Monoclonal antibody-mediated detection of lung cancer antigens in serum

We assessed the ability of three monoclonal antibodies (MAbs) (5E8, 5C7, and 1F10) to detect tumor-associated antigens (TAAs) in the sera of patients seen in consultation by the Pulmonary Disease Section at the Philadelphia Veterans Administration Medical Center from September through November 1987. Eighteen of the 61 sera were obtained from patients with histologically established lung cancer. Using a semiquantitative enzyme-linked immunoassay (ELISA), TAAs were detected by the MAb panel in the sera of 12 lung cancer patients, yielding a sensitivity of 67% with a 95% confidence interval of 44 to 84%. The frequency of TAA detection varied among cell types and stages of disease. There were eight false positives and 35 true negatives, giving a specificity of 81% with a 95% confidence interval of 67 to 90%. Two of the false positives came from patients with nonpulmonary tumors known to cross-react with the MAbs (laryngeal and gastric carcinoma). The panel was able to distinguish patients with lung cancer from those without to a highly significant degree (chi 2 = 11.2 with 1 df, p less than 0.001). This study suggests that MAb-mediated detection of serum TAAs may be useful in diagnosing and characterizing lung cancers.     

The effect of ketanserin on cardiovascular reflexes in conscious normotensive and spontaneously hypertensive rats

The effect of ketanserin (3 mg/kg i.v.) on the baroreceptor heart rate reflex and the Bezold-Jarisch reflex was examined in conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the control situation (before ketanserin treatment), reflex bradycardia in response to phenylephrine (baroreflex) and phenyldiguanide (Bezold-Jarisch reflex) were impaired in SHR as compared with WKY, while reflex tachycardia in response to nitroprusside was similar in the two groups. However, after ketanserin administration in SHR, there was a reversal of the baroreflex-mediated tachycardia in response to nitroprusside into a bradycardic response. The nitroprusside-induced bradycardia was not caused by the release of 5-HT stimulating chemosensitive vagal afferents since the 5-HT3 receptor antagonist MDL 72222 did not block this response. In the same SHR, the Bezold-Jarisch reflex evoked by phenyldiguanide and the phenylephrine-induced bradycardia were potentiated by ketanserin. All the above effects of ketanserin were less evident in the WKY. Ketanserin did not alter vagal efferent function in anaesthetized SHR since it did not affect bradycardia induced by electrical stimulation of the vagus nerve. Therefore, it is suggested that ketanserin has sensitised cardiac vagal afferent mechanisms in SHR, which led to a normalization of reflex bradycardic function to a level normally observed in conscious normotensive WKY (i.e. prior to ketanserin treatment).     

The role of microsomal oxidation processes in the development of haloperidol tolerance during melatonin administration and epiphysectomy in rats

A pineal hormone melatonin (1 mg/kg, 24 days) facilitated the formation of tolerance to haloperidol and eliminated the changes produced by it in the processes of microsomal oxidation in rats. Pinealectomy yielded the opposite result. After pinealectomy the normalizing effect of the hormone on the condition of the liver monoxygenase system and the effects of haloperidol weakened.     

Interaction of midazolam and morphine in the spinal cord of the rat

The antinociceptive properties, as measured by the tail-flick and hot-plate tests, and the motor effects of an intrathecally-administered benzodiazepine agonist midazolam, alone, and in combination with morphine, was examined in rats. Midazolam alone produced a weak but dose-dependent (20-60 micrograms) antinociceptive effect in addition to a clear motor dysfunction at larger doses (60-100 micrograms). An inactive dose of intrathecally-administered midazolam (20 micrograms) produced a leftward shift in the dose-response curve for intrathecally administered morphine, in the thermal antinociceptive tests. This supra-additive effect was antagonized by naloxone (1 mg/kg). The data suggest a synergistic interaction between mu- and GABAA-receptors in the spinal processing of thermally-evoked pain.     

Development of tolerance to the CNS effects of aminoglutethimide in mice

Initially, there is a high incidence of CNS-depressant side-effects when the aromatase inhibitor, aminoglutethimide, is used in the treatment of patients with advanced breast cancer. Tolerance to these effects develops with continued dosing. This study examines the development of tolerance to various indices of CNS depression with the drug in mice. Single doses of aminoglutethimide induced a dose-dependent depression of spontaneous locomotor activity, rotarod performance, righting reflex and body temperature and a dose-related antileptazol activity. On repeated dosing with the drug, tolerance to these various activities occurred. The tolerance was found to be dose-dependent in the rotarod and righting reflex tests and time-dependent in the locomotor and body temperature tests. Although the results do not allow a determination of whether this clearly demonstrated phenomenon in the mouse is primarily functional or dispositional, the slow onset (14 days) for complete tolerance may be indicative of a functional mechanism.     

Inhibitory effects of amitriptyline on the stimulation-induced Ca2+ increase in parotid acini

The present study demonstrates the effects of the antidepressant, amitriptyline, and the acetylcholine antagonist, atropine, on the stimulation-induced rise in cytosolic, free Ca2+ (Cai2+). The changes in Cai2+ of collagenase-isolated rat parotid acini were measured by means of the Ca2(+)-sensitive dye, fura-2. It was found that stimulation by carbachol resulted in a maximal increase of 582 +/- 34 nM (mean +/- S.E.) in Cai2+ with a ks of 5.8 +/- 1.3 microM. Adrenaline caused a rise of 380 +/- 22 nM in Cai2+ with a ks of 0.5 +/- 0.2 microM. Amitriptyline and atropine were found to inhibit the carbachol-induced rise in Cai2+ with dissociation constants (kI) of 105 and 1.25 nM, respectively, in the absence of agonist. The adrenergic-induced rise in Cai2+ was inhibited by amitriptyline with a kI of 45 nM. Amitriptyline was found to inhibit both receptor classes by a competitive or mixed type of inhibition. Similarly, atropine exerted the same type of inhibition on the acetylcholine receptor. Amitriptyline and atropine were found to be mutually exclusive for competing for substrate binding on the receptor. These findings are consistent with a common binding site for amitriptyline and atropine on the acetylcholine receptor, possibly in close proximity with, but different from the substrate binding site. The stimulation-induced cell shrinkage evoked by the loss of electrolytes and water from the acini was measured by a 90 degree light scattering signal. It was found that this method makes possible the detection of autonomic side-effects of antidepressants on acini suspended in protein-containing media.     

Giant aneurysm arising from the anterior cerebral artery and causing an isolated homonymous hemianopsia

A case of a giant aneurysm arising from the anterior cerebral artery and producing a left homonymous hemianopsia is presented. The aneurysm caused lateral compression of the posterior part of the optic chiasm. After preoperative dynamic assessment of the circle of Willis by angiography and by electroencephalographic recording during carotid artery compression, the aneurysm was trapped with microclips on the anterior cerebral artery proximal and distal to it. Visual field examination 6 months postoperatively showed complete visual field recovery. This is the first case of homonymous hemianopsia caused by an angiographically proven giant aneurysm of the ACA.     

Medical technology in the United States. The last decade.

This paper reviews the evolution of U.S. policy toward medical technology in areas such as cost containment, regulation of devices and drugs, and third party reimbursement. In addition the authors chronicle the diffusion of major medical technologies, procedures, and organizational innovations in the United States. Finally, the article provides tentative observations on the effect of recent policy changes and concludes with some recommendations for the future.     

Medical technology in the United Kingdom.

This article describes and explains the impact of the National Health Service bureaucracy on the diffusion of medical technology in the United Kingdom. Through case studies of six medical technologies, the author demonstrates how health care authorities may exercise control by using the central financing system to dampen the general diffusion of technology. However, the United Kingdom has less control in specific cases due to the absence of a bureaucratic body to coordinate the evaluation and introduction of new technology.     

Kinship versus friendship: social adaptation in married and widowed elderly women

The qualities of daughter versus same-sex friend relationships were described by 151 married and widowed elderly women. The relation of these qualities to life satisfaction was assessed. Relationship qualities predicted life satisfaction in widowed women but not in married women. Significant predictors of life satisfaction for widows included the emotional support of daughters, the instrumental support of friends and friendship strength. In a comparison of the relationship qualities, both married and widowed respondents described daughters as providing more stimulation, ego support and utility than friends. Respondents also reported that relationships with daughters were stronger than those with friends. Married women described relationships with both daughters and friends as more stimulating than widowed women. The value of assessing qualitative indices compared to quantitative indices of later life relationships is discussed.