Septal Lesions Research Articles

In vivo co‐ordinated interactions between inhibitory systems to control glutamate‐mediated hippocampal excitability

We present an overview of the long-term adaptation of hippocampal neurotransmission to cholinergic and GABAergic deafferentation caused by excitotoxic lesion of the medial septum. Two months after septal microinjection of 2.7 nmol alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), a 220% increase of GABA(A) receptor labelling in the hippocampal CA3 and the hilus was shown, and also changes in hippocampal neurotransmission characterised by in vivo microdialysis and HPLC. Basal amino acid and purine extracellular levels were studied in control and lesioned rats. In vivo effects of 100 mm KCl perfusion and adenosine A(1) receptor blockade with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) on their release were also investigated. In lesioned animals GABA, glutamate and glutamine basal levels were decreased and taurine, adenosine and uric acid levels increased. A similar response to KCl infusion occurred in both groups except for GABA and glutamate, which release decreased in lesioned rats. Only in lesioned rats, DPCPX increased GABA basal level and KCl-induced glutamate release, and decreased glutamate turnover. Our results evidence that an excitotoxic septal lesion leads to increased hippocampal GABA(A) receptors and decreased glutamate neurotransmission. In this situation, a co-ordinated response of hippocampal retaliatory systems takes place to control neuron excitability.

The changes in thermal preference, sleep–wakefulness, body temperature and locomotor activity in the rats with medial septal lesion

The effects of the destruction of the medial septal neurons (MS) with N-methyl- d-aspartic acid on sleep–wakefulness (S–W), body temperature ( T b), locomotor activity (LMA) and thermal preference were studied in male Wistar rats. When these rats were given a choice of three ambient temperatures ( T amb) of 24, 27 and 30 °C, they preferred 27 °C before the lesion. But they chose 30 °C during the initial days and 24 °C by the third week after the MS lesion. The MS lesion produced an increase in paradoxical sleep (PS) though this change was not very evident when the rats were not allowed to choose their T amb. Though there was a decrease in slow wave sleep (SWS), it recovered considerably, when the lesioned rats chose their preferred T amb. However, the frequency of SWS episodes did not show any recovery. There was a decrease in both T b and LMA by the third week after the MS lesion. It can, therefore, be concluded that the MS lesion affected the initiation of SWS, as there was a decrease in the frequency of SWS episodes. Study of S–W in the rats that were given freedom to select T amb helped to demonstrate the role of the MS in the inhibition of PS. It also showed that the thermostat of the rats was reset at a lower level by the third week after the MS lesion. Decrease in heat production resulting from a decrease in LMA, could have contributed towards the animals’ efforts to maintain a lower T b.

Pro- and anti-apoptotic evidence for cholinergic denervation and hippocampal sympathetic ingrowth in rat dorsal hippocampus

In rat, injection of the specific cholinotoxin, 192 IgG-saporin, into the medial septum results not only in a selective cholinergic denervation of hippocampus, but in an ingrowth of peripheral sympathetic fibers, originating from the superior cervical ganglion, into the hippocampus. A similar process, in which peripheral noradrenergic axons invade hippocampus, may also occur in Alzheimer's disease. Since apoptotic cell death has been demonstrated in the selective neuronal loss found in Alzheimer's disease, the aim of this study was to measure apoptotic protein expression and DNA fragmentation in hippocampal sympathetic ingrowth and cholinergic denervation. Western blot, TdT-mediated dUTP nick end labeling, and oligo ligation techniques were used. Choline acetyltransferase activity and norepinephrine concentrations were also measured. As seen in our previous results, an increase in apoptotic markers was induced by cholinergic denervation alone (medial septum lesion + ganglionectomy), while hippocampal sympathetic ingrowth (medial septum + sham ganglionectomy) reduced or normalized apoptotic effects to control group levels. A decrease in choline acetyltransferase activity was also found in the dorsal hippocampus of hippocampal sympathetic ingrowth and cholinergic denervation groups. An increase in norepinephrine concentration was found in hippocampal sympathetic ingrowth but not in cholinergic denervation group. Results of this study suggest that cholinergic denervation is responsible for most of the proapoptotic responses, while hippocampal sympathetic ingrowth produces a protective effect in the process of programmed cell death in rat dorsal hippocampus. This effect may be a secondary to an altered relationship between norepinephrine–acetylcholine.

The effect of central cholinergic and noradrenergic denervation on hippocampal sympathetic ingrowth and apoptosis-like reactivity in the rat

In this study, the effect of intraseptal injection of specific cholinotoxin 192-IgG saporin (SAP) ± intraperitoneal injection of N-[chloroethyl]- N-ethyl-2-bromobenzylamine (DSP-4) (noradrenergic fiber neurotoxin) was examined in rat hippocampus. Medial septal lesions resulted not only in selective cholinergic denervation of hippocampus (Medial septal lesion + ganglionectomy; SAP + Gx) but also in hippocampal sympathetic ingrowth (IG) of adrenergic fibers (Medial septal lesion + sham ganglionectomy; SAP + IG). Saporin-induced septal lesions produced a significant reduction in hippocampal choline acetyltransferase activity in all tested groups (SAP + IG ± DSP-4 and SAP + Gx ± DSP-4), and an increase in noradrenaline concentration in the SAP + IG group. Visualization of noradrenergic fibers by histofluorescence revealed a mixture of fine and thick varicosities in the SAP + IG but only fine fibers in control and SAP + Gx animals. SAP + IG + DSP-4 lesions produced significant reduction in noradrenaline concentration in all groups with a concomitant decrease in visualization of central noradrenergic fibers in dorsal and ventral hippocampus. Treatment of SAP + IG animals with DSP-4 left mostly thick fibers, probably derived from peripheral sympathetic ingrowth. No fluorescence was seen in either the control + DSP-4 or SAP + Gx + DSP-4 animals. Apoptotic-like changes, using in situ oligonucleotide ligation techniques, were also assessed. Proapoptotic changes were seen in the SAP + Gx ± DSP-4 group as compared to CON ± DSP-4 groups. SAP + IG regardless of DSP-4 treatment protected hippocampal cells from apoptotic cell death when compared to positive control and SAP + Gx ± DSP-4 groups. In summary, elevated noradrenaline concentration following specific cholinergic denervation probably reflects compensatory hippocampal ingrowth originating from the peripheral sympathetic system which may be responsible for neuroprotective effects, i.e., antiapoptosis-like effect. Since cholinergic and noradrenergic systems are known to be involved in Alzheimer's disease and related cognitive function, knowing how these neurotransmitters work after specific lesions may be of importance as an animal model of Alzheimer's disease and as a potential target for Alzheimer's disease drug therapies.

Case Report: Histologic Features of Steatohepatitis in Patients with a Clinical Diagnosis of Autoimmune Cholestasis

Nonalcoholic steatohepatitis (NASH) is a disease included in the spectrum of nonalcoholic fatty liver disease, which is able to continue progression toward cirrhosis (1). The definition of NASH relies on the common exclusion of significant alcohol use (<20 g/day) and the characteristic histological lesions include some degree of steatosis in addition to mixed lobular inflammation and hepatocyte damage (ballooning degeneration with or without Mallory’s hyaline) (2). NASH has been found in patients suffering from chronic hepatitis C (3) and also in other forms of liver diseases, such as chronic hepatitis B, autoimmune hepatitis, drug-induced liver disease, and α-1 antitrypsin deficiency (4). Primary biliary cirrhosis (PBC) should be considered when patients show a biochemical and histological cholestatic pattern along with positive serum antimitochondrial antibodies (AMA), including immunoblot studies, or PBC-specific antinuclear antibodies (ANA), mainly anti-SP100 and anti-GP210 (5), while patients showing a cholestatic pattern together with negative AMA and positive ANA (different from rim-like or multiple nuclear dots) need to be classified as having autoimmune cholangitis (AIC) (5, 6). Differences found between both groups according to biochemical or histological features are minimal. Indeed, histopathologic features of both entities consist of characteristic interlobular and septal bile ducts lesions (florid duct lesion), cholestasis, ductular proliferation, portal and periportal hepatitis, usually mild

ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders.

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride salt] is a selective neuronal nicotinic receptor (NNR) modulator with cognitive enhancing properties in animal models of cognitive functioning. Amongst NNR subtypes, ABT-089 shows selectivity for the cytisine binding site on the alpha4beta2 receptor subtype as compared to the alpha-bungarotoxin (alpha-BgT) binding sites on the alpha7 and alpha1beta1deltagamma receptor subtypes. In functional in vitro electrophysiological and cation flux assays, ABT-089 displays differential activity including agonism, partial agonism and antagonism depending upon the NNR subtype and assay. ABT-089 is as potent and efficacious as (-)-nicotine at evoking acetylcholine (ACh) release from hippocampal synaptosomes. Furthermore, ABT-089 is neuroprotective against excitotoxic glutamate insults, with even greater potency seen after chronic treatment. Similarly, ABT-089 is effective in models of cognitive functioning, including enhancement of baseline functioning as well as improvement of impaired cognitive functioning seen following septal lesioning and natural aging. In neuroprotective assays the compound is most potent by chronic administration. In stark contrast to the positive effects in the cognitive models, ABT-089 shows little propensity to induce adverse effects such as ataxia, hypothermia, seizures, cardiovascular or gastrointestinal side effects. Together these data suggest that ABT-089 is a NNR modulator with the potential for treating cognitive disorders with markedly limited adverse cardiovascular and gastrointestinal side effects.

Medial Septal Lesions Mimic Effects of Both Selective Dorsal and Ventral Hippocampal Lesions.

Electrolytic medial septal (MS) lesions, which depleted acetylcholinesterase staining in both dorsal and ventral hippocampus, produced a constellation of behaviors, combining aspects of both selective dorsal and ventral hippocampal lesion effects. MS lesions impaired spatial working memory on the T maze, thus resembling the effects of dorsal hippocampal lesions. In addition, MS lesions reduced anxiety during successive alleys (a modified form of the elevated plus-maze), social interaction, and hyponeophagia tests. MS lesions also reduced postshock freezing. These effects more closely resemble those of ventral hippocampal lesions. Therefore, the effects of electrolytic MS lesions derive from the resulting combined deafferentation of dorsal and ventral hippocampal regions, suggesting that previously reported effects of cytotoxic dorsal hippocampal lesions are unlikely to be due to a demyelination of fibers of passage coursing through the septal pole.

Effects of Methanol Extract of Uncariae Ramulus et Uncus on Ibotenic Acid-Induced Amnesia in the Rat

In the present study, we investigated the effects of Uncariae Ramulus et Uncus (UR) on learning and memory in the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired performance of the maze test and severe cell losses in the septohippocampal cholinergic system (SHC), as indicated by decreased choline acetyltransferase-immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily administrations of UR (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus induced by ibotenic acid. These results demonstrated that impairments of spatial learning and memory may be attributable to degeneration of SHC neurons and that UR ameliorated learning and memory deficits partly through neuroprotective effects on the central acetylcholine system. Our studies suggest that UR may be useful in the treatment of Alzheimer’s disease.

Effects of Medial Septal Lesions on Action-Outcome Associations in Rats Under Conditions of Delayed Reinforcement.

In operant tasks, control rats maintain high response rates under positive contingencies, when the probability of reinforcement is greater following a response (contingent reinforcement) than during the absence of that response. However, as contingencies approach zero, response rates decrease. In this experiment, under immediate contingent reinforcement, rats with medial septal lesions reduced their response rates, just like controls, when contingencies were shifted from positive toward zero. However, the septal rats were less sensitive to this contingency shift, compared with controls, when there was a 5-s delay between lever presses and contingent reinforcements. This lesion effect appeared to be due to a failure of voluntary response memory, which impaired sensitivity to operant contingencies when there was a delay between action and outcome.

518 The localization of the septal ablation lesion is predicted by the septal contrast depot during echo-guided septal ablation

518 The localization of the septal ablation lesion is predicted by the septal contrast depot during echo-guided septal ablation

Long-term results of endonasal sinus surgery in sinonasal papillomas.

To assess the value of endonasal sinus surgery in the management of sinonasal papillomas. Retrospective study including 43 patients operated on for sinonasal papilloma in a long-term follow-up. In 26 cases (60%) an endonasal approach, in eight cases (19%) an external approach, and in four cases (9%) a combined procedure was performed to remove these tumors. Five septal lesions (12%) were resected under direct vision. The original sections and charts of all patients were reviewed to assess clinical data. Follow-up information was available for 42 of our patients (98%) with a mean follow-up of 62 months. Histologic examination revealed 34 cases of inverted papilloma (79%), five cases of exophytic papilloma (12%), and four cases of columnar cell papilloma (9%). Malignancy occurred in 4 of 43 patients (9%), and recurrences developed in 8 of 42 patients (19%). Two of these recurrences happened after endoscopic sinus surgery (two inverted papillomas), three after lateral rhinotomy (three inverted papillomas), one after a combined procedure (one inverted papilloma), and two after simple resection (two exophytic papilloma). In keeping with our experience, the endonasal endoscopic approach, often in combination with a medial maxillectomy, is favored for the treatment of sinonasal papilloma because of a lower recurrence rate and a better cosmetic result. In some larger tumors and lesions in difficult locations, better visualization can be obtained by a combined external and endonasal approach.

A double dissociation between serial reaction time and radial maze performance in rats subjected to 192 IgG-saporin lesions of the nucleus basalis and/or the septal region.

The cholinergic basal forebrain has been implicated in aspects of cognitive function including memory and attention, but the precise contribution of its major components, the basalocortical and the septohippocampal systems, remains unclear. Rats were subjected to lesions of either the nucleus basalis magnocellularis (Basalis), the medial septum/vertical limb of the diagonal band of Broca (Septum), or both nuclei (Basalis + Septum), using the selective cholinotoxin 192 IgG-saporin. Cognitive performance was evaluated in tasks taxing attention (the five-choice serial reaction time task, 5-CSRTT) and spatial working memory (radial arm maze, RAM). Nucleus basalis lesions disrupted performance of the 5-CSRTT, as demonstrated by decreased choice accuracy, increased incidence of missed trials, increased latencies to respond correctly, and a disrupted pattern of response control. Combined lesions of the Basalis and Septum resulted in qualitatively similar deficits to Basalis lesions alone, although interestingly, these rats were unimpaired on measures of response speed, and showed weaker deficits on accuracy and omissions. Decreasing the attentional load by lengthening stimulus duration reversed some of the deficits in Basalis and Basalis + Septum rats, suggesting an attentional deficit rather than motivation or motor perturbations. Performance in rats with septal lesions was only affected when task difficulty was increased. In the RAM an opposing pattern of effects was observed, with Septum and Basalis + Septum rats showing dramatic impairments, and Basalis rats performing normally. Taken together, these data provide clear evidence for a functional dissociation between septohippocampal and basalocortical cholinergic systems in aspects of cognitive function.

Anesthetic Considerations for Adult Cardiac Surgery Patients with Congenital Heart Disease

The number of adults with congenital heart disease surviving into adulthood is increasing. The proportion of adults undergoing revision of a previous repair is increasing in comparison to those that present for a palliative or curative operation. At the Toronto Congenital Cardiac Centre for Adults, 528 patients underwent cardiac surgery between January 1, 1992 and December 31, 2001. The anesthetic management of the surgical correction of simple and complex congenital heart lesions includes general physiologic considerations such as dysrhythmias, hypoxemia, polycythemia, and pulmonary hypertension. Palliative shunts from early childhood have anatomical and physiologic implications for the adult. Preparation for the operating room and postoperative care are natural extensions of the anesthetic management of the surgical correction of the congenital heart lesions. Anesthetic management of septal lesions in the interventional suite and operating room is discussed. Complex lesions such as tetralogy of Fallot, transposition of the great arteries, Glenn anastomosis, and the Fontan operation are reviewed. The anesthetic management of these patients is rewarding but impossible without an integrated team approach involving cardiologists, surgeons, perfusionists, and nursing staff.

Improvement of shuttle-box performance by anterodorsal medial septal lesions in rats

Septal lesions impair a variety of tasks, including inhibitory avoidance and one way active avoidance. In contrast, these lesions improve two-way active avoidance, probably by reducing anxiety. The present work aimed to study whether anterodorsal medial septal lesion (a) improves performance of two-way active avoidance task (Experiment I), as it has been observed with wider septal lesion, and (b) affect anxiety and/or locomotor activity (Experiment II).This precise region was chosen because some evidences suggest that its lesion do not lead to a reduction of anxiety. Lesioned rats tended to make a higher, but statistically non-significant ( P=0.074), number of avoidances regardless of the session, being this difference statistically significant on the retention session (RT). The same lesion did not appear to have an anxiolytic effect, and did not affected basal locomotor activity. Different possible explanations of our results are discussed.

ラットの視覚刺激と聴覚刺激の短期記憶に及ぼす抗コリン作動薬投与と内側中隔破壊の効果

This study examined the effects of administration of anticholinergic drugs and medial septum lesion on the performance of the successive delayed matching-to-sample (S-DMTS) task in rats in order to clarify the relationship between the central cholinergic system and the modality effect in rats' short-term memory. A pair of visual and/or auditory stimuli was presented with delay intervals to rats. They were required to distinguish whether the modality of the 2nd stimulus (S2) for the pair was the identical to or different from that of the 1st stimulus (S1). Scopolamine at 0.03-0.1mg/kg (i. p.) and mecamylamine at 1-3mg/kg (i. p.) disrupted the performance of S-DMTS task irrespective of the modality of S1, whereas methyl-scopolamine and hexamethonium did not. These results suggest that muscarinic and nicotinic receptors in rats' brain are correlated with short-term memory for both visual and auditory stimuli. Lesion to medial septum also disrupted the performance of S-DMTS task when the visual stimulus was presented as S1, however, the performance was not changed when the auditory stimulus was employed. These findings suggest that the medial septum is correlated with the mnemonic processes of visual but not of auditory stimuli.

Diagnosis and Imaging of Adenomyotic Disease of the Retroperitoneal Space

This manuscript discusses the diagnosis and imaging of adenomyotic disease of the retroperitoneal space, a pathology that we have defined as retroperitoneal adenomyotic disease (RAD). By prospective analysis, comparing barium enema, magnetic resonance imaging (MRI) and transrectal ultrasonography, we distinguished three types of retroperitoneal adenomyotic lesions. The most frequently encountered types were posterior vaginal fornix lesions, followed by hourglass-shaped or diabolo-like lesions, and then by rectovaginal septum lesions. This anatomical classification based on clinical examination and imaging will allow us in the future to define the most appropriate treatment for each entity.

Mnemonic Deficits in Animals Depend upon the Degree of Cholinergic Deficit and Task Complexity

The role of cholinergic basal forebrain (CBF) neurons in mnemonic behaviors was investigated using the immunotoxin 192IgG-saporin. We assessed two routes of immunotoxin administration: intracerebroventricular (ICV) and intraparenchymal (INTRA). INTRA lesions of the medial septum (MS) and/or the nucleus basalis magnocellularis (NBM) were compared with ICV-lesions, INTRA-phosphate-buffered saline injected, and naive controls. The INTRA-NBM/MS and ICV NBM/MS lesions produced a similar depletion of choline acetyltransferase activity of 80% across all CBF projections. Water maze performance was similarly impaired for ICV- and INTRA-NBM/MS animals during various phases of testing, whereas animals with individual lesions of the NBM or MS performed at the level of controls. In contrast to the allocentric demands of water maze performance, the egocentric-based T-maze task revealed a vast group difference between the ICV- and the INTRA-NBM/MS animals. INTRA-NBM/MS animals showed a severe deficit in the non-match- and match-to-position version, whereas again, animals with single lesions were unimpaired. In addition, a dichotomy between animals with complete cholinergic deafferentation was observed in the inhibitory avoidance task. ICV-NBM/MS showed a diminished retention for the aversive stimulus while the INTRA-NBM/MS animals remembered well. During plus maze testing, only the INTRA-NBM/MS animals had a reduced level of anxiety. Although non-CBF regions may have been differently affected by the two routes of immunotoxin administration, global measures of arousal, motivation, and motor initiation did not reveal a different behavioral pattern. Our findings suggest that a dynamic interplay exists between the degree of cholinergic deficit and task demands revealing different types of mnemonic impairments.

Ibotenic acid lesions of the medial septum retard delay eyeblink conditioning in rabbits (Oryctolagus cuniculus).

S. Berry and R. Thompson (1979) reported that electrolytic lesions of the medial septum significantly retard eyeblink conditioning. However, these electrolytic lesions were nonselective and may have also damaged the subcortical inputs to the hippocampus via the fimbria-fornix. In the present study, the medial septum was selectively lesioned with ibotenic acid in rabbits (Oryctolagus cuniculus), whose performance in a delay eyeblink conditioning paradigm was compared with that of intact controls. sham-operated controls, and intact controls given a systemic injection of scopolamine. Rabbits with selective medial septal lesions and rabbits receiving systemic scopolamine were significantly slower to condition than were intact and sham-lesioned rabbits. This finding demonstrates that the selective removal of the medial septum retards delay eyeblink conditioning in a manner similar to the disruption seen after systemic administration of scopolamine.

Tianeptine and its enantiomers: effects on spatial memory in rats with medial septum lesions

Tianeptine, an atypical antidepressant that exhibits clinical efficacy in measures of depression and anxiety, has been reported to enhance learning and memory in rats under certain conditions, an effect not observed with other tricyclic antidepressants. The present study explores further the possibility that tianeptine or its enantiomers (S 16190 and S 16191) can enhance either learning or retention in animals in which the hippocampus has been made partially dysfunctional. The effects of tianeptine and its enantiomers were tested using an open field watermaze test, in rats with partial lesions of the medial septum/diagonal band of Broca (MSDB). When given to normal rats, tianeptine (10 mg/kg, i.p.) did not significantly affect learning as compared to animals injected with saline. We therefore created, in other animals, partial ibotenic acid lesions of MSDB and showed histochemically that these lesions reduced but did not abolish the density of acetylcholinesterase staining in the hippocampus. They impaired both the acquisition of place-navigation and the long-term retention of spatial information over 7 days. Against the baseline of impaired performance in animals with these lesions, neither tianeptine (10 mg/kg) nor its enantiomers (5 mg/kg) affected the rate of acquisition of place navigation. However, tianeptine did enhance the retention of spatial memory over 7 days. These results are discussed in relation to different effects that tianeptine may have on learning including its ability to block stress-induced dendritic re-modelling of the hippocampus.

The investigation of nasal septal perforations and ulcers.

This is a retrospective review of 74 consecutive patients who presented with a nasal septal perforation or ulcer. The aim of this study was to evaluate the contribution of the investigations used to identify the pathology underlying their septal perforation or ulcer. In the majority of cases there was an anterior (85 per cent) smooth, well-circumscribed septal lesion with an occasional bleeding point. Seventy-seven per cent were less than two cm in diameter. The primary presenting symptom was intermittent epistaxis, with the exception of patients with granulomatous disease, who presented more frequently with nasal obstruction. Thirty-five patients (47 per cent) were idiopathic, 29 (39 per cent) traumatic, eight (11 per cent) inflammatory and two (three per cent) infectious. The nasal septum was biopsied in 71 cases, and histology showed non-specific or non-diagnostic findings in 39 (55 per cent), chronic inflammation in 12 (17 per cent), acute inflammation in six (eight per cent), acute to chronic inflammation in four (six per cent) and histological changes consistent with trauma in nine (13 per cent). The anti-neutrophil cytoplasmic antibody test (ANCA) successfully identified six patients with Wegener's granulomatosis, and the angiotensin converting enzyme test (ACE) supported a clinical diagnosis of sarcoidosis in one patient. The remaining investigation methods (CRP, ESR, chest radiograph, biochemistry and coagulation screen) did not contribute to the diagnosis. In this study, the appearance of a nasal septal perforation or ulcer or its location did not predict the clinical diagnosis. A nasal septal bopsy did not significantly contribute toward the clinical diagnosis. On the basis of these findings, a biopsy of a septal perforation or ulcer is unlikely to contribute to the management of patients unless the supportive tests of ANCA or ACE are abnormal or unless malignancy is suspected. This conclusion is restricted to the management of septal perforations as we have found nasal biopsies of polyps of other lesions to be of value.