Neuroendocrine Tests during Treatment with Neuroleptic Drugs. I. Plasma Prolactin Response to Haloperidol Challenge

SummaryThe plasma prolactin (PRL) response to haloperidol 2 or 4 mg i.m. was studied in 18 schizophrenic men during their routine treatment with neuroleptic drugs. A substantial rise of the PRL level above the treatment baseline occurred in all but four of the 20 tests showing that the PRL elevation induced by treatment was not maximal. The challenge was ineffective only in patients receiving very high daily doses of medication. The increment was inversely correlated to the daily dose of medication but unrelated to plasma haloperidol concentrations during the test. Chronic schizophrenics who were receiving long term treatment and had low basal PRL levels did not show tolerance to the prolactin stimulating effect of haloperidol. That prolactin rose during the test in patients who had improved during their current treatment indicates that the degree of dopamine receptor blockade required for therapeutic effects is below that which produces a maximal PRL response.

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Treatment of tardive dyskinesia

Drug and Therapeutics Bulletin ◽

10.1136/dtb.16.14.55 ◽

1978 ◽

Vol 16 (14) ◽

pp. 55-56

Keyword(s):

Tardive Dyskinesia ◽

Late Onset ◽

Psychiatric Patients ◽

Term Treatment ◽

Neuroleptic Drugs ◽

Abnormal Movements ◽

Long Term Treatment ◽

The Face ◽

Schizophrenic Patients

Neuroleptic drugs cause many forms of extra-pyramidal syndromes. One of these, tardive dyskinesia,1 occurs only after the patient has been taking the drug for some time (‘tardive’ refers to the late onset). The movements are involuntary and repetitive usually involving the face and tongue, but they may also affect the limbs and trunk. Tongue protrusion, licking and smacking of the lips, sucking and chewing movements, grimacing, grunting, blinking and furrowing of the forehead have all been described and attributed to long-continued medication with neuroleptic drugs of the phenothiazine, butyrophenone and thioxanthene groups. The patient can inhibit the movements, but anxiety makes them worse. Many of these symptoms were noticed in schizophrenic patients before neuroleptic drugs were introduced2 and they can occur in otherwise normal untreated elderly people. Nevertheless it is generally accepted that in most cases tardive dyskinesia is an unwanted effect of neuroleptic medication. Despite suggestions to the contrary, the abnormal movements are not necessarily associated with high dosage of neuroleptic drugs or with pre-existing brain damage.3 4 Tardive dyskinesia has been reported in 3–6% of a mixed population of psychiatric patients5 and over half of a group of chronic schizophrenics on long-term treatment.4 The more careful the neurological examination, the greater the apparent incidence.

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SERUM FOLATE IN PSYCHIATRIC PATIENTS UNDER LONG-TERM TREATMENT WITH TRICYCLIC NEUROLEPTIC DRUGS

Acta Psychiatrica Scandinavica ◽

10.1111/j.1600-0447.1969.tb10369.x ◽

1969 ◽

Vol 45 (2) ◽

pp. 133-136 ◽

Cited By ~ 8

Author(s):

Hans Josrgen G. Gundersen

Keyword(s):

Psychiatric Patients ◽

Term Treatment ◽

Serum Folate ◽

Neuroleptic Drugs ◽

Long Term Treatment

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Long-Term Treatment with Aqueous Garlic and/or Tomato Suspensions Decreases Ehrlich Ascites Tumors

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/381649 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Jenifer Bom ◽

Patrícia Gunutzmann ◽

Elizabeth C. Pérez Hurtado ◽

Jussara M. R. Maragno-Correa ◽

Silvia Regina Kleeb ◽

...

Keyword(s):

Tumor Growth ◽

Term Treatment ◽

Therapeutic Effects ◽

Short Term ◽

Volume Number ◽

Aqueous Suspensions ◽

Ehrlich Ascites ◽

Long Term Treatment ◽

Ascites Tumors

We evaluated the preventive and therapeutic effects of aqueous suspensions of garlic, tomato, and garlic + tomato in the development of experimental Ehrlich tumors in mice. The aqueous suspensions (2%) were administered over a short term for 30 days before tumor inoculation and 12 days afterward, and suspensions at 6% were administered for 180 days before inoculation and for 12 days afterward. The volume, number, and characteristics of the tumor cells and AgNOR counts were determined to compare the different treatments. Aqueous 6% suspensions of garlic, tomato, and garlic + tomato given over the long term significantly reduced tumor growth but when given over the short term, they did not alter tumor growth.

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JAK1-dependent transphosphorylation of JAK2 limits the antifibrotic effects of selective JAK2 inhibitors on long-term treatment

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210911 ◽

2017 ◽

Vol 76 (8) ◽

pp. 1467-1475 ◽

Cited By ~ 18

Author(s):

Yun Zhang ◽

Ruifang Liang ◽

Chih-Wei Chen ◽

Tatjana Mallano ◽

Clara Dees ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Chronic Treatment ◽

Term Treatment ◽

Janus Kinase ◽

Prolonged Treatment ◽

Therapeutic Effects ◽

Long Term Treatment ◽

Jak2 Inhibition ◽

Jak2 Inhibitors

ObjectivesJanus kinase 2 (JAK2) has recently been described as a novel downstream mediator of the pro-fibrotic effects of transforming growth factor-β. Although JAK2 inhibitors are in clinical use for myelodysplastic syndromes, patients often rapidly develop resistance. Tumour cells can escape the therapeutic effects of selective JAK2 inhibitors by mutation-independent transactivation of JAK2 by JAK1. Here, we used selective JAK2 inhibition as a model to test the hypothesis that chronic treatment may provoke resistance by facilitating non-physiological signalling pathways in fibroblasts.MethodsThe antifibrotic effects of long-term treatment with selective JAK2 inhibitors and reactivation of JAK2 signalling by JAK1-dependent transphosphorylation was analysed in cultured fibroblasts and experimental dermal and pulmonary fibrosis. Combined JAK1/JAK2 inhibition and co-treatment with an HSP90 inhibitor were evaluated as strategies to overcome resistance.ResultsThe antifibrotic effects of selective JAK2 inhibitors on fibroblasts decreased with prolonged treatment as JAK2 signalling was reactivated by JAK1-dependent transphosphorylation of JAK2. This reactivation could be prevented by HSP90 inhibition, which destabilised JAK2 protein, or with combined JAK1/JAK2 inhibitors. Treatment with combined JAK1/JAK2 inhibitors or with JAK2 inhibitors in combination with HSP90 inhibitors was more effective than monotherapy with JAK2 inhibitors in bleomycin-induced pulmonary fibrosis and in adTBR-induced dermal fibrosis.ConclusionFibroblasts can develop resistance to chronic treatment with JAK2 inhibitors by induction of non-physiological JAK1-dependent transactivation of JAK2 and that inhibition of this compensatory signalling pathway, for example, by co-inhibition of JAK1 or HSP90 is important to maintain the antifibrotic effects of JAK2 inhibition with long-term treatment.

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Report Form for Aggressive Episodes: Preliminary Report

Perceptual and Motor Skills ◽

10.2466/pms.1996.83.3f.1139 ◽

1996 ◽

Vol 83 (3_suppl) ◽

pp. 1139-1152 ◽

Cited By ~ 15

Author(s):

Stål Bjørkly

Keyword(s):

Preliminary Report ◽

Rating Scale ◽

Term Treatment ◽

Clinical Use ◽

Long Term Treatment ◽

Case Vignettes ◽

Secure Unit ◽

One Year ◽

Very High

This paper gives a description of the development and initial empirical testing of the Report Form for Aggressive Episodes, a behavioural rating scale used to measure displayed aggressive behaviour and the situational determinant(s) according to a list of 30 potential precipitants to aggression. Findings from a one-year study in a special secure unit for the long-term treatment of dangerous patients show very high rates of underreporting of aggressive episodes in ward journals and patient files compared to this scale. Illustrations of the clinical use of the scale are provided by scoring examples and two case vignettes.

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