Defective recognitive immunity in family aggregates of colon carcinoma.

Cancer-free individuals from family agregates of seemingly hereditary colon carcinoma were studied to determine the nature of their cell-mediated immune capacities in miexed leukocyte culture. Members of families who demonstrated no evidence of a precancerous condition such as polyposis coli did demonstrate substantial cellular immunopathology. Of these, 44% showed a decreased responsiveness of their peripheral mononuclear cells to allogeneic stimuli, and in a number of these individuals this deficiency clearly manifested itself as an inappropriate suppression of potentially normal lymphocyte blastogenic capacities by an adherent population of mononuclear leukocytes. This in vitro defect of recognitive immunity appears to be the same type of defect that has already been described for individuals with established maligancies. The pattern of phenotypic expression of this immunopathology within these families is not inconsistent with an hereditary disorder. Individuals from families with a known hereditary somatic precancerous condition usually did not demonstrate this immunopathology. It is appropriate to speculate that the defect of recognitive immunity in the former families could be contributory to the genesis of the colon carcinoma.

Aggressive combined modality treatment of progressive sinonasal fungal infections in immunocompromised patients.

PURPOSE: Invasive fungal infections of the paranasal sinuses in immunocompromised hosts are often fatal despite therapeutic interventions. In an effort to achieve a better outcome in patients with these infections, aggressive management was combined with medical/surgical intervention. PATIENTS AND METHODS: A series of 18 immunocompromised patients with invasive sinonasal fungal infections was retrospectively analyzed. Management consisted of a combined modality clinical approach, including aggressively sought early diagnosis; early amphotericin use; extensive surgical debridement; and liberal use of granulocyte transfusion support. RESULTS: Eight of 13 patients with eventual neutrophil recovery survived with control of all local and systemic signs of fungal infection. All patients with persisting neutropenia died of progressive infection. CONCLUSION: We conclude that meticulous surveillance of patients in high-risk groups for fungal infection should be maintained due to the apparent value of rapid intervention with a combination of surgical resection and medical management (antifungal chemotherapy and white blood cell transfusions). Infection control and survival are ultimately dependent on recovery of marrow function and circulating neutrophils.

Sinusitis in immunodeficient and immunosuppressed patients.

Sinusitis tends to occur in immunodeficient and immunosuppressed patients during periods of severe leukopenia. This group of patients includes those with primary immunodeficiency diseases, patients with leukemia receiving chemotherapy, and those undergoing bone marrow transplantation or kidney transplantation. The clinical and radiographic signs may be minimal or initially unimpressive. Sinusitis due to Aspergillus, Phycomycetes, or Pseudomonas may be fulminant and even fatal, requiring extensive surgical procedures for control.

Deficient immunity in head and neck cancer due to excessive monocyte production of prostaglandins.

Monocytes from patients with head and neck cancer produce excessive PGE2 which seems to be associated with decreased lymphoproliferation in vitro. This may be a pathological exaggeration of a normal homeostatic mechanism. It is speculated that a stimulus for excessive PGE2 production could be immune complexes. Although PGE2 suppresses many important immune processes relevant for neoplasia, it can also have complex and diverse effects on tumor cells. Caution should be exercised with human trials of prostaglandin synthetase inhibitors such as indomethacin.

Myofibroblasts in chronic otitis media.

Cells which may be tentatively described as myofibroblasts have been identified by transmission electron microscopy from samples of inflammatory tissue present in the tympanic cavity of ears demonstrating clinical chronic otitis media. These cells possess the ultrastructural characteristics of a markedly indented nucleus, well organized bundles of cytoplasmic microfilaments, and plasmalemma specializations resembling desmosomes. Myofibroblasts are contractile cells which are present in a number of pathological conditions characterized by tissue contraction or distortion such as hepatic cirrhosis, Dupuytren's contracture, and hypertrophic scars. It is possible to hypothesize that myofibroblasts in chronic otitis media may exert synchronized contractile forces which distort the tympanic membrane or ossicular chain and thus lead to conductive hearing loss.

Relationship of optic neuritis to disease of the paranasal sinuses.

The relationship of paranasal sinusitis to optic neuritis remains an intriguing curiosity to both the otolaryngologist and the ophthalmologist. The literature is replete with anecdotal case reports of patients whose sinusitis appears to have caused optic neuritis. There is much speculation about the pathophysiological mechanisms which relate these two distinct disease entities. Five new cases are described which highlight distinct pathophysiologic routes through which paranasal sinus disease has caused optic neuritis. These include compressive optic neuropathy secondary to mucoceles and/or pyoceles; direct extension of sinus infection to the optic nerve from suppurative paranasal sinusitis; and, in one case, from osteomyelitis of the ethmoid and sphenoid sinuses. The usefulness of computerized axial tomography of the orbits and paranasal sinuses to evaluate optic neuritis and to elucidate in detail the pathophysiology of its relationship to disease of the paranasal sinuses is emphasized. Currently, optic neuritis is felt to be a rare complication of paranasal sinusitis. Paranasal sinus surgery is advocated in those cases where sinus suppuration is suspected, or when a compressive optic neuropathy is caused by a sinus mucocele or pyocele. Since in most cases, however, optic neuritis is self-limited, it is difficult to evaluate the results of surgery in circumstances other than those mentioned already. Continued careful evaluation, management, and documentation of this group of patients is necessary to help better define the relationship between these two disease entities.

Prostaglandins in squamous cell carcinoma of the head and neck: a preliminary study.

It has already been demonstrated in human and animal systems that PGE2 is a suppressor signal for many immune functions. These include T-lymphocyte blastogenesis, natural killer cell activity, and cytolytic T-lymphocyte activity. These functions are important for destruction of tumor cells. Conceivably, suppression of these functions by excessive PGE2 restricts tumor cell kill, and reversal of suppression by an inhibitor of prostaglandin synthesis such as indomethacin could increase tumor cell kill. The purpose of this study was to determine the kind of prostaglandins (PGs) produced by tissues with squamous cell carcinoma of head and neck and to measure the concentrations of PGE2, 6-keto-PGF1 alpha, and thromboxane (Tx) B2 in the tumor tissue and in the corresponding control tissue. Tumor and normal control tissues at the margin of the resection were obtained from surgical specimens. The production of PGs was determined by incubation of tissue homogenates with 14C-arachidonic acid, by thin layer chromatography, autoradiography, and scintillation counting. Concentrations of PGs were measured by radioimmunoassay. Tumor tissues produced PGD2, E2, TxB2, F2 alpha, and 6-keto-F1 alpha, and 15-, 12-, and 5-monohydroxyeicosatetraenoic acid (HETE). Concentrations of PGE2 were four times higher in the tumor tissues compared to those in control tissues. There was no difference between the levels of TxB2 and 6-keto-PGF1 alpha in the tumor tissues and those in control tissues. The results of this study will serve as basic information necessary for the potential use of inhibitors of PG-synthesis in the treatment of head and neck carcinoma.

Patterns of involvement of the temporal bone in metastatic and systemic malignancy.

The temporal bone appears to be involved with secondary malignant processes in discrete histologic patterns with rather characteristic clinical presentations. Five distinct types of involvement can be recognized: isolated metastasis from a distant primary tumor; direct extension from a regional primary tumor; meningeal carcinomatosis; leptomeningeal extension from an intracranial primary tumor; and leukemic or lymphomatous infiltration. The typical histopathological patterns are described with correlative clinical symtomatology. Differential diagnosis is considered, and guidelines for surgical management are discussed.

Prognostic significance of lymph node histology in patients with squamous cell carcinoma of the larynx, pharynx, or oral cavity.

In a double-blind retrospective analysis, sections of lymph nodes regional to head and neck squamous cell carcinomas were microscopically examined to assess morphologically the immunologic pattern of response. Patients whose nodes showed evidence of immunologic stimulation had five-year survival rates significantly higher than those whose nodes showed no evidence of immunologic stimulation. None of the patients whose nodes showed the lymphocyte depletion pattern survived five years. The stage or histologic grade of the tumors did not influence these correlations. Metastases occurred much more frequently in patients whose nodes showed immunologic activity than in those whose did not. The data support the concept that immunologic capacities are important host defense mechanisms against malignancy. Histologic assessment of immunologic activity in regional nodes seems to be an important parameter for predicting survival.

Deficient cell-mediated immunity in head and neck cancer patients secondary to autologous suppressive immune cells.

Fifty-four patients with epidermoid head and neck cancer were studied with routine and modified mixed leukocyte culture (MLC) techniques to quantify and characterize their cell-mediated immunity (CMI). Of these, 67% demonstrated deficient CMI in MLC. Employing G-10 column filtration to remove adherent cells selectively, the authors found that 56% of these deficient individuals demonstrated significantly increased lymphocyte responsiveness in MLC. Returning the adherent cells to the cultures usually recaptured the suppressive effect of these adherent cells. Cell marker analyses reveal that the macrophage is the most likely candidate for this suppressive cell. Therapeutic measures which address this paradoxically suppressive cell could be of benefit in enhancing CMI and gaining tumor control.

A comparison of flow cytometric DNA analyses of fresh and fixed squamous cell carcinomas.

Aberrations in chromosome number, ploidy abnormalities, have been associated with malignancy and are predictive of outcome. Automated flow cytometry has made DNA analysis applicable to many solid tumors. Analysis can be performed on fixed specimens, allowing archival retrieval. The techniques, however, are unique and must be individually tested for each tumor type. Presently, few studies have been applied to head and neck cancers. This series of flow cytometric DNA analyses compares the results of 17 fresh and fixed head and neck squamous cell carcinoma specimens. Aneuploidy was present to a significant degree (47%). The method produced interpretable results in 100% of cases, with 100% reproducibility. Fresh and fixed tumor specimens yielded comparable results 76% of the time and, in fact, interpretability of fixed specimens was superior. This series demonstrates a practical and accurate flow cytometric DNA assay for fixed squamous cell carcinoma specimens, facilitating rapid retrospective ploidy analysis.

Electronic reanimation of facial paralysis--a feasibility study.

We set out to adapt the concept of functional electrical stimulation to the reanimation of the paralyzed face. In the New Zealand white rabbit model we studied the strength-duration curves of both innervated and denervated facial muscles. We next studied the electromyographic signals corresponding to different strengths of contraction of innervated facial muscles. With Teflon-coated stainless steel electrodes implanted at opposite ends of the denervated muscle groups under study, bipolar stimulation yielded useful mimetic function that was modifiable by varying the voltage output and the rate of pulse generation. We demonstrated that an electronic circuit can indeed respond to the voltage generated within a functioning facial muscle, and then reproducibly trigger a corresponding graphic signal in synchrony with the mimetic function. The next step will be to adapt an electronic circuit that will deliver a predetermined electrical current to a denervated facial muscle in response to a determined generated voltage in the contralateral corresponding innervated facial muscle.

Acute airway obstruction due to necrotizing tracheobronchial aspergillosis in immunocompromised patients: a new clinical entity.

Two immunocompromised patients with severe neutropenia developed acute airway obstruction due to Aspergillus mycetoma formation in the trachea and main bronchi. The mycetomas caused transmural necrosis of the airway. In one patient, the necrosis extended through the bronchus intermedius into the pulmonary artery, resulting in a fatal hemorrhage during bronchoscopy.

Pulmonary arteriopexy to relieve tracheobronchial compression by dilated pulmonary arteries.

Adequate treatment of pulmonary artery compression of the tracheobronchial tree requires a high index of suspicion for the diagnosis, precise localization of the sites of airway compromise by bronchoscopy, and accurate identification of the anatomy of the obstructing vascular structures. Surgical correction of this vascular anomaly to relieve airway compression is necessary in many infants and should be performed promptly. Pulmonary artery plication, arteriopexy, or aneurysmorrhaphy is well tolerated and can be dramatically successful in improving airway patency.

Tracheobronchial compression in acyanotic congenital heart disease.

Children with acyanotic congenital heart disease frequently develop respiratory difficulties such as atelectasis, pneumonia, or infantile lobar emphysema. In some cases, the cause of the respiratory difficulty is compression of the tracheobronchial tree by hypertensive dilated pulmonary arteries, since this type of heart disease frequently demonstrates large left-to-right intracardiac shunts. Sites of predilection for compression include the left main bronchus, the left upper lobe bronchus, the junction of the right bronchus intermedius and right middle lobe bronchus, and the left side of the distal trachea. Cardiac anomalies which predispose to this type of compression include ventricular septal defect, patent ductus arteriosus, interruption of the aortic arch, and tetralogy of Fallot. Pulmonary arteriopexy may relieve the tracheobronchial compression.

Infantile lobar emphysema.

Infantile lobar emphysema is a symptom complex representing a spectrum of diseases characterized by overdistention of a pulmonary lobe by a check valve mechanism. The earlier in life infantile lobar emphysema presents, the more severe are the symptoms. Half of the cases appear in the first 4 weeks of life. The chest radiograph is the best diagnostic tool but can be misinterpreted. Computed tomography sometimes discloses the cause, which appears to be bronchial obstruction in 25% of cases. The bronchial obstruction may be due to intrinsic defects or to extrinsic compression. Bronchoscopy should be performed only in certain cases and then only with careful anesthetic management.

Resolution of obstructive sleep apnea in Hurler syndrome after bone marrow transplantation.

Hurler syndrome, a lethal inborn error of lysosomal metabolism, results from the systemic accumulation of glycosaminoglycan. The progressive deposition of glycosaminoglycan in tissues of the upper aerodigestive tract has been suspected as the cause of airway obstruction, and many children have required tracheostomy. In a 3-year-old patient with Hurler syndrome, polysomnography confirmed the clinical impression of obstructive sleep apnea. Biopsy of an enlarged tonsil demonstrated that more than half the tissue volume resulted from abnormal lysosomal inclusions in macrophages. Three months after transplantation, repeat testing demonstrated resolution of airway obstruction, and 6 months after transplantation, tonsil biopsy showed complete absence of lysosomal inclusions. Bone marrow transplantation produces effective metabolic correction for Hurler syndrome and may be life-saving for patients with obstructive apnea.