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Objectives: Degeneration of nigrostriatal neurons and subsequent striatal dopamine deficiency produce many of the symptoms of Parkinson disease (PD). Initially restoration of striatal dopamine with oral levodopa provides substantial benefit, [...]

Pleomorphic, enveloped, virus-like particles were detected by electron microscopy in the stools of symptomatic infants during an outbreak of gastrointestinal illness in a neonatal intensive-care unit. To determine the incidence of virus-like particles in the stool and their relation to gastrointestinal symptoms, eight surveys of stools for the particles were conducted over 40 weeks. The incidence of virus-like particles in the stool decreased from 69% to <10% over the study period. Most infants surveyed were premature; overall, 32 (36%) of 88 neonates were positive for virus-like particles. Statistically significant associations were found between virus-like particles in the stool and gastrointestinal symptoms within one week of each survey. These symptoms included water-loss stools, blood in the stool, gastric retention, bilious gastric aspirates, and abdominal distention. Several infants with virus-like particles whose mothers had gastrointestinal or “flu-like” symptoms before delivery were identified in the community (not part of the survey study). [ABSTRACT FROM PUBLISHER]

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults. [ABSTRACT FROM AUTHOR]

Summarizes the clinical course and outcome of Rocky Mountain Spotted Fever (RMSF) in four children from four regions of the United States. Details of cases in West Virginia, Michigan, Tennessee, and Oklahoma; Suggestion that doctors consider RMSF in children with rash and fever, especially those with a history of tick bite or who present during the April to September period when most cases occur.

On September 4, 2015, the West Virginia Bureau for Public Health (WVBPH) was notified by an urban ophthalmology practice of 13 patients with epidemic keratoconjunctivitis (EKC) diagnosed during the preceding 3 weeks. EKC is an eye infection characterized by severe inflammation of the conjunctiva and cornea, and can result in vision loss. Pathogens commonly detected in EKC outbreaks are human adenovirus (HAdV) serotypes 8, 19, and 37, which are spread person-to-person or by fomites; no vaccines or effective antiviral treatments are available. HAdVs that cause EKC are resistant to desiccation and certain common surface disinfectants. Incubation periods of approximately 14 days, prolonged viral shedding, and persistence of live virus on some surfaces for up to 30 days hamper outbreak prevention and control efforts. EKC often occurs simultaneously in health care settings and the community. EKC is not a reportable disease and outbreak reporting is often delayed; the incidence in West Virginia is unknown.

Front line staff identified skin tears and stage one pressure ulcers on post-surgical patients undergoing surgical interventions lasting longer than 2 hours. Collaboration between unit-based councils from the operating room, post-anesthesia care unit, and post-surgical units established a new process for early identification and prevention of surgical acquired pressure ulcers (SAPUs). Interdepartmental collaboration was essential to identifying patient safety concerns and developing a new process of pre-evaluation, early identification, and prevention of SAPUs. Specific skin evaluation reports were created to assess the occurrence and prevalence of SAPUs within moments of initial discovery and continuing through the remainder of hospitalization. Patients would have a skin assessment post-operatively performed by the operating room and post-anesthesia care unit nurses together. An internal prevalence study revealed occurrence rates of 7.1% before implementation of interventions. After evaluating 3,035 patients over 2 years and implementation of a new screening process, the prevalence rate was reduced to 3.3%. The resultant decline in SAPUs supports the value of this no-cost change in workflow., (Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Two small case series of platelet mitochondrial complex I activity assays in Huntington's Disease (HD) report discrepant results. We measured platelet complex I and complex I/III activity in 21 subjects with early gene-positive HD and 14 age-matched controls. The 21 participants with HD that we studied are greater than the total of 16 in the two previously published of platelet ETS activity in HD. Reductions > 10% were excluded with 80% confidence. A systemic defect in complex I activity is not present in early HD when striatal neuronal degeneration is already present.

Activity of complexes II, III, and IV of the mitochondrial electron transport system (ETS) is reduced in postmortem Huntington's disease (HD) striatum, suggesting that reduced cerebral oxidative phosphorylation may be important in the pathogenesis of neuronal death. We investigated mitochondrial oxidative metabolism in vivo in the striatum of 20 participants with early, genetically proven HD and 15 age-matched normal controls by direct measurements of the molar ratio of cerebral oxygen metabolism to cerebral glucose metabolism (CMRO(2)/CMRglc) with positron emission tomography. There was a significant increase in striatal CMRO(2)/CMRglc in HD rather than the decrease characteristic of defects in mitochondrial oxidative metabolism (6.0 +/- 1.6 vs. 5.1 +/- 0.9, P = 0.04). CMRO(2) was not different from controls (126 +/- 37 vs. 134 +/- 31 micromol 100 g(-1) min(-1), P = 0.49), whereas CMRglc was decreased (21.6 +/- 6.1 vs. 26.4 +/- 4.6 micromol 100 g(-1) min(-1), P = 0.01). Striatal volume was decreased as well (13.9 +/- 3.5 vs. 17.6 +/- 2.0 ml, P = 0.001). Increased striatal CMRO(2)/CMRglc with unchanged CMRO(2) is inconsistent with a defect in mitochondrial oxidative phosphorylation due to reduced activity of the mitochondrial ETS. Because HD pathology was already manifest by striatal atrophy, deficient energy production due to a reduced activity of the mitochondrial ETS is not important in the mechanism of neuronal death in early HD. Because glycolytic metabolism is predominantly astrocytic, the selective reduction in striatal CMRglc raises the possibility that astrocyte dysfunction may be involved in the pathogenesis of HD.

Parkinson disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies, since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than 3 standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to "PET definite PD." The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14 +/- 0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36 +/- 1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree., (Copyright 2006 Wiley-Liss, Inc.)

Manganese exposure reportedly causes a clinically and pathophysiologically distinct syndrome from idiopathic Parkinson's disease (PD). We describe the clinical features and results of positron emission tomography with 6-[18F]fluorodopa ([18F]FDOPA PET) of a patient with parkinsonism occurring in the setting of elevated blood manganese. The patient developed parkinsonism associated with elevated serum manganese from hepatic dysfunction. [18F]FDOPA PET demonstrated relatively symmetric and severely reduced [18F]FDOPA levels in the posterior putamen compared to controls. The globus pallidum interna had increased signal on T1-weighted magnetic resonance imaging (MRI) images. We conclude that elevated manganese exposure may be associated with reduced striatal [18F]FDOPA uptake, and MRI may reveal selective abnormality within the internal segment of the pallidum. This case suggests that the clinical and pathophysiological features of manganese-associated parkinsonism may overlap with that of PD., (Copyright 2005 Movement Disorder Society.)

We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon., ((c) 2004 Movement Disorder Society.)

Background: La Crosse encephalitis is a mosquito-borne disease that can be mistaken for herpes simplex encephalitis. It has been reported in 28 states but may be underrecognized., Methods: We investigated the manifestations and clinical course of La Crosse encephalitis in 127 patients hospitalized from 1987 through 1996. The diagnosis was established by serologic testing for IgM and IgG antibodies to La Crosse virus. Data were collected by chart review., Results: Most of the patients were school-aged children (mean [+/-SD] age, 7.8+/-3.5 years; range, 0.5 to 15.0). Symptoms included headache, fever, and vomiting (each in 70 percent or more of the patients), seizures (in 46 percent), and disorientation (in 42 percent). Thirteen percent had aseptic meningitis. Hyponatremia developed in 21 percent, and there were signs of increased intracranial pressure in 13 percent. Six patients, including three with cerebral herniation, underwent intracranial-pressure monitoring. The 13 patients (11 percent) whose condition deteriorated in the hospital had decreases in serum sodium levels (P=0.007), and increases in body temperature (P=0.003) at the time of deterioration. At admission, these patients more often had a history of vomiting (P=0.047) and a score of 12 or lower on the Glasgow Coma Scale (P=0.02) than the others; a trend toward a greater prevalence of seizures at admission was also evident in this group (P=0.07). All the patients survived, but 15 of them (12 percent) had neurologic deficits at discharge. Follow-up assessments, performed in 28 children, suggested an increase in cognitive and behavioral deficits 10 to 18 months after the episode of encephalitis., Conclusions: La Crosse virus infection should be considered in children who present with aseptic meningitis or encephalitis. Hyponatremia and increasing body temperature may be related to clinical deterioration.

Objective: To determine whether welding-related parkinsonism differs from idiopathic PD., Background: Welding is considered a cause of parkinsonism, but little information is available about the clinical features exhibited by patients or whether this is a distinct disorder., Methods: The authors performed a case-control study that compared the clinical features of 15 career welders, who were ascertained through an academic movement disorders center and compared to two control groups with idiopathic PD. One control group was ascertained sequentially to compare the frequency of clinical features, and the second control group was sex- and age-matched to compare the frequency of motor fluctuations., Results: Welders were exposed to a mean of 47,144 welding hours. Welders had a younger age at onset (46 years) of PD compared with sequentially ascertained controls (63 years; p < 0.0001). There was no difference in frequency of tremor, bradykinesia, rigidity, asymmetric onset, postural instability, family history, clinical depression, dementia, or drug-induced psychosis between the welders and the two control groups. All treated welders responded to levodopa. Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the two control groups. PET with 6-[18F]fluorodopa obtained in two of the welders showed findings typical of idiopathic PD, with greatest loss in posterior putamen., Conclusions: Parkinsonism in welders is distinguished clinically only by age at onset, suggesting welding may be a risk factor for PD. These preliminary data cannot exclude a genetic contribution to susceptibility in these exposed individuals.

We investigated the efficacy and safety of botulinum toxin A (BTX) manufactured from a new bulk strain for the treatment of cervical dystonia. This was a single-blinded retrospective comparison of length of benefit, subjective improvement, and complications of treatment in 50 patients treated with the old form of toxin designated 79-11 and the new toxin strain BCB2024. The mean duration of benefit of the 79-11 strain and the BCB2024 strain were the same. Subjective efficacy, measured on a -4 to +4 scale, demonstrated no difference between the two strains. Dysphagia occurred in 12% of patients injected with the 79-11 strain and 14% of subjects injected with the BCB2024 strain. We also used a clinician's global assessment that incorporated the duration of benefit, subjective efficacy, and complications as a secondary analysis. There was no significant difference between the two forms of botulinum toxin A according to this scale. We conclude that the 79-11 strain and the BCB2024 strain offer similar peak efficacy duration of benefit, and adverse events.

Systemic hypotension causes a greater degree of vasoconstriction in intestine from 3- than from 35-day-old postnatal swine. To determine the basis for this age-dependent difference, systemic hypotension (pressure reduction to approximately 50% of baseline) was induced by creating pericardial tamponade in postnatal swine instrumented to allow measurement of intestinal hemodynamics and oxygenation in vivo. Hypotension caused gut vascular resistance to increase 77 +/- 6% in 3-day-old subjects but only 18 +/- 3% in 35-day-old subjects. Prior blockade of alpha1-receptors with phentolamine, vasopressin receptors with [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP, or surgical denervation of the gut loop had no effect on hypotension-induced gut vasoconstriction. Losartan, which blocks angiotensin AT1 receptors, significantly attenuated hypotension-induced gut vasoconstriction in both age groups. BQ-610, which blocks endothelin ETA receptors, also limited the magnitude of vasoconstriction but only in younger subjects. This effect may have been consequent to an interaction between endothelin and angiotensin, inasmuch as a subpressor concentration of endothelin increased the contractile response to angiotensin in mesenteric artery rings. The substantial rise in 3-day-old gut vascular resistance was partly consequent to a locally mediated vasoconstriction that occurred in response to pressure and/or flow reduction during hypotension, as evidenced by the significant attenuation of this constriction when blood flow was held constant by controlled-flow perfusion to the gut loop during hypotension. Intestinal O2 uptake was compromised to a significantly greater degree in 3- than in 35-day-old subjects during hypotension. This difference was primarily due to the inability of younger intestine to increase O2 extraction in the face of reduced blood flow and may be mediated, in part, by an effect of angiotensin II on intestinal capillary perfusion.

Parkinson's disease (PD) is a progressive neurologic condition characterized by tremor, slowness, stiffness, and unstable posture. Degeneration of dopamine-producing neurons in the substantia nigra causes PD. Treatment with levodopa, a precursor of dopamine, initially ameliorates the clinical manifestations of PD. However, chronic levodopa treatment can produce severe involuntary movements (so-called dopa-induced dyskinesias or DID), limiting treatment. Pallidotomy, placement of a surgical lesion in the internal segment of the globus pallidus, reduces DID. Because this result is inconsistent with current theories of both basal ganglia function and DID, it prompted us to investigate the brain's response to levodopa. We measured regional cerebral blood flow response to levodopa with positron-emission tomography in 6 PD patients with DID, 10 chronically treated PD patients without DID, 17 dopa-naïve PD patients, and 11 normals. The dose of levodopa was chosen to produce clinical benefit without inducing DID. This strategy allowed us to examine the brain response to levodopa across groups without the confounding effect of differences in motor behavior. We found that the DID group had a significantly greater response in ventrolateral thalamus than the other groups. This was associated with decreased activity in primary motor cortex. These findings are consistent with increased inhibitory output from the internal segment of the globus pallidus to thalamus after levodopa administration. They provide a physiological explanation for the clinical efficacy of pallidotomy and new insights into the physiology of the basal ganglia.

In this study we have investigated the pathophysiology of two idiopathic focal dystonias: hand cramp with excessive cocontractions of agonist and antagonist hand or forearm muscles during specific tasks, such as writing, and facial dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial and jaw spasms (oromandibular dystonia). We used positron emission tomography (PET) to measure the in vivo binding of the dopaminergic radioligand [18F]spiperone in putamen in 21 patients with these two focal dystonias and compared the findings with those from 13 normals. We measured regional cerebral blood flow and blood volume in each subject as well as the radiolabeled metabolites of [18F]spiperone in arterial blood. A stereotactic method of localization, independent of the appearance of the images, was used to identify the putamen in all of the PET images. We analyzed the PET and arterial blood data with a validated nonsteady-state tracer kinetic model representing the in vivo behavior of the radioligand. An index of binding called the combined forward rate constant was decreased by 29% in dystonics, as compared with normals (p < 0.05). There were no significant differences between dystonics and normals in regional blood flow, blood volume, nonspecific binding, permeability-surface area product of [18F]spiperone or the dissociation rate constant. These findings are consistent with a decrease of dopamine D2-like binding in putamen and are the first demonstration of a receptor abnormality in idiopathic dystonia. These results have important implications for the pathophysiology of dystonia as well as for function of the basal ganglia.

Acute lower respiratory illnesses were prospectively investigated in a cohort of 1246 healthy infants who were enrolled at birth in the Tucson Children's Respiratory Study and followed through the first 3 years of life. Respiratory syncytial virus (RSV) infection was documented by culture, antigen detection or both in 276 episodes. In 21 (7.6%) of these 276, other viruses were simultaneously detected. Further serologic studies of 50 episodes in which RSV had been found increased the apparent viral codetection rate to 24%. When culture results for Chlamydia trachomatis and Mycoplasma pneumoniae were also considered, the rate of codetection was found to be 10.9% (30 of 276); this increased to 28% for the subgroup of episodes (14 of 50) that was further studied serologically. Illnesses associated with more than one agent were not significantly different from those involving RSV alone, with respect to month of onset, age at illness, illness type or duration of illness. We conclude that when RSV has been detected in previously healthy infants, routine searches for the concomitant presence of other viruses are usually not warranted.

Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.

During an 8-yr period, 862 stool specimens from patients with gastroenteritis were examined by electron microscopy after negative staining with 2% phosphotungstic acid (pH 6.5). Forty-one percent of the specimens submitted over an 8-yr period were determined to be positive for virus or viruslike particles belonging to one or more of seven morphologically distinct viral groups. Coronavirus-like particles (CVLPs) were present in 69.8% of the positive stool specimens. Membranous profiles containing "complement-type" holes (10 nm in diameter) were identified in some preparations containing CVLPs. The second most prevalent viral agent found in stool specimens was the rotavirus (17% of all positive stools). The incidence of other viruses identified in the survey were as follows: adenovirus 4.5%, picorna/parvovirus agents 2.9%, Norwalk-like agent 2.9%, astrovirus 1.9%, and calicivirus 0.5%. Unclassified small round viruses (approximately 25-30 nm in diameter) represented 0.5%. It was also determined that there was a seasonal distribution in excretion of all viruses except for CVLPs. A greater number of viruses were identified in the cooler, drier months of the year.

Coronaviruslike particles (CVLPs) were visualized by direct electron microscopy (EM) of diarrheal stools in 49 of 126 infants and children between 1 month and 12 years of age during a three-year observation period. The clinical and epidemiologic features of these patients were analyzed and compared with patients with diarrhea who were shedding rotaviruses, or whose stools were negative for enteric viruses by EM. Seasonal and age distributions for CVLP shedding were similar to those for rotaviruses (in most cases less than 1 year of age; peak months were September through January), as were the symptoms and median durations of illness. Prospective studies of three subsequent patients suggest that the duration of shedding in acute illness is five to at least 25 days. Multiple attempts to cultivate the CVLPs were unsuccessful. In addition, partial purification of CVLPs from stool specimens was performed, and immunologic analysis by immunoelectron microscopy and radial immunodiffusion showed no antigenic relatedness to prototype human (OC43 and 229E) or animal (bovine and canine) coronaviruses. These findings suggest that CVLPs may be an important cause of acute gastrointestinal illness in infancy, and may represent a virus antigenically unrelated to known human and animal coronaviruses.

A fluorescein isothiocyanate-conjugated pool of monoclonal antibodies (MoAb) to respiratory syncytial virus (RSV) was prospectively evaluated for its utility as a direct, 1-hr test for the diagnosis of RSV infection. Direct nasopharyngeal swab smears collected from 109 infants and children with acute respiratory illnesses were studied and compared with results obtained by indirect immunofluorescence using bovine polyclonal anti-RSV antibody on eluted cells derived from pooled nasopharyngeal and throat swab specimens (a 2.5-3 hr procedure), and culture. The MoAb-direct smear method was at least 86%-89% sensitive and 95%-100% specific compared with either of the other procedures. Additional prospective evaluations, as well as retrospective studies on a selected bank of slides stored from the preceding year, established that this MoAb could also be used with confidence in testing where direct smears are not employed.

Quantitation of T and B lymphocytes in infants and children is an important test in the diagnosis of a suspected immuno-deficiency. Previous studies indicated that the absolute and relative numbers of lymphocyte subpopulations vary with age, but these data in the pediatric age group are incomplete and often contradictory. We reviewed the literature and investigated the relationship between age and lymphocyte subpopulations in healthy infants and children using common methods and recent methodologic improvements. We found that absolute numbers of T and B cells followed the same trend as the total lymphocyte count, which was elevated at birth, increased in the first six months, and then gradually decreased to adult levels at approximately 13 years of age. Compared with adult values, the percentage of B cells also was higher at birth and continued to increase for six months, followed by a gradual decrease to adult levels by late childhood or early adolescence. The percentage of T cells gradually increased to adult levels by the same age range.

The purpose of this study was to evaluate, prospectively, the clinical usefulness of the rate nephelometric method for determining rheumatoid factor (RF) activity, measured in International Units (IU), in patients with rheumatoid arthritis. These results were compared with those of standard latex agglutination titration. The overall correlation between clinical activity and RF activity measured by rate nephelometry and serologic titration are similar, i.e., r = 0.47 (P less than 0.001) and r = 0.43 (p less than 0.001), respectively. However, on an individual patient basis, the nephelometric determination appears to correlate better with disease activity and response to therapy than do titers. The RF activity measured in IU would give the clinician a more sensitive and precise tool with which to follow RF activity in individual patients with active disease.