Early and late brain resonance findings of two siblings with Hunter syndrome. / Hallazgos tempranos y tardíos en la resonancia cerebral de dos hermanos con síndrome de Hunter.

INTRODUCTION: Mucopolysaccharidosis type II (MPS II) is a lysosomal disease caused by deficiency of the enzyme iduronate-2-sulfatase (IDS), linked to the X chromosome, producing a wide spectrum of clinical manifestations. CASE REPORT: We present the case of two siblings with MPS II of different paternal origin with the same genetic mutation; the age at the time of diagnosis was 5 years of age (case 1) and 8 months of age (case 2). These brethren present different findings in brain magnetic resonance imaging (MRI) with each other, case 1 presented classic findings for age, case 2 presented multiple early findings, such as dilated perivascular spaces up to 9.5 mm, magna megacisterna, among others; without neurological manifestations. CONCLUSION: This patient's brain compromise was presented before the year of age and prior to hepatosplenomegaly, thus, MRI becomes an early diagnostic tool for MPS II.

TITLE: Hallazgos tempranos y tardíos en la resonancia cerebral de dos hermanos con síndrome de Hunter.Introducción. La mucopolisacaridosis de tipo II (MPS II) es una enfermedad lisosómica causada por deficiencia de la enzima iduronato-2-sulfatasa, ligada al cromosoma X, y produce un gran espectro de manifestaciones clínicas. Caso clínico. Se presenta el caso clínico de dos hermanos con MPS II de diferente origen paterno con la misma mutación genética; la edad en el momento del diagnóstico fue de 5 años (caso 1) y de 8 meses (caso 2). Dichos hermanos presentan hallazgos diferentes en la resonancia magnética cerebral entre sí: el caso 1 presentó hallazgos clásicos para la edad, y el caso 2 presentó múltiples hallazgos tempranos, como espacios perivasculares dilatados de hasta 9,5 mm y megacisterna magna, entre otros, sin presentar manifestaciones neurológicas. Conclusiones. La afectación cerebral del paciente del caso 2 se presentó antes del año de edad y previa a la hepatoesplenomegalia. La resonancia magnética se convierte en una herramienta de diagnóstico temprano para la MPS II.

Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction.

Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

Tracheal cryopreservation: caspase-3 immunoreactivity in tracheal epithelium and in mixed glands

Cryopreservation has an immunomodulating effect on tracheal tissue as a result of class II antigen depletion due to epithelium exfoliation. However, not all epithelium is detached. We evaluated the role of apoptosis in the remaining epithelium of 30 cryopreserved tracheal grafts. Caspase-3 immunoreactivity of tracheal epithelium was studied in canine tracheal segments cryopreserved with F12K medium, with or without subsequent storage in liquid nitrogen at -196°C for 15 days. Loss of structural integrity of tracheal mixed glands was observed in all cryopreserved tracheal segments. Caspase-3 immunoreactivity in tracheal mucosa and in mixed glands was significantly decreased, in contrast to the control group and to cryopreserved tracheal segments in which it remained high, due to the effect of storage in liquid nitrogen (P < 0.05, ANOVA and Tukey test). We conclude that apoptosis can be triggered in epithelial cells during tracheal graft harvesting even prior to cryopreservation, and although the epithelial caspase-3 immunoreactivity is reduced in tracheal cryopreservation, this could be explained by increased cell death. Apoptosis cannot be stopped during tracheal cryopreservation.

Tracheal cryopreservation: caspase-3 immunoreactivity in tracheal epithelium and in mixed glands.

Cryopreservation has an immunomodulating effect on tracheal tissue as a result of class II antigen depletion due to epithelium exfoliation. However, not all epithelium is detached. We evaluated the role of apoptosis in the remaining epithelium of 30 cryopreserved tracheal grafts. Caspase-3 immunoreactivity of tracheal epithelium was studied in canine tracheal segments cryopreserved with F12K medium, with or without subsequent storage in liquid nitrogen at -196 degrees C for 15 days. Loss of structural integrity of tracheal mixed glands was observed in all cryopreserved tracheal segments. Caspase-3 immunoreactivity in tracheal mucosa and in mixed glands was significantly decreased, in contrast to the control group and to cryopreserved tracheal segments in which it remained high, due to the effect of storage in liquid nitrogen (P < 0.05, ANOVA and Tukey test). We conclude that apoptosis can be triggered in epithelial cells during tracheal graft harvesting even prior to cryopreservation, and although the epithelial caspase-3 immunoreactivity is reduced in tracheal cryopreservation, this could be explained by increased cell death. Apoptosis cannot be stopped during tracheal cryopreservation.

Clinical characteristics of trigeminal nerve injury referrals to a university centre.

The aim of this retrospective study was to determine the aetiology and characteristics of trigeminal nerve injuries referred to a university centre with nerve injury care. Fifty-nine patients with 73 injured trigeminal nerves were referred in 10 months. The most common aetiologies were odontectomy (third molar surgery) (52.1% of nerves), local anaesthetic (LA) injections (12.3%), orthognathic surgery (12.3%) and implant surgery (11.0%). The inferior alveolar nerve (IAN) was most commonly injured nerve (64.4%), followed by the lingual nerve (LN) (28.8%). About a quarter of IAN injuries (27.3%) and half of LN injuries (57.1%) from odontectomy had severe sensory impairment. There were twice as many LN than IAN injuries from local anaesthetic injections, but all had mild or no sensory impairment. Nerve injuries from implant surgery occurred only in IAN injuries; none had severe sensory impairment. Neuropathic pain occurred in 14.9% of IAN injuries and only in those with mild or no sensory impairment. Nerve surgery was offered to 45.8% of patients; a third underwent surgery.

[Effect of the hyaluronic acid on tracheal healing. A canine experimental mode]. / Efecto del ácido hialurónico sobre la cicatrización traqueal en un modelo experimental canino.

Several drugs have been used to modulate of the tracheal healing process in order to prevent tracheal stenosis. Hyaluronic acid (HA) is a modulator of the fibrogenesis. In this work we evaluate the effect in order the application of hyaluronic acid has on tracheal healing, after cervical tracheoplasty in dogs. A cervical tracheal resection and tracheoplasty was performed in 12 dogs and they were treated following surgery as follows: Group I (n = 6) Topical application of normal saline solution (0.9%) on the anastomosis site. Group II Topical application of hyaluronic acid on the trachea anastomosed. The animals were evaluated clinical, radiological and tracheoscopically during 4 weeks and were submitted to euthanasia. Macroscopic and microscopic examinations of the tracheal anastomotic healing were evaluated. Biochemical collagen quantification by the Woessner method was performed to evaluate the collagen development at the anastomotic site. All the animals survived the surgical procedure and the study time. No animal presented differences in clinical evaluation. Radiological and endoscopical findings both two showed more development of the tracheal stenosis in-group than in group II. The tracheoscopy and macroscopic studies showed major inflammation and development of fibrotic tissue with a firm consistency in the healing of the group I than in group II. Microscopic examination in group I showed severe fibrosis and inflammatory reaction. The group II presented deposits of a thin and organized collagen fibers and minimal inflammatory reaction. Biochemical collagen concentration was larger in-group I, however significantly. We conclude that the hyaluronic acid applied after cervical tracheoplasty in dogs reduces postsurgical tracheal stenosis and inflammation, as well as improve the quality of the tracheal healing.

Surgical management of trigeminal neuropathic pain.

Surgical treatment of mechanical trigeminal nerve injuries resulting in neuropathic pain varies with the type of injury (i.e., amputation or compression), presence of painful neuromas, and adjacent hard/soft tissues. Microsurgical principles that include access, preparation, and repair of the various nerve injuries are recommended for surgical treatment. The choice of surgical repair depends on the microscopic pathology and the presence or absence of adequate distal nerve tissue.

Suture-line reinforcement with glutaraldehyde-preserved bovine pericardium for nonanatomic resection of lung tissue.

In this study we assessed the usefulness of glutaraldehyde-preserved bovine pericardium (GPBP), preparated in our laboratory, in nonanatomic resection of lung tissue in dogs. A 30% resection of the right cranial lobe of the lung was performed in 18 mongrel dogs. The suture line was reinforced with GPBP strips. For group I (n = 6), the GPBP strips were fixed on the lung with nonabsorbable suture by thoracotomy. In Group II (n = 6), the resection and fixation of the GPBP strips were performed with an endoscopic linear stapler by thoracotomy. In Group III (n = 6), the resection and fixation of the GPBP strips were performed with a linear stapler by thoracoscopy. The animals were evaluated each day during the first week after surgery and every other day during the study time. At the end of the study all animals were euthanized with an overdose of pentobarbital. Macroscopic and microscopic examinations of the bioprosthesis and lung were evaluated. All animals survived the surgical procedure and study time (8 weeks). In the three groups, macroscopic examination of the bioprosthesis showed good adaptation to the lung tissue. Microscopically, all groups of animals presented good healing, with the presence of fibrotic tissue layer on the GPBP and its periphery as well as in the lung. However, in group I we observed the presence of giant cells in the suture line. GPBP proved to be a useful material for reinforcement of the nonanatomic resection suture line of lung tissue in dogs.

Trigeminal ganglion cell response to mental nerve transection and repair in the rat.

PURPOSE: Animal studies have suggested that peripheral nerve transection results in substantial loss of ganglion cells and the selective survival of cells based on size. The implications are that subsequent repair of peripheral nerve injuries will be determined by the numerical density and character of the surviving cells. The purpose of this study was twofold: First, to determine the effect of mental nerve transection without repair on trigeminal ganglion cell density and morphology in adult rats, and second, to determine the variation of trigeminal ganglion cell density and morphology after immediate and delayed repair. MATERIALS AND METHODS: In the first part of the study, 12 adult male Sprague-Dawley rats had their mental nerves exposed bilaterally (n = 24). Twelve mental nerves were then transected and prevented from regenerating, and the remaining 12 nerves were uninjured. Ninety and 180 days after transection or sham surgery, the trigeminal ganglia were serially cut into 5 microm longitudinal sections along the dorsoventral axis. The volume and volume density of the mandibular mental subdivision containing sensory cells was determined at each section level with point-counting methods. The numerical density and total number of cells was estimated on the same section, using an unbiased three-dimensional stereological probe, the dissector. Cell size and shape determinants were estimated using the dissector and computerized planimetry. In the second part of the study, six rats had the mental nerves transected bilaterally and immediately repaired by microscopic sutures. In six additional rats, the repair was delayed for 90 days. In both groups, the trigeminal ganglia were serially cut at 30, 60, and 90 days post-repair and stereologic estimates of numerical density and histomorphometry were examined using the dissector and computed planimetry. RESULTS: In the trigeminal ganglia of the 12 sham-operated animals, the mean number of cells was 20.6 x 10(3) (+/-2.9 X 10(3)). After nerve section, the mean number of cells was 10.88 X 10(3) (+/-0.9 X 10(3)), representing a 47% reduction. The mean volume of the mandibular subdivision cells in the ganglia of the sham surgery animals was 0.3 mm3 (+/-0.05) and 0.22 mm3 (+/-0.04) in nerve-sectioned ganglia, a 38% difference. There were no ganglia cell size or shape differences between the two groups. The mean number of cells in the ganglia of immediately repaired nerves was 10.66 x 10(3)(+/-1.1 X 10(3)), and it was 12.45 x 10(3) (+/-0.9 x 10(3)) after delayed repair. The numerical density was significantly less than in the sham surgery ganglia but not different from that of the transection/no repair ganglia. The weighted mean reference volume of the mandibular subdivision after immediate and delayed repair was similar and was significantly greater than the transection/no repair group, but not different from the sham surgery group. The cell size was slightly larger in delayed-repair ganglia compared with immediate-repair ganglia, but the differences were not significant. There were no significant differences in any of the stereologic estimates when analyzed across treatment time. CONCLUSIONS: The results of this study agree with previous reports that peripheral nerve transection produces a substantial loss of nerve cells within specified regions of sensory ganglions. However, the results conflict with evidence that cells survive transection based on size and shape. These findings also indicate that in the adult rat the substantial loss of nerve cells was unaltered by the reconnection of their severed axons. Neither immediate or delayed repair of the transected nerve altered the spectrum of surviving cells based on size or shape. The reestablishment of the mean reference volume of the mandibular subdivision after section and repair suggests that demands made on regenerating axons appear to result in the restoration of ganglionic volume normally lost after axotomy, probably the result of axo

The use of nonopioid drugs in management of chronic orofacial pain.

Although controversial, opioid analgesics have been prescribed for patients with chronic facial pain. Based primarily on survey data and a few well-controlled clinical trials, long-term opioid treatment provides adequate pain reduction in 41% to 100% of patients with chronic nonmalignant pain. However, only 25% of chronic facial pain patients reported adequate pain relief with chronic opioid treatment. Work, home, and school function are generally reestablished or maintained during chronic opioid treatment, but 25% to 38% of patients remain dysfunctional, and one study indicated that 20% of patients became dysfunctional during treatment. Chronic opioid treatment is associated with many transient side effects; constipation, dizziness, nausea, vomiting, itching, and fatigue have been reported in 5% to 42% of patients taking opioids over 1 year. Although survey studies suggest that the risks of addiction are low in typical patients, drug abuse rates up to 17.3% and prescription abuse rates up to 27.6% were reported within groups of chronic opioid users. Chronic opioid use induces analgesic tolerance and physical dependence, which may result in a serious abstinence syndrome in users and children born to users. Chronic opioid use also may induce harmful immune system changes, diminish cognitive and motor function, and produce nociceptive hyperexcitability. This article shows that the use of long-term opioids for chronic facial pain is not justified based on the available data. Despite these perceived problems, there is anecdotal evidence that chronic facial pain patients will respond positively to opioid analgesics. In our experience, the pain assessment scale and a modification of the World Health Organization's three-step analgesic ladder, which prescribes nonopioid analgesics, can be the starting point for the successful management of chronic facial pain.

A retrospective analysis of lingual nerve sensory changes after mandibular bilateral sagittal split osteotomy.

PURPOSE: The purpose of this retrospective study was to determine the patient-reported incidence, duration, and perceived deficit in daily activities associated with lingual nerve (LN) sensory changes after bilateral sagittal split osteotomy (BSSO) of the mandible and to compare them with inferior alveolar nerve (IAN) sensory changes in the same study population. MATERIALS AND METHODS: Questionnaires were mailed to 316 patients who had undergone BSSO procedures between 1980 and 1993. The patients were queried for perceived sensory changes in the distribution of the IAN and LN; duration of these sensory changes; and alteration in daily activities caused by these sensory changes. The same questionnaire was mailed to 47 patients who had undergone isolated genioplasty (GP) to control for the normal variance of non-BSSO surgery on perceived LN sensory changes. RESULTS: Forty-three percent of the BSSO patients and 38% of the GP patients returned the questionnaires. Within the BSSO group, 19.4% reported LN sensory changes, of which 69.3% reported that these changes resolved within 1 year; 88% reported altered daily activities. By comparison, 95.5% reported a perceived IAN sensory change, of which 27.3% reported that these changes resolved within 1 year; 57% reported altered daily activities. Within the GP control group, 11% reported LN sensory changes; none of the reported sensory changes lasted longer than 1 month. CONCLUSIONS: A small percentage of patients report LN sensory changes after BSSO. When compared with IAN reported sensory changes, LN sensory changes resolve more frequently and sooner, but they are associated with greater perceived deficits in daily activity. The interpretation of the reported incidence of LN change must be critically reviewed because control subjects also responded positively.

Propofol and fentanyl compared with midazolam and fentanyl during third molar surgery.

PURPOSE: The purpose of this study was to measure the safety and efficacy of propofol combined with fentanyl as sedative agents during third molar outpatient surgery. PATIENTS AND METHODS: A double-blind, prospective, randomized clinical trial involving 57 patients undergoing removal of third molars under intravenous sedation between November 1994 and December 1995 was performed. Patients randomly received either propofol and fentanyl (P + F, th = 24) or midazolam and fentanyl (M + F, M = 33). Patient demographics, Corah anxiety scores, and physiologic parameters were determined preoperatively. All medications were titrated to the same clinical end point for sedation. Intraoperative physiologic parameters, cooperation, alertness, and pain scores were assessed. Postoperative recovery and degree of amnesia also were determined. RESULTS: There were no significant differences in either patient demographics or surgical characteristics between groups. The P + F group was significantly less cooperative than the M + F group. Pain during injection of propofol was a significant adverse side effect. Both groups experienced a small percentage of apneic episodes, but mechanical ventilation was never required. There were no differences in recovery between groups as measured by the Treiger dot test and psychomotor recovery scores. The degree of anterograde amnesia was greater for the M + F group, although the difference was not statistically significant. Sedation was rated good to excellent by the patient, surgeon, and observer, and there were no statistically significant differences between groups. CONCLUSION: Propofol appears to be a safe and efficacious drug for use during outpatient oral surgical procedures.

The accuracy of clinical neurosensory testing for nerve injury diagnosis.

PURPOSE: The accuracy of the clinical neurosensory test to diagnose trigeminal nerve injuries has never been statistically evaluated. The purpose of this study was to determine the statistical efficacy of the clinical neurosensory test using surgical findings as the "gold" standard, and to determine whether a correlation existed between the sensory impairment score obtained by preoperative testing and the degree of nerve injury found at surgery. MATERIALS AND METHODS: A multisite, randomized, prospective, blinded, clinical trial was conducted on 130 patients with inferior alveolar nerve (IAN) and lingual nerve (LN) injuries. Preoperatively, patients were provided a sensory impairment score using a three-level drop-out clinical neurosensory test (NST), and blind comparisons were made with the surgical findings postoperatively. RESULTS: The positive predictive and negative predictive values for LN-injured patients were 95% and 100%, respectively. The positive predictive and negative predictive values for IAN patients were 77% and 60%, respectively. There were statistically significant differences in the distribution of age, duration of injury, cause of injury, presence of neuropathic pain, presence of trigger pain, and degree of injury between the IAN and LN patient populations. There was a statistically significant positive relationship found between the sensory impairment score and the degree of nerve injury. CONCLUSIONS: The NST is a clinically useful method to diagnose IAN and LN injuries. However, the NST results are less efficient for IAN injuries than LN injuries, and have a high incidence of false-positive (23%) and false-negative (40%) results when testing patients with IAN injuries. The different rates of statistical efficiency between the two groups of patients may be attributable to differences in prevalence and biologic covariates.

[Quantitative studies of taste and fungiform papillae on the anterior human tongue].

OBJECTIVE: To study qantitatively in the taste and fungiform papillae on the anterior human tongue. METHODS: Sixty normal adults were evaluated the spatial taste and the fungiform papilla density at spatially-matched sides on the right and left sides of the anterior tongue. The taste stimulative solutions were delivered to a spatially-matched flow chamber attached to the surface of the right or left anterior tongue. RESULTS: (1) There is no statistical difference in number of the fungiform papillae, taste threshold and magnitude matching between right/left, male/female and races; (2) There is a significant difference in fungiform papilla density and taste functions in different individuals; (3) The fungiform papilla density is the key to taste function on 2/3 anterior of tongue, and is positively correlated to it; (4) The use of a spatially-matched flow chamber is a valid test system for overall, objective and accurate evaluating taste on the 2/3 anterior of tongue, and can be used to study quantitatively the fungiform papilla density. CONCLUSION: It is of clinical significance for the diagnosis of taste diseases and the dynamic studies of the taste and the fungiform papillae after lingual nerve injury and repair.

Effect of amiloride on suprathreshold NaCl, LiCl, and KCl salt taste in humans.

The purpose of this study was to investigate normal variances in the response magnitudes of suprathreshold concentrations of NaCl, LiCl, and KCl salts and amiloride on the anterior human tongue. Random equimolar concentrations of salt solutions were delivered to spatially matched flow chambers of 20 volunteers at 3 different sessions. A cross-modal magnitude matching procedure was used to scale salt taste-intensity judgments. After each salt test, amiloride (100 microns) was delivered for 5 min and the test was repeated. At least-square regression analysis of each subjects' function between log molar concentration and log response demonstrated that every subject scaled the dynamic range of salts. There were no differences in either the mean regression or intercept among the 3 salts. Repeated-measures analysis demonstrated a statistical effect of amiloride on the before/after difference in the regression (p = 0.02) and intercept (p < 0.0001) of NaCl and LiCl functions. Postamiloride NaCl and LiCl coefficient of variance of response was increased. Amiloride had no effect on the before/after difference in the regression and intercept of KCl power functions or the variance of response. The results suggest that, after amiloride, NaCl and LiCl suprathreshold salt taste intensities are reduced, but there are individual variabilities of reduced intensity that are never completely eliminated.

Chemosensory and somatosensory regeneration after lingual nerve repair in humans.

PURPOSE: The objective of these studies was to measure the impact of Class IV and V lingual nerve injuries on taste sensitivity and taste receptor density of the anterior tongue before and after microneurosurgical repair. MATERIALS AND METHODS: Citric acid detection threshold and suprathreshold magnitude response were measured on the anterior tongue in 12 adult volunteers with unilateral lingual nerve Class IV or V injuries. The right and left sides of the anterior tongue were tested at each session to assess the effect of nerve damage before and 1, 3, 6, and 12 months after repair. Whole-mouth threshold and suprathreshold scales of citric acid taste intensity were measured. The level of sensory impairment was scaled at each test session using a clinical neurosensory test algorithm. Finally, patients completed an 11-item instrument survey that queried the patient's perceived expectations of surgery on sensory, taste, and general health before surgery and the patient's perceived outcome of surgery at each postrepair session. The patient's perceived global satisfaction of surgery was also assessed. RESULTS: All 12 patients failed to detect and scale citric acid and had complete or severe sensory impairment on the injured side of the anterior tongue. One year after repair, 50% of the patients demonstrated a substantial increase in the number of fungiform papillae, pores, and ratio of pores/papilla at the same time as they demonstrated the ability to detect and scale citric acid. After repair, patients perceived the greatest improvements in the categories of eating, chewing, feeling, and taste, and the least in speech. CONCLUSION: Lingual nerve repair may result in significant changes in somatosensory and chemosensory function and taste bud anatomy on the anterior tongue over time.

[Evaluating methods and effects of repairing injured lingual nerves on human].

We evaluated the regenerations of sense and taste on the anterior 2/3 of the tongue following repairing injured lingual nerve. Injured lingual nerves in 14 patients were repaired with anastomosis of the nerve epineurium. On the anterior 2/3 of the ipsilateral tongue, most of the fungiform papillae atrophied and disappeared, the sense and taste degenerated after severe injury to lingual nerve. Following repair of the injured lingual nerve with anastomosis of nerve epineurium, the papillae and their taste pores can regenerated, 50% of the patients recovered their tongue sense and 35.71% of the patients recovered their tongue taste 1 year after the repair. It is objective, accurate and reliable to evaluate the regenerations of sense and taste on the anterior 2/3 of the tongue after repair of injured lingual nerve by sensory test, taste evaluation, quantitative observation of fungiform papillae, and their taste pores.

Experimental topical tetracycline-induced neuritis in the rat.

PURPOSE: Recent studies have reported that tetracycline may induce chronic inflammatory responses in the adjacent soft tissues. The purpose of the present study was to determine if dry, powdered tetracycline evoked an inflammatory response in nerve tissue. MATERIALS AND METHODS: Twenty male Sprague-Dawley rats were anesthetized and bilateral mental nerves were exposed. Half of the 40 nerves were intentionally injured by removing the epineurium, and the remaining nerves were uninjured. In a prospective, randomized, double-blind manner, equal volumes of color-matched, precoded tetracycline powder or Gelfoam (Upjohn, Kalamazoo, MI) powder control was placed in intimate contact with the nerves and sealed in polyethylene tubes. Forty-five days later the animals were killed and 5-micron sections of the nerves were prepared for histologic examination. The presence of epineurium, fascicular number, and fascicular area were measured. An inflammatory response in nerve tissue and the intrafascicular and epifascicular inflammatory index was measured by counting darkly stained nuclei with a Jandel Video Analysis System (Jandel Scientific, Corte Madera, CA). RESULTS: Experimental injury (ie, epineurectomy) of nerves resulted in a statistically significant increase in fascicular number (P = .034), but not in fascicular area. For the intrafascicular inflammatory index, there was a significant main effect for drug (P = .002) and injury (P = .002). Experimental injury in both Gelfoam control and tetracycline grouped nerves resulted in an increase in intrafascicular inflammation. There was no significant increase in intrafascicular inflammation in either Gelfoam control or tetracycline grouped nerves when the epineurium was intact. The combination of both tetracycline and epineurectomy resulted in the largest increase in intrafascicular inflammation found among the groups studied. For epifascicular inflammatory index, there was a significant main effect for drug (P = .003) and injury (P = .001) that mirrored the intrafascicular inflammatory pattern. CONCLUSION: The results of the present study suggest that dry, powdered tetracycline accentuates the inflammatory response in intrafascicular and epifascicular nerve tissue following epineurectomy. The maintenance of epineurium inhibited the inflammatory response in intrafascicular and epifascicular nerve tissues. Gel-foam was an inert material when placed against exposed nerve tissue. These findings suggest that tetracycline should not be placed in extraction sockets when injury of the inferior alveolar and/or lingual nerves are present.