Chronic Granulation Research Articles

A 75-Year-Old Man with New Onset Dyspnea and Haemoptysis

Foreign body aspiration (FBA) is a common life-threatening condition which mostly occurs in children and elderly due to lack of airway protection mechanisms. A 75-year- old man was admitted to our outpatient clinic with complaints of a permanent shortness of breath for approximately 2 months and haemoptysis for two weeks. He had prescribed bronchodilators and levofloxacin with a diagnosis of COPD exacerbation but he didn't experience any relief though he used the medication regularly. He was a water-pipe smoker for 50 years. He reported to swallow 3 olive seeds in a day, after he watched an herbalist which had advised to do so, on a TV program. On presentation, wheezing was heard over the right hemi thorax and crackles were noted at the left base. His chest radiograph showed a suspicious heterogenic density behind the left heart silhouette. Bronchoscopy showed a polypoid lesion on the posterior wall of the left main bronchus, whereas an oval shaped mobile body (olive seed) was observed over the right main bronchus, under the right upper lobe division. The pathological diagnosis of the specimen taken from the polypoid lesion was compatible with active chronic granulation. We removed the olive seed by grasping forceps and the symptoms of the patient dissolved as well as the radiological findings. This is a demonstrative case reminding to consider FBA in elderly with sub acute respiratory symptoms.

Clinical and Pathological Analysis of Epidural Inflammation in Intervertebral Disk Extrusion in Dogs

Little is known about the pathologic changes in the epidural space after intervertebral disk (IVD) extrusion in the dog. To analyze the pathology of the epidural inflammatory response, and to search for correlations between this process and clinical findings. Clinical data from 105 chondrodystrophic (CD) and nonchondrodystrophic (NCD) dogs with IVD extrusion were recorded. Epidural material from these dogs was examined histopathologically and immunohistochemically. Using statistical analysis, we searched for correlations between severity of epidural inflammation and various clinical and pathologic variables. Most dogs exhibited an epidural inflammatory response, ranging from acute invasion of neutrophils to formation of chronic granulation tissue. The mononuclear inflammatory infiltrates consisted mostly of monocytes and macrophages and only few T and B cells. Surprisingly, chronic inflammatory patterns also were found in animals with an acute clinical history. Severity of the epidural inflammation correlated with degree of the epidural hemorrhage and nucleus pulposus calcification (P = .003 and .040), but not with age, chondrodystrophic phenotype, neurologic grade, back pain, pretreatment, or duration. The degree of inflammation was statistically (P = .021) inversely correlated with the ability to regain ambulation. Epidural inflammation occurs in the majority of dogs with IVD extrusion and may develop long before the onset of clinical signs. Presence of calcified IVD material and hemorrhage in the epidural space may be the triggers of this lesion rather than an adaptive immune response to the nucleus pulposus as suggested in previous studies. Because epidural inflammation may affect outcome, further research is warranted.

Histological and Transcriptional Expression differences between Diabetic Foot and Pressure Ulcers

Decubitus and diabetic foot ulcers remain as important clinical challenges with significant socioeconomic impact. Both are individual forms of chronic wounds with diverse proximal ethiopathogenic triggers. This study aimed to characterize and compare the main histological features as the transcriptional expression profile of a set of wound-healing relevant genes of the ulcers’ granulation tissue. Following patients’ consent, biopsies were collected from sacrolumbar pressure ulcers (N=5, stage IV) and diabetic foot ulcers (N=9, both of neuropathic and ischemic origin) with clean, non-infected granulation tissue. Biopsies fragments were processed for histological analysis and for RNA extraction and subsequent transcriptional expression characterization via RT-PCR. The group of targeted genes included cell proliferation control, extracellular matrix, glucose metabolism, anabolismsurvival, as anti-hypoxia and anti-oxidant defense. Gene expression was determined, normalized with an internal housekeeping gene, and statistically compared. Each class of chronic ulcer granulation tissue: decubitus, and diabetics’ ischemic and neuropathic proved to develop a particular histological pattern thus establishing individual differences. Moreover, diabetes appeared to significantly reduce the expression of numerous genes irrespective to their biological significance. Most importantly, we found that diabetic granulation tissue cells exhibit a sort of “genetic or epigenetic imprinting” for the expression of glucose-metabolism related genes which are deeply involved in type-2 diabetes pathophysiology. Our data indicate that in addition to a protracted inflammation and abnormal angiogenesis, diabetic granulation tissue cells are affected by gene expression failures that may lead to a negative pro-anabolic and energetic balance.

Plasma Cell Balanitis Presenting in a Patient with a History of Syphilis

Plasma cell balanitis (PCB), also knows as Zoon balanitis, is a benign asymptomatic but chronic and erosive inflammatory condition of the glans penis and prepuce that generally affects uncircumcised men in later years. Clinical presentation involves a single, shiny, well defined reddish patch. We describe the first case of PCB ever reported in a patient with a previous history of syphilis, and include a review of the current literature. A 57-year-old Hispanic man with a remote history of syphilis presented with a 6-month nonhealing, granulating ulcer of the foreskin and glans penis that had been repeatedly mistaken for syphilis and treated unsuccessfully with circumcision 3 weeks previously. Biopsy of the glans penis demonstrated sections with denuded chronic granulation tissue showing a fibrotic stroma with numerous blood vessels and a mixed inflammatory infiltrate including scattered plasma cells. It is important to differentiate PCB from a syphilitic chancre in a patient presenting with a nonhealing penile lesion. This case report demonstrates that these entities may be seen in the same patient at different times.

A Large Mutational Study in Pachyonychia Congenita

Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder characterized predominantly by nail dystrophy and painful palmoplantar keratoderma. Additional clinical features include oral leukokeratosis, follicular keratosis, and cysts (steatocysts and pilosebaceous cysts). PC is due to heterozygous mutations in one of four keratin genes, namely, KRT6A, KRT6B, KRT16, or KRT17. Here, we report genetic analysis of 90 new families with PC in which we identified mutations in KRT6A, KRT6B, KRT16, or KRT17, thereby confirming their clinical diagnosis. A total of 21 previously unreported and 22 known mutations were found. Approximately half of the kindreds had mutations in KRT6A (52%), 28% had mutations in KRT16, 17% in KRT17, and 3% of families had mutations in KRT6B. Most of the mutations were heterozygous missense or small in-frame insertion/deletion mutations occurring within one of the helix boundary motif regions of the keratin polypeptide. More unusual mutations included heterozygous splice site mutations, nonsense mutations, and a 1-bp insertion mutation, leading to a frameshift and premature termination codon. This study, together with previously reported mutations, identifies mutation hotspot codons that may be useful in the development of personalized medicine for PC.

Guided Surgical Debridement: Staining Tissues With Methylene Blue

Precise surgical debridement of wounds is required to achieve wound closure. The authors describe their experience with a technique using topical methylene blue to facilitate precise surgical debridement. In this technique, methylene blue dye is applied topically to the wound surface at the onset of surgery. The stained wound site is then wiped to remove dye from the surface of normal epithelium; eschar, nonviable tissue, and granulation tissue remain stained. The methylene blue-stained tissue is surgically removed, and the newly debrided surface of the wound is assessed for adequate vascularity and biopsied to verify presence of bacteriologic balance before closure. The authors have used this technique in more than 200 wound debridements during the past year, including acute surgical or traumatic wounds, acute and subacute burn wounds, chronic granulating wounds, partially epithelialized wounds, sinus tracts, and fistulae. No adverse reactions have been noted, even on patients undergoing multiple applications through serial operations. Topical application of methylene blue to wounds with mixed tissue content helps to distinguish between viable and nonviable tissue and between epithelialized and nonepithelialized areas, facilitating more precise and complete wound debridement.

Congenital Ureteral Ectopia in Continent and Incontinent-Related Entlebucher Mountain Dogs: 13 Cases (2006-2009)

Ectopic ureters (EUs) associated with varying combinations of urinary incontinence, hydronephrosis, and urinary tract infection have been identified in related North American Entlebucher Mountain Dogs. To characterize the disease phenotype in affected dogs and evaluate possible modes of inheritance. Twenty client-owned Entlebucher Mountain Dogs. Nine dogs had clinical signs of urinary tract disease. Prospective case series in which 17 dogs were evaluated with excretory urography, ultrasonography, and urethrocystoscopy. Three additional dogs were evaluated by necropsy alone. Clinical and pedigree histories from 165 North American Entlebuchers were compiled for analysis. Eleven female and 2 male dogs were found to have EUs. Six females and 1 male were continent. Bilateral intravesicular ectopic ureters (IVEUs) were identified in 9 dogs, bilateral extravesicular ectopic ureters (EVEUs) in 3 dogs, and 1 dog had IVEU and EVEU. Hydronephrosis was identified in 5 dogs, 3 of which had bilateral IVEUs. Two necropsied dogs had bilateral hydronephrosis with presumed ureterovesical junction obstruction associated with chronic granulation tissue or lymphoplasmacytic inflammation. Twenty-six dogs with EUs were identified in the pedigree. Because of incomplete penetrance, mode of inheritance could not be determined. Ureteral ectopia is common in North American Entlebucher Mountain Dogs and clinical signs alone could not reliably predict disease phenotype. EVEUs were associated with urinary incontinence and occasionally hydronephrosis. IVEUs were clinically silent or associated with hydronephrosis. Further analyses are necessary to confirm and characterize the hereditary nature of the disorder.

Immunohistochemical localization of galectin-3 in the granulomatous lesions of paratuberculosis-infected bovine intestine

The presence of galectin-3 was immunohistochemically quantified in bovine intestines infected with paratuberculosis (Johne's disease) to determine whether galectin-3 was involved in the formation of granulation tissue associated with the disease. Mycobacterium avium subsp. paratuberculosis infection was histochemically confirmed using Ziehl-Neelsen staining and molecularly diagnosed through rpoB DNA sequencing. Galectin-3 was detected in the majority of inflammatory cells, possibly macrophages, in the granulomatous lesions within affected tissues, including the ileum. These findings suggest that galectin-3 is associated with the formation of chronic granulation tissues in bovine paratuberculosis, probably through cell adhesion and anti-apoptosis mechanisms.

Sea Urchin Spine Injuries of the Hand

Sea urchin spine injuries are common. They usually cause local pain and swelling that subsides. Chronic granulation is rare. We report two cases of sea urchin granulomata involving finger metacarpophalangeal joints. Both resolved following surgery.

Laparoscopic Witzel gastrostomy—a reappraised technique

Laparoscopic gastrostomy is the best alternative for long-term enteral feeding when percutaneous endoscopic gastrostomy is not possible. The aim of the present study was to determine the feasibility, complications, adequacy of feeding support, and tolerability of laparoscopic Witzel gastrostomy (LWG) in head and neck cancer patients. The initial results and the results of extended follow-up were evaluated. A consecutive series of 48 patients with stenotic head and neck or esophageal cancer were referred for laparoscopic gastrostomy. The patients consisted of 42 men and 6 women aged 36 to 82 years (mean, 54 years). After laparoscopic placement of a Foley catheter of 16 F into the stomach, a seromuscular tunnel 4 cm in length is created, embedding the catheter by interrupted sutures. Three stay sutures for gastropexy are fixed and tied on the abdominal skin at the end of the procedure. The mean duration of the procedure was 62.4 +/- 11 min (52-124 min). Laparoscopic Witzel gastrostomy could be performed successfully in all patients with aerodigestive cancer. None of the laparoscopic gastrostomy tube placement procedures was converted to an open surgery, and none of the 48 patients in this series died as a result of the laparoscopic procedure. All LWG complications (11%) were minor, consisting of superficial wound infections, balloon rupture, and chronic granulation. No major complications were encountered. The mean usage time of gastrostomy was 6.3 +/- 5.3 months. Current techniques of LWG could be an alternative to percutaneous endoscopic gastrostomy (PEG) for long-term enteral access, because it has proved to be safe and reproducible with relatively few complications.

Verbesserte Einheilrate von Mesh-graft-Transplantaten bei Patienten mit Ulcus cruris durch postoperativen Einsatz von Vakuumversiegelung

Vacuum-assisted closure (V.A.C.) is an established therapeutic option in the management of acute and chronic granulating wounds. In recent years, little data has been published concerning skin graft transplantation and postoperative V.A.C. therapy. We report a consecutive case series of 54 patients with chronic leg ulcer who received a total of 74 mesh grafts. A postoperative V.A.C. therapy was performed in 28 mesh grafts, and 46 mesh grafts were treated with standard gauze therapy. In the V.A.C. group, 92.9 % grafts showed complete healing. In the treatment group without postoperative V.A.C. therapy, 67.4 % of the mesh grafts had taken. Differential analysis revealed a correlation in patients over 70 years of age or in patients suffering from diabetes mellitus or dermato-lipo-sclerosis. Particularly patients with diabetes mellitus and of greater age exhibited improved take rates in the V.A.C. group. The results of our study demonstrate for the first time the significant benefit of V.A.C. therapy after mesh-graft-transplantation in chronic leg ulcer patients as evaluated in a clinical trial with a control group.

Chronic axillary wound repair in a cat with omentalisation and omocervical skin flap

A mature, neutered male domestic cat was presented with a chronic axillary wound of unknown origin and at least three years' duration. The diagnostic investigation included screening tests for feline leukaemia virus and feline immunodeficiency virus, tissue culture and histological examination. No underlying aetiology or perpetuating cause could be identified. An omental flap was created, passed via a subcutaneous tunnel, and packed into the wound site after excision of all chronic granulation tissue. The skin defect was closed using an omocervical axial pattern skin flap. A small area of the distal edge of the flap became necrotic but the defect healed by second intention. To the author's knowledge, this is the first clinical report of the use of an omocervical skin flap for repair of a chronic axillary wound in a cat. This flap offers a useful alternative where the use of a thoracodorsal axial pattern flap is not possible due to the extent of the lesion.

Redistributions of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation

Cell surface lectins are known to regulate trafficking of cells in the immune system, yet the role of macrophage galactose-type C-type lectin 1 and 2 (MGL1/2) is poorly understood. In this study, antigen-specific chronic inflammation was induced in a subcutaneous air pouch model in mice, and distribution of cells expressing MGL1/2 was investigated. Azobenzenearsonate-conjugated acetylated BSA, used as an antigen, was introduced into an air pouch of immunized mice, and tissue formation and distribution of MGL1/2-positive cells in the sub-dermal regions was examined. Thickness of the inflammatory tissue and number of MGL1/2-positive cells simultaneously reached the maximum at day 4 and returned to the control level at day 6 or 8. When additional antigenic challenges were given, a chronic granulation tissue, which had two distinct layers, was generated. In the chronic tissue, CD11b-positive/MGL1/2-negative cells were abundant in the area close to the antigenic stimulus, while the area far from the antigenic stimulus was dominated by MGL1/2-positive/CD11b-negative or -low cells. Flow cytometric analyses of isolated cells from the granulation tissue revealed that MGL1/2-positive cells expressed MHC class II at high levels, CD11b at low levels but no CD11c. MGL1/2-positive and -negative fractions were separated from cells in the granulation tissue and a higher level of IL-1alpha messenger RNA than negative populations was detected in the MGL1/2-positive fraction by the semi-quantitative reverse transcription-PCR method. IL-1alpha production by MGL1/2-positive cells was also immunohistochemically detected. Results suggest that MGL1/2-positive cells represent a distinct sub-population of macrophages, having unique functions in the generation and maintenance of granulation tissue induced by antigenic stimuli.

Otologic Effects of Topical Mitomycin C: Phase I-Evaluation of Ototoxicity

To determine ototoxicity of topical mitomycin C when placed in the middle ear at varying concentrations. Despite meticulous surgical technique and diligent postoperative care, some patients develop excessive scar and granulation tissue in the middle ear or mastoid cavity. Poor wound healing may result in infection, tympanic membrane perforation, or conductive hearing loss, which may necessitate further surgery. Use of topical mitomycin C in the ear may be beneficial in reducing scar and granulation tissue formation. This phase of the study was developed to determine the safety of topical mitomycin C in the rat model relative to ototoxicity. Twelve Sprague-Dawley rats were evaluated with auditory brainstem response testing before and after treatments. Topical mitomycin C was injected in the middle ear of the right ear of eight animals. Varying concentrations of 0.125 to 0.5 mg/ml were used. Saline was injected in the left ear of each animal to serve as a control. Four separate animals were evaluated with placement of topical mitomycin C on Gelfoam into the middle ear. In two animals, Gelfoam was placed in the middle ear for 1 minute and then removed. In two animals, Gelfoam was placed in the middle ear and left in place. Auditory brainstem response testing was performed at 4 weeks and at 8 weeks. Using a high concentration of mitomycin C (>0.25 mg/ml) resulted in ototoxicity, with an increase in the auditory brainstem response threshold at 4 weeks and at 8 weeks. At low concentrations (<0.20 mg/ml), no change in auditory brainstem response threshold was noted. Animals treated with Gelfoam soaked in mitomycin C showed no change in auditory brainstem response threshold. The results of this study indicate that topical mitomycin C on Gelfoam applied in the middle ear appears safe when low concentrations are used, even in the rat, which has a higher susceptibility to gentamycin toxicity than humans. Higher concentrations may lead to ototoxicity based on changes in Wave V on auditory brainstem response. This treatment may prove to be an important option for patients suffering from chronic granulation tissue or scar tissue in the external or middle ear.

An unusual N-terminal deletion of the laminin 3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome

An unusual N-terminal deletion of the laminin 3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome

An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome.

Laryngo-onycho-cutaneous (LOC or Shabbir) syndrome (OMIM 245660) is an autosomal recessive epithelial disorder confined to the Punjabi Muslim population. The condition is characterized by cutaneous erosions, nail dystrophy and exuberant vascular granulation tissue in certain epithelia, especially conjunctiva and larynx. Genome-wide homozygosity mapping localized the gene to a 2 Mb region on chromosome 18q11.2 with an LOD score of 19.8 at theta=0. This region includes the laminin alpha3 gene (LAMA3), in which loss-of-expression mutations cause the lethal skin blistering disorder Herlitz junctional epidermolysis bullosa. Detailed investigation showed that this gene possesses a further 38 exons (76 exons in total) spanning 318 kb of genomic DNA, and encodes three distinct proteins, designated laminin alpha3a, alpha3b1 and alpha3b2. The causative mutation in 15 families was a frameshift mutation 151insG predicting a stop codon 7 bp downstream in an exon that is specific to laminin alpha3a. This protein is secreted only by the basal keratinocytes of stratified epithelia, implying that LOC is caused by dysfunction of keratinocyte-mesenchymal communication. Surprisingly, the 151insG mutation does not result in nonsense-mediated mRNA decay due to rescue of the transcript by an alternative translation start site 6 exons downstream. The resultant N-terminal deletion of laminin alpha3a was confirmed by immunoprecipitation of secreted proteins from LOC keratinocytes. These studies show that the laminin alpha3a N-terminal domain is a key regulator of the granulation tissue response, with important implications not only in LOC but in a range of other clinical conditions associated with abnormal wound healing.

Complications of Hydroxyapatite Use for Transnasal Closure of Cerebrospinal Fluid Leaks

Hydroxyapatite cement (HAC) was first introduced in the 1980s as a new method for bone replacement. However, it has not been recommended for use in areas exposed to air. Despite this, surgeries have been performed using HAC to close nasal/sinus cerebrospinal fluid (CSF) leaks or in the treatment of encephaloceles. This study retrospectively documented four patients in whom HAC was used for closure of ethmoid and sphenoid sinus CSF leaks. This study showed that exposed hydroxyapatite could be extremely problematic resulting in scarring, chronic granulation, infection, and prolonged healing. Oftentimes, revision surgery was necessary to help control the reaction to hydroxyapatite. Because of the frequent complications occurring with use of hydroxyapatite in the paranasal sinuses, its use should be limited to selected individuals in whom difficulty in achieving closure of the CFS leak could be anticipated and in whom adequate tissue coverage could be provided.

30-day intravenous administration of VRCTC-310-ONCO in rabbits

VRCTC-310-ONCO, an agent based on the snake phospholipase A 2 (crotoxin), is currently under clinical development. After phase I study in patients by intramuscular administration, the interest of intravenous (IV) dosing arose. To evaluate IV administration of VRCTC-310-ONCO in rabbits, ten animals were subjected to surgical implant of fixed jugular catheter, by which they received daily IV doses of 0.03 mg/kg body weight of VRCTC-310-ONCO for 30 days ( n=8) or saline ( n=2). The procedure was well tolerated in all rabbits. One of the animals died after the sixth dose of VRCTC-310-ONCO with CNS involvement; two additional rabbits required dose-reduction. All other rabbits achieved 30 days of treatment and were sacrificed. All rabbits (even controls) developed lymphocytosis and mild anaemia, without changes in blood neutrophils. No changes were found in serum transaminases (GOT and GPT), cholesterol, triglycerides, and γ-glutamyl transpeptidase. At necropsy, chronic granulation tissue was found surrounding the implant in all rabbits. VRCTC-310-ONCO-treated rabbits presented generalised and marked swelling of hepatocytes, with areas of cytoplasmic vacuolisation. No abnormalities were found in kidney, heart, lung, spleen, adrenal gland, uterus, testes and ovary. Additional studies with IV route for VRCTC-310-ONCO, including humans, are required to define its toxicity in the clinical setting.

Protein Gene Product 9.5 is Expressed by Fibroblasts in Human Cutaneous Wounds

In a study initially designed to evaluate reinnervation of human cutaneous wounds using an antibody to the neuroneal marker protein gene product (PGP) 9.5, we observed marked immunostaining of cells with morphologic features of fibroblasts in the wounds. PGP 9.5 has recently been shown to be an important enzyme in the highly conserved ubiquitin system of proteolysis. Because the ubiquitin system is known to play an important role in regulating the cell cycle, the presence of PGP 9.5 in cells at a wound site was of considerable interest. Our objectives were to clarify the time frame for the appearance of PGP 9.5 and ubiquitin in wounds, to verify that PGP 9.5 is produced by wound fibroblasts, and to evaluate a potential role for these proteins in the tissue repair process. Standard incisional human wounds were stained with antibodies specific for PGP 9.5 and ubiquitin. At 7 d, stellate cells with morphologic features of fibroblasts stained for PGP 9.5, whereas earlier wounds were generally negative. In 14 and 21 d incised wounds and in chronic granulation tissue from nonhealing ulcers there was strong cellular staining for PGP 9.5 and for ubiquitin. These stellate cells also showed expression of mRNA for PGP 9.5 by reverse transcriptase-polymerase chain reaction in situ hybridization. PGP 9.5 was detected in cultured fibroblasts both by reverse transcriptase-polymerase chain reaction and by northern blot analysis. Confocal microscopy showed colocalization of antibodies to PGP 9.5 and prolyl-4-hydroxylase (a fibroblast marker) as well as colocalization of PGP 9.5 and the platelet derived growth factor beta receptor. We conclude that ubiquitin and PGP 9.5 were expressed by fibroblasts during the granulation tissue and remodeling phases wound healing. The mRNA for PGP 9.5 was demonstrated in stellate cells in chronic wounds and in fibroblasts in culture. The appearance of these degradative proteins in later wounds suggests a downregulation function in the wound healing response.

A conservative one-stage method of surgically correcting chronic intractable otitis media in children who have failed antibiotic therapy

The manifestations of chronic otitis media with an associated dysfunction of the eustachian tube include chronic atelectasis of the middle ear; formation of retraction pockets, cholesteatomas, or cholesterol granulomas; tympanosclerosis; ossicular fixation or erosion; and hearing loss. 1-3 In countries where early medical and surgical intervention are not readily available, life-threatening complications are often observed, including abscesses of the brain or petrous apex, or cholesteatoma that penetrates the cranial vault. However, even early and aggressive antibiotic therapy, in some forms of chronic otitis media, may not prevent the above complications. The necessity for repeated placement of ventilation tubes indicates that the underlying process requires a more assertive treatment than temporarily reventilating the mesotympanum. There are often underlying anatomic variations that can create obstructive sites within the middle ear cleft. These sites can easily be obstructed by adhesions, hypertrophic mucosa, or chronic granulation tissue. Our flexible approach tympanoplasty was developed as a conservative surgical method for systematically identifying (evaluating) and treating these anatomic and pathological factors that contribute to chronic otitis media. The schematic in Fig I depicts sites of obstruction which the surgeon must evaluate in the process of performing the procedure. Figure 1 shows anatomic sites that may, as a result of bony anomalies, be predisposed to narrowing and obstruction. Therefore, indigenous bony obstruction may create a critical mass effect whereby relatively small amounts of mucosal hypertrophy would render a particular anatomic site completely dysfunctional. The development of chronic otitis media can be influenced by sites of obstruction along the middle ear cleft, at the protympanum, mesotympanum (prominent promontory or retraction of the malleus), isthmus, attic, aditus ad antrum, or mastoid air-cells. Obstruction of the eustachian tube can create a generalized pathological environment in the middle ear and mastoid. The combination of a high promontory and a retracted long process of the malleus can be found in many patients with chronic otitis media, leading to an obstructive site in the mesotympanum.