The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Jan 12, 2001
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when adm... more Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [ 11 C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (Ͻ6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, ϩ19%; putamen, ϩ16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.
Objective: The role of dopamine in the addictive process (loss of control and compulsive drug int... more Objective: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D 2 receptors. In cocaine abusers, low levels of D 2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when adm... more Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [ 11 C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (Ͻ6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, ϩ19%; putamen, ϩ16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when adm... more Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +...
IEEE MTT/ED/AP/LEO Societies Joint Chapter United Kingdom and Republic of Ireland Section. 1997 Workshop on High Performance Electron Devices for Microwave and Optoelectronic Applications. EDMO (Cat. No.97TH8305), 1997
During the past 5 years numerous mixed signal circuits have been designed, processed, and charact... more During the past 5 years numerous mixed signal circuits have been designed, processed, and characterized based on our 0.2 μm gate length AlGaAs/GaAs/AlGaAs E/D quantum well HEMT technology. Utilizing the inherent advantages of this material system, optical, analogue, microwave, and digital functions have been integrated monolithically. Examples are a chip set for 40 Gbit/s optoelectronic data transmission system, PLL circuits
Background. Little is known on the prevalence of peripheral artery disease (PAD) in developing co... more Background. Little is known on the prevalence of peripheral artery disease (PAD) in developing countries. Study design. Population-based study in Atahualpa. In Phase I, the Edinburgh claudication questionnaire (ECQ) was used for detection of suspected symptomatic PAD; persons with a negative ECQ but a pulse pressure ≥65 mmHg were suspected of asymptomatic PAD. In Phase II, the ankle-brachial index will be used to test reliability of screening instruments and to determine PAD prevalence. In Phase III, participants will be followed up to estimate the relevance of PAD as a predictor of vascular outcomes. Results. During Phase I, 665 Atahualpa residents aged ≥40 years were enrolled (mean age: 59.5 ± 12.6 years, 58% women). A poor cardiovascular health status was noticed in 464 (70%) persons of which 27 (4%) had a stroke and 14 (2%) had ischemic heart disease. Forty-four subjects (7%) had suspected symptomatic PAD and 170 (26%) had suspected asymptomatic PAD. Individuals with suspected P...
An abnormal ankle-brachial index has been associated with overt stroke and coronary heart disease... more An abnormal ankle-brachial index has been associated with overt stroke and coronary heart disease, but little is known about its relationship with silent cerebral small vessel disease. To assess the value of ankle-brachial index as a predictor of silent small vessel disease in an Ecuadorian geriatric population. Stroke-free Atahualpa residents aged ≥60 years were identified during a door-to-door survey. Ankle-brachial index determinations and brain magnetic resonance imaging were performed in consented persons. Ankle-brachial index ≤0·9 and ≥1·4 were proxies of peripheral artery disease and noncompressible arteries, respectively. Using logistic regression models adjusted for age, gender, and cardiovascular health status, we evaluated the association between abnormal ankle-brachial index with silent lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. Mean age of the 224 participants was 70 ± 8 years, 60% were women, and 80% had poor cardiovascular health status. Ankle-brachial index was ≤0·90 in 37 persons and ≥1·4 in 17. Magnetic resonance imaging showed lacunar infarcts in 27 cases, moderate-to-severe white matter hyperintensities in 47, and cerebral microbleeds in 26. Adjusted models showed association of lacunar infarcts with ankle-brachial index ≤ 0·90 (OR: 3·72, 95% CI: 1·35-10·27, P = 0·01) and with ankle-brachial index ≥ 1·4 (OR: 3·85, 95% CI: 1·06-14·03, P = 0·04). White matter hyperintensities were associated with ankle-brachial index ≤ 0·90 (P = 0·03) and ankle-brachial index ≥ 1·4 (P = 0·02) in univariate analyses. There was no association between ankle-brachial index groups and cerebral microbleeds. In this population-based study conducted in rural Ecuador, apparently healthy individuals aged ≥60 years with ankle-brachial index values ≤0·90 and ≥1·4 are almost four times more likely to have a silent lacunar infarct. Ankle-brachial index screening might allow recognition of asymptomatic people who need further investigation and preventive therapy.
Time-lapse imaging of human preimplantation IVF embryos has enabled objective algorithms based on... more Time-lapse imaging of human preimplantation IVF embryos has enabled objective algorithms based on novel observations of development (morphokinetics) to be used for clinical selection of embryos. Embryo aneuploidy, a major cause of IVF failure, has been correlated with specific morphokinetic variables used previously to develop an aneuploidy risk classification model. The purpose of this study was to evaluate the effectiveness and potential impact of this model for unselected IVF patients without biopsy and preimplantation genetic screening (PGS). Embryo outcomes - no implantation, fetal heart beat (FHB) and live birth (LB) - of 88 transferred blastocysts were compared according to calculated aneuploidy risk classes (low, medium, high). A significant difference was seen for FHB (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and LB (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) rates between embryos classified as low and medium risk. Within the low-risk class, relative increases of 74% and 56%, compared with rates for all blastocysts, were observed for FHB and LB respectively. The area under the receiver operating characteristic curve was 0.75 for FHB and 0.74 for LB. This study demonstrates the clinical relevance of the aneuploidy risk classification model and introduces a novel, non-invasive method of embryo selection to yield higher implantation and live birth rates without PGS.
Health care concepts and practices are changing dramatically because of demographic and economic ... more Health care concepts and practices are changing dramatically because of demographic and economic factors. The routine integration of behavioral and biomedical care is completely compatible with these changes and such integration would provide clinical and economic benefits to patients and to society.
The International Journal of Psychiatry in Medicine, 2005
These case reports examine the potential efficacy and safety of ziprasidone for the treatment of ... more These case reports examine the potential efficacy and safety of ziprasidone for the treatment of agitation or psychosis in dementia. The authors performed a retrospective chart review of three patients with DSM-IV diagnoses of dementia, treated with ziprasidone for agitation/psychosis on an academic psychiatric inpatient unit in 2002-2003. In addition, these three case reports are supplemented by a clinical report of the first outpatient with DSM-IV diagnosis of dementia completing a prospective open-label six-week study in 2004 evaluating the use of oral ziprasidone for agitation/psychosis in dementia. Qualitative descriptions of clinical improvement provide outcome data for these case reports. Four patients with dementia with agitation/psychosis experienced marked behavioral improvement after receiving oral doses of ziprasidone (20-160 mg/day), without any evidence of problematic cardiac or other side-effects. Two of the four patients had final EKGs and both of these patients demonstrated no change of QTc interval after administration of ziprasidone. These case reports suggest that oral ziprasidone may be an effective and safe medication for the treatment of agitation or psychosis in patients with dementia.
International Journal of Geriatric Psychiatry, 2005
To assess the prevalence of physical aggression against caregivers by Alzheimer&amp;amp;amp;a... more To assess the prevalence of physical aggression against caregivers by Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s patients. One hundred and ninety-eight individuals with dementia, primarily Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) were evaluated with the Cohen-Mansfield Agitation Inventory, the Mini Mental Status Examination, two measures of Activities of Daily Living, portions of the Conflict Tactics Scale to measure physical aggression against partner, questions about conduct problems during childhood/adolescence of the patients, and chart records of delusion and paranoia. 25% of the patients engaged in physical aggression against their caregivers in the past year, and 33% of the patients engaged in some act of physical aggression against any individual in the past two weeks. Physical aggression against a caregiver was more likely in the middle (34%) than the early stage of AD (4%). Physical aggression against a partner and agitation were more likely if the patient had a history of symptoms of conduct disorder. Delusions and paranoia were both associated with general physical aggression and general verbal aggression but not physical aggression against a caretaker. 25% of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease and Multi-Infarct dementia patients engaged in acts of physical aggression against their caregivers. The rate of aggression seen in this clinical sample was much higher than the rate of physical aggression in a community sample of the elderly.
Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The... more Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The authors recently reported that decreases in dopamine transporters (used as markers of dopamine terminals) in the striatum of methamphetamine abusers recover with protracted abstinence and that relative to comparison subjects, recently detoxified methamphetamine abusers have lower metabolism in the striatum and thalamus. In this study, the authors assessed whether metabolism recovers with protracted abstinence. Brain glucose metabolism was measured with positron emission tomography and [18F]fluorodeoxyglucose in five methamphetamine abusers who were evaluated after both a short (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 months) and protracted (12-17 months) abstinence interval, eight methamphetamine abusers tested only after protracted abstinence, and 11 comparison subjects who were not drug users. Significantly greater thalamic, but not striatal, metabolism was seen following protracted abstinence relative to metabolism assessed after a short abstinence interval, and this increase was associated with improved performance in motor and verbal memory tests. Relative to the comparison subjects, the methamphetamine abusers tested after protracted abstinence had lower metabolism in the striatum (most accentuated in the caudate and nucleus accumbens) but not in the thalamus. The persistent decreases in striatal metabolism in methamphetamine abusers could reflect long-lasting changes in dopamine cell activity, and decreases in the nucleus accumbens could account for the persistence of amotivation and anhedonia in detoxified methamphetamine abusers. The recovery of thalamic metabolism could reflect adaptation responses to compensate for the dopamine deficits, and the associated improvement in neuropsychological performance further indicates its functional significance. These results suggest that while protracted abstinence may reverse some of the methamphetamine-induced alterations in brain function, other deficits persist.
Objective: The role of dopamine in the addictive process (loss of control and compulsive drug int... more Objective: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D 2 receptors. In cocaine abusers, low levels of D 2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.
The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Jan 12, 2001
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when adm... more Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [ 11 C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (Ͻ6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, ϩ19%; putamen, ϩ16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.
Objective: The role of dopamine in the addictive process (loss of control and compulsive drug int... more Objective: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D 2 receptors. In cocaine abusers, low levels of D 2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when adm... more Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [ 11 C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (Ͻ6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, ϩ19%; putamen, ϩ16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when adm... more Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +...
IEEE MTT/ED/AP/LEO Societies Joint Chapter United Kingdom and Republic of Ireland Section. 1997 Workshop on High Performance Electron Devices for Microwave and Optoelectronic Applications. EDMO (Cat. No.97TH8305), 1997
During the past 5 years numerous mixed signal circuits have been designed, processed, and charact... more During the past 5 years numerous mixed signal circuits have been designed, processed, and characterized based on our 0.2 μm gate length AlGaAs/GaAs/AlGaAs E/D quantum well HEMT technology. Utilizing the inherent advantages of this material system, optical, analogue, microwave, and digital functions have been integrated monolithically. Examples are a chip set for 40 Gbit/s optoelectronic data transmission system, PLL circuits
Background. Little is known on the prevalence of peripheral artery disease (PAD) in developing co... more Background. Little is known on the prevalence of peripheral artery disease (PAD) in developing countries. Study design. Population-based study in Atahualpa. In Phase I, the Edinburgh claudication questionnaire (ECQ) was used for detection of suspected symptomatic PAD; persons with a negative ECQ but a pulse pressure ≥65 mmHg were suspected of asymptomatic PAD. In Phase II, the ankle-brachial index will be used to test reliability of screening instruments and to determine PAD prevalence. In Phase III, participants will be followed up to estimate the relevance of PAD as a predictor of vascular outcomes. Results. During Phase I, 665 Atahualpa residents aged ≥40 years were enrolled (mean age: 59.5 ± 12.6 years, 58% women). A poor cardiovascular health status was noticed in 464 (70%) persons of which 27 (4%) had a stroke and 14 (2%) had ischemic heart disease. Forty-four subjects (7%) had suspected symptomatic PAD and 170 (26%) had suspected asymptomatic PAD. Individuals with suspected P...
An abnormal ankle-brachial index has been associated with overt stroke and coronary heart disease... more An abnormal ankle-brachial index has been associated with overt stroke and coronary heart disease, but little is known about its relationship with silent cerebral small vessel disease. To assess the value of ankle-brachial index as a predictor of silent small vessel disease in an Ecuadorian geriatric population. Stroke-free Atahualpa residents aged ≥60 years were identified during a door-to-door survey. Ankle-brachial index determinations and brain magnetic resonance imaging were performed in consented persons. Ankle-brachial index ≤0·9 and ≥1·4 were proxies of peripheral artery disease and noncompressible arteries, respectively. Using logistic regression models adjusted for age, gender, and cardiovascular health status, we evaluated the association between abnormal ankle-brachial index with silent lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. Mean age of the 224 participants was 70 ± 8 years, 60% were women, and 80% had poor cardiovascular health status. Ankle-brachial index was ≤0·90 in 37 persons and ≥1·4 in 17. Magnetic resonance imaging showed lacunar infarcts in 27 cases, moderate-to-severe white matter hyperintensities in 47, and cerebral microbleeds in 26. Adjusted models showed association of lacunar infarcts with ankle-brachial index ≤ 0·90 (OR: 3·72, 95% CI: 1·35-10·27, P = 0·01) and with ankle-brachial index ≥ 1·4 (OR: 3·85, 95% CI: 1·06-14·03, P = 0·04). White matter hyperintensities were associated with ankle-brachial index ≤ 0·90 (P = 0·03) and ankle-brachial index ≥ 1·4 (P = 0·02) in univariate analyses. There was no association between ankle-brachial index groups and cerebral microbleeds. In this population-based study conducted in rural Ecuador, apparently healthy individuals aged ≥60 years with ankle-brachial index values ≤0·90 and ≥1·4 are almost four times more likely to have a silent lacunar infarct. Ankle-brachial index screening might allow recognition of asymptomatic people who need further investigation and preventive therapy.
Time-lapse imaging of human preimplantation IVF embryos has enabled objective algorithms based on... more Time-lapse imaging of human preimplantation IVF embryos has enabled objective algorithms based on novel observations of development (morphokinetics) to be used for clinical selection of embryos. Embryo aneuploidy, a major cause of IVF failure, has been correlated with specific morphokinetic variables used previously to develop an aneuploidy risk classification model. The purpose of this study was to evaluate the effectiveness and potential impact of this model for unselected IVF patients without biopsy and preimplantation genetic screening (PGS). Embryo outcomes - no implantation, fetal heart beat (FHB) and live birth (LB) - of 88 transferred blastocysts were compared according to calculated aneuploidy risk classes (low, medium, high). A significant difference was seen for FHB (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and LB (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) rates between embryos classified as low and medium risk. Within the low-risk class, relative increases of 74% and 56%, compared with rates for all blastocysts, were observed for FHB and LB respectively. The area under the receiver operating characteristic curve was 0.75 for FHB and 0.74 for LB. This study demonstrates the clinical relevance of the aneuploidy risk classification model and introduces a novel, non-invasive method of embryo selection to yield higher implantation and live birth rates without PGS.
Health care concepts and practices are changing dramatically because of demographic and economic ... more Health care concepts and practices are changing dramatically because of demographic and economic factors. The routine integration of behavioral and biomedical care is completely compatible with these changes and such integration would provide clinical and economic benefits to patients and to society.
The International Journal of Psychiatry in Medicine, 2005
These case reports examine the potential efficacy and safety of ziprasidone for the treatment of ... more These case reports examine the potential efficacy and safety of ziprasidone for the treatment of agitation or psychosis in dementia. The authors performed a retrospective chart review of three patients with DSM-IV diagnoses of dementia, treated with ziprasidone for agitation/psychosis on an academic psychiatric inpatient unit in 2002-2003. In addition, these three case reports are supplemented by a clinical report of the first outpatient with DSM-IV diagnosis of dementia completing a prospective open-label six-week study in 2004 evaluating the use of oral ziprasidone for agitation/psychosis in dementia. Qualitative descriptions of clinical improvement provide outcome data for these case reports. Four patients with dementia with agitation/psychosis experienced marked behavioral improvement after receiving oral doses of ziprasidone (20-160 mg/day), without any evidence of problematic cardiac or other side-effects. Two of the four patients had final EKGs and both of these patients demonstrated no change of QTc interval after administration of ziprasidone. These case reports suggest that oral ziprasidone may be an effective and safe medication for the treatment of agitation or psychosis in patients with dementia.
International Journal of Geriatric Psychiatry, 2005
To assess the prevalence of physical aggression against caregivers by Alzheimer&amp;amp;amp;a... more To assess the prevalence of physical aggression against caregivers by Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s patients. One hundred and ninety-eight individuals with dementia, primarily Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) were evaluated with the Cohen-Mansfield Agitation Inventory, the Mini Mental Status Examination, two measures of Activities of Daily Living, portions of the Conflict Tactics Scale to measure physical aggression against partner, questions about conduct problems during childhood/adolescence of the patients, and chart records of delusion and paranoia. 25% of the patients engaged in physical aggression against their caregivers in the past year, and 33% of the patients engaged in some act of physical aggression against any individual in the past two weeks. Physical aggression against a caregiver was more likely in the middle (34%) than the early stage of AD (4%). Physical aggression against a partner and agitation were more likely if the patient had a history of symptoms of conduct disorder. Delusions and paranoia were both associated with general physical aggression and general verbal aggression but not physical aggression against a caretaker. 25% of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease and Multi-Infarct dementia patients engaged in acts of physical aggression against their caregivers. The rate of aggression seen in this clinical sample was much higher than the rate of physical aggression in a community sample of the elderly.
Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The... more Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The authors recently reported that decreases in dopamine transporters (used as markers of dopamine terminals) in the striatum of methamphetamine abusers recover with protracted abstinence and that relative to comparison subjects, recently detoxified methamphetamine abusers have lower metabolism in the striatum and thalamus. In this study, the authors assessed whether metabolism recovers with protracted abstinence. Brain glucose metabolism was measured with positron emission tomography and [18F]fluorodeoxyglucose in five methamphetamine abusers who were evaluated after both a short (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 months) and protracted (12-17 months) abstinence interval, eight methamphetamine abusers tested only after protracted abstinence, and 11 comparison subjects who were not drug users. Significantly greater thalamic, but not striatal, metabolism was seen following protracted abstinence relative to metabolism assessed after a short abstinence interval, and this increase was associated with improved performance in motor and verbal memory tests. Relative to the comparison subjects, the methamphetamine abusers tested after protracted abstinence had lower metabolism in the striatum (most accentuated in the caudate and nucleus accumbens) but not in the thalamus. The persistent decreases in striatal metabolism in methamphetamine abusers could reflect long-lasting changes in dopamine cell activity, and decreases in the nucleus accumbens could account for the persistence of amotivation and anhedonia in detoxified methamphetamine abusers. The recovery of thalamic metabolism could reflect adaptation responses to compensate for the dopamine deficits, and the associated improvement in neuropsychological performance further indicates its functional significance. These results suggest that while protracted abstinence may reverse some of the methamphetamine-induced alterations in brain function, other deficits persist.
Objective: The role of dopamine in the addictive process (loss of control and compulsive drug int... more Objective: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D 2 receptors. In cocaine abusers, low levels of D 2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.
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Papers by Mark Sedler