The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments

Pentylenetetrazol (PTZ), a GABA(A) receptor antagonist and prototypical anxiogenic drug, has been extensively utilized in animal models of anxiety. PTZ produces a reliable discriminative stimulus which is largely mediated by the GABA(A) receptor. Several classes of compounds can modulate the PTZ discriminative stimulus including 5-HT(1A), 5-HT(3), NMDA, glycine, and L-type calcium channel ligands. Spontaneous PTZ-lever responding is seen in trained rats during withdrawal from GABA(A) receptor compounds such as chlordiazepoxide and diazepam, and also ethanol, morphine, nicotine, cocaine, haloperidol, and phencyclidine. This effect is largely mediated by the GABA(A) receptor, which suggests that anxiety may be part of a generalized withdrawal syndrome mediated by the GABA(A) receptor. There are also important hormonal influences on PTZ. Corticosterone plays some role in mediation of its anxiogenic effects. There is a marked sex difference in response to the discriminative stimulus effects of PTZ, and estrogens appear to protect against its anxiogenic effects. Further work with the PTZ drug discrimination is warranted for characterization of anxiety during withdrawal, and the hormonal mechanisms of anxiety.     

Inhibitory role of Syzygium cumini on autacoid-induced inflammation in rats

The ethanolic extract of Syzygium cumini bark has been reported to possess anti-inflammatory activity in our previous studies. The present study is an attempt to elucidate the anti-inflammatory activity of S. Cumini bark against inflammation induced by individual autacoid insult. Histamine (1 mg/ml), 5-HT (1 mg/ml), bradykinin (0.02 mg/ml) and PGE2 (0.001 mg/ml) were used as inflammogens. One of these agents (0.1 ml) was injected s.c. into the right hind paw of each rat. The ethanolic extract of S. cumini bark was tested at the doses of 100, 300 and 1000 mg/kg, p.o. The results indicated the anti-inflammatory activity of S. cumini bark in histamine, 5-HT and PGE2-induced rat paw oedema. However, there was no such significant inhibition of oedema volume observed in bradykinin-induced rat paw oedema at any dose level. Thus, it is concluded that S. cumini exhibits inhibitory role on inflammatory response to histamine, 5-HT and PGE2.     

Rickets in children (An analysis of forty-two cases)

Summary Forty-two selected cases of rickets, substantiated with radiological evidences, were studied etiologically and clinically with special emphasis on the environment and dietary regime. Forty-one of these came from towns and only one was from rural area. Twenty-four were between 2 to 4 years of age, four being below the age of 2, and the youngest was 6 months old. All these forty-two children belonged to poor socio-economic status and in thirty-three families, the incomeper captia per month ranged from Rs. 5 to Rs. 20. Thirty four were stated to have a daily sun exposure of approximately two to four hours, especially in the winter. The dietary of these children consisted mainly of cereals with hardly any source of protein and calcium. This imbalanced dietary seems to be the most important single factor in the etiology of rickets. Chronic recurrent diarrhoea was found in twenty-seven cases. In fifteen families, there was evidence of rickets in one or other sibs in addition to the patient. Seventeen cases presented with gross deformities of the skeletal system, and fifteen were virtually crippled. Other associated gross nutritional deficiencies were anaemia (thirty-seven cases), wasting (twenty cases), vitamin B deficiency (twelve cases) and vitamin A deficiency (seven cases). From The Department of Pediatrics, Medical College, Amritsar.     

Determinants of blood loss during primary burn excision

BACKGROUND: Excisional therapy for burn wounds is frequently associated with large operative blood losses. Our objective was to identify patient and operative factors that affect surgical blood loss and determine strategies to minimize hemorrhage. METHODS: Data from 92 consecutive pediatric patients with severe burns (>40% total body surface area) were evaluated. Patient demographics, burn characteristics, operative factors, and clinical course variables were correlated with blood loss. Blood loss at the time of initial total burn excision was determined by a standardized, previously validated method. Data were analyzed sequentially and cumulatively through univariate and cross-sectional multivariate linear regression. RESULTS: Demographic factors that correlated with increased blood loss were older age, male sex, and larger body size. Area of full-thickness (third-degree) burn correlated with blood loss, whereas total burn size did not. High wound bacteria counts (derived from quantitative tissue cultures), total wound area excised, and operative time were the strongest predictors of the volume of operative hemorrhage. Blood loss increased with delay to primary burn excision at a maximum at 5 to 12 days after burn injury. CONCLUSIONS: Early definitive surgical therapy before extensive bacterial colonization and rapid operative excision is a strategy that may decrease operative hemorrhage and transfusion requirements during burn surgical procedures.     

Right-sided non-bacterial thrombotic endocarditis in a chronic hemodialysis patient with Muir-Torre syndrome

Endocarditis is a recognised complication ofhemodialysis. This is generally only thought of in terms of infective vegetations. We present a case of right-sided NBTE in a patient with an indwelling venous catheter who also had advanced pelvic malignancy. The unusual side of this patient's endocarditic lesions implicates a role for the venous catheter in determining the site of non-bacterial thrombus formation. It is also a reminder that endocarditis is always a risk when using central venous catheters, even after appropriate sterile precautions have been taken.     

Encounters with pseudoaneurysms in orthopaedic practice

Thirteen pseudoaneurysms are presented of which five were caused as a complication of pin/wire placement of external fixators (one conventional and four Ilizarov frames). The most common symptom was the presence of profuse persistent bleeding from either the wound or the pin/wire site. In nine patients the pseudoaneurysm was directly caused by a fracture or subsequent fracture stabilisation. Pre-operative evaluation included radiography, arteriography, Doppler and computed tomography (CT) angiography. Depending on the site and size of the pseudoaneurysm management consisted of either ligation, resection and end-to-end anastamosis/vein grafting, lateral suture, endoaneurysmorrhaphy or selective embolisation.

A high index of suspicion needs to be maintained following penetrating injury in the vicinity of a major vessel, particularly in the presence of persisting symptoms. External fixators are widely used to treat complex orthopaedic problems. The procedure is technically demanding, requiring a sound knowledge of cross-sectional limb anatomy. Injudicious use may result in potentially life/limb threatening complication of pseudoaneurysm.     

In-stent restenosis after carotid angioplasty-stenting: incidence and management

PURPOSE: Carotid angioplasty-stenting (CAS) has been advocated as an alternative to carotid endarterectomy (CEA) in patients with restenotic lesions after prior CEA, primary stenoses with significant medical comorbidities, and radiation-induced stenoses. The incidence of restenosis after CAS and its management remains ill defined. We evaluated the incidence and management of in-stent restenosis after CAS. METHODS: Patients with asymptomatic (61%) and symptomatic (39%) carotid stenosis of > or = 80% underwent CAS between September 1996 and May 2000; there were 50 procedures and 46 patients (26 men and 20 women). All patients were followed up clinically and underwent duplex ultrasonography (DU) at 3- to 6-month intervals. In-stent restenoses > or = 80% detected with DU were further evaluated by means of angiography for confirmation of the severity of stenosis. RESULTS: No periprocedural or late strokes occurred in the 50 CAS procedures during the 30-day follow-up period. One death (2.2%) that resulted from myocardial infarction was observed 10 days after discharge following CAS. During a mean follow-up period of 18 +/- 10 months (range, 1-44 months), in-stent restenosis was observed after four (8%) of the 50 CAS procedures. Angiography confirmed these high-grade (> or = 80%) in-stent restenoses, which were successfully treated with balloon angioplasty (3) or angioplasty and restenting (1). No periprocedural complications occurred, and these patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 10 +/- 6 months. CONCLUSIONS: We recommend CAS for post-CEA restenosis, primary stenoses in patients with high-risk medical comorbidities, and radiation-induced stenoses. In-stent restenoses occurred after 8% of CAS procedures and were managed without complications with repeat angioplasty or repeat angioplasty and restenting.     

Status of lifestyle modifications in hypertension

Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients.     

Effects of NG-nitro-L-arginine methyl ester, 7-nitro indazole, and agmatine on pentylenetetrazol-induced discriminative stimulus in Long-Evans rats

This study was undertaken to determine any role that nitric oxide (NO) may play in the discriminative stimuli produced by pentylenetetrazol (PTZ). The PTZ-induced discriminative stimulus is pharmacologically similar to anxiety in humans and is used in a behavioral assay of anxiety (the PTZ model of anxiety). In the present study, effects of L-N(G)-nitro arginine methyl ester (L-NAME), 7-nitroindazole (7-NI) and agmatine, NO synthase (NOS) inhibitors, on PTZ-induced discriminative stimulus were investigated in male Long-Evans rats (330-350 g). Rats were trained to discriminate PTZ (16 mg/kg) from saline using a two-lever, food-reinforced choice procedure (FR 10). The rats that met the training criteria were injected with L-NAME (15, 30, and 60 mg/kg), 7-NI (15 and 30 mg/kg), agmatine (20, 40, and 60 mg/kg), and saline or vehicle intraperitoneally before each test. They were tested for the PTZ-discrimination to determine if the NOS inhibitors produce discriminative stimulus similar to PTZ or if they block PTZ-induced discrimination. Treatment with the NOS inhibitory drugs neither substituted for PTZ nor altered the PTZ lever selection in any other way. These findings suggest that PTZ-induced discriminative stimulus may not be related to NO-mediated central mechanisms.