Partial Pyridoxine Responsiveness in PNPO Deficiency.

OBJECTIVE: Autosomal-recessive pyridox(am)ine phosphate oxidase (PNPO) deficiency causes pyridoxal-5-phosphate (PLP)-dependent epilepsy. We describe partial PNPO deficiency with a transient response to pyridoxine (B6). METHODS: CSF neurotransmitter metabolites, PLP, and amino acids were analyzed while the patient was receiving pyridoxine. PNPO gene sequencing was performed by standard techniques. RESULTS: A full-term 3,220 g male with refractory neonatal seizures became seizure free for 6 weeks on pyridoxine (B6). Breakthrough seizures followed. These stopped upon the first dose of PLP although episodes occurred as a dose became due. An unidentified peak was detected on the chromatographic system used to measure CSF PLP. PNPO gene sequencing identified a homozygous mutation in a highly conserved area in exon 3: c.352G>A p.G118R, predicting substitution of arginine for glycine. At age 28 months the child has hypotonia and developmental delay, both mild in severity. CONCLUSIONS: Transient pyridoxine responsiveness may be seen in partial PNPO deficiency. A CSF metabolite peak, likely pyridoxine phosphate, is identifiable in patients with PNPO deficiency who are taking supplemental pyridoxine. Partial B6 responsiveness is an indication for possible PNPO deficiency and trial of PLP.

SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells.

Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. (3)H-SR48692 bound with high affinity (IC(50) = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific (125)I-NT binding with high affinity (IC(50) values of 2 and 200 nM). In contrast, the NT(2) receptor agonist, levocabastine, had little effect on specific (125)I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 microM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 microM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT(1) receptor antagonist which inhibits SCLC growth.

The Texas Medication Algorithm Project (TMAP) schizophrenia algorithms.

BACKGROUND: In the Texas Medication Algorithm Project (TMAP), detailed guidelines for medication management of schizophrenia and related disorders, bipolar disorders, and major depressive disorders have been developed and implemented. DISCUSSION: This article describes the algorithms developed for medication treatment of schizophrenia and related disorders. The guidelines recommend a sequence of medications and discuss dosing, duration, and switch-over tactics. They also specify response criteria at each stage of the algorithm for both positive and negative symptoms. The rationale and evidence for each aspect of the algorithms are presented.

Implementing effectiveness research and improving care for schizophrenia in real-world settings.

OBJECTIVE: To review recent advances in medication practices and standards of care in the treatment of schizophrenia and examine the disparity between the knowledge base and clinical practice. DATA SOURCES: Key literature on medication practices, novel pharmacotherapies, and the evolution of practice guidelines for schizophrenia were reviewed. DISCUSSION: Emerging data demonstrate a lack of consistent application of current knowledge and best practices, in part due to major structural inconsistencies in the public mental health system. Implementation of results from effectiveness research as well as the incorporation of practice guidelines may help bridge this gap. CONCLUSION: As standards of care for schizophrenia are developed, the following issues will need particular attention: coordination with the criminal justice system, comprehensive treatment of comorbid illnesses, outcomes based on symptoms in all domains, and continuous and integrated collection of data to produce rational cost justification.

Medication treatment for the severely and persistently mentally ill: the Texas Medication Algorithm Project.

This article provides an overview of the issues involved in developing, using, and evaluating specific medication guidelines for patients with psychiatric disorders. The potential advantages and disadvantages, as well as the essential elements in the structure of algorithms, are illustrated by experience to date with the Texas Medication Algorithm Project, a public-academic collaboration. Phase 1 entailed assembling research findings on the efficacy of medications for schizophrenic, bipolar, and major depressive disorders. This knowledge was evaluated for its quality and relevance, integrated with expert clinical judgment as well as input by practicing clinicians, family advocates, and patients. Phase 1 (the design and development of the algorithms) was followed by a feasibility test (Phase 2). Phase 3 is an ongoing evaluation comparing the clinical and economic effects of using specific medication guidelines (algorithms) versus treatment as usual in public sector patients with severe and persistent mental illnesses.

Mosquito-Plasmodium interactions in response to immune activation of the vector.

During the development of Plasmodium sp. within the mosquito midgut, the parasite undergoes a series of developmental changes. The elongated ookinete migrates through the layers of the midgut where it forms the oocyst under the basal lamina. We demonstrate here that if Aedes aegypti or Anopheles gambiae, normally susceptible to Plasmodium gallinaceum and P. berghei, respectively, are immune activated by the injection of bacteria into the hemocoel, and subsequently are fed on an infectious bloodmeal, there is a significant reduction in the prevalence and mean intensity of infection of oocysts on the midgut. Only those mosquitoes immune activated prior to, or immediately after, parasite ingestion exhibit this reduction in parasite development. Mosquitoes immune activated 2-5 days after bloodfeeding show no differences in parasite burdens compared with naive controls. Northern analyses reveal that transcriptional activity for mosquito defensins is not detected in the whole bodies of Ae. aegypti from 4 h to 10 days after ingesting P. gallinaceum, suggesting that parasite ingestion, passage from the food bolus through the midgut, oocyst formation, and subsequent release of sporozoites into the hemolymph do not induce the production of defensin. However, reverse transcriptase-PCR of RNA isolated solely from the midguts of Ae. aegypti indicates that transcription of mosquito defensins occurs in the midguts of naive mosquitoes and those ingesting an infectious or noninfectious bloodmeal. Bacteria-challenged Ae. aegypti showed high levels of mature defensin in the hemolymph that correlate with a lower prevalence and mean intensity of infection with oocysts. Because few oocysts were found on the midgut of immune-activated mosquitoes, the data suggest that some factor, induced by bacterial challenge, kills the parasite at a preoocyst stage.

The Texas Medication Algorithm Project: development and implementation of the schizophrenia algorithm.

The Texas Medication Algorithm Project is a program designed to improve the quality of care of persons with serious mental disorders across sites in the Texas public mental health system and to create a uniform clinical environment from which cost estimates can be made. This paper describes the process of developing a pharmacological treatment algorithm for schizophrenia that addresses use of antipsychotics as well as other medications for side effects and co-existing symptoms. Input from clinicians, consultants, and consumers informed development of the algorithm, which was based on existing expert consensus guidelines. Information about the project can be found on the Internet at www.mhmr.state.tx.us/meds/tmap.htm. The authors present and describe the original and current versions of the algorithm, outline the feedback process by which it will be refined, and discuss how new medications will be incorporated as they enter the market.

Biochemical analysis of a blood meal-induced Aedes aegypti glutamine synthetase gene.

Glutamine synthetase (GS) in the mosquito, Aedes aegypti, is induced in the midgut following a blood meal. Mosquito GS message is detected as soon as 1 h post-blood feeding and remains stable for 18 h. Using a PCR product encoding mosquito GS, a lambda gt10 adult female mosquito cDNA library was screened. A cDNA clone, pCl5A2, encoding the full translation product of mosquito GS was isolated and sequence analyses performed. Mosquito GS cDNA is 2.5 kb in length and its putative translation product shares all the conserved regions characteristic of the GS gene family, including the presumed ATP biding site. Glutamine synthetase activity in the mosquito midgut is highest at 18 h post-blood feeding. Activity can be detected over a broad pH range, from 6.0 to 7.5. Unlike other cellular GS enzymes, mosquito GS is not active in the presence of ATP. Very low dosages (0.05 mM) of L-methionine S-sulfoximine are sufficient to partially inhibit mosquito GS activity. Inhibition of GS disrupts the normal formation of the midgut peritrophic matrix, suggesting that GS enzyme might be involved in the initial pathway of chitin synthesis. The unique expression pattern and inducible nature of the mosquito GS gene make it an interesting candidate for studying promoter function. Additionally, the blood meal activation of the GS gene makes this a potentially valuable tool in mosquito transformation studies.

Prediction of suicide intent in hospitalized parasuicides: reasons for living, hopelessness, and depression.

This study examined the risk prediction efficiency of the Reasons for Living Inventory Survival and Coping Beliefs Scale, Beck Hopelessness Scale, Beck Depression Inventory, and the Life Experiences Survey with a sample of 51 newly hospitalized parasuicides. The index of suicidal potential chosen for this study was suicide intent as measured by Beck's Suicide Intent Scale. Regression analyses indicated that the Survival and Coping Beliefs Scale emerged as the single most important predictor of suicide intent. Hopelessness and depression made secondary and nonsignificant contributions. Hopelessness was a significant predictor of suicide intent when analyzed apart from Survival and Coping Beliefs, but not among a subsample of 43 repeat parasuicides. Classification analyses showed that neither hopelessness nor survival and coping beliefs were accurate at classifying low- or high-intent parasuicides. Factors contributing to the efficacy of survival and coping beliefs as a risk prediction index are discussed, as is the false-negative dilemma in suicide risk assessment and prediction.

Tardive dyskinesia in the mentally retarded: comparison of prevalence, risk factors and topography with a schizophrenic population.

Thirty mentally retarded patients treated with neuroleptics for aberrant behavior were compared with 30 neuroleptic-treated schizophrenics for the presence, topography and risk factors associated with tardive dyskinesia (TD). In the total sample (n = 60), female sex, schizophrenic diagnosis and increasing age were associated with TD. The length of neuroleptic treatment and current neuroleptic dose were not significantly associated with TD. The only topographical difference in TD presentation was that the mentally retarded group had significantly more tongue involvement.

Weight gain associated with clozapine.

Six of seven patients treated with clozapine gained 6-69 lb. Because of clozapine's anticipated availability in the United States, clinicians should be aware of this possible side effect, which, to the authors' knowledge, has not been reported previously.

Who smokes? Why?: Psychiatric aspects of continued cigarette usage among lawyers in Washington State.

Eight-hundred two lawyers, a random sample of the Washington State Bar, were surveyed to determine the prevalence of medical and psychological distress. Approximately 15% of this group reported current cigarette use. Greater levels of dysphoric symptoms and greater misuse of alcohol differentiated male smokers from male nonsmokers, whereas no differences were found for females. The implications of these findings for pharmacologic and counseling strategies to further promote smoking cessation are discussed.

The mentally ill in prisons: a review.

Mentally ill persons who have been charged with crimes present difficult dilemmas for correctional authorities and mental health system administrators. The authors examine the scope of the problem, the legal issues and treatment needs of this population during incarceration, and the obstacles in caring for them after their eventual release from prison. They recommend that mentally ill offenders be afforded the same level of mental health care available to mentally ill residents in other institutions and in the community. The need for postrelease supervision and coordination between mental health and correctional authorities are central issues in reintegrating mentally ill offenders into the community.

Depression, hopelessness, and suicidal behavior in Chinese and American psychiatric patients.

The authors compared 37 patients in the People's Republic of China and 46 patients in the United States who were having difficulty with suicidal thinking or behavior. Hopelessness, reasons for living, and suicidal efficacy showed none of the expected relationships with suicidal intent among the Chinese patients, but the two groups were similar on many variables theoretically related to suicidality. Chinese patients were less likely to communicate suicidal intent and rated suicide as less effective at solving problems. The authors examine such variations in the light of possibly different cultural approaches to suicidal behavior.

Intermittent medication for schizophrenic outpatients: who is eligible?

The Medication Clinic of a large, urban Mental Health Center was screened for schizophrenic patients eligible for an intermittent medication approach. A total of 112 patients were evaluated, and 39, or 34.8 percent of the sample, met our basic inclusion criteria. No sex or age differences were found for eligibility. Sufficient eligible patients were found to make the intermittent medication approach a useful part of a comprehensive psychopharmacological program for schizophrenia, if the efficacy of the approach is demonstrated in clinical trials.