Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists

The resolution of three 2-substituted derivatives of idazoxan is described. The enantiomers show large separations in activity in a variety of in vitro and in vivo tests, and the active isomers are all potent and selective antagonists at the alpha 2-adrenoreceptor. The significance of these results in relation to those published on the enantiomers of idazoxan and to those on optically active alpha 2-adrenoreceptor agonists is discussed.     

Synthesis of estradiol haptens

Synthesis of Estradiol Haptens Two estradiol haptens, 4-(3β,17β-dihydroxyestran-7α-yl)butanoic acid ( 9 ) and 7α-(4-aminobutyl)-3β,17β-estradiols ( 13 ), were prepared from 19-nortestosterone by partial synthesis. The binding activity for the cytosol estrogen receptor was determined by competition against [³H]-estradiol; at a concentration of 2×10^?7mol/l, compound 9 displaces 50% of [³H]-estradiol. Attached to AH-Sepharose 4B compound 9 allows the cytosol estrogen receptor from calf uterus to be concentrated 1800-fold by affinity chromatography.     

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.     

Telephone dissatisfaction in pediatric practice: Denver and Baltimore

A survey of pediatricians in private practice in the Denver and Baltimore metropolitan areas was conducted to assess pediatricians' satisfaction with the telephone in their practices. The response rates were 84% (89/106) in Denver and 72% (90/125) in Baltimore. In both cities, 42% of the physicians were dissatisfied with their telephone systems. Dissatisfied physicians were less likely to provide a morning telephone hour (P less than .02), less likely to delegate calls to office staff (P less than .01), more likely to believe that they lacked sufficient time to handle daytime calls (P less than .0001), and more likely to be in group rather than solo practice (P less than .05). Younger age of the respondent approached, but did not reach, statistical significance in its association with dissatisfaction.     

Cor triatriatum associated with partial anomalous pulmonary venous connection to the coronary sinus: Echocardiographic and angiocardiographic features

Summary An infant girl is described who had cor triatriatum and partial anomalous pulmonary venous connection of the left pulmonary veins to the coronary sinus, the first report of this combination of lesions. The infant also had a Dandy-Walker malformation and multiple facial and intrathoracic hemangiomas. The cardiac diagnosis was made by two-dimensional echocardiography. Cardiac catheterization and angiography confirmed the findings and also demonstrated a persistent left superior vena cava draining to the coronary sinus. The infant underwent successful surgical repair. Partial anomalous pulmonary venous connection and left superior vena cava not infrequently are associated with cor triatriatum. Although two-dimensional echocardiography is sensitive for the detection of cor triatriatum, preoperative cardiac catheterization is necessary to identify unequivocally systemic and pulmonary venous connections.     

Ultrastructural observations of organelle accumulation in the equine recurrent laryngeal nerve

Summary The left recurrent laryngeal nerves from five horses with sub-clinical neuropathy were examined by light and electron microscopy in a study designed to examine accumulation of axonal organelles at paranodal and internodal locations. Transverse sections of the nerve showed scattered fibres with split myelin sheaths and axonal accumulation of organelles. On longitudinal sections these collections were seen to result from an axonal outpouching in which dense lamellar bodies and mitochondria had accumulated. These paranodal collections, which could be found on both sides of the node, were often associated with infoldings of the terminal loops of myelin and with occasional paranodal demyelination. The fact that many of the organelles in the outpouches were lysosomal in nature was confirmed by their positive staining for cathepsin D activity. Longitudinal sections demonstrated a number of axons which were swollen over a long distance and which contained focal accumulations of similar organelles. In places, however, there was a clear separation between these organelles and the cytoskeletal proteins. In each case these swollen axons were surrounded by Schwann cell nuclei and their processes, forming well-ordered onion bulbs. The possibility that these two types of changes, i.e. the paranodal accumulations and the axonal swellings could result from a disturbance in axonal transport in this distal axonopathy is discussed.     

Trends in analgesic self-poisoning in West-Fife, 1971-1985

All admissions for analgesic self-poisoning to a district poisons unit over a 15-year period have been reviewed. During this time overdose with analgesic drugs increased to represent almost half of all admissions for self-poisoning. The types of analgesics taken in overdose also changed significantly during the period of this review. Aspirin and Distalgesic poisoning declined in incidence and more cases of self-poisoning by paracetamol and non-steroidal anti-inflammatory agents were seen. The impact of these changes on the medical management and outcome of deliberate self-poisoning is analysed. The reasons behind the trends described in this paper are assessed and their implications for future prevention and treatment are discussed.