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Biomedical subjects

J S Kennerdell

Publications and source records attributed to J S Kennerdell.

At least 37 records · Page 2Linked to original sources
PubMed1996

Antibody-dependent cell-mediated cytotoxicity against orbital target cells in thyroid-associated ophthalmopathy and related disorders; close relationship between serum cytotoxic antibodies and parameters of eye muscle dysfunction.

We have carried out tests for antibody-dependent cell-mediated cytotoxicity (ADCC) against extra ocular muscle (EOM), Müller's muscle, orbital fibroblasts and skeletal muscle in patients with thyroid-associated ophthalmopathy (TAO) and related eye disorders. Cytotoxicity was measured as lactate dehydrogenase (LDH) release and results expressed as % cytotoxicity. Tests were positive, with EOM cells, in 65% of patients with TAO, 75% with ocular myopathy, a variant of TAO in which periorbital inflammation is minimal, 50% with euthyroid Graves' disease defined as ophthalmopathy associated with subclinical thyroiditis and in 50% of patients with stable lid lag and retraction but no other signs of progressive ophthalmopathy, but in only 13% of patients with Graves' hyperthyroidism without ophthalmopathy, 10% with Hashimoto's thyroiditis and 14% of patients with other thyroid disorders. Tests were positive, with Müller's muscle cells, in 40% of patients with TAO, 25% with ocular myopathy, 40% with euthyroid Graves' disease, 44% with lid lag, 19% with Graves'hyperthyroidism, 50% with Hashimoto's thyroiditis and in 37.5% of patients with other thyroid disorders. When skeletal muscle cells were used as target, tests were positive in 13% of patients with TAO, 31% with lid lag, 25% with Graves' hyperthyroidism and in 29% of patients with Hashimoto's thyroiditis, but in no patient with euthyroid Graves' disease or other thyroid disorders. Tests were negative in all patients and normals tested when EOM-derived fibroblasts were used as targets in ADCC. A significant positive correlation between % cytotoxicity against EOM cells and the severity of the eye muscle dysfunction expressed as an eye muscle index, was observed in patients with TAO. There was a significant negative correlation between the duration of eye disease and % cytotoxicity against EOM cells, suggesting higher titers of cytotoxic antibodies in the early stages of TAO. There was no correlation between % cytotoxicity and serum level of anti-TSH receptor antibodies, measured in a radioreceptor assay. These findings suggest that autoimmunity against Müller's muscle may play a role in the pathogenesis of persistent lid lag and retraction. The nature of the EOM and Müller's muscle autoantigens recognized by cytotoxic antibodies in the serum of patients with TAO and related eye disorders is unknown.

Adult↗
PubMed1996

The role of postoperative irradiation in the management of sphenoid wing meningiomas. A preliminary report.

PURPOSE: To determine whether postoperative radiation therapy decreases recurrence rates in subtotally excised and recurrent sphenoid wing meningiomas. METHODS: Patients with primary subtotally excised and recurrent sphenoid wing meningiomas who underwent surgery between 1981 and 1994 (n = 105) were prospectively followed for recurrence. Postoperative radiation was not recommended in patients who had complete excision; therefore, their recurrence rates were not evaluated in this study. Patients with malignant meningiomas also were excluded from analysis. Recurrence was defined as evidence of tumor growth on neuroimaging with or without clinical symptoms. RESULTS: Follow-up information was available for 86 patients; 69 had primary subtotally excised tumors and 17 had recurrent tumors. Follow-up information was unavailable in the remaining 19 patients. Tumor location and histopathology, type of surgery performed, and patient sex and age were similar in the irradiated and nonirradiated subgroups. Postoperative irradiation was delivered to 31 patients with primary tumors and 11 with recurrent tumors; none of these 42 patients had recurrence during a mean observation period of 4.2 and 3.5 years, respectively. The nonirradiated group consisted of 38 patients with primary tumors and 6 with recurrent tumors; 16 of 18 patients who had primary meningiomas had a recurrence and 5 of 6 who had recurrent tumors had another relapse (mean interval between resection and recurrence, 4.4 years and 14 months, respectively). CONCLUSIONS: Postoperative radiation appeared to delay recurrence in subtotally excised and recurrent sphenoid wing meningiomas during the time frame of this study.

Adolescent↗
PubMed1995

Serum antibodies reactive with eye muscle membrane antigens are detected in patients with nonspecific orbital inflammation.

PURPOSE: Nonspecific orbital inflammation, also called "orbital pseudotumor," has many of the features of thyroid-associated ophthalmopathy, especially when localized to the eye muscle. The purpose of this study is to test for circulating autoantibodies against eye muscle antigens and features of possible thyroid autoimmunity in patients with nonspecific orbital inflammation. METHODS: The authors studied eight patients with diffuse or localized nonspecific orbital inflammation. The presence of autoantibodies reactive with pig eye muscle membrane antigens and 1D, a recombinant 64 kilodaltons (kd) thyroid and eye muscle protein, were tested in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. RESULTS: The most frequently detected antibodies were those reactive with eye muscle membrane proteins of 55 and 64 kd, which were demonstrated in 62.5% and 62.5%, respectively, of patients with nonspecific orbital inflammation; antibodies against 95- and 45-kd proteins were each detected in 50% of patients. In health subjects, antibodies reactive with the 55- and 64-kd proteins were detected in 16% and 20% of patients, respectively; those reactive with the 95-kd protein were detected in 24% of patients and with the 45-kd protein in 20% of patients. On the other hand, antibodies to 1D were demonstrated in only one patient with nonspecific orbital inflammation and not at all in healthy subjects. The prevalence of positive tests were significantly greater in patients with nonspecific orbital inflammation than healthy patients only for antibodies reactive with a 55-kd protein. Of the four antigens, only the 55-kd protein was expressed in other (systemic) skeletal muscle. No patient had overt thyroid disease or detectable serum antibodies reactive with the thyroid-stimulating hormone receptor, and only one had antibodies reactive with the thyroid microsomal antigen. CONCLUSION: Serum autoantibodies reactive with eye muscle membrane proteins are demonstrated in the majority of patients with nonspecific orbital inflammation. Although the pathogenesis of this condition is unknown, autoimmunity against eye muscle antigens is a likely mechanism. While antibodies reactive with the thyroid microsomal antigen were detected in only one patient and anti-thyroid-stimulating hormone receptor antibodies in none of the patients, a possible association of nonspecific orbital inflammation with thyroid autoimmunity has not been excluded.

Adolescent↗
PubMed1995

Should Graves' disease be considered a collagen disorder of the thyroid, skeletal muscle and connective tissue?

Graves' disease comprises hyperthyroidism, ophthalmopathy, pretibial myxedema and acropachy, which occur separately or in various combinations. We have used the indirect immunofluorescence test to investigate reactivity of sera from patients with autoimmune thyroid disorders with and without ophthalmopathy, with porcine extra ocular muscle (EOM) and control tissue substrates. Sera from 75% of patients with Graves' hyperthyroidism (GH) and ophthalmopathy, which we call thyroid-associated opthalmopathy (TAO), contained one or more antibodies reactive with EOM compared to 32% of those with GH without the eye disorder, 41% of patients with Hashimoto's thyroiditis (HT), and 16% of normals. Antibodies reactive with an EOM connective tissue antigen(s), seen as fluorescence of the interstitium and endomysium, were found in sera from 10% of patients with TAO and 16% of those with GH, but not from any patient with HT or normal subject. Similar patterns of connective tissue reactivity were also found in lacrimal gland, skeletal muscle, kidney and salivary gland. Antinuclear antibodies were detected in sera from 31% of patients with TAO, but from only 8% with HT, in no patient with GH and in only 3% of normal subjects. The most common pattern was a fine speckled fluorescence, found in 45% of sera, consistent with reactivity against the Sm antigen or nuclear RNP. The finding of a high prevalence of ANA and, less often, anti-connective tissue antibodies in patients with thyroid autoimmunity and ophthalmopathy, is consistent with Graves' disease being a "collagen-like disorder". The reason why inflammation and resulting tissue damage is limited to the thyroid, connective tissue of the skin and orbit, skeletal muscle and, possibly, the lacrimal gland, is unclear. One possibility is cross reaction of ANA with tissue specific membrane proteins in these sites. The extent of immunologic abnormalities, and the resulting clinical features, in patients with Graves' disease may reflect the severity of a putative defect in immune regulation.

Antibodies, Antinuclear↗
PubMed1995

Extreme eyelid swelling as an unusual presentation of dysthyroid orbitopathy.

We describe seven cases of dysthyroid orbitopathy initially seen as severe periocular lid swelling. Imaging techniques typically demonstrate normal extraocular muscles, although moderate muscle enlargement may occur. Patients do not respond to steroids, radiation therapy, antihistamines, or diuretics. We believe this clinical picture represents a unique population of dysthyroid orbitopathy patients who are best managed by long-term observation followed by cosmetic surgery.

Adult↗
PubMed1994

Recurrent spheno-orbital meningioma.

A series of 15 patients who underwent neurosurgical procedures for recurrent spheno-orbital meningioma is reported. There were 11 women and four men, with a mean age of 46 years. The mean duration between the first and second operations was 46 months. Progressive proptosis without neurological deficit was the most common symptom. All tumors were large at the time of reoperation and involved the greater and lesser wings of the sphenoid bone and the orbit. Aggressive resection in all patients resulted in no deaths and only slight morbidity, with the exception of one patient who developed blindness 24 hours after surgery due to central retinal artery occlusion. Fourteen patients were improved cosmetically and one patient, treated early in the series, had persistent proptosis due to inadequate bone removal. No attempt was made to remove tumor within the cavernous sinus in patients who were neurologically normal. Although postoperative imaging demonstrated complete gross excision of tumor in nine patients, 10 underwent conventional radiation therapy for residual tumor visualized at the time of surgery in the dura of the superior orbital fissure, the cavernous sinus, or the basal optic canal. Although this study is inconclusive and requires further long-term documentation, no recurrences have been seen to date in the follow-up period, ranging from 16 to 95 months. The following important points are discussed: 1) the failure by experienced surgeons to radically excise bone, tumor, and involved dura at the first operation; 2) the importance of early aggressive therapy, depending upon the patient's age and medical condition; 3) the almost invariable intracranial dural involvement, which at times was seen only by gadolinium-enhanced magnetic resonance imaging and not visualized on computerized tomography; 4) an illustrated stepwise surgical technique for complete resection through a small craniotomy without the need for complicated reconstruction of the orbit or temporal fossa; 5) the role of radiation therapy when removal is incomplete or deemed hazardous because of cavernous sinus involvement; and 6) the excellent cosmetic results possible with minimal morbidity and no mortality.

Adult↗
PubMed1993

Serum antibody production to botulinum A toxin.

PURPOSE: Conflicting data have been reported regarding development of serum antibodies to botulinum A toxin. The purpose of this study is to determine conclusively whether antibody production to this toxin occurs in humans, and, if so, to determine its relationship, if any, to length of treatment, total cumulative dose, and clinical response to treatment. METHODS: Sixty-five sera samples from 42 adults treated with botulinum A toxin for essential blepharospasm, hemifacial spasm, or spasmodic torticollis were analyzed via a sphere-linked immunodiagnostic assay for antibody production. Results were plotted against length of treatment, number of injections, cumulative dose, and treatment effect produced. RESULTS: Twenty-four (57%) of the 42 patients produced antibodies in all three diagnostic groups. No significant differences were found between antibody producers and nonproducers with respect to age (P = 0.216), length of treatment (P = 0.586), number of injections (P = 0.619), or total cumulative dose (P = 0.286). Within the antibody-producing group, there was no significant correlation between amount of antibody and length of treatment (P = 0.081), number of injections (P = 0.134), or cumulative dose (P = 0.250). The presence of demonstrable antibodies in serum did not affect the clinical responsiveness to injection. CONCLUSION: Antibody production is present in a majority of patients treated with botulinum A toxin. The sphere-linked immunodiagnostic assay is a reliable and reproducible method for detecting and quantifying these antibodies. When antibody production occurs, it is likely due to variations in individual immune responsiveness and appears to have no direct effect on the patient's clinical response to treatment.

Adult↗
PubMed1993

Temperature distributions in porcine orbital tissues following the use of CO2 and Nd:YAG lasers.

Temperature distributions in the orbital tissues of a live porcine model were obtained during and immediately following the application of CO2 and Nd:YAG (both contact and noncontact) laser irradiation to muscle tissue adjacent to the optic nerve. Temperatures were measured with thermocouples and an infrared-sensitive thermographic camera system. Significant thermal spread was observed only in the case of the contact Nd:YAG laser, along with histologic evidence of damage to the optic nerve. After the laser was switched off, the target cooled with a time constant on the order of 10 seconds.

Adipose Tissue↗
PubMed1992

Choristoma of the optic nerve and chiasm.

A 21-year-old patient with a biopsy-proved choristomatous malformation of the optic nerve and chiasm is presented. The patient experienced progressive unilateral vision loss and optic atrophy. A gadolinium-enhanced magnetic resonance image demonstrated chiasmal involvement that was not evident on computed tomographic scan or visual field testing. We believe this is the third reported case of a choristomatous malformation of the optic nerve and chiasm and the first report of magnetic resonance imaging findings.

Adult↗
PubMed1992

Orbital lymphangioma. Correlation of magnetic resonance images and intraoperative findings.

BACKGROUND: Orbital lymphangiomas generally are invasive, slow-growing lesions that can produce proptosis, motility impairment, and compressive optic neuropathy. Successful surgical management requires detailed preoperative radiologic imaging with the capacity to determine the location and size of the tumors, the presence of cystic or solid components, and extent of infiltration of the tumor into normal orbital structures. METHODS: The records of 12 patients with orbital lymphangioma were reviewed with attention to the clinical, radiologic, operative, and histologic findings. RESULTS: Preoperative magnetic resonance imaging (MRI) produced highly detailed renderings of the orbital mass that were both diagnostic and predictive of the intraoperative findings. Magnetic resonance imaging was particularly sensitive to the presence of cysts within the tumor and was able to predict the contents of the cysts. CONCLUSION: Using preoperative MRI, a more detailed and accurate surgical plan can be formulated than with any other noninvasive technique.

Adolescent↗
PubMed1992

Immunohistochemical evidence for C3bi involvement in Graves ophthalmopathy.

PURPOSE: To determine by immunohistochemical methods if components of the complement system are present in Graves ophthalmopathy extraocular and periocular tissues compared with non-Graves ophthalmopathy ocular tissues, and, if so, whether a qualitative difference exists. METHODS: Orbital muscle, periorbital muscle, and adipose tissue from 10 Graves ophthalmopathy patients were studied with in situ assays using monoclonal antibodies for C3bi and C5b-9 (the terminal attack complex) complement components. Extraocular muscle, periocular muscle, and adipose tissue from 12 patients treated for unrelated orbital disorders were used as controls. RESULTS: All nine Graves extraocular and periocular muscle tissues exhibited C3bi positive staining in an intense, localized oval- to spindle-shaped reaction that appeared to represent cells on a diffuse staining background of the endomysial and perimysial connective tissues with no staining of the muscle fibers themselves. Some reactivity was seen in 6 of the 12 control muscles, but this was much less intense than that of Graves ocular muscle tissue. Only two Graves muscle samples stained minimally with the monoclonal antibody for the C5b-9 terminal attack complex while none of the control muscle samples demonstrated reactivity. Orbital fat from Graves and control patients did not demonstrate any reactivity for C3bi or C5b-9. CONCLUSION: C3bi and not C5b-9 (the terminal attack complex) is present in Graves ophthalmopathy extraocular and periocular tissues in a qualitatively greater way than in control non-Graves ophthalmopathy ocular tissue. Consequently, C3bi may contribute to the pathophysiology of Graves ophthalmopathy.

Adult↗
PubMed1992

Correlation of serum immunoglobulin E elevations with clinical stages of dysthyroid orbitopathy.

Total immunoglobulin E (IgE) was measured by an enzyme-linked immunoassay in serum samples from patients with dysthyroid orbitopathy and from a group of healthy volunteers. All the serum donors had no symptoms of allergy or infection and were not given any immunoregulative treatments for at least 6 months before the sampling. One hundred thirty-seven dysthyroid orbitopathy patients were rated clinically as belonging to one of the following groups: (1) stable dysthyroid orbitopathy; (2) active dysthyroid orbitopathy; (3) chronic or recurrent dysthyroid orbitopathy; or (4) dysthyroid orbitopathy characterized by limited myopathy. The serum IgE levels of all these groups were compared with 26 healthy, nonatopic volunteers. The mean IgE levels of groups 3 and 4 were significantly higher than the mean IgE level of the control group as well as that of the group with stable dysthyroid orbitopathy. Furthermore, serial readings on several patients were consistent with the hypothesis that serum IgE is elevated in connection with certain stages of rapid dysthyroid orbitopathy progression and also with two unusual clinical forms of dysthyroid orbitopathy.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Immunohistochemical evidence for IgA1 involvement in Graves ophthalmopathy.

Orbital muscle, adipose tissues, and periorbital muscle from 11 patients with Graves ophthalmopathy were studied with in situ assays using monoclonal antibodies for IgA1, IgA2, IgM, and IgG. Tissue biopsies were taken from varied extraocular muscles and orbital sites. All cases were from patients with severe disease or disease of long duration. Control specimens of extraocular muscle tissues were obtained from nine patients treated for unrelated orbital disorders. Only connective tissue associated with the extraorbital muscles and periorbital muscles showed any reactivity. Of the muscle tissue obtained from patients with Graves disease all exhibited IgA1 positive staining of the endomysium and perimysium, without staining of the muscle fibers themselves. Parallel sections of orbital muscles reacted with anti-IgA2 or anti-IgM antibody failed to demonstrate staining. Control extraocular muscle tissue did not stain with anti-IgM and one control muscle of seven reacted minimally with anti-IgA2. Some reactivity with anti-IgA1 was seen in four of the seven control muscles but this was qualitatively much less than that of muscle tissue from patients with Graves disease. Monoclonal anti-IgG did not stain tissue from the six Graves specimens and three control specimens tested.

Adipose Tissue↗
PubMed1992

Cryosurgery re-visited for the removal and destruction of brain, spinal and orbital tumours.

Advances in neuroimaging and cryosurgical techniques have prompted us to re-evaluate the potential of cryosurgical techniques for the removal and the destruction of various neoplasms. We have used cryosurgical instrumentation to remove tumours in the brain, spine and orbit in 71 patients without complications. Cryosurgery was used to facilitate removal and extraction in 64 and to destroy residual neoplasms when removal was incomplete in 7. Intraoperative real time ultrasonic imaging permitted precise delimitation of tumours from surrounding tissues and allowed monitoring during the production of cryosurgical lesions thus permitting heretofore unavailable visualization of the production of cryogenic lesions in the central nervous system. New cryosurgical instrumentation was used to produce lesions up to three times larger than similar sized probes previously available. Our results reconfirm that cryosurgery facilitates the removal of tumours in the brain, spinal cord and orbit, reduces blood loss in vascular tumours, and is effective in ablating residual neoplasms involving the superior sagittal sinus, torcula and parasagittal areas. A Doppler flowmeter proved useful for monitoring sagittal sinus blood flow during the production of cryosurgical ablation of residual tumour attached to the walls of the sagittal sinus. Recent advances in ultrasonic and neuroimaging coupled with stereotactic techniques and improvements in cryosurgical instrumentation may prove useful in the future percutaneous destruction of selective intracranial neoplasms.

Adult↗
PubMed1992

Treatment of dysthyroid lower lid retraction with autogenous tarsus transplants.

Lower lid retraction is commonly seen in dysthyroid orbitopathy. We have treated 55 lower lids in 38 patients with lower lid retraction by a tarsal transplant from the upper lid to the lower lid. An overall effect of 2-mm improvement +/- 0.7 mm occurred. Eighty-nine percent of the lids achieved the position of the lower lid within 1 mm of the limbus. We think that the upper to lower tarsal transplant offers a technically easy and reasonable solution to moderate lower lid retraction associated with dysthyroid orbitopathy.

Adult↗
PubMed1992

Re-examination of peripheral blood T cell subsets in dysthyroid orbitopathy.

Patients with dysthyroid orbitopathy (DO) were grouped according to a multifactorial assessment of disease severity and the rate of disease progression. Using this system and flow cytometric measurements of T cell subsets in the peripheral blood, a significant increase in the percentage of CD4+ lymphocytes correlated with disease severity in DO patients with progressive disease. These observations are consistent with the hypothesis that the CD4+ peripheral blood T helper cells play a significant role in the progression of DO.

Adult↗