS. Kaposi's sarcoma should be considered in the differential diagnosis of pericardial effusion in these patients.

Development of REM sleep drive and clinical implications.

Rapid eye movement (REM) sleep in the human declines from approximately 50% of total sleep time ( approximately 8 h) in the newborn to approximately 15% of total sleep time (approximately 1 h) in the adult, and this decrease takes place mainly between birth and the end of puberty. We hypothesize that without this developmental decrease in REM sleep drive, lifelong increases in REM sleep drive may ensue. In the rat, the developmental decrease in REM sleep occurs 10-30 days after birth, declining from >70% of total sleep time in the newborn to the adult level of approximately 15% of sleep time during this period. Rats at 12-21 days of age were anesthetized with ketamine and decapitated, and brain stem slices were cut for intracellular recordings. We found that excitatory responses of pedunculopontine nucleus (PPN) neurons to N-methyl-D-aspartic acid decrease, while responses to kainic acid increase, over this critical period. During this developmental period, inhibitory responses to serotonergic type 1 agonists increase but responses to serotonergic type 2 agonists do not change. The results suggest that as PPN neurons develop, they are increasingly activated by kainic acid and increasingly inhibited by serotonergic type 1 receptors. These processes may be related to the developmental decrease in REM sleep. Developmental disturbances in each of these systems could induce differential increases in REM sleep drive, accounting for the postpubertal onset of a number of different disorders manifesting increases in REM sleep drive. Examination of modulation by PPN projections to ascending and descending targets revealed the presence of common signals modulating ascending arousal-related functions and descending postural/locomotor-related functions.

A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis.

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows assessment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory trials. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive techniques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T on two occasions 24-72 h apart using a conventional imaging protocol with T1-weighted MRI at single-dose (0.1 mmol/kg) Gd-DTPA and a potentially more sensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturation for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) were assessed. The total number of enhancing lesions seen was 347/75 on conventional brain/cord MRI respectively, and 754/123 on modified brain/cord MRI. The respective numbers of new enhancing lesions were 168/40 on conventional and 276/71 on modified scans. Smaller increases were seen in the proportion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study but a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either trial design. A combined modified brain and cord imaging protocol markedly improves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces sample size requirements for crossover studies but not necessarily for parallel design trials.

Bone mineral density and body composition in lean women with polycystic ovary syndrome.

OBJECTIVE: To examine bone mineral density (BMD) and fat distribution in lean women with polycystic ovary syndrome (PCOS) compared with matched control women. DESIGN: Controlled clinical study. SETTING: An academic clinical research center. PATIENT(S): Twelve non-Hispanic white women with PCOS and a body mass index of <26 and 10 healthy control women matched for age, ethnicity, and weight. INTERVENTION(S): Biometric measures, blood sample collection, and total body/regional bone density and fat analysis were performed. MAIN OUTCOME MEASURE(S): Serum levels of androgens, glucose, and insulin were measured. Bone density and fat distribution were measured by total body dual-energy x-ray absorptiometry. RESULT(S): Androgen levels were elevated significantly in the lean women with PCOS compared with the controls. There was no statistically significant difference in total body BMD between the two groups. A significant increase in BMD was noted in the left arm, right arm, and left ribs of the lean PCOS group. Evaluation of upper body BMD showed a significant correlation between testosterone levels and BMD. No statistically significant differences were noted in body fat distribution, although the lean PCOS group tended to have lower mean percentages of body fat. CONCLUSION(S): Lean women with PCOS have regional differences in BMD, with significantly increased BMD in the upper skeleton compared with control women.

Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long?

OBJECT: The authors examined images obtained in 52 children with intracranial ependymomas to determine risk factors for tumor recurrence and to assess the impact of surveillance imaging on patient outcome. METHODS: Data obtained in all children with intracranial ependymomas were prospectively entered into a database from January 1987 to June 2000. The imaging and clinical details in all patients were reviewed. Fifty-two children with histologically proven intracranial ependymomas were treated at the authors' institution; recurrences developed in 28 (54%) of them, with a median time from surgery to first recurrence of 14.5 months (range 3-65 months). Of these tumor recurrences, 43% were asymptomatic and were noted on surveillance imaging. Seventeen children died, all of whom had recurrences. Incomplete excision of the primary tumor was significantly associated with reduced time to recurrence (p = 0.0144) and time to death (p = 0.0472). The age of the patient, location of the primary tumor, histological findings, and the presence or absence of spinal metastases on preoperative imaging were not significantly associated with outcome. The risk of death at any given time was 12-fold greater in patients in whom a recurrence was identified due to symptoms rather than on surveillance images (p = 0.016). CONCLUSIONS: Recurrent childhood ependymoma has a poor prognosis. The extent of the initial local tumor resection is the factor most closely associated with outcome. Surveillance imaging reveals a substantial number of asymptomatic recurrences, and survival appears to be improved in these patients compared with those identified by symptoms. The improvement in survival is thought to be greater than that expected just from earlier diagnosis.

Pioneer medical missions in colonial Africa.

Protestant and Roman Catholic missions pioneered Western medicine and public health in much of Africa decades in advance of health services provided by colonial governments. A century later church-based hospitals and health care programs continue to account for 25% to 50% of available services in most African countries. In view of the important historical and continuing role of medical missions it is remarkable that there have been no systematic scholarly studies of the impacts of these pioneer institutions on the geography of health and social change in colonial Africa. How, for example, was the health of African populations and the areas they inhabited changed by the activities of medical missions? And how did Africans respond to Western medicine and its alien institutional social and technological structures and relations? This paper develops the historical context and conceptual framework for investigating such topics. It presents a detailed research agenda organized around nine themes, each of which suggests a series of interrelated questions. The methodology employs the techniques of medical and historical geography, and is based on comparative, longitudinal case-studies of medical missions at the local level coupled with archival study.