Rare Encounters: Medical Students Give Assertive Community Treatment Team Visits Rave Reviews.

OBJECTIVE: For 8 years, Albert Einstein College of Medicine students have worked with the Bronx Psychiatric Center Assertive Community Treatment (ACT) team. We relate the medical student ACT team experience using the ratings and words of the students themselves. We describe the history, evolution, and structure of this novel program. METHODS: Third-year medical students (N = 120) spent 1 day of their 6-week psychiatry clerkship visiting patients with the multidisciplinary ACT team. At the end of the clerkship, they were asked to complete a voluntary, anonymous survey of the entire clerkship experience, one component of which was the ACT team experience. A Likert scale of 1-5 was used (5 = excellent and 1 = unsatisfactory). The ACT program was initiated in October 2007, had a 3-year hiatus, and was restarted in 2011. RESULTS: Fifty-five of the students completed the survey. Seven of the students gave no numerical rating to the ACT team experience and wrote only very favorable comments. In the remaining 48 evaluations, 61% gave the ACT team experience an excellent rating; an additional 30% gave it a very good rating. The students expressed their enthusiasm for this program, calling it a "great" experience. Other student comments included the following: "Good example of how patients can have continuity of care and stability." "A MUST. It was worth seeing how patients live and interact in home environments." "Incredible experience seeing the role psychiatrists play in the community." "One-of-a-kind experience that is different from anything else in medical school." CONCLUSIONS: ACT teams are an underutilized medical student teaching tool. It is hoped that this review will encourage other schools and program directors to adopt an ACT team training model.

The assertive community treatment team: an appropriate treatment for medical disorders that present with prominent psychiatric symptoms.

Physical diseases are difficult to treat in psychiatric patients, whether they are comorbid disorders or mental disorders due to a general medical condition. The psychiatric symptoms are difficult to treat in a medical ward or clinic, and the physical symptoms are difficult to treat in a psychiatric ward or clinic. For this reason, medical-psychiatric units have been developed but remain uncommon. It has been suggested that assertive community treatment (ACT) teams are a way in which to integrate medical and psychiatric treatments. We review the case of a woman with psychiatric symptoms caused by Graves disease that went untreated due to medication noncompliance and unmanageable irritability, aggression, and mood variability. We make a case for the use of the assertive community treatment team in the treatment of patients with mental disorders due to a general medical condition when the psychiatric manifestations are severe and cannot be managed in a medical ward or clinic.

A case of acute renal failure in a patient recently treated with clozapine and a review of previously reported cases.

Clozapine has been reported to cause acute renal failure due to acute interstitial nephritis. We discuss a case of clozapine-induced acute renal failure and compare it to 7 other cases reported in the literature. We review the signs and symptoms of the hypersensitivity response, such as fever and eosinophilia, caused by clozapine and make recommendations for early detection. Early detection and prompt discontinuation of clozapine can prevent renal damage, as can the avoidance of other nephrotoxic drugs like antibiotics.

Girard's reagent P derivative of beta-Apo-8'-carotenal: a potent photoprotective agent.

A cationic carotenoid derivative (GRP-carotenal) was synthesized by the reaction of Girard's reagent P and beta-apo-8'-carotenal. The singlet-oxygen quenching constants for GRP-carotenal were 1.3 +/- 0.1 x 10(10) and 1.0 +/- 0.1 x 10(10) M-1 s-1 in acetonitrile and in detergent micelles, respectively. Photosensitized damage to K562 leukemia cells from cis-di(4-sulfonatophenyl)diphenylporphine, hypericin and protoporphyrin IX was inhibited by GRP-carotenal under conditions where beta-apo-8'-carotenal, beta-carotene and crocetin were ineffective. The unique cytoprotective properties of GRP-carotenal, relative to the other carotenoids studied, could not be explained by the differences in the cell content of the various carotenoids or by the changes in the cell content of the photosensitizers used. Photosensitizer fluorescence from labeled K562 cells was reduced by GRP-carotenal but not by the other carotenoids studied. The novel photoprotective properties of GRP-carotenal may be due to its subcellular distribution. In photosensitizer-containing detergent micelles, novel properties of GRP-carotenal were not apparent. None of the carotenoids studied reduced photosensitizer fluorescence or singlet-oxygen generation. Singlet-oxygen quenching by GRP-carotenal and by beta-apo-8'-carotenal were roughly the same. Crocetin has a singlet-oxygen quenching constant that is about a factor of five lower. Singlet-oxygen quenching by beta-carotene was limited by its aggregation.

Preferential cytotoxicity for multidrug-resistant K562 cells using the combination of a photosensitizer and a cyanine dye.

The cyanine dye 1,1',3,3,3',3'-hexamethylindodicarbocyanine iodide (HIDC) protects K562 leukemia cells from photodynamic membrane damage caused by cis-di(4-sulfonatophenyl)diphenylporphine (TPPS2) and 420 nm light. This wavelength of light is chosen because it is absorbed by TPPS2, but not by HIDC. The photodynamic system studied may be useful as a model for antineoplastic therapy. A subline of K562 leukemia (K562/DOX), expressing the multidrug-resistance (MDR) phenotype, is found to accumulate smaller amounts of HIDC than the parent cell line and thus has less photoprotection. In the absence of added HIDC, the K562/DOX cell line is more resistant to photodynamic cytotoxicity than the K562 cell line. The resistance of the K562/DOX cell line is not due to a smaller accumulation of TPPS2 than the K562 cell line. However, when both cell lines are incubated with HIDC and TPPS2, and then exposed to light, the K562/DOX cell line becomes more sensitive to photodynamic cell damage than the K562 cell line. The combination of a photosensitizer with a cationic or lysomorphotropic photoprotector represents a novel strategy for the eradication of malignant cells expressing the MDR phenotype.

Cyanine dyes as protectors of K562 cells from photosensitized cell damage.

Several cyanine dyes were found to protect K562 leukemia cells against toxicity mediated by cis-di(4-sulfonatophenyl)diphenylporphine (TPPS2) and light. Most cyanine dyes derived from dimethylindole were better photoprotectors than cyanine dyes with other structures. This correlated with the fact that cyanine dyes derived from dimethylindole were predominately monomeric at millimolar concentrations within K562 cells, while other cyanine dyes formed aggregates. For cyanine dyes that are derived from dimethylindole and have absorption band wavelengths greater than 700 nm, fluorescence-energy transfer from TPPS2 to the cyanine dye was the most important mechanism for photoprotection. There was no spectroscopic evidence for complex formation between the cyanine dyes and TPPS2. The dimethylindole derivative, 1,1',3,3,3',3'-hexamethylindodicarbocyanine, was an excellent photoprotector, but a poor quencher of TPPS2 fluorescence and a relatively poor singlet-oxygen quencher. This cyanine dye may act by quenching excited triplet TPPS2. Singlet-oxygen quenching may contribute to the photoprotection provided by cyanine dyes not derived from dimethylindole. Differences in the subcellular distribution of the various cyanine dyes studied may have contributed to the different apparent mechanisms of photoprotection.

Inactivation of glucose oxidase by diperoxovanadate-derived oxidants.

Inactivation of glucose oxidase occurred in the presence of bromide, vanadate, H(2)O(2), and phosphate (the bromide system), and this was prevented by NADH or phenol red, a bromine acceptor. Glucose oxidase present during the reaction between diperoxovanadate and a reduced form of vanadate, vanadyl (the vanadyl system), but not added after mixing the reactants, was inactivated, and this was accompanied by a loss of binding of the dye, Coomassie blue, to the protein. The transient intermediate of the type OVOOV(O(2)), known to form in these reactions and used in the oxidation of bromide ion and NADH, appears to be responsible for inactivating glucose oxidase. In both systems, the inactivation of the enzyme was prevented by histidine and DTT, known to quench singlet-oxygen. By direct measurement of 1270-nm emission of singlet-oxygen, its generation was demonstrated in the bromide system, and in the reaction of hypohalous acids with diperoxovanadate, but not in the vanadyl system. By themselves both hypohalous acids, HOCl and HOBr inactivated glucose oxidase, and their prior reaction with H(2)O(2) during which singlet-oxygen was released, protected the enzyme. The results provide support for possible oxidative inactivation of glucose oxidase by diperoxovanadate-derived oxidants.

Singlet oxygen-mediated inactivation of acetylcholinesterase: a comparison of purified enzyme in solution and enzyme bound to K562 leukemia cells.

We have compared the singlet oxygen-mediated inactivation of acetylcholinesterase (ACE) in solution with the inactivation of ACE on the surface of K562 leukemia cells. In solution, the actions of the singlet-oxygen quenchers, methionine, azide, disodium [N,N'-ethylenebis (5-sulfosalicylideneimminato)]nickelate(II) (Ni-chelate 1) and disodium [(N,N'-2,3-propionic acid)bis(5-sulfosal-icylideneimminato)] nickelate(II) (Ni-chelate 2) could be explained quantitatively by assuming their only mechanism of action was to quench singlet oxygen. The singlet oxygen quenchers, azide, Ni-chelate 1 and Ni-chelate 2, caused smaller inhibitions in the rate of singlet oxygen-mediated inactivation of ACE on K562 cells than ACE in solution. The effects of these quenchers and of deuterium oxide were interpreted using a mathematical model of singlet-oxygen quenching and diffusion to estimate the lifetime of singlet oxygen near the cell surface. The azide quenching data and the deuterium-oxide data gave lifetimes of 0.9 +/- 0.2 microsecond and 0.45 +/- 0.15 microsecond, respectively. The increases in ACE inactivation lifetime caused by the nickel chelates were anomalously large. The unexpectedly large quenching due to the nickel chelates may have been due to a nonuniform distribution of the chelates in the cytoplasm with a large concentration of the chelate near the cell membrane.

On the synthesis of neurotransmitter receptor agonists with antagonist potential.

The synthesis of a new type of antagonist is described, capable of inactivating neuroreceptors with heretofore unattainable selectivity and permanence. These antagonists are referred to as mazek agonists (i.e. direct, inhibitory agonists) as they have the high receptor affinity and initial receptor-stimulatory effect of direct agonists and are positively coupled to effector systems. However, like direct antagonists, they have a high receptor affinity and the potential to inhibit or prevent receptor stimulation. The synthesis of the present compounds consisted of the covalent attachment of a tethered dye to three different neurotransmitter analogues, resulting in dye-neuropeptide conjugates with a high affinity for the FMRFa receptor. The dye was prepared from azure B (Az), the neurotransmitter was the neuropeptide FMRFamide (FMRFa), and the dye-neuropeptide conjugates synthesized were Az-CFMRFa; Az-CFMRF and Az-CLRFa. In this procedure, the analogues serve as carrier molecules, bound at one end to the receptor and at the other end to the dye, which is thereby brought into close contact with the receptor. The receptor can then be inactivated by singlet oxygen generated by laser irradiation of the photosensitized receptor.

Receptor inactivation by dye-neuropeptide conjugates. 3. Comparative binding of dye-neuropeptide conjugates to FMRFamide receptors of Helix aspersa and Loligo pealei.

Three neuropeptide analogues of FMRFamide (FMRFa) were covalently attached to a tethered derivative of methylene blue to form dye-neuropeptide conjugates. The comparative binding of the latter to FMRFa receptors was subsequently examined in both Helix aspersa (circumesophageal ganglia) and squid (optic lobe membrane). In Helix, the FMRFa analogue CFMRFamide (CFMRFa) inhibited the specific binding of the FMRFa ligand [125I]daYFnLRFa in a dose-dependent manner. Az-CFMRFa, one of the dye-neuropeptide conjugates, also dose-dependently inhibited the specific binding of [125I]daYFnLRFa. Moreover, their potencies equaled or exceeded that of FMRFamide. In squid, the binding of CFMRFa and FMRFa was similar. However, the dye-neuropeptide conjugate (IC50 of 14 nM) was about 44-fold less potent than FMRFa. The conjugates were synthesized as part of a study seeking to target and inactivate preselected receptors with heretofore unattainable selectivity and permanence.

Receptor inactivation by dye-neuropeptide conjugates: 1. The synthesis of Cys-containing dye-neuropeptide conjugates.

In an attempt to attenuate specifically identified receptors through photolysis, a four-step synthesis is of a useful tethered derivative of Azure-B (Az) was developed After characterization, this derivative was covalently attached to CFMRFamide, CFMRF, and CLRFamide (i.e., three different neuropeptide analogues of the putative neurotransmitter FMRFamide. This resulted in the formation of three dye-neuropeptide conjugates: Az-CFMRFamide, Az-CFMRF, and Az-CLRFamide.

Receptor inactivation by dye-neuropeptide conjugates: 2. Characterization of the quantum yield of singlet oxygen generated by irradiation of dye-neuropeptide conjugates.

Different neuropeptide analogues of the neurotransmitter FMRFamide were covalently attached to a tethered dye, forming dye-neuropeptide conjugates capable of stably binding to the FMRFamide receptors. Singlet oxygen (1 delta O2) generated by laser irradiation of the conjugates bound to this receptor should inactivate it if (a) the distance 1 delta O2 must diffuse to reach the photo-sensitized receptor is less than 1000 A, (b) the conjugate binds the receptor with the same affinity as the indigenous neurotransmitter, and (c) the quantum yield (phi) of 1 delta O2 is sufficient. Previous studies determined that the first two constraints are satisfied. The results of the present study confirm that the third constraint is also satisfied, as the phi of 1 delta O2 resulting from the laser irradiation of the conjugates were uniformly large, exceeding those for the dye itself, ranging from 0.25 at pD 6.0 to 0.93 at pD 9.0.