Bradykinin-induced plasma exudation in guinea-pig airways: involvement of platelet activating factor.

1. We studied the effect of bradykinin on plasma exudation in the airways of the anaesthetized guinea-pig in vivo. Tissue content of extravasated Evans blue dye was used as an index of protein exudation in the larynx, trachea, main bronchi and intrapulmonary airways (i.p.a.). 2. Bradykinin increased the content of Evans blue in all tissues studied in a dose-related manner. The response was greatest in the main bronchi and i.p.a., less in the trachea and least in the larynx. A dose of 47 nmol kg-1 was the lowest tested which caused significant (P less than 0.001) plasma exudation with increases in leakage above control values of 256% in the larynx, 405% in the trachea, 394% in the main bronchi and 485% in intrapulmonary airways. 3. Leakage was significantly (P less than 0.05) increased above control values by 1 min after bradykinin (47 nmol kg-1) in the main bronchi and intrapulmonary airways and was maximal in all airways 5 min after bradykinin. Although reduced by 15 min, the tissue content of dye was still significantly (P less than 0.05) increased 2 h after bradykinin. 4. The prolonged tissue dye retention was due to a later phase of slow and maintained exudation preventing full clearance of dye after the initial response. 5. The initial phase of leakage was partially attenuated by the platelet activating factor (PAF) receptor antagonists WEB 2086 or BN 52021, by indomethacin or by inhibiting sensory nerve activation by opioid anaesthesia: it was not affected by mepyramine and cimetidine nor by the sulphidopeptide leukotriene receptor antagonists FPL 55712 or ICI 198,615.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carcinoma of the thyroid in black patients.

In the period from January 1, 1976 to December 31, 1988, we reviewed the charts of 33 patients treated for carcinoma of the thyroid at Howard University Hospital. The three non-black patients (two Whites and one Pakistani) were excluded from the study. There were 19 females and 11 males. Of the 30 cases elevated, 10 were papillary, 7 were follicular variant of papillary, 8 were follicular, 3 were undifferentiated (anaplastic), and 2 were medullary. Ten patients had either distant metastasis (Hoffman, South Med J 80:741, 1987) or locally advanced disease in the neck (Woolner et al., Am J Surg 102:354, 1961.) at the time of diagnosis. The treatment of these lesions depended on, among other variables, the cell type, the extent of the lesion, and the personal preference of the attending surgeon. Carcinoma of the thyroid remains an uncommon lesion in Black patients. Because of its rarity, the diagnosis may often be delayed and, as a result, patients may first come to attention with a more advanced stage of this disease. To prevent this occurrence, a high index of suspicion must be maintained for all thyroid nodules, and appropriate diagnostic steps taken. Diagnostic and treatment options are discussed.     

Activation of mu- and delta-opioid receptors present on the same nerve terminals depresses transmitter release in the mouse hypogastric ganglion.

1. The inhibitory actions of mu- and delta-opioid receptor agonists on the strong, single fibre synaptic input to neurones contained in the mouse hypogastric ganglion have been examined. 2. The opioid agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO, 10 nM-10 microM), morphine (10-30 [D-Ser2,Leu5,Thr6]enkephalin (DSLET, 3 nM-1 microM), [D-Pen2,D-Pen5]enkephalin (DPDPE, 10 nM-10 microM), all depressed the single fibre, all-or-nothing, nicotinic, excitatory synaptic potential (e.p.s.p.) recorded in mouse hypogastric ganglion neurones. U50488H (0.3-1 microM) was without effect. 3. The effect of DSLET, but not that of DAMGO, was reversed by the delta-opioid receptor-selective antagonist, ICI 174864 (0.3 microM). Naloxone (0.3 microM) antagonized the effect of both DSLET and DAMGO. 4. The site of action of the mu- and delta-receptor agonists was on the presynaptic terminals, since at the concentrations which depressed the e.p.s.p. these drugs did not affect the resting membrane potential or input resistance of the postganglionic neurone body, nor did they depress the postganglionic, nicotinic response to exogenously applied acetylcholine. 5. Quantal analysis further confirmed the presynaptic site of action; mu- and delta-opioid receptor agonists decreased the mean number of quanta released per stimulus but did not reduce the mean amplitude of the quantal unit. 6. It was concluded that mu- and delta-opioid receptors were located on the same presynaptic nerve terminals since, in the same neurones, mu- and delta-opioid receptor agonists depressed the same single fibre inputs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical Abnormality Associated with Smith-Lemli-Opitz Syndrome in an Infant with Features of Rutledge Multiple Congenital Anomaly Syndrome Confirms that the Latter Is a Variant of the Former

We describe a female infant with morphologic features of Rutledge multiple-congenital-anomaly syndrome (RMCAS) and biochemical features of Smith-Lemli-Opitz syndrome (SLOS). She had microcephaly with hypoplastic cerebral frontal lobes and cerebellum, agenesis of the splenium of corpus callosum, abnormal facies including hypertelorism with bilateral inner epicanthal folds, a broad nasal bridge with slightly anteverted nares and patent choanae, low set ears and complex conchal formation, high-arched palate and thick maxillary alveolar ridges, and micrognathia. Her chest was broad, genitalia were ambiguous, and uterus was bicornuate. Skeletal abnormalities included a hypoplastic appendicular skeleton, post-axial hexadactyly of the right hand and the left foot, syndactyly of bilateral 2nd-3rd toes and left 5th-6th toes, right talipes varus and left talipes valgus, and fused L5-S1 vertebrae. Congenital heart disease consisted of hypoplastic left heart, coronary sinus agenesis, ostium secundum and ostium primum defects, and a thickened septum primum. The lungs were hypolobated and the kidneys manifested oligopapillary hypoplasia. Total colonic Hirschsprung disease was noted microscopically. Analysis of liver tissue taken at postmortem examination revealed the ratio of 7-dehydrocholesterol and cholesterol to be 143 (expected, 0.28 +/- 0.28). Although initially described as a distinct syndrome, RMCAS was merged with the severe form of SLOS, because of significantly overlapping features [Online Mendelian Inheritance in Man (OMIM) #268670]. The biochemical data showing an excess of 7-dehydrocholesterol and low cholesterol in the liver tissue of our case supports this viewpoint.     

Cognitive impairment in multiple sclerosis: evidence-based analysis and recommendations.

Cognitive impairment is common in multiple sclerosis (MS), occurring at all stages of the disease, and can be a major source of vocational disability, social impairment, and impoverished quality of life. Dysfunction in free recall from long-term memory, speed of information processing, working memory, and abstract reasoning are frequently observed in MS. Despite weak correlation with disease duration and physical disability status, the degree of cognitive impairment in MS has been related to the extent of topographically specific neuronal tissue damage and loss. Additional clinical factors including disease course, fatigue, affective disturbance, and medication can impact on the degree of MS-related cognitive impairment. We suggest that the symbol digits modalities test, paced auditory serial addition task, the clock drawing test and the MS neuropsychological screening questionnaire be considered as valid and relevant screening tests for cognitive impairment in MS.     

The expression of somatostatin receptors 1 and 2 in benign,pre‐malignant and malignant laryngeal lesions

The expression of somatostatin receptors 1 and 2 in benign, pre‐malignant and malignant laryngeal lesions The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane‐bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre‐malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre‐malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low‐to‐moderate levels in only 2/6 (33%) pre‐malignant and 3/12 (25%) malignant specimens (P < 0.01). This ‘loss’ of epithelial SSTR2 expression may provide a growth advantage in pre‐malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre‐malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.