Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer.

We report a case of osteonecrosis in a patient treated with adjuvant chemotherapy for breast cancer. A 68-year-old woman presented with severe right hip pain. Seven months after completing a course of 6 cycles of adjuvant Cyclophosphamide, Methotrexate and 5-Fluorouracil with standard anti-emetic prophylaxis of Dexamethasone and Domperidone for a T2N0M0 breast cancer. Investigations revealed evidence of osteonecrosis of the right femoral head. Due to ongoing hip pain, she underwent an elective total hip replacement and her mobility has returned almost to normal. Osteonecrosis has been associated with corticosteroids and cytotoxic regimens which omit these agents. Osteonecrosis is a rare complication of cytotoxic therapy but with the increasing use of chemotherapy it should be considered in the differential diagnosis of joint pain in patients who have received anti-tumour therapies.

Platelet serotonin-2 receptors in schizophrenia: effects of illness and neuroleptic treatment.

To examine the role of serotonin2 (5-hydroxytryptamine2, 5-HT2) receptors in schizophrenia, we determined the binding indices of 5-HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the radioligand in platelets obtained from 40 normal control subjects and 42 drug-free schizophrenic patients. We also examined the effect of neuroleptic drug treatment on the binding parameters (Bmax and Kd) of 5-HT2 receptors in platelets of schizophrenic patients. We observed that the Bmax of 125I-LSD binding in platelets of schizophrenic patients was significantly higher than in platelets of normal subjects. There was no significant difference, however, between the Kd of 125I-LSD binding in platelets of schizophrenic patients and normal control subjects. Furthermore, we found no correlation between Brief Psychiatric Rating Scale scores and either Bmax or Kd of 125I-LSD binding at the end of the drug washout period. We also observed that neither treatment with haloperidol nor treatment with thiothixine caused significant changes in Bmax and Kd of 125I-LSD binding in platelets of schizophrenic patients. However, both fluphenazine and trifluoperazine did significantly increase the Bmax of 125I-LSD binding without any significant change in the Kd values in platelets of schizophrenic patients. Our results thus suggest that platelet 5-HT2 receptors are increased in schizophrenia and that chronic treatment with fluphenazine and trifluoperazine, but not haloperidol or thiothixine, further increases the 5-HT2 receptor binding sites in platelets of schizophrenic patients.

Association of nonsuppression of cortisol on the DST with primary polydipsia in chronic schizophrenia.

Thirteen polydipsic and 40 nonpolydipsic chronic schizophrenic patients received the dexamethasone suppression test while stabilized on psychotropic medication regimens. Thirty-eight percent (N = 5) of those with polydipsia but only 5% (N = 2) of those without polydipsia were nonsuppressors of cortisol (i.e., had an abnormal response). It is suggested that hippocampal dysfunction could cause both polydipsia and cortisol dysregulation in these patients.

Synthesis and evaluation of radioiodinated 2-(2(RS)-aminopropyl)-5- iodothiophenes as brain imaging agents.

Methods have been developed for the preparation of 2-(2(RS)-aminopropyl)-5-iodothiophenes. The syntheses and physical properties of 2-(2(RS)-aminopropyl)-5-iodothiophene and N-isopropyl-2-(2(RS)-aminopropyl)-5-iodothiophene are described. The radioiodinated agents are of interest because of the high expected uptake and prolonged brain retention that may result from binding to high-capacity, relatively nonspecific amine binding sites. Radioiodine was introduced into the 5-position of 2-(2(RS)-aminopropyl)-5-iodothiophene and N-isopropyl-2-(2(RS)-aminopropyl)-5-iodothiophene by radioiodination of the corresponding 5-boronic acid or 5-(trimethylstannyl) derivatives. Tissue distribution studies in rats with 2-(2(RS)-aminopropyl)-5-[125I]iodothiophene showed high brain uptake (5 min, 2.77% dose/g; 30 min, 2.51% dose/g) and good brain/blood (B/B) ratios (5 min, 6/1; 30 min 3.8/1. A comparison of the brain uptake of the N-isopropyl derivative with the 2(RS)-aminopropyl analogue demonstrated higher initial brain uptake and brain to blood ratios (5 min, 3.2% dose/g; 10.3/1) but more rapid washout (30 min, 1.37% dose; 2.8/1). These data suggest that radiolabeled 2-(2(RS)-aminopropyl)-5-iodothiophenes are potentially useful agents for cerebral perfusion imaging by single-photon-emission computerized tomography (SPECT).

Infiltration of anomalous lumbosacral articulations. Steroid and anesthetic injections in 10 back-pain patients.

In 10 patients with severe, chronic low back pain, we studied the effect of steroid and local anesthetic infiltration of anomalous lumbosacral articulations, formed between a transitional lumbosacral vertebra and the sacrum. There was immediate total relief of pain in 8 patients, and in 1 patient immediate partial relief that became total after approximately 7 days. Five patients subsequently relapsed to their former pain level in periods ranging from 1 day to 12 weeks, 3 patients continued to report adequate partial pain relief after periods of 7 to 41 months, and 1 patient remained free from pain 2 years after infiltration. IN some cases, infiltration of these articulations may be therapeutic, as well as diagnostic.

Antipsychotic medications and seizures.

This chapter will review the in vitro laboratory as well as animal and clinical studies of the comparative effect of antipsychotic medications on the seizure threshold. It will critically examine current theories relating antipsychotic medications and seizure induction. Finally, it will provide guidelines for the clinical applications of this literature to treatment of both epileptic and non-epileptic populations.

Platelet serotonin-2 receptor binding sites in depression and suicide.

In order to examine the role of serotonin-2 (5HT2) receptors in depression and suicide, we determined 5HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the binding ligand in platelets obtained from 20 normal control and 23 drug-free depressed patients. Our results indicate significantly increased 125I-LSD binding sites (Bmax) in the platelets of depressed patients compared with normal control subjects. We also observed that a subgroup of depressed patients with a recent history of suicide attempts or suicidal ideation had significantly higher 5HT2 binding sites as compared with nonsuicidal depressed patients and normal controls. There were no significant differences in the apparent dissociation constant (Kd) values in the platelets of depressed patients compared with normal control subjects. To examine if the baseline 5HT2 receptors are related to either the severity of illness or treatment response, we determined the relationships of the baseline Bmax and Kd with baseline Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale (BPRS) scores and change in scores after treatment. We found no significant correlation between baseline Bmax and Kd with the baseline HDRS or BPRS scores or change in these scores after psychoactive drug treatment. These results thus indicate increased platelet 5HT2 receptors in depression, but much more so in depressed patients with suicidal ideation or attempts.

Disulfiram encephalopathy as a cause of the catatonia syndrome.

The authors describe a case of the catatonia syndrome associated with disulfiram therapy. Although useful in the management of chronic alcoholism, disulfiram is being increasingly associated with a wide spectrum of side effects and untoward medical sequelae, which now include catatonia. The authors note that catatonia is a clinical syndrome associated with multiple medical conditions as well as psychiatric disorders.