Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients.

Ethanol is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. Ethanol dependence upregulates NMDA receptors and contributes to crosstolerance with selective NMDA receptor antagonists in animals. This study evaluated whether recovering ethanol-dependent patients show evidence of a reduced level of response to the effects of the NMDA receptor antagonist, ketamine. In this double-blind study, 34 recently detoxified alcohol-dependent patients and 26 healthy comparison subjects completed 3 test days involving a 40-min infusion of saline, ketamine 0.1 mg/kg, or ketamine 0.5 mg/kg in a randomized order. Recovering ethanol-dependent patients showed reduced perceptual alterations, dysphoric mood, and impairments in executive cognitive functions during ketamine infusion relative to the healthy comparison group. No attenuation of ketamine-induced amnestic effects, euphoria, or activation was observed. The alterations in NMDA receptor function observed in recovering ethanol-dependent patients may have important implications for ethanol tolerance, ethanol dependence, and the treatment of alcoholism.     

A man with osteoblastic metastasis and hypocalcaemia

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

Genetic causes of familial hypercholesterolaemia in a Malaysian population

A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts.     

Computed tomography diagnosis of tracheobronchopathia osteochondroplastica

Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease characterized by the presence of osseous and cartilaginous submucosal nodules projecting into the tracheobronchial tree. Most cases are asymptomatic and discovered incidentally at post‐mortem. We identified a case of TO on thoracic spiral CT and confirmed the diagnosis on bronchoscopy. This article reviews the imaging characteristics of TO, and shows the 3‐D virtual bronchoscopic and multiplanar reconstruction appearances of TO.     

Ranolazine for the treatment of refractory angina in a veterans population

BackgroundPivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population.ResultsA total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III–IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III–IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes.ConclusionThe addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.