Transmission of methicillin-resistant Staphylococcus aureus via deceased donor liver transplantation confirmed by whole genome sequencing.

Donor-derived bacterial infection is a recognized complication of solid organ transplantation (SOT). The present report describes the clinical details and successful outcome in a liver transplant recipient despite transmission of methicillin-resistant Staphylococcus aureus (MRSA) from a deceased donor with MRSA endocarditis and bacteremia. We further describe whole genome sequencing (WGS) and complete de novo assembly of the donor and recipient MRSA isolate genomes, which confirms that both isolates are genetically 100% identical. We propose that similar application of WGS techniques to future investigations of donor bacterial transmission would strengthen the definition of proven bacterial transmission in SOT, particularly in the presence of highly clonal bacteria such as MRSA. WGS will further improve our understanding of the epidemiology of bacterial transmission in SOT and the risk of adverse patient outcomes when it occurs.

Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients.

Hospitalized bipolar and unipolar endogenously depressed patients who showed an antidepressant response to the monoamine oxidase (MAO) inhibitor, tranylcypromine sulfate, relapsed (ie, depression returned) when relatively small doses of parachlorophenylalanine (PCPA) were added for brief periods. Considered together with our findings that PCPA similarly reversed the antidepressant effects of the tricyclic drug, imipramine hydrochloride, implications are (1) serotonergic mechanisms are likely involved in the antidepressant effects of both the tricyclic drugs and MAO inhibitors in man and (2) this indolamine may also play a role in the endogenous clinical state of depression.

Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison.

Clozapine is a unique compound belonging to a relatively new group of antipsychotic agents, the dibenzazepines. To our knowledge, the present study represents the first double-blind, controlled comparison recorded in the United States. The data suggest that clozapine in the present population of newly admitted, acutely psychotic schizophrenic individuals, and in the doses employed, was more effective in overall improvement response, discharge rate, and ameliorating discrete symptoms across the different objective rating scales used than was chlorpromazine (Thorazine) hydrochloride. Placebo was ineffective. Unlike chlorpromazine, no extrapyramidal reactions occurred in those patients ingesting clozapine. Clozapine was also beneficial in reversing abnormal involuntary motor movements. It is an excellent anxiolytic and hypnotic agent. Sedation, hypotension, and hypersalivation are among the more common side effects observed.

Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol.

Lithium carbonate, haloperidol, and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics. Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation. Although producing considerable sedation, chlorpromazine did little to alter the underlying mania qualitatively. Qualitative differences between lithium carbonate and haloperidol indicate that, while haloperidol has a more dramatically rapid impact on behavior-motor activity, lithium carbonate acted more evenly on the entire manic picture, with total normalization realized during active treatment. The majority of lithium carbonate-treated patients met discharge criteria at study termination, but not the patients receiving either neuroleptic drug. The rating scales are not sensitive enough to monitor manic psychopathology; this accounts for the lack of statistically significant differences among drug groups at treatment termination, despite the widely disparate discharge rates.

Monoamine oxidase inhibitors: potential for drug abuse.

Both the amphetamines and MAO inhibitors share common clinical and pharmacological properties, namely, (i) to clinically induce euphoriant-stimulating type and psychotomimetic effects in certain individuals, and (ii) to increase, albeit by different mechanisms, the amount of functionally available neurotransmitter (catecholamines and indoleamines) at the receptor site. The present data now indicate that, like the amphetamines, the use of MAO inhibitors can be clinically associated with dependence-tolerance. Perhaps these clinical findings will converge with other clinical-biochemical data in helping to define the specific amine(s) responsible for not only the clinical effects of these drugs but also the etiopathogenesis of major psychiatric illnesses such as the affective disorders and schizophrenia.

Cogwheel rigidity related to lithium maintenance.

Neurological examinations of 27 outpatients receiving lithium carbonate maintenance therapy for recurrent affective illness revealed that most of the patients receiving lithium for more than 8 months had cogwheel rigidity. The data suggest a positive correlation between the duration of lithium maintenance and the severity of cogwheeling. Intravenous administration of benztropine, an antiparkinsonian drug, did not abolish or significantly ameliorate this symptom.

Bupropion's prophylactic efficacy in bipolar affective illness.

Three bipolar manic-depressive patients are described who, after responding to bupropion treatment for an acute depressive relapse, were maintained on the drug alone for a 1-year period, without recurrences of mania or depression. Discontinuation of medication was followed within 8 weeks by a manic or depressive recurrence in all three cases. Data are presented to suggest that bupropion probably exerted a prophylactic effect in preventing acute affective recurrences in these cases. This drug merits investigational attention as an alternative approach to current maintenance chemotherapy of recurrent affective disorder.

Second generation antidepressants.

One approach to research into depressive illness includes a clinical pharmacotherapeutic tack such as the use of investigational drugs with defined pharmacological and biochemical activity. Using this research strategem, a variety of new compounds have been investigated in recent years all of which are unique chemically; all differ from the classic tricyclic-MAOI compounds. Animal pharmacology and neurochemical studies also show a profile which largely differs from the standard reference compounds. Their effects on central monoamine metabolism differ widely; some act pre- and others postsynaptically, some act by re-uptake inhibition, others by enhancing release, others are precursors, while still others are receptor agonists; some have no apparent central effect. The data, considered collectively and critically evaluated, suggest that many of the newer compounds used investigationally, because of their clinical efficacy, seriously question the involvement of monoamines as responsible for either the antidepressant effect of the standard psychotropic drugs or as etiopathogenic in the affective disorders. The classic animal screening profiles used for predicting antidepressant drug efficacy in man do not hold for many of these newer antidepressants. the animal-laboratory models need be revised and reoriented towards finding similar molecules that are devoid of the addling side effects and contraindications of the existing standard tricyclic-MAOI genre. The newer second generation antidepressants stand as a hallmark of progress in research and treatment with psychotropic drugs.

Penfluridol: an open phase III study in acute newly admitted hospitalized schizophrenic patients.

An open study was carried out in 17 acutely ill, newly admitted, floridly psychotic schizophrenic patients to a city hospital in New York. Penfluridol was given on a daily basis up to doses of 120 mg and patients were rated objectively by means of different psychometric evaluations; vital signs were monitored daily as were side effects. The drug was found to be a rapid acting, well-tolerated, and highly effective antipsychotic agent within the population of patients explored and within the dose range used. It was particularly effective in acutely agitated floridly paranoid schizophrenics; a statistically significant impact was achieved by 7 days and usually within 72 h after initiating treatment. The drug appears unique in that (1) its effects are realized without the untoward and usually troublesome effects of nonspecific sedation attendant upon the use of many other 'neuroleptic' medications, and (2) even within the relatively high doses used it produced no hypotensive effects. It is concluded that this appears to be a unique antipsychotic agent and a potentially important addition to the treatment armamentarium of both acute and chronic schizophrenic individuals.

Resistance rather than virulence selects for the clonal spread of methicillin-resistant Staphylococcus aureus: implications for MRSA transmission.

The population structure of methicillin-resistant Staphylococcus aureus (MRSA) is predominantly clonal, which may be related to the fitness of the genetic background of the methicillin-susceptible S. aureus (MSSA) into which the mecA chromosomal resistant determinant has inserted. To test this idea, we assessed whether the genotypes of New York MRSA are present in MSSA populations by using a combination of protein A gene sequence typing (spa typing) and pulsed-field gel electrophoresis (PFGE). Although about 16% of colonizing MSSA isolated from community subjects were related to MRSA, only one of the five predominant New York MRSA clonal types was found among the MSSA isolates. Similarly, among nosocomial MSSA, only four MRSA homologues were observed, two of which may have arisen through deletion of the mec element. Thus, MRSA clonal types represent a limited spectrum of the diversity seen in community and hospital S. aureus populations. The data are best explained by antibiotic selection pressure, as opposed to increased transmissibility or virulence, being responsible for the clonal dissemination of the resistance phenotype in MRSA genetic backgrounds, an in turn, the limited spread of these strains outside of the hospital environment.

Lithium as an immunologic adjuvant.

Lithium, an adenylate cyclase inhibitor, stimulates a variety of in vitro indices of immune function, including proliferation of lymphocytes in response to mitogens, rosette formation by T-cells and phagocytosis by macrophages. Lithium enhances these immunologic responses at concentrations comparable to those achieved in patients receiving lithium for treatment of manic-depressive disorders. Lithium may prove to have important therapeutic applications as an immune adjuvant, particularly in immune deficiency states associated with excessive C-AMP production.