Reserpine and chlorpromazine,their use in alcoholic and geriatric patients

Although reserpine and chlorpromazine had tranquilizing effect on a number of geriatric and alcoholic patients in a state hospital, several complicating results were noted, some with a bearing on the patients' health and others that might affect the assignment of personnel. Lipoprotein studies carried out on patients receiving reserpine seemed to indicate that a reduction in the blood levels of the denser lipoprotein molecules took place during therapy. Several elderly patients receiving chlorpromazine died of diseases that were not as sharply manifest by symptoms as they might be expected to be. Hence the need for closer observation than a limited staff could afford seemed a matter for consideration. Another consideration of the same order was the possible need for increased personnel for psychotherapy in light of the more receptive condition of the patients.     

RESERPINE AND CHLORPROMAZINE—Their Use in Alcoholic and Geriatric Patients

Although reserpine and chlorpromazine had tranquilizing effect on a number of geriatric and alcoholic patients in a state hospital, several complicating results were noted, some with a bearing on the patients'' health and others that might affect the assignment of personnel.Lipoprotein studies carried out on patients receiving reserpine seemed to indicate that a reduction in the blood levels of the denser lipoprotein molecules took place during therapy.Several elderly patients receiving chlorpromazine died of diseases that were not as sharply manifest by symptoms as they might be expected to be. Hence the need for closer observation than a limited staff could afford seemed a matter for consideration. Another consideration of the same order was the possible need for increased personnel for psychotherapy in light of the more receptive condition of the patients.     

Chlorpromazine: Case report and review of its ocular side-effects

Chlorpromazine has been an effective anti-psychotic medication in the treatment of schizophrenia since the 1960s. However, the long-term dermatological and ocular complications have been well documented. This article reviews a case in which a patient had been treated with chlorpromazine for schizophrenia for 30 years and displayed the characteristic ocular side-effects. The ocular and dermatological side-effects of chlorpromazine are reviewed.     

The effect of chlorpromazine on SCE frequency in human chromosomes: An in vitro and in vivo study

Schizophrenic patients who were receiving, or who had received chlorpromazine showed SCE levels similar to those in a normal control population. Of 8 normal individuals whose lymphocytes were exposed in vitro to chlorpromazine (0.05–2.00 μg/ml) for two cell cycles, 4 showed a significant increase in SCE, 3 showed no increase and 1 a decrease compared with untreated lymphocytes. Lymphocytes from a further 8 donors treated with 2.0 μg/ml chlorpromazine prior to mitogen stimulation (G₀ lymphocytes) showed a similar SCE response. Only 3 of the 8 donors showed a significant increase in SCEs over the baseline level. When proliferating lymphocytes were exposed to chlorpromazine 38 h after culture initiation and prior to the addition of BrdUrd to the culture medium, metaphase chromosomes from only 3 of the 8 individuals studied showed increased levels of exchange. These results indicate that chlorpromazine can induce SCEs in vitro but that there is considerable variation in SCE response among individuals. Furthermore, our data emphasises the importance of using more than 1 or 2 donors when analysing SCE response in human chromosomes.     

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. METHODS: This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. CONCLUSIONS: The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. Trial registration Clinicaltrials.gov Identifier NCT01046942.     

Chlorpromazine alone and with reserpine; use in the treatment of mental diseases

One hundred psychiatric patients were treated with chlorpromazine, alone or combined with reserpine. Fifty-six per cent of patients with chronic schizophrenic reactions showed moderate or pronounced improvement when treated with chlorpromazine alone. The results of treatment with the combined drugs were not so good as that. Indications are that treatment of patients with chronic schizophrenic reactions is more efficacious with these drugs than with other forms of somatic therapy. Complications of treatment were far greater with combined use of chlorpromazine and reserpine. For this reason, the combination appears to have limited usefulness. The Parkinson syndrome was the most frequent complication of large doses of these drugs. It appears to be a toxic reaction, requiring reduction in dosage. Jaundice appears to be neither a frequent nor a serious complication of treatment.     

Bleeding complications after pacemaker or cardioverter-defibrillator implantation in patients receiving dual antiplatelet therapy

Introduction. The aim of the study was to define the prevalence of bleeding events in patients treated with dual antiplatelet therapy (DAT) in comparison with patients receiving only acetylsalicylic acid (ASA). Methods. Prospective two-centre registry of all first implantations of pacemakers, cardioverter-defibrillators and cardiac resynchronisation therapy units in patients receiving ASA (n=194) or DAT (n=53). Results. Bleeding complications were detected in 27 (16.2%) patients in the ASA group and in 13 (24.5%) in the DAT group. There was no significant difference in the overall number of complications between the patients receiving ASA or DAT, although there was a trend towards a higher incidence of overall complication rates in the DAT group (p=0.0637). The incidence of major complications (requiring blood transfusion or surgical intervention or prolonging hospital stay) was low (3.6%), and similar in both groups (3.6 and 3.8% respectively, ns). The rate of minor complications (subcutaneous haematomas) was greater in the DAT group (p=0.015). Conclusions. Treatment with DAT does not increase the risk of major bleeding complications as a result of device implantation; however, minor complications are significantly more frequent. Our results suggest that DAT could be continued in patients undergoing device implantation with a moderate risk of bleeding complications. (Neth Heart J 2010;18:230-5.)     

The Use and Abuse of Tranquillizing Drugs for Chronic Mental Patients

The purpose of this study was to determine the necessity of administering maintenance doses of tranquillizing drugs to chronic mental patients. The behaviour of 16 female psychotic patients in a mental hospital was measured while they received maintenance doses of chlorpromazine (average dose, 50 mg. q.i.d.) and again while receiving identical doses of a placebo. The double-blind technique was employed. Nurses used a behaviour rating scale to measure noisiness, personal cleanliness, interpersonal relations among patients, occupational activities, hostility, activity, co-operation, dress, eating, and sleeping. Patients'' behaviour over a six-week period of chlorpromazine administration was compared with behaviour over an equal period of placebo administration. There was no evident difference in behaviour in 90% of the cases. Among the others there was a slight trend towards improved behaviour while the patients received placebo. It was concluded that tranquillizing drugs are often used needlessly for chronic mental patients. Implications of the use of tranquillizing drugs with chronic mental patients are discussed.     

Bisphosphonates and Osteonecrosis of the Jaw: A Retrospective Study

ObjectiveTo assess the prevalence of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonate therapy and in those who were bisphosphonate naïve.MethodsWe undertook a retrospective review of medical records of patients at the New York Harbor Health Care System from 1999 through 2004. Charts were selected for review if patients had a Current Procedural Terminology (CPT) code suggestive of ONJ or if they had ever received bisphosphonate therapy.ResultsAmong 1,951 medical records reviewed, we identified 2 patients with ONJ who had received bisphos-phonates and 2 patients with ONJ who were bisphospho-nate naïve. Both patients treated with bisphosphonates had multiple myeloma and were receiving monthly infusions. They had initially received pamidronate before treatment was changed to zoledronic acid. In each case, ONJ was precipitated by a routine dental extraction. The prevalence of ONJ in our patient population receiving intravenously administered bisphosphonates was 1 in 71.5. Of the 2 cases of ONJ in bisphosphonate-naïve patients, osteora-dionecrosis was clearly incriminated in 1 patient and potentially the causative factor in the other patient as well. No patients receiving orally administered bisphosphonates had ONJ, nor did this complication occur in any patients receiving parenteral bisphosphonate therapy for disorders such as osteoporosis or Paget’s disease of bone.ConclusionBisphosphonates remain an important option for management of metabolic bone disease and complications of malignant disease. The overall prevalence of ONJ in patients receiving bisphosphonates seems to be very low; however, patients receiving intense parenteral therapy for an underlying malignant condition appear to have a uniquely elevated risk for the development of this complication. A causal relationship between bisphosphonates and ONJ remains to be proved and merits further investigation. (Endocr Pract. 2007;13:232-238)     

Therapy of Chlorpromazine Melanosis: A Preliminary Report

Melanosis observed in association with prolonged chlorpromazine therapy has become a serious problem in mental institutions. Skin pigmentation has produced an appearance which is cosmetically undesirable. Ocular deposits have caused visual impairment. Diffuse visceral involvement has been accompanied by functional disturbances of the involved organs.Withholding chlorpromazine did not diminish the pigment deposits already present in eight patients with chlorpromazine-induced melanosis. Therefore therapy for existing cases and means of preventing this side effect were investigated. A method of blocking melanin synthesis by depressing tyrosinase activity was devised. A copperchelating agent, D-penicillamine, was administered for a period of four weeks (300 mg. three times daily for six days each week, with mineral supplement substituted on the seventh day). Four of six days patients thus treated improved markedly as evidenced by diminution of skin pigmentation. Urinary copper excretion was substantially increased during the trial period. An alternative method of treatment designed to stimulate melatonin production by the pineal gland was employed. Two patients were kept in darkness for a period of four weeks. One improved markedly, the other only slightly.     

CHLORPROMAZINE ALONE AND WITH RESERPINE—Use in the Treatment of Mental Diseases

One hundred psychiatric patients were treated with chlorpromazine, alone or combined with reserpine. Fifty-six per cent of patients with chronic schizophrenic reactions showed moderate or pronounced improvement when treated with chlorpromazine alone. The results of treatment with the combined drugs were not so good as that. Indications are that treatment of patients with chronic schizophrenic reactions is more efficacious with these drugs than with other forms of somatic therapy.Complications of treatment were far greater with combined use of chlorpromazine and reserpine. For this reason, the combination appears to have limited usefulness. The Parkinson syndrome was the most frequent complication of large doses of these drugs. It appears to be a toxic reaction, requiring reduction in dosage. Jaundice appears to be neither a frequent nor a serious complication of treatment.     

Gastrointestinal Disturbances Associated with Withdrawal of Ataractic Drugs

The psychological effects of abrupt withdrawal of ataractic drugs have been studied by others. Physical symptoms also occur under such circumstances and include abdominal pain, nausea and vomiting. Forty patients were divided into four groups of 10, each group receiving one of the following drugs: chlorpromazine, thioridazine, perphenazine or chlorprothixene. This medication was then suddenly withdrawn. In each of the chlorpromazine and thioridazine groups, three patients had gastrointestinal symptoms within 48 hours, lasting one to eight days. One patient on chlorprothixene, 450 mg. daily, experienced symptoms for six days. Perphenazine withdrawal produced no such symptoms. Thioridazine has little antiemetic action but perphenazine is prescribed for vomiting; hence it seems unlikely that the reported symptoms are due to a rebound action on the vomiting centre.These findings are relevant to the situation of withdrawal of ataractics prior to administration of anesthetics and to drug studies involving cross-over from an active compound to a placebo. The increasing use of ataractics suggests that this additional diagnostic possibility should be considered in the presence of obscure gastrointestinal symptoms.     

Neurosurgical complications of anticoagulant therapy

Ten cases of subdural hematoma and one case of spinal epidural hematoma encountered in patients who were receiving anticoagulant therapy are discussed.This surprisingly large number of complications was observed within three years in a single hospital and represents 36.6% of all chronic and subacute subdural hematomas seen during the same period. The cases are analyzed and the conclusion reached that the causal relationship between anticoagulant therapy and hemorrhage cannot be denied.Suggestions are made as to how to decrease the danger of such complications.     

Impact of Pelvic Radiotherapy on Gut Microbiota of Gynecological Cancer Patients Revealed by Massive Pyrosequencing

Although pelvic irradiation is effective for the treatment of various cancer types, many patients who receive radiotherapy experience serious complications. Gut microbial dysbiosis was hypothesized to be related to the occurrence of radiation-induced complications in cancer patients. Given the lack of clinical or experimental data on the impact of radiation on gut microbiota, a prospective observational study of gut microbiota was performed in gynecological cancer patients receiving pelvic radiotherapy. In the current study, the overall composition and alteration of gut microbiota in cancer patients receiving radiation were investigated by 454 pyrosequencing. Gut microbial composition showed significant differences (P < 0.001) between cancer patients and healthy individuals. The numbers of species-level taxa were severely reduced after radiotherapy (P < 0.045), and the abundance of each community largely changed. In particular, the phyla Firmicutes and Fusobacterium were significantly decreased by 10% and increased by 3% after radiation therapy, respectively. In addition, overall gut microbial composition was gradually remolded after the full treatment course of pelvic radiotherapy. In this set of cancer patients, dysbiosis of the gut microbiota was linked to health status, and the gut microbiota was influenced by pelvic radiotherapy. Although further studies are needed to elucidate the relationship between dysbiosis and complications induced by pelvic radiotherapy, the current study may offer insights into the treatment of cancer patients suffering from complications after radiation therapy.     

Live varicella vaccine: prevention of nosocomial infection and protection of high risk infants from varicella infection

For prevention of nosocomial infection, 25 infants including high risk patients received an emergency injection of live varicella vaccine. Three patients developed a rash within 5 days after vaccination, but their symptoms were mild. The other 22 showed no clinical symptoms and gave an immune response. Twenty-two patients receiving immunosuppressive therapy were vaccinated and 20 of them showed a positive response in the varicella skin test. Of 14 vaccinated patients with malignancies, 2 giving a positive skin test, later showed clinical varicella, but their symptoms were not severe. One case with ALL was immunized safely under very poor conditions during the first induction therapy. No complications were observed in any patients.     

Metabolic activation of the phenothiazine antipsychotics chlorpromazine and thioridazine to electrophilic iminoquinone species in human liver microsomes and recombinant P450s

The phenothiazine-derived antipsychotics, namely chlorpromazine and thioridazine, have been associated with very rare but severe incidences of hepatotoxicity in patients. While the mechanism of idiosyncratic hepatotoxicity remains unknown, it is possible that metabolic activation and subsequent covalently binding of reactive metabolites to cellular proteins play a causative role. Studies were initiated to determine whether chlorpromazine and thioridazine undergo cytochrome P450 (P450)-mediated bioactivation in human liver microsomes to electrophilic intermediates. LC/MS/MS analysis of incubations containing chlorpromazine or thioridazine in the presence of NADPH and glutathione (GSH) revealed the formation of GSH conjugates derived from the addition of the sulfydryl nucleophile to monohydroxy metabolites of chlorpromazine and thioridazine, respectively. Formation of reactive intermediates of chlorpromazine and thioridazine was primarily mediated by heterologously expressed recombinant CYP2D6, and to a less extent, CYP1A2. The 7-hydroxyl metabolites of chlorpromazine and thioridazine were also detected by tandem mass spectrometry. A tentative pathway states that after initial 7-hydroxylation, a bioactivation sequence involves P450-catalyzed oxidation of the phenothiazine core to an electrophilic quinone imine intermediate, which is subsequently attacked by glutathione yielding the sulfydryl conjugates. The results from the current investigation constitute the first report on the cytochrome P450-catalyzed bioactivation of the phenothiazine antipsychotics chlorpromazine and thioridazine.     

Cerebral venous sinus thrombosis after gender reassignment surgery

Background: Many factors have been implicated in the etiology of cerebral venous sinus thrombosis (CVT). These include head injury, cancer, infections (sepsis, sinusitis, and mastoiditis), coagulopathies, pregnancy, systemic lupus erythematosus, and dehydration.Case summary: We present the case of a patient who received long-term estrogen therapy for ~15 years after feminizing genitoplasty. The patient experienced a CVT with an excellent clinical outcome. A similar case has not been reported in the literature.Conclusion: Because CVT may be associated with morbidity, mortality, and risks from the complications and treatments of the condition, further research is needed to clarify the factors that may contribute to the long-term risk of CVT in patients receiving long-term estrogen therapy after feminizing genitoplasty.     

Plasma Prolactin Activity in Inappropriate Lactation

Using a bioassay dependent on the development of a lactogenic response in rabbit mammary tissue cultured in vitro, prolactin distinct from immunoreactive growth hormone has been found in the plasma of patients of both sexes with inappropriate lactation with and without evidence of pituitary tumours. It has also been found in one patient with primary hypothyroidism and galactorrhoea, and in another during chlorpromazine therapy, but not in nine patients with gynaecomastia without galactorrhoea. Plasma prolactin levels were examined in seven patients during oral glucose tolerance tests: no change occurred in the four patients with pituitary tumours, but the levels were suppressed in the three patients with normal pituitary fossae. Prolactin appears to be a distinct pituitary hormone in man, as in animals, and also to be aetiologically related to states of inappropriate lactation.     

The coincidence of TRAM flaps and prostheses in the setting of breast reconstruction

It is well known that transverse rectus abdominis myocutaneous (TRAM) flaps can be used to replace unsatisfactory prosthetic breast reconstructions; however, little has been written about the scope of breast implant use in TRAM flap patients. In this study, to ascertain the range of such therapeutic options, their frequency, and their clinical outcomes, the authors retrospectively reviewed the senior author's breast reconstruction experience from 1989 to 2000 with patients in whom both a TRAM flap and an implant were used for breast reconstruction. The authors examined the surgical indications, body habitus, bra size, chest wall irradiation history, flap type, implant type, complications, and outcomes for those patients with TRAM flap and breast implant combinations.Thirty-two women who had 50 (various) combinations of a TRAM flap and a breast implant were identified. There were more clinical scenarios than patients because many of the women had multiple scenarios. The 50 combination scenarios were then divided into six groups. Group I consisted of 14 patients who had elective prostheses placed beneath simultaneous TRAM flaps; group II consisted of 10 patients who had TRAM flaps with contralateral prosthetic reconstruction (in which two implants were received before the TRAM flaps, five implants were received simultaneously with the TRAM flaps, and three implants were received after the TRAM flaps); group III consisted of eight patients who had contralateral augmentation in addition to their TRAM flaps; group IV consisted of 11 patients who had TRAM flaps that were used to cover or replace previous prosthetic reconstructions; group V consisted of four patients in whom prostheses were used to augment or improve previous TRAM flap reconstructions; and group VI consisted of three patients who required prostheses to either reconstruct or salvage total or near-total TRAM flap failures. A broad range of implant types was used, although anatomic saline implants predominated. Forty-one percent of the patients in the review had undergone irradiation during the course of their treatment for breast cancer. Eight of the 32 patients experienced a total of twelve complications, four of which were related to the implants and eight of which involved the TRAM flaps and abdominal donor sites.Although complex, the wide variety of potential TRAM flap/breast implant combinations can be useful for patients with challenging reconstructive scenarios, particularly those that involve radiation therapy. In the group of patients reviewed by the authors, TRAM flaps were most often used in successful partnership either on the same side as or opposite to an implant reconstruction. A TRAM flap was used to salvage or replace an unsatisfactory implant reconstruction in less than a third of the patients. From a risk point of view, implants used opposite a TRAM flap reconstruction had a lower incidence of complication than did implants used beneath TRAM flaps.