Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor V beta-specific monoclonal antibodies.

Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.     

Dorsal fracture of the hamate: distinctive radiographic appearance

Six patients who injured their wrists had radiographs documenting a dorsal, 5- to 10-mm oblong fragment of bone immediately proximal to the base of the fourth and/or fifth metacarpal bones. The fragment was seen on the pronation oblique and/or lateral projections, but not on the posteroanterior projection. The radiographic appearance of the fragment was remarkably similar in all cases. In the one patient in which it was performed, pluridirectional tomography demonstrated that the fragment originated from the dorsal surface of the hamate. Five of the six patients also had associated posterior dislocation of the fourth and/or fifth metacarpals. We conclude that this fragment represents a coronal fracture through the body of the hamate resulting from posterior dislocation or subluxation of the fourth and/or fifth metacarpal.     

Extracranial-intracranial bypass surgery for the management of vasospasm after subarachnoid hemorrhage

A case is presented which demonstrates the potential utility of the extracranial-intracranial bypass procedure for the treatment of vasospasm after subarachnoid hemorrhage. Extracranial-intracranial bypass surgery offers another alternative to the treatment of patients with vasospasm who have failed aggressive medical management.     

Both alpha- and beta-adrenoreceptors contribute to the central depressor effect of catecholamines

We compared the effects of alpha 2- and beta-adrenoreceptor blockade on the central actions of catecholamines and metabolites of alpha-methyldihydroxyphenylalanine, epinephrine, alpha-methylnorepinephrine, and alpha-methylepinephrine were studied. I.c.v. and nucleus tractus solitarii (NTS) injections were carried out under anesthesia. Following i.c.v. injection, both epinephrine and methylepinephrine rapidly reduced blood pressure and heart rate, but the effects of methylnorepinephrine occurred somewhat later. Following microinjection into the nucleus of the solitary tract, epinephrine, methylepinephrine, and methylnorepinephrine all caused hypotension and bradycardia. The hypotensive effects of all 3 amines in the NTS were attenuated in additive fashion by yohimbine, an alpha 2 adrenoreceptor antagonist, and timolol, a beta-adrenoreceptor antagonist, whereas only yohimbine attenuated the bradycardia. The combination of yohimbine and timolol abolished the effects of the amines. These data suggest that in the NTS both alpha 2 and beta adrenoreceptor stimulation contribute to the hypotensive effects of these amines, but that only alpha 2 adrenoreceptors are principally involved in the heart rate response.     

Pressure suppresses serotonin release by guinea pig striatal synaptosomes

Exposure to high pressure produces neurologic changes in humans which manifest as tremor, EEG changes, and convulsions. Since previous studies have implicated the involvement of the serotoninergic system in these symptoms, it was of interest to study serotonin release at high pressure. Synaptosomes isolated from guinea pig striatum were used to follow serotonin efflux at 68 ATA. The major observation was a decrease in [3H]serotonin release from depolarized striatal synaptosomes at 68 ATA. In view of the role of serotonin as an inhibitory neurotransmitter in this area, the observed decrease in synaptic release leads us to conclude that decreased serotoninergic activity in striatal neurons probably is contributing to the hyperexcitability associated with HPNS.     

Assessment of sodium and potassium intakes

The sodium, potassium and creatinine contents of three non-consecutive 24-h urine samples collected by 34 selected adult individuals (10 m; 24 f) living in Cork City were determined. The pooled mean 24-h excretion of sodium and potassium in collections adjudged to be complete were 152 mmol and 78 mmol, respectively. There was no significant difference between group average weekday and weekend-day excretion of Na or K, for either males or females. This suggests that weekend 24-h urinary collections, which most subjects find more convenient, are suitable for studies of sodium and potassium intakes of groups. The ratios of intra- to inter-individual variation for 24-h urinary sodium were 1.4 and 2.1 for males and females, respectively. The corresponding ratios for 24-h urinary potassium were 6.6 for males and 4.9 for females. These ratios indicated that there were large individual day-to-day variations in urinary sodium and potassium excretion in this group. It was estimated that a sample size of 35-60 individuals would be required to estimate group mean sodium and potassium intakes by means of single 24-h urine collections.     

Disc haemorrhages and glaucoma in a general ophthalmic practice

The composition of the clientele from an ophthalmological practitioner's office is described with special reference to the occurrence of glaucoma and disc haemorrhages (h in singular; hh in plural). This study could not be planned as an epidemiological survey and gives no clue to sensitivity or specificity of hh in glaucoma. During a period of about 10 years ending with 1986 there were 731 patients with h and/or glaucoma. When detected, 185 patients had h but no glaucoma, 33 had both h and glaucoma and 513 had glaucoma but no h. During the follow-up period hh were detected in 83 cases of glaucoma, and glaucoma developed in 27 cases with hh. The detection rate of hh among glaucoma was low but steady, indicating that hh may occur at any stage of the glaucoma process. This study shows no predilection for hh in cases with general hypertension or diabetes, nor is the frequency of hh among pseudoexfoliation cases significantly lower than among cases without this stigma.     

Estimating Potency for the E max-Model Without Attaining Maximal Effects

The most widely applied model relating drug concentrations to effects is the E_max model. In practice, concentration–effect relationships often deviate from a simple linear relationship but without reaching a clear maximum because a further increase in concentration might be associated with unacceptable or distorting side effects. The parameters for the E_max model can only be estimated with reasonable precision if the curve shows sign of reaching a maximum, otherwise both EC₅₀ and E_max estimates may be extremely imprecise. This paper provides a solution by introducing a new parameter (S₀ ) equal to E_max/EC₅₀ that can be used to characterize potency adequately even if there are no signs of a clear maximum. Simulations are presented to investigate the nature of the new parameter and published examples are used as illustration.     

“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β₁-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β₁-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.