Diphenyl Diselenide Through Reduction of Inflammation, Oxidative Injury and Caspase-3 Activation Abates Doxorubicin-Induced Neurotoxicity in Rats.

Neurotoxicity associated with chemotherapy is a debilitating side effect of cancer management in humans which reportedly involves inflammatory and oxidative stress responses. Diphenyl diselenide (DPDS) is an organoselenium compound which exhibits its anti-tumoral, anti-oxidant, anti-inflammatory and anti-mutagenic effects. Nevertheless, its possible effect on chemotherapy-induced neurotoxicity is not known. Using rat model, we probed the behavioral and biochemical effects accompanying administration of antineoplastic agent doxorubicin (7.5 mg/kg) and DPDS (5 and 10 mg/kg). Anxiogenic-like behavior, motor and locomotor insufficiencies associated with doxorubicin were considerably abated by both DPDS doses with concomitant enhancement in exploratory behavior as demonstrated by reduced heat maps intensity and enhanced track plot densities. Moreover, with exception of cerebral glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, biochemical data demonstrated reversal of doxorubicin-mediated decline in cerebral and cerebellar antioxidant status indices and the increase in acetylcholinesterase (AChE) activity by both doses of DPDS. Also, cerebellar and cerebral lipid peroxidation, hydrogen peroxide as well as reactive oxygen and nitrogen species levels were considerably diminished in rats administered doxorubicin and DPDS. In addition, DPDS administration abated myeloperoxidase activity, tumour necrosis factor alpha and nitric oxide levels along with caspase-3 activity in doxorubicin-administered rats. Chemoprotection of doxorubicin-associated neurotoxicity by DPDS was further validated by histomorphometry and histochemical staining. Taken together, DPDS through offsetting of oxido-inflammatory stress and caspase-3 activation elicited neuroprotection in doxorubicin-treated rats.

Revascularization of near total amputation of the hand: A viable salvage procedure in a resource-constraint setting.

Traumatic near total amputation of the hand with major vascular injury may lead to loss of the hand with dire consequences to the patient. A prompt attempt at salvaging the hand is key to prevent the untoward consequences. In addition, the awareness of the possibility of salvage in our environment should be spread among health care personnel as well as the need for multispecialty approach to the management. We report 2 patients with near total unilateral amputation of their hands proximal to the wrist who underwent salvage procedures.

Caring for Children with Congenital Heart Diseases:Economic Burden of Pre-Surgical Management on Nigerian Families.

BACKGROUND AND OBJECTIVES: Managing children with Congenital Heart Disease (CHD) attracts enormous cost especially in resource-poor settings like Nigeria. This study sought to determine the healthcare costs of pre-surgical management of CHD and describe its catastrophic effects on households. METHODS: Using a semi-structured interviewer-administered questionnaire, caregivers of children with CHD were interviewed. Family income, type of CHD, co-morbidity, healthcare payment mechanism and healthcare cost were explored over 3 months prior to the study. Healthcare costs were then averaged to obtain monthly estimates. Catastrophic health expenditure (CHE) was defined as healthcare spending above 10% family monthly income. Factors associated with increased healthcare spending in CHD management were explored using the Kruskal Wallis test of significance. RESULTS: Of the 108 parents interviewed, 81.0% paid for healthcare using out-of-pocket payment mechanism. The median direct monthly medical and non-medical costs were N==3,625 (range: N==200 - N==59,350) [$10.07; range:$0.56-$164.86] and N==420 (range: N==150 -N ==11,000) [$1.17; range $0.42-$30.56] respectively. Hospitalisation and transportation accounted for majority of the direct medical and non-medical costs, respectively. About 36.1% of families suffered financial catastrophe. Catastrophic overshoot and mean positive overshoot were 5.6% and 30.8% above the 10% income threshold, respectively. The healthcare spending was significantly higher in families of children with CHD complicated with heart failure (p=0.001) and pulmonary hypertension (p=0.038) and those who suffered financial catastrophe (p=0.001). Health insurance did not significantly reduce healthcare spending among the insured(p=0.630). CONCLUSION: The economic burden of pre-surgical management of children with CHD is high in Nigeria. Appropriate interventions governmental and non-governmental organisations are needed to cushion the burden of healthcare costs on affected families.

Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder.

ANK3, encoding the adaptor protein Ankyrin-G (AnkG), has been implicated in bipolar disorder by genome-wide association studies. ANK3 has multiple alternative first exons, and a bipolar disorder-associated ANK3 variant has been shown to reduce the expression of exon 1b. Here we identify mechanisms through which reduced ANK3 exon 1b isoform expression disrupts neuronal excitation-inhibition balance. We find that parvalbumin (PV) interneurons and principal cells differentially express ANK3 first exon subtypes. PV interneurons express only isoforms containing exon 1b, whereas excitatory principal cells express exon 1e alone or both 1e and 1b. In transgenic mice deficient for exon 1b, PV interneurons lack voltage-gated sodium channels at their axonal initial segments and have increased firing thresholds and diminished action potential dynamic range. These mice exhibit an Ank3 gene dosage-dependent phenotype including behavior changes modeling bipolar disorder, epilepsy and sudden death. Thus ANK3's important association with human bipolar susceptibility may arise from imbalance between AnkG function in interneurons and principal cells and resultant excessive circuit sensitivity and output. AnkG isoform imbalance is a novel molecular endophenotype and potential therapeutic target.

Cohort event monitoring of patients treated for uncomplicated malaria with artemisinin-based combination therapies in selected hospitals and community pharmacies in Nigeria.

AIMS AND OBJECTIVES: The study was designed with the broad objective of determining the safety profile of artemisinin-based combination therapies amongst Nigerian population. PATIENTS AND METHODS: This was a cohort event monitoring (CEM) programme involving monitoring adverse events (AEs) in malaria patients treated with either artemether-lumefantrine (AL) or artesunate-amodiaquine (AA) in healthcare facilities in Nigeria. The study involved continuous enrolment of patients with malaria and treated with either AL or AA at the various sites until a total cohort of 600 patients were enrolled at each site. Patients were monitored from the onset of therapy, and on days 3 and 7 from the first day of treatment to identify AEs that may occur. RESULTS: A total of 6102 AEs were recorded in 10,259 patients monitored during the programme. Of 4896 patients who received AA, 4233 (86.5%) patients reported at least one AE while 1869 (34.8%) AEs out of 5363 patients who received AL were reported (P = 0.010). The predominant incidence of each specific AE reported in each group among the patients who received AA and AL includes body weakness 30.8%/7.5%, dizziness 10.3%/3.9%, restlessness 5.02/1.12%, vomiting 3.5/1.03% and drowsiness 3.1/1.5% for AA and AL, respectively. There were more AEs among patients with co-morbid conditions and patients in the younger age groups (9-<15 years), P = 0.000. CONCLUSIONS: Various types of AEs were seen and documented during the CEM programme. The findings suggested that the AA/AL monitored during this programme was generally safe and remarkably well tolerated among the Nigerian populations.

Suitability of stem latex of jatropha gossypifolia as a protein precipitant for biochemical analysis.

The extract of Jatropha Gossypifolia stem was obtained by cutting the stem with a sharp knife and the fluid expressed out. The suitability of the stem latex extract as a precipitant for biochemical analysis was determined. The precipitating efficacy of the extract for creatinine and protein estimation was found to be optimum at 1/4 and 1/5 dilutions respectively aqueous solution. Plasma protein was precipitated with stem extract of J. Gossypifolia at the stated dilution. The mean plasma creatinine values obtained from 0.5 % sodium tungstate as a protein precipitant were compared with the values of plasma creatinine obtained when » dilution of stem extract of J. Gossypifolia was used as protein precipitant. Similarly mean cerebrospinal fluid (CSF) and urinary protein values obtained from 3 % Tricholoro-acetic acid as protein precipitant were compared with values obtained from 1/5 dilution of stem extract of J. Gossypifolia as protein precipitant. The values obtained from the stem latex extract at the stated dilutions were comparable with values obtained from the conventional protein precipitants (p < 0.05). The stem latex extract of J. Gossypifolia is suitable as a protein precipitant for creatinine, CSF and urinary protein estimations. However further work need to be done to purify the extract and determine the exact concentration at the stated dilutions as well as the active ingredient in stem latex.

Experimental and computational approach on the development of a new Green corrosion inhibitor formulation for N80 steel in 20% formic acid.

Organic acids are employed as scale dissolvers in the oil & gas industry during production to stimulate oil recovery by pumping in the formations. Corrosion of metallic surfaces in organic acid solutions poses a significant issue in the oil and gas sector. In recent years, considering the stringent environmental regulations, there has been a growing research interest in environmentally safe inhibitors. This paper explores the synthesis of 2-(3-(carboxymethyl)-1H-imidazol-3-ium-1-yl) acetate (IZ) and its first-time application for corrosion mitigation of N80 steel in 20% formic acid. A detailed experimental study involving gravimetric, electrochemical, and surface analytical techniques is reported herein. The electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) analyses suggest a rise of impedance with IZ and a mixed-type inhibition behavior, respectively. The inhibition efficiency (IE) is 99.54% at 200 mg/L at 308 K, reaching 99.4% at 363 K with the introduction of KI as a synergistic agent. Computational studies revealed that the inhibitor IZ gets protonated in the experimental environment. The protonated form shows a tendency to receive electrons from the metal surface and shows a greater energy of adsorption compared to that of the neutral form.

Persistent oxidative injury and neurobehavioral impairment in adult male and female Nauphoeta cinerea exposed to perfluorooctanoic acid.

This study aimed to elucidate if the toxicity of perfluorooctanoic acid (PFOA), an emerging persistent organic contaminant, is reversible or not in adult male and female Nauphoeta cinerea. Both sexes of Nauphoeta cinerea were separately exposed to 0, 1 and 5 mg/L PFOA in drinking water for 21 consecutive days. PFOA-exposed Nauphoeta cinerea exhibited significant deficits in the locomotor and exploratory capabilities with concomitant increase in anxiogenic behaviors which persisted after cessation of PFOA exposure. Moreover, PFOA-induced decrease in acetylcholinesterase activity persisted after cessation of PFOA exposure in both insects' sexes. Catalase and superoxide dismutase activities were increased in the midgut but restored to control following cessation of PFOA exposure. The increased reactive oxygen and nitrogen species, nitric oxide and hydrogen peroxide levels persisted in the head whereas they were abated in the midgut after cessation of PFOA exposure. However, PFOA-induced persistent increase in lipid peroxidation and protein carbonyl levels in the head and midgut of insects. Collectively, PFOA exposure elicited persistent neurobehavioral and oxidative injury similarly in both sexes of adult Nauphoeta cinerea during this investigation.

'Research is the last thing on our minds, we are in crisis': Experiences of Lagos state nurses towards research and scholarly endeavours.

AIM: To explore the experiences of Nigerian nurses in research and scholarly endeavours. DESIGN: Descriptive phenomenological qualitative study design. METHOD: In-depth interviews were conducted among 30 nurses until data saturation was reached. Data were analysed using the thematic analysis method, and consolidated criteria for reporting qualitative research guidelines (COREQ) were adhered to in reporting this study. RESULTS: Three themes emerged: (1) challenges of nurses with research; (2) the state of nursing research in Lagos state; (3) strategies to improve the state of nursing research in Lagos state. Some challenges nurses in Lagos State encounter with research include heavy workload and nursing shortage due to brain drain, faulty research foundation, lack of continuing education in research and the stressful nature of conducting research in Lagos. CONCLUSION: As research is essential in addressing healthcare challenges, policymakers are encouraged to employ more nurses to reduce the workload and provide time for research activities. Training and continuing education in research can be incorporated into professional development programmes. Lagos State will benefit from nursing research units in the hospitals, and a coordinating centre for the units should be provided with adequate funding. Support could be obtained from the Institute of Nursing Research Nigeria in establishing these structures. Hospital management should embrace and welcome research output from nurses and ensure such results are implemented to improve patients' care. Nurses who excel in research might be recognised with awards and other incentives to inspire their peers.

Attenuation of doxorubicin-induced hypothalamic-pituitary-testicular axis dysfunction by diphenyl diselenide involves suppression of hormonal deficits, oxido-inflammatory stress and caspase 3 activity in rats.

BACKGROUND: Doxorubicin (DOX) is one of the popular anti-cancer drugs in the world and several literatures have implicated it in various toxicities especially cardiotoxicity and reproductive toxicity. Diphenyl diselenide (DPDS) is well acknowledged for its compelling pharmacological effects in numerous disease models and chemically-mediated toxicity. This study was carried out to investigate the effect of DPDS on DOX-induced changes in the reproductive indices of male Wistar rats. METHODS: Rats were intraperitoneally injected with 7.5 mg/kg body weight of DOX alone once followed by treatment with DPDS at 5 and 10 mg/kg for seven successive days. Excised hypothalamus, testes and epididymis were processed for biochemical and histological analyses. RESULTS: DPDS treatment significantly (p < 0.05) abated DOX-induced oxidative damage by decreasing the levels of oxidative stress indices such as hydrogen peroxide, reactive oxygen and nitrogen species, and lipid peroxidation with a respective improvement in the level of glutathione in the hypothalamic, testicular and epididymal tissues of DOX-treated rats. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase were upregulated in the DPDS co-treated group. DPDS co-treatment alleviates the burden of DOX-induced inflammation by significant reductions in myeloperoxidase activity, levels of nitric oxide and tumor necrosis factor alpha with concomitant decline in the activity of caspase-3, an apoptotic biomarker. Consequently, significant improvement in the spermiogram, levels of reproductive hormones (follicle stimulating hormone, luteinizing hormone, prolactin, serum testosterone and intra-testicular testosterone) levels in the DPDS co-treatment group in comparison to DOX alone-treated group were observed. Histology results of the testes and epididymis showed that DPDS significantly alleviated pathological lesions induced by DOX in the animals. CONCLUSION: DPDS may modulate reproductive toxicity associated with DOX therapy in male cancer patients.

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents.

OBJECTIVES: Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. METHODS: Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. RESULTS: The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. CONCLUSIONS: The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

Datura stramonium abrogates depression- and anxiety-like disorders in mice: possible involvement of monoaminergic pathways in its antidepressant activity.

OBJECTIVES: Ethno-botanical surveys uncovered the use of Datura stramonium in the management of mental health abnormalities. Antidepressant- and anxiolytic-like activities of hydroethanol leaf extract of D. stramonium (HLDS) in mice and its possible mechanism of action were investigated in this study. METHODS: The hole-board test (HBT), open field test (OFT), elevated plus maze test (EPMT), and social interaction test (SIT) were used to investigate the anxiolytic-like activity while forced swim test (FST) and tail suspension test (TST) were employed for the antidepressant effect. Mice were pre-treated orally with purified water (10 mL/kg), bromazepam (1 mg/kg), fluoxetine (20 mg/kg) and D. stramonium (25, 50, 100 and 200 mg/kg). One hour post-treatment, mice were subjected to the various tests. RESULTS: In HBT, D. stramonium increased the head dips and sectional crossings turnover. D. stramonium increased the number of square crossed and rearings/assisted rearings in OFT. DS increased the time spent in open arms of EPM. In SIT, D. stramonium increased the frequency/duration of interactions. In FST and TST, D. stramonium decreased the duration of immobility which were reversed by doxazosin (α1 adrenoceptor antagonist) and ondasentron (5-HT3 receptor antagonist). CONCLUSIONS: HLDS has anxiolytic- and antidepressant-like activities through modulation of serotoninergic and adrenergic neurotransmissions.

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents.

OBJECTIVES: Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. METHODS: Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. RESULTS: The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. CONCLUSIONS: The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

The synergistic influence of polyethyleneimine-grafted graphene oxide and iodide for the protection of steel in acidizing conditions.

Herein, graphene oxide (GO) was chemically functionalized with polyethyleneimine (PEI) in a single step to obtain PEI-GO, which was characterized via FTIR spectroscopy, SEM, and TEM. Additionally, for the first time, PEI-GO was employed for the corrosion mitigation of carbon steel in a solution of 15% HCl. The corrosion performance of the inhibitor was evaluated by utilizing weight loss tests, electrochemical measurements with impedance analysis, electrochemical frequency modulation, and potentiodynamic polarization studies. Thorough surface analysis was performed using 3D profilometry and static water contact angle measurements. PEI-GO was adsorbed on the steel surface and showed mixed-type corrosion inhibition behavior with the prevalence of cathodic characteristics. Additionally, potassium iodide was incorporated in the acid solution as a synergistic agent to enhance the corrosion inhibition behavior of PEI-GO. The obtained results showed that PEI-GO alone provided a high corrosion inhibition efficiency of 88.24% at a temperature of 65 °C and in the presence of KI, it showed an I.E. of 95.77% due to their synergistic effect. These interesting results demonstrate that PEI-GO can act as a potential corrosion inhibitor in acidizing conditions. The DFT-based computational studies showed that the inhibitor functioned in both its neutral and protonated forms.

Community gate keepers' awareness and perception of prevention of mother-to-child transmission of HIV services in Ibadan, Nigeria.

Each year, around half a million children aged under 15 become infected with HIV and more than 90% are the result of mother-to-child transmission. Services to prevent mother-to-child HIV transmission (PMTCT) are therefore important entry points for HIV/AIDS prevention, treatment and care services for women, their children and families. The study aimed at identifying level of awareness and knowledge of PMTCT services that can be utilized in improving access. The methodology consisted of 20 individual in-depth interviews spread over Adabeji, Adeoyo/Agbadagbudu, Jakiru/Onipasan and Eleta communities, in Ibadan among household heads, religious and community based leaders. Key factors identified were low knowledge of mother to child transmission, lack of knowledge of the PMTCT services, inadequate community sensitization, inadequate healthcare facilities. The success of PMTCT programmes demands a shift towards a more community-based approach which calls for strong advocacy, enlightenment and community mobilization for improved awareness and utilization of PMTCT services.

Factors predicting failure of labour induction.

Our objective was to identify risk factors for failed labour induction. From January 2001 to December 2005, we conducted a retrospective case-control study in a Nigerian University Hospital. Cases were women who failed to deliver vaginally after labour induction, and therefore had caesarean section. Controls were patients who were similarly induced and achieved vaginal delivery. Univariate followed by Logistic regression analysis were performed. Failed induction occurred in 37.6%. Variables significantly and independently associated with failed induction were cervical effacement < 70% (adjusted odds ratio [OR] 5.12; 95% confidence interval [CI] 2.65-9.90), Bishop's score < 6 (OR 3.47; CI 1.75 - 6.85), nulliparity (OR 3.91; CI 1.92 - 7.99). Prolonged pregnancy independently reduced failure rate (OR 0.44: CI 0.24 - 0.81). These variables can help determine patients that will require early recourse to caesarean delivery in order to avoid prolonged induction-delivery interval.

Fatal Epstein-Barr virus meningitis: an autopsy report.

A 3-year-old Asian female presented with fever for 1 week and neck swelling for 1 day. Serology revealed a recent Epstein-Barr virus (EBV) infection. Late on the evening of admission, she developed confusion and would not follow commands. A CT scan showed diffuse cerebral edema and a cerebral flow scan demonstrated no blood flow to the brain. She was declared brain dead and expired on the following day. At autopsy, the brain weighted 1175 grams and grossly showed significant edema. Microscopically, the entire neuraxis revealed extensive leptomeningeal infiltrate of mainly CD8+ T lymphocytes, the majority of which expressed activated markers, HLA-DR and/or CD45RO, and monocytes/macrophages with intermixed numerous apoptotic/karyorrhectic nuclear fragments. These nuclear fragments were considered to be due to apoptosis of the expanded population of CD8+ T lymphocytes. Focal venulitis was noted. EBV-encoded small nuclear RNA in situ hybridization revealed positivity in the occasional lymphocytes. Interestingly, most intraparenchymal as well as leptomeningeal vascular endothelium showed HLA-DR immunoreactivity. This finding has been reported primarily in the acute inflammatory/demyelinating conditions, not in the viral meningitis/meningoencephalitis, and was thought to be related to cytokines due to widespread inflammation in our case. Massive edema secondary to severe EBV-meningitis can be fatal.

p53 gene mutation and mdm2 gene amplification are uncommon in medulloblastoma.

Loss of heterozygosity is common for the short arm of chromosome 17 in medulloblastomas, and putative medulloblastoma suppressor loci have been localized to 17p13. The colocalization of the p53 tumor suppressor gene to 17p13 raises the possibility that its mutant alleles may play a role in the malignant transformation of "medulloblasts." Mutations and deletions of the p53 gene have been described in many tumor types and in the germline of some individuals with the Li-Fraumeni syndrome, but reports on the status of the p53 and mdm2 (a gene coding for a p53-associated protein reportedly amplified in human sarcomas) genes in medulloblastomas are few and an indication of their roles, if any, in the etiology of this important childhood tumor has yet to emerge. Here we have analyzed polymerase chain reaction-amplified products of exons 4-9 (95% of reported p53 mutations occur within this region) of the p53 gene in 9 medulloblastomas for potential mutations using the technique of single strand conformation polymorphism analysis and DNA sequencing. We found only one mutation, an A-T to T-A transversion involving the second base of codon 285 and resulting in the substitution of valine for glutamic acid, amplification of the mdm2 gene could be detected in zero of eight of these tumors. These findings suggest that genetic events associated with the inactivation of p53 gene occur in only a minor subset of medulloblastomas.

MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder caused by thymidine phosphorylase (TP) deficiency, resulting in severe gastrointestinal dysmotility and skeletal muscle abnormalities. A patient is reported with a classical MNGIE clinical presentation but without skeletal muscle involvement at morphological, enzymatic, or mitochondrial DNA level, though gastrointestinal myopathy was present. MNGIE was diagnosed by markedly raised plasma thymidine and reduced thymidine phosphorylase activity. Molecular genetic analysis showed a homozygous novel splice site mutation in TP. On immunohistochemical studies there was marked TP expression in the CNS, in contrast to what has been observed in rodents. It is important to examine the most significantly affected tissue and to measure TP activity and plasma thymidine in order to arrive at an accurate diagnosis in this condition.

Benign autosomal dominant syndrome of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and dementia.

We present a kindred with a previously undescribed combination of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and mild dementia. The propositus, a 72-year-old man, had pes cavus, peripheral neuropathy, ptosis, parkinsonism, hyperreflexia, orthostatic hypotension, central hypoventilation, and mild dementia. Peripheral electrophysiologic studies showed features of an axonal neuropathy. The electroencephalogram showed intermittent 2 to 4 Hz activity symmetrically in the hemispheres. Several family members in 3 generations had pes cavus, neuropathy, ptosis, parkinsonism, and dementia although not all of the features were consistently present. Survival past the 7th decade was common. Autopsy in 2 affected members revealed the neuropathy to be axonal in type and showed mild to moderate loss of anterior horn cells in the spinal cord and pigmentary loss with gliosis in the substantia nigra. This is a unique, benign, autosomal dominant syndrome which shows complete penetrance, variable expression, and both central and peripheral nervous system involvement.