Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys.

OBJECTIVE: The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. APPROACH: To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. MAIN RESULT: A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. SIGNIFICANCE: FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Nerve cuff stimulation and the effect of fascicular organization for hand grasp in nonhuman primates.

The overall goal of this work is to introduce nerve cuff electrodes into upper extremity hand grasp systems. The first challenge is to develop a nerve cuff electrode that can selectively activate multiple hand functions from common upper extremity peripheral nerves. The Flat Interface Nerve Electrode (FINE) has shown selective stimulation capability in animal trials. The FINE wraps around the nerve and gently reshapes the nerve and aligns the fascicles within the nerve. Our hypothesis is that the FINE can selectively stimulate multi-fascicular nerves in the human upper extremity resulting in selective hand function. To assess the ability of the FINE to produce control of a hand with many degrees of freedom, we have tested the FINE in nonhuman primates. Fascicular organization and fascicle count are important factors to consider when determining electrode placement. The proximal nerve is an attractive electrode location to access both extrinsic and intrinsic muscles in the upper extremity. A challenge with the nonhuman primate model is that the nonhuman primate median and ulnar nerves both have uni-fascicular regions proximally. The human proximal median and ulnar nerves have an encouraging anatomy of multi-fasciculated nerves with redundant fascicles that may result in more selective hand function than is capable in the nonhuman primate.

Pathways to functional outcomes in schizophrenia: the role of premorbid functioning, negative symptoms and intelligence.

BACKGROUND: Social and intellectual premorbid functioning are generally estimated retrospectively, and related to clinical or hospitalization outcomes in schizophrenia. Yet the relationship between premorbid functioning assessed prior to psychiatric hospitalization and postmorbid functional outcomes has not been examined. OBJECTIVES: To test competing models of the relationship between (a) functional outcomes with (b) premorbid functioning assessed on nationally administered tests prior to psychiatric hospitalization, postmorbid intellectual functioning and symptomatology using a historical prospective design. METHODS: Ninety one inpatient and outpatient males with schizophrenia or schizoaffective disorder, aged 19 to 35, were examined using the Positive and Negative Syndrome Scale, the WAIS-III and Strauss and Carpenter social and occupational functional outcome scale. Premorbid intelligence and social functioning data were obtained from national standardized tests administered during high school prior to first hospitalization for schizophrenia. RESULTS: Path modeling showed that premorbid intelligence and behavioral functioning directly predicted postmorbid IQ and negative symptoms, and indirectly predicted postmorbid social and occupational functioning via negative symptoms. Item level analysis indicated that better social and occupational outcomes occurred in a group with few negative symptoms. CONCLUSIONS: Premorbid functioning, postmorbid IQ and negative symptoms are related, yet the relationship between premorbid functioning and postmorbid functional outcomes appears to be mediated by postmorbid negative symptoms.

Validity of the premorbid adjustment scale.

BACKGROUND: The aim of the current study was to test the predictive and concurrent validity of the Premorbid Adjustment Scale (PAS) by comparing it with another similar but more elaborate retrospective measure and with data collected during late adolescence. METHODS: We compared PAS late adolescence scores (age 16-18 years) of 91 males with schizophrenia or schizoaffective disorder with data on behavior collected in adolescence, before the first psychotic episode as part of standardized Draft Board screening, and with the same measure readministered during adulthood and modified to collect the same data again retrospectively. RESULTS: The correlation of the PAS social withdrawal and social relations items with the social behavior scale of the Draft Board were .76 and .80, respectively, for the concurrent ratings and .52 and .53, respectively, for the data collected at age 17 years. The correlation of the PAS school achievements and school adjustment items with the functioning in structured environments scale of the Draft Board were .71 and .72, respectively, for the concurrent ratings and .43 and .47, respectively, for the data collected at age 17 years. CONCLUSIONS: Our results support the predictive and concurrent validity of the PAS and the validity of self-reported data on premorbid functioning in persons with schizophrenia.

Accuracy of self-reported premorbid functioning in schizophrenia.

BACKGROUND: Information on premorbid functioning is often based on patients recalling their past. Premorbid functioning is relevant as it is associated with treatment response and other outcomes. The extent to which memory impairments of persons with schizophrenia may bias such reporting has not been investigated. The purpose of the current study was to assess the extent to which persons with schizophrenia might exhibit biased reporting relative to controls. METHODS: Seventy males with schizophrenia or schizoaffective disorder and 51 males with no psychiatric symptoms participated in the study. Contemporaneous and retrospective reports from a behavioral functioning assessment conducted as part of the Israeli Draft Board were compared. This assessment routinely administered to all 17 years old males in the country assesses social functioning, individual autonomy, organizational ability, physical activity and functioning in structured environments. We compared the groups on the Draft Board behavioral measures at age 17 and at re-assessment. We also examined the relationship between symptom severity, neuropsychological performance and differences between age 17 and current behavioral assessment scores. RESULTS: In a repeated measures MANCOVA of the five measures there was no overall significant difference in accuracy of reporting between persons with schizophrenia and those without. Both groups showed a slight tendency to glorify their past. Consistency of reporting was not significantly correlated with neuropsychological performance or levels of psychotic symptoms. CONCLUSIONS: We found that when reporting on personal and social functioning during teen age years persons with schizophrenia report with the same level of consistency as persons without schizophrenia. This suggests that self-report of premorbid functioning of persons with schizophrenia can be trusted as being reasonably accurate.

Increased incidence of cancer in adult Gaucher disease in Western Europe.

The adult form of Gaucher disease (type I GD) is associated with a high prevalence of hypergammaglobulinemia and monoclonal gammopathy of undetermined significance (MGUS). A significantly increased risk of cancer, especially of hematological types, has been found in Ashkenazi-Jewish GD type 1 patients. In this study, incidence and mortality of cancer were assessed in a total of 131 GD patients of mixed ancestry in a population from Western Europe, i.e. 2 Gaucher referral centers in Germany (Düsseldorf) and the Netherlands (Amsterdam). Standardized rate ratios were determined by indirect standardization, using age- and sex-specific incidence and mortality rates of the Dutch population. A total of 14 GD patients of non-Ashkenazi-Jewish descent were identified of whom 5 had a hematologic malignancy. These numbers correspond to an increased risk of cancer of 2.5 (95% CI 1.1-4.7) and an increased risk of hematologic cancer of 12.7 (95% CI 2.6-37.0) among GD patients compared to the general population. In particular, the incidences of multiple myeloma and hepatocellular carcinoma in absence of preexisting cirrhosis were highly elevated, with standardized rate ratios of 51.1 (95% CI 6.2-184) and 141.3 (95% CI 17.1-510.5), respectively. These strongly increased risks on developing cancer suggest that measures for early detection and prevention of hematological and hepatic malignancies in patients with Gaucher type I disease are mandatory.

Improvement in cognition associated with novel antipsychotic drugs: a direct drug effect or reduction of EPS?

BACKGROUND: Administration of novel, versus classic, antipsychotic agents to patients suffering from psychosis is associated both with moderately better scores on cognitive tests, and with fewer extrapyramidal symptoms (EPS). Because improved motor functioning may enable better performance on some components of cognitive test batteries, and because the advantages of the novel antipsychotics on cognitive performance are not very large, it is sometimes difficult to discern if improvement in a given cognitive task is due to a direct effect of the novel antipsychotic drug, or is secondary to the novel drug's decreased propensity to induce EPS. In an attempt to distinguish between these two possibilities, the present study examined the ability of patients suffering from schizophrenia receiving classic, versus novel antipsychotics, to perform a computerized visuo-motor test (VMT). VMT assesses planning capabilities, attention and executive functions known to be impaired in schizophrenia, which are suggested to be affected by novel antipsychotics. METHODS: Seventy-six patients suffering from schizophrenia or schizophreniform disorder, receiving haloperidol (23 patients, mean dose 10.01+/-6.1mg/day), olanzapine (26 patients, mean dose 10.56 +/- 4.9 mg/day) or risperidone (27 patients, mean dose 4.35 +/- 1.7 mg/day) were assessed for EPS using the parkinsonian subscale of the Extrapyramidal Symptom Rating Subscale (ESRS), and with the VMT. RESULTS: Cognitive functioning as measured by the VMT was better for patients receiving risperidone or olanzapine, compared with those receiving haloperidol (F=6.636, df=2,67, P=0. 002), while the patients receiving haloperidol or risperidone suffered from more severe EPS compared with the patients receiving olanzapine (F=3.996, df=2,71, P=0.023). DISCUSSION: Although the patients receiving risperidone suffered from EPS similar in severity to the EPS of the patients receiving haloperidol, their performance on a task involving visuo-motor and attentional skills was similar to that of the patients receiving olanzapine. This finding implies that there is a dissociation between the antipsychotic drug's ability to affect cognitive functioning, and EPS. This dissociation indirectly suggests that the advantages offered by novel antipsychotics on cognitive performance are a direct effect, rather than being entirely mediated by improved movement abilities.

Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease.

BACKGROUND: Chemotherapeutic treatment for patients with symptomatic coronary artery disease to reduce cardiovascular events may be initiated in response to elevated antibody titers against Chlamydia pneumoniae or cytomegalovirus. How antibody titers are associated with the endovascular presence of these microorganisms is still unclear. METHODS AND RESULTS: Antibody titers against C pneumoniae (microimmunofluorescence) and cytomegalovirus (ELISA) in patients undergoing primary (coronary desobliterates, n=80) or repeated CABG (occluded vein grafts, n=45) were correlated with the endovascular presence of the 2 microorganisms. C pneumoniae was detected by means of a nested polymerase chain reaction (PCR) and by culturing. Both conventional PCR and quantitative PCR were applied for detection of cytomegalovirus. C pneumoniae (PCR/culture) was detected in 19/9% (15/80 and 7/80) of coronary desobliterates and in 18/11% (8/45 and 5/45) of occluded vein grafts. There was no statistical evidence that IgG values differed between patients with or without C pneumoniae detection who were undergoing primary CABG. In contrast, repeated-CABG patients with a positive PCR (P=0.0027) or C pneumoniae culture (P=0.0018) had distinctly elevated IgG titers compared with patients in whom C pneumoniae was not detected. Cytomegalovirus could not be detected in the examined specimens. CONCLUSIONS: Cytomegalovirus infection does not seem to be associated with advanced coronary artery lesions. C pneumoniae antibody titers are not associated with the endovascular presence of C pneumoniae in patients with coronary artery disease. The observed strong association between elevated IgG titers and the detection of C pneumoniae in occluded vein grafts warrants further investigation.

Detection of Chlamydia pneumoniae but not cytomegalovirus in occluded saphenous vein coronary artery bypass grafts.

BACKGROUND: A causal relation between atherosclerosis and chronic infection with Chlamydia pneumoniae and/or cytomegalovirus (CMV) has been suggested. Whether the unresolved problem of venous coronary artery bypass graft occlusion is related to infection with C pneumoniae and/or CMV has not been addressed. METHODS AND RESULTS: Thirty-eight occluded coronary artery vein grafts and 20 native saphenous veins were examined. Detection of C pneumoniae DNA was performed by use of nested polymerase chain reaction (PCR). Homogenisates from the specimen were cultured for identification of viable C pneumoniae. Both conventional PCR and quantitative PCR for detection of CMV DNA were applied. Differential pathological changes (degree of inflammation, smooth muscle cell proliferation [MIB-1]) were determined and correlated to the detection of both microorganisms. C pneumoniae DNA could be detected in 25% of occluded vein grafts. Viable C pneumoniae was recovered from 16% of occluded vein grafts. Except for 1 native saphenous vein, all control vessels were negative for both C pneumoniae detection and culture. All pathological and control specimens were negative for CMV DNA detection. Pathological changes did not correlate with C pneumoniae detection. CONCLUSIONS: Occluded aorto-coronary venous grafts harbor C pneumoniae but not CMV. The detection of C pneumoniae in occluded vein grafts warrants further investigation.

The effect of topical fluoride agents on saliva secretion.

The aim of this study was to assess the possible influence of various topical fluoride agents on the rate of saliva secretion. Fifteen healthy volunteers, both males and females, aged 20-60 years, participated in this study. Aminfluorides and monofluorophosphate products in gel, toothpaste and rinse states were used. Each subject brushed or rinsed the teeth and mouth for 2 minutes. Secreted saliva was collected for 5 minutes. Salivary secretion was significantly greater after toothbrushing with aminfluoride compounds as compared to toothbrushing with monofluorophosphate. There was a tendency for an increased saliva flow rate with higher fluoride concentration of the aminfluoride.

Alcohol use in primiparous women older than 30 years of age: relation to infant development.

The effects of maternal alcohol use on mental development, growth, and dysmorphogenesis was studied in a sample of 1-year-old infants born to elderly primiparous mothers. Alcohol intake was measured using Jessor's AA score and a simple count of maximum number of drinks consumed in one day. Infant cognition was assessed using the Bayley Scale of Mental Development. Alcohol levels prior to, during, and following pregnancy were obtained. Alcohol intake was greatly reduced during pregnancy, returning to pregnancy levels following birth. A significant linear relationship between drinking prior to pregnancy and infant mental development was found. The average mental development score of infants whose mothers consumed less than or equal to 3, 3.3 to 29.7, or greater than or equal to 30 mL (less than or equal to 0.10, 0.11 to 0.99, or greater than or equal to 1.0 average fluid ounces) of absolute alcohol per day was 115, 108, and 95, respectively. Maximum number of drinks consumed in a day related to physical anomalies. No alcohol measure was significantly correlated with condition at birth, postnatal illness, or growth parameters of height, weight, and head circumference at 1 year. Deficits found were less pronounced than those reported in infants with fetal alcohol syndrome.

The dental management of patients with bipolar disorder.

Bipolar disorder (manic depressive disease) affects 1% of the United States population. These persons suffer from prolonged episodes of extreme elation and depression. There is a significant incidence of dental pathosis and a need for dental care among these patients. The medications used for the treatment of this disease, their physiologic effects, and their interactions with the drugs used in dentistry are reviewed.

Bone-marrow transplantation for metachromatic leucodystrophy.

An 11-month-old boy with late infantile metachromatic leucodystrophy was given a bone-marrow transplant (BMT) from an HLA-identical sister; 6 months later his cerebrospinal fluid leucocytes were exclusively of donor origin. Coupled with the patient's continued developmental progress, as assessed 33 months after the procedure, the findings suggest that BMT may be an effective treatment for some congenital metabolic disorders which affect the central nervous system.