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Biomedical subjects

A L Abramson

Publications and source records attributed to A L Abramson.

At least 19 recordsLinked to original sources

Clinical effects of photodynamic therapy on recurrent laryngeal papillomas.

Thirty-three patients with moderate to severe recurrent laryngeal papillomatosis underwent photodynamic therapy at our institution. All received 2.5 mg/kg of dihematoporphyrin ether intravenously either 48 or 72 hours prior to photoactivation with an argon pump dye laser system. Photosensitivity was the only side effect seen. Statistical analysis showed a significant decrease, by approximately 50%, in the average rate of laryngeal papilloma growth following treatment. The response was especially pronounced in patients with the worst disease. In addition, three patients have now remained free of disease for extended periods following photodynamic therapy. Latent infection with human papillomavirus continues to persist in clinically normal tissue following photodynamic therapy. The results and potential of this exciting new therapy for laryngeal papillomatosis are described.

Adolescent

Human papillomavirus type 6a DNA in the lung carcinoma of a patient with recurrent laryngeal papillomatosis is characterized by a partial duplication.

Transcriptionally active human papillomavirus type 6a (HPV-6a) DNA was detected in a lung carcinoma of a patient with recurrent laryngeal papillomatosis. The carcinoma contained episomal HPV-6a genomes that had a duplication of the upstream regulatory region, the late region and a portion of the early region. HPV-6a genomes found in benign laryngeal papillomas from the same patient did not contain this duplication. A role for the mutant molecules in the pathogenesis of the malignancy is suggested.

Adult

Retinoic acid regulates, in vitro, the two normal pathways of differentiation of human laryngeal keratinocytes.

We have investigated the regulation of the two normal differentiation pathways followed by laryngeal epithelium. Using a tissue culture system that permits growth of cells at the air-liquid interface in serum-free medium, we found that modulating the concentration of retinoic acid is sufficient to determine which pathway is used. At 10(-8) M retinoic acid, the cells form a stratified squamous epithelium which expresses the differentiation-specific keratin K13. At 10(-7) M retinoic acid, the cells form a ciliated pseudostratified epithelium, with no expression of K13. These results are distinct from those seen with foreskin keratinocytes, which have only a single pathway of normal differentiation.

Cell Differentiation

In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid.

We have defined conditions permitting the in vitro growth of human laryngeal papilloma cells at the air-liquid interface. Using this model system, retinoic acid has been found to modulate the differentiation of human laryngeal papilloma cells along two different pathways. At low concentrations of retinoic acid [10(-9) mol/L and 10(-8) mol/L], the cells formed a stratified squamous epithelium with a differentiation-specific protein staining pattern identical to that found in vivo. At higher concentrations of retinoic acid [10(-7) mol/L and 10(-6) mol/L], the cells differentiated into a columnar epithelium with occasional ciliated cells, lacking the markers of squamous differentiation. Analysis of the human papillomavirus DNA content revealed that as the concentration of retinoic acid increased, the viral DNA content decreased. This system is proposed as a model to further investigate the differentiation defects of human laryngeal papilloma cells and the regulatory role of retinoic acid in the clinical expression of human laryngeal papillomatosis.

DNA, Viral

Endolaryngeal jet ventilation: a 10-year review.

Jet ventilation for microsurgery of the larynx has been in common use at our institution since 1978. There were 942 cases performed, with ages ranging from 7 days to 90 years. A specially modified laryngoscope with multiple ports into which a 14- or 16-gauge ventilation needle can be advanced just distal to the vocal cords simplifies this form of anesthesia and ventilation. Jet ventilation has been advocated in place of conventional ventilation methods during carbon dioxide laser surgery because it eliminates the potential fire hazard of the endotracheal tube and allows superior visibility of the vocal cords. Despite these advantages, it is still not in common use. We will review the airway mechanics and special anesthesia considerations that make jet ventilation a safe and time-proven technique.

Adolescent

Is papillomavirus detectable in the plume of laser-treated laryngeal papilloma?

The carbon dioxide laser is widely used for the vaporization of lesions in patients with laryngeal papillomatosis. In this study, the smoke plume resulting from the laser treatment of laryngeal papillomas was analyzed for the presence of human papillomavirus DNA. Plumes were collected with a suction tip and trapped in phosphate-buffered saline. The aspirates were then analyzed for the presence of human papillomavirus DNA by Southern blot hybridization. Human papillomavirus DNA cannot be detected in the smoke plume from vaporization of laryngeal papillomas unless direct suction contact is made with the papilloma tissue during surgery. The implications of these findings are discussed.

Adult

The pathologic and thermal effects of gold vapor laser photodynamic therapy on the larynx. Experimental study.

A gold vapor laser, which emits short pulses of light at a wavelength of 628 nm, was used to deliver varying amounts of energy (30 to 120 J/cm2) to the presensitized (dihematoporphyrin ether) canine larynx. Between 30 and 60 J/cm2, the larynx appeared normal, and when 70 to 100 J/cm2 was applied, only mild edema and erythema were seen. Simultaneously, a thermocouple probe was used and a 0.4 degrees C to 1.5 degrees C temperature rise found. Thus, the gold vapor laser seems capable of achieving the therapeutic photosensitizing effect without causing significant laryngeal edema or thermal activity.

Animals

Abnormal differentiation of human papillomavirus-induced laryngeal papillomas.

We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.

Cell Division

Dihematoporphyrin ether-induced photosensitivity in laryngeal papilloma patients.

Twenty-six patients with recurrent laryngeal papillomatosis received 2.5 mg/kg of Dihematoporphyrin Ether (DHE) intravenously prior to photodynamic therapy. All patients experienced some degree of photosensitivity, the only known side effect of DHE. Reported reactions included mild erythema and inflammation (88%), swelling (58%), blistering (23%), ocular discomfort (61.5%), pruritus (38%), and skin hyperpigmentation (46%). Length of sensitivity ranged from 4-17 weeks, with an average duration of 9 weeks. No long-term debilitating sequelae were noted. Degree of skin reaction mainly depended on how compliant the patient was in following precaution instructions. Although restrictive precautions were often difficult to strictly adhere to, most patients felt the potential benefits of the therapy far outweighed any inconvenience.

Adolescent

Association of papillomavirus with cancers of the head and neck.

One hundred one squamous cell carcinomas (SCC) (study group) and 116 tissues without SCC or papilloma from matched anatomic sites (control group) were evaluated for the presence of human papillomavirus (HPV) DNA. Squamous cell carcinomas of the tongue (18%), tonsil (29%), and pharynx (13%) specifically harbored HPV-16-related sequences. In contrast, the nose, mouth, and esophagus proved completely negative. In the larynx, a low prevalence of HPV-11/16-related DNA was found in both cancers (5%) and control tissues (4%), suggesting that the associations lacked specificity. Our results indicate that anatomic site plays a role in determining the susceptibility to infection, and that the clinical entities with which HPV infections are associated include both subclinical infection with no history of papilloma, and malignant disease.

Blotting, Southern

Voice restoration following laryngectomy: the role of primary versus secondary tracheoesophageal puncture.

A protocol was established at our institution to compare a series of primary and secondary tracheoesophageal punctures using the Singer-Blom voice prosthesis. Over a 24-month period, 20 primary and 18 secondary punctures were performed. Voice production, fluency of voice, and functional use were graded. Our data support the use of both primary and secondary voice restoration following laryngectomy.

Adult

Voice restoration after laryngopharyngoesophagectomy.

Although various methods of alaryngeal communication after laryngectomy have been described, little attention has been given to voice restoration after laryngopharyngoesophagectomy. This article deals with our experience reconstructing the hypopharynx and cervical esophagus in five patients by the use of microvascular free tissue grafts. Voice restoration procedures with use of a Blom-Singer prostheses were used uniformly and resulted in the attainment of functional voice in each patient. It is our feeling that this method should be used equally in patients undergoing both traditional laryngectomy and laryngopharyngoesophagectomy.

Adult

Persistence and expression of human papillomavirus during interferon therapy.

Alpha interferon did not prevent the persistence or expression of human papillomavirus (HPV) types 6 or 11 in respiratory tract papillomas. Seventeen patients receiving interferon therapy for a minimum of six months and a maximum of 39 months still had one to ten copies per cell genome of HPV DNA in their laryngeal tissues, seen by Southern blot hybridization. In papillomas that recurred during treatment, HPV RNA could be detected by in situ hybridization, and capsid protein could be detected by immunoperoxidase staining. Persistence of the HPV DNA, and recurrences that occurred during therapy, are attributed to the failure of interferon therapy to eliminate latent virus.

Antigens, Viral

The pathologic effects of photodynamic therapy on the larynx. Experimental study.

Using an argon pump dye laser at a wavelength of 630 nm, varying amounts of energy (10 to 170 J/cm2) were delivered to the presensitized (hematoporphyrin derivative) canine larynx. There appear to be four energy zones that result in progressive degrees of tissue response. Between 10 and 40 J/cm2 the larynx appears normal, with only mild erythema noted at 60 J/cm2. Above 100 J/cm2 moderate to severe erythema and edema were seen, with two upper-airway deaths observed. Transmission pattern analysis revealed that by either increasing the total energy applied and/or positioning the cylindrical diffuser tip at different levels of the larynx, the entire structure including the undersurface of the vocal cord and subglottic region could be exposed to red light.

Animals

Histological and molecular analysis of cottontail rabbit papillomavirus-induced papillomas treated with hematoporphyrin derivative photodynamic therapy.

The clinical regression of cottontail rabbit papillomavirus-induced cutaneous papillomas on Dutch-belted rabbits following treatment with hematoporphyrin derivative photodynamic therapy was recently reported. Those papillomas that underwent total regression failed to recur at 18 months. Tissues from totally regressed papillomas and adjacent sites failed to reveal the presence of papilloma on histological examination. These findings were confirmed by the absence of viral DNA following analysis by Southern blots for cottontail rabbit papillomavirus viral copy number and DNA restriction pattern. Partially regressed papillomas and untreated papillomas revealed histologically typical papillary features with approximately equal amounts of viral DNA.

Animals

The clinical treatment of laryngeal papillomas with hematoporphyrin therapy.

Photodynamic activation of hematoporphyrin derivative was originally developed for the treatment of cancer. This article demonstrates that it may also be an effective therapy for papillomavirus infections of the larynx. Seventy-two hours prior to surgery, hematoporphyrin derivative (6 mg/kg) was given intravenously to two patients with the adult-onset form of this disease. Three days later, endoscopic surgery was performed and 32 J/cm2 was delivered to the endolarynx via an argon pump dye laser with a red light output of 630 nm. No significant complications such as swelling or hemorrhage occurred. At follow-up (13 months) there has been no recurrence of the laryngeal papilloma in either of these patients. The surgical technique, molecular biology, and clinical implications of this work to control laryngeal papillomatosis are described.

Adult

Chromosomal analysis of recurrent laryngeal papillomas.

Recurrent laryngeal papillomas are tumors believed to be induced by human papillomaviruses. Severity of this disease varies due to the unpredictability of clinical remissions and recurrences. However, the severity of the disease does not affect the classification of these tumors as benign, and the rate of spontaneous conversion of recurrent laryngeal papillomas to carcinomas is very low. Laryngeal papillomas from six patients were evaluated cytogenetically after short-term culture. All six specimens were chromosomally normal, consistent with their classification as benign tumors with a low rate of malignant conversion. The presence of human papillomaviruses has no detectable effect on the chromosomes of these tumors.

Adult