PubMed Health⌕ Search

Biomedical subjects

W J Richtsmeier

Publications and source records attributed to W J Richtsmeier.

At least 19 recordsLinked to original sources
PubMed1992

Juvenile nasopharyngeal angiofibroma tumor models. Failure of androgens to stimulate growth in nude mice and in vitro.

Juvenile nasopharyngeal angiofibroma is a tumor with a predilection for adolescent boys. It has been shown to contain cytosolic androgen receptors and to regress with estrogen therapy; however, the results have not been consistent. Extensive investigation has been unable to settle this issue in patients owing, in part, to the rarity of these tumors. We have attempted to establish a tumor model for juvenile nasopharyngeal angiofibroma by transplanting the tumor into the subdermal space of athymic mice and also by culturing it in vitro, to study the effect of hormonal manipulation. The tumor did survive in male and female athymic mice but has failed to grow. Androgen treatment of the mice of either sex did not alter its survival or growth behavior. The in vitro tissue culture grew fibroblastoid cells that were not stimulated by androgen supplementation. This study suggests that factors other than androgens are at least complementary, if not essential, in promoting the growth of juvenile nasopharyngeal angiofibroma in tumor models, and that androgens are not, in and of themselves, sufficient growth stimuli.

Animals↗
PubMed1992

Radiolabeled antibody therapy for squamous cell carcinoma of the head and neck.

Immunohistochemical staining for ferritin was performed on 11 human head and neck squamous cell carcinomas transplanted in nude mouse xenografts. Seven tumors were found to be positive. Using ferritin as a tumor antigen target, escalating doses of yttrium-90-labeled antiferritin antibodies were injected intravascularly into nude mice that were transplanted with a ferritin-positive human squamous cell carcinoma. Forty-five days after injection, the mean treated tumor size was 25.6% of control in the 100-microCi group, and 20.6% of control in the 200-microCi group. Ninety days after injection the mean tumor size was 27.5% that of control in the 100-microCi group and 31.7% in the 200-microCi group. Higher doses of radiation (300 and 400 microCi per mouse) caused death of most of the animals due to radiation toxicity. Presensitization of the animal, before antibody injection, with a bolus intraperitoneal injection of 7.5 mg of cisplatin per kilogram of body weight, resulted in further reduction in tumor size when compared with antibody alone or cisplatin alone. This study demonstrates that radioimmunotherapy with selected doses of yttrium-90-labeled antiferritin antibodies is effective against human head and neck squamous cell carcinoma xenografts in nude mice.

Animals↗
PubMed1992

Nuclear morphometry for prediction of metastatic potential in early squamous cell carcinoma of the floor of the mouth.

Quantitative morphometric analyses of the nuclear shape have been successfully used with prostatic carcinoma to predict tumor metastatic potential and provide the most sensitive indicator of tumor aggressiveness in the individual case. We have studied the nuclear morphometric characteristics of 22 patients with T1 and T2 squamous cell carcinoma of the floor of the mouth to see if a correlation existed between lack of nuclear roundness and presence of cervical metastatic disease. A significant difference was identified between the morphology of cancer cell nuclei and normal squamous epithelium. Nuclear morphology could not be used to distinguish between patients with cervical node-negative and node-positive disease. Some patients both with and without cervical metastases who are long-term survivors had nuclear roundness scores in the highest range, reflecting greatest variation from normal.

Adult↗
PubMed1992

Complications and early outcome of anterior craniofacial resection.

OBJECTIVE: To evaluate the complications of anterior craniofacial resection and correlate their impact with tumor control status. DESIGN: We conducted a retrospective review of 32 consecutive, operable patients' records seen over a 6-year period, requiring 35 procedures. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Twenty-six patients (81%) had malignant lesions (esthesioneuroblastoma, squamous cell carcinoma, and a group of miscellaneous malignant tumors). Six patients had various benign neoplasms. INTERVENTION: The surgical approach involved bifrontal craniotomy coupled with lateral rhinotomy in 19 cases (61%), facial degloving in 10 cases (32%), a total rhinectomy in one case, and endoscopic sinusectomy without facial incision in two cases. OUTCOME MEASURE: Clinically noted complications and oncologic outcome. RESULTS: There was one avoidable perioperative death indirectly associated with the patient's procedure. Nine patients suffered significant intracranial neurological complications such as tension pneumocephalus and delayed epidural abscess. All of these complications were managed successfully. Of patients with malignant tumors, 13 (52%) are alive with no evidence of disease and one is alive with recurrence after a mean follow-up period of 28.9 months. The 10 patients who succumbed to disease had a mean postoperative survival of 22.9 months. CONCLUSIONS: In contrast to the perspective of only a decade ago, we conclude that craniofacial resection is a relatively safe, versatile, and effective procedure for surgical management of tumors involving the anterior skull base.

Adult↗
PubMed1992

Medical and surgical management of sinusitis in adults.

Sinusitis may be caused by bacteria, viruses, or trauma and may appear in immunosuppressive settings. Acute sinusitis is most commonly diagnosed on the basis of pain and discharge; endoscopic or fiberoptic examination may be helpful in less obvious cases. Radiography can identify maxillary, frontal, and sphenoid sinusitis; transillumination can be used if radiography is undesirable. Culture and Gram stains may help determine the appropriate antibiotic therapy. Surgery may be necessary if the frontal or sphenoid sinus is involved, or if ethmoiditis is progressing to orbital cellulitis. In chronic sinusitis, endoscopic examination and computed tomographic scanning are useful for diagnosis. Chronic sinusitis may be associated with airway disease, aspirin allergy, and such diseases as cystic fibrosis. Antibiotic therapy that acts against anaerobes and beta-lactamase-producing organisms should be chosen. Surgical treatment includes intranasal and external ethmoidectomy, antrostomy, and, on occasion, obliteration of the involved cavity.

Acute Disease↗
PubMed1992

Head and neck cancer.

Explore the source record for details and available documents.

Carcinoma, Squamous Cell↗
PubMed1992

Utility of immediate on-site cytopathological procurement and evaluation in fine needle aspiration biopsy of head and neck masses.

The utility of on-site microscopic evaluation of fine needle aspirates (FNAs) of the head and neck was assessed by comparing the diagnostic yield in 336 specimens obtained with immediate on-site cytopathological procurement and evaluation to that achieved in 548 cases performed without immediate on-site evaluation. Three hundred six (91%) of 336 immediate evaluation specimens were adequate for cytopathologic diagnosis, compared to 391 (71%) of 548 specimens not evaluated immediately (P < .001, chi-squared test). The higher satisfactory rate in immediate evaluation cases was related primarily to 1. immediate reaspiration of the masses until sufficient cytopathologic material was obtained for diagnosis; and 2. optimal specimen preparation. It is concluded that immediate on-site cytopathological procurement and evaluation of fine needle aspirates of head and neck masses is a valuable practice which assures a higher yield of adequate specimens compared to biopsies taken without immediate evaluation. The technique of immediate on-site evaluation of FNAs is discussed and a cost-benefit analysis of immediate on-site evaluation of FNAs is presented.

Biopsy, Needle↗
PubMed1991

Effect of viruses and interferon on chick embryo otocyst cultures.

Chick embryo otocyst organ cultures were subjected to live vesicular stomatitis virus and rubella virus preparations, to interferon (IFN), and to a combination of both virus and IFN, and compared to control untreated otocysts. We observed morphologic and microscopic changes suggestive of individual cell death and delayed organ differentiation in the virus-treated groups, along with an appreciable decrease in size of the otocyst. Low-dose IFN treatment prior to virus inoculation appeared to partially prevent these effects. The addition of IFN alone did not seem to affect the differentiation process. Time-lapse videophotography further confirmed the above findings. This study suggests that the peripheral component of congenital deafness associated with viral infections is likely to be an effect of the virus itself, and not of the IFN. Interferon provides a partial protective effect against the insult from the virus in vitro and does not seem to be toxic to the developing otocyst.

Animals↗
PubMed1990

Phase I-II study of advanced head and neck squamous cell carcinoma patients treated with recombinant human interferon gamma.

The association of immunodeficiency with head and neck squamous cell carcinoma has generated the concept of supplying immunologically active agents as a means of treating these cancers. One of the most active immunologic messengers is interferon gamma, which has been observed in our laboratories to also have a direct cytotoxic effect on cultures of squamous cell carcinoma derived from the head and neck. To test the feasibility of treating patients with advanced but resectable head and neck cancer with this agent, we designed a phase I-II trial of recombinant human interferon gamma using a 24-hour infusion repeated weekly for four times. In this study, both tumor and immunologic parameters were studied before and after treatment. Eight patients were entered into the study with the highest recombinant human interferon gamma dose attempted being 0.25 mg/m2 per 24 hours. Minimal side effects were observed. Three patients had clinically measurable responses, four had stabilization of disease, and one had progression while receiving treatment. Histopathologic results of treatment were similar to in vitro observations. Necrosis, as well as differentiation of tumor cells, was observed. In some tumors there was a marked decrease in cellularity without a change in tumor volume due to increased extracellular keratin deposition. Our study indicates that evaluation of adoptive immunotherapy trials in head and neck cancer needs to include parameters other than simple tumor regression as an end point, otherwise therapeutically important lymphokine-induced changes may be missed. Further evaluation of recombinant human interferon gamma and agents that induce human interferon gamma are warranted.

Adult↗
PubMed1989

Lysis of squamous cell carcinoma via antibody-dependent cellular cytotoxicity.

We have developed a system in which antibody-dependent cellular cytotoxicity (ADCC) can be consistently demonstrated against squamous cell carcinoma (SCC) of the head and neck. Serum samples from patients with pemphigus vulgaris (PV) provided antibodies for ADCC. The effector cells were lymphocytes from the peripheral blood of healthy human donors. The SCC cell lines served as targets. Lysis of SCC, as measured by 51Cr release, was significantly enhanced by the presence of serum from patients with PV, but not by healthy human serum. Serum alone produced no target cell killing. Nonepithelial cell lines were not affected by the presence of PV antibodies. The results demonstrate that SCC is susceptible to ADCC. Thus, tumor-specific antibodies may have a role in the treatment of cancer of the head and neck. This system can serve as a positive control for further testing of ADCC against SCC.

Antibodies↗
PubMed1989

Inhibitory effects of mitochondrial metabolic inhibitors on interferon action.

The expression of the antiviral action of the human interferons (IFNs) HuIFN-alpha and HuIFN-gamma was inhibited in human cells treated with antimetabolites affecting different mitochondrial functions. We confirmed earlier observations that cycloheximide, a specific inhibitor of cytoplasmic protein synthesis, failed to inhibit IFN action completely. Chloramphenicol, which inhibits mitochondrial protein synthesis, suppressed IFN effect when present in high concentration; in human foreskin cells, the inhibitory effect on HuIFN-alpha activity of 500 micrograms/ml chloramphenicol (which caused only 20% inhibition of overall cellular protein synthesis) was greater than that observed with 25 micrograms/ml cycloheximide (which caused 98% inhibition of overall cellular protein synthesis). Cycloheximide combined with chloramphenicol further inhibited the antiviral effect of IFN than that observed by either drug alone. Similar observations were made with mouse IFN-alpha/beta in mouse L cells. Treatment with cycloheximide, in combination with oligomycin, an inhibitor of oxidative phosphorylation, also produced an inhibition of the antiviral effect. Oligomycin, dinitrophenol, and 1799, a fluorinated uncoupler of oxidative phosphorylation, all produced IFN-suppressive effects in heteroploid human cells. These data indicate that intact mitochondrial functions are required for the full expression of the antiviral actions of IFN-alpha and IFN-gamma.

Antimetabolites↗
PubMed1989

Hyperthermia effects on the growth of a laryngeal squamous cell carcinoma cell line treated with recombinant human interferons alpha and gamma.

Clinical therapy with either interferon alpha or interferon gamma is associated with a febrile response. However, the effects of hyperthermia on the response to these interferons have not been elucidated fully. In this study, a cell line derived from a laryngeal squamous cell carcinoma (JHU-011-SCC-L-P) was grown in the presence of recombinant human interferon alpha (rHuIFN alpha) or recombinant human interferon gamma (rHuIFN gamma) and incubated at either 37 degrees or 39 degrees C, and cell growth rates were measured. Cells incubated with rHuIFN alpha demonstrated no difference in growth rates from control cells. Cells treated with rHuIFN gamma showed significant inhibition of growth at both temperatures, and the ratio of decreased growth at 39 degrees C was significantly greater than for the rHuIFN alpha and control groups. This hyperthermic effect did not depend on the continued exposure to rHuIFN gamma, and the effect appeared to depend on the duration of hyperthermia instead of the time sequence of hyperthermic exposure. Moreover, initial treatment at 39 degrees C for 24 hours was ineffective in producing the hyperthermic response produced with continuous hyperthermic exposure. These findings would indicate that the effect of rHuIFN gamma on this laryngeal squamous cell carcinoma cell line is enhanced significantly at 39 degrees C compared with 37 degrees C. There appears to be no similar hyperthermia-augmented antiproliferative effect of rHuIFN alpha-treated cells.

Carcinoma, Squamous Cell↗
PubMed1988

Interferon gamma induced oncolysis. An effect on head and neck squamous carcinoma cultures.

We have measured an oncolytic effect of recombinant human interferon gamma on squamous cell carcinoma (SCC) tissue cultures. The decrease in viable cells from an established culture was visually observed directly and measured by the loss of cell protein mass as determined by the staining of cultures with naphthol blue-black dye. We avoided confusion with tumor necrosis factor effects by using recombinant human interferon gamma cloned from a single gene as opposed to natural human interferon gamma. Oncolysis induced by recombinant human interferon gamma requires four days after exposure for a significant loss of total cellular protein to be measured, although changes can be observed visually after one day. This sensitivity to recombinant human interferon gamma was observed in SCC cultures obtained from head and neck mucosa, in addition to those from cervix and skin. Several head and neck cultures are sensitive to the oncolytic effect of recombinant human interferon gamma at less than 30 U/mL concentration. The actual time of treatment observations dictates changes in current recombinant human interferon gamma treatment regimens if the oncolytic effect is desired.

Carcinoma, Squamous Cell↗
PubMed1988

The effect of whole virus influenza vaccination on theophylline pharmacokinetics.

The effect of whole virus influenza vaccination on theophylline pharmacokinetics was evaluated in 16 normal subjects. Because previous reports had suggested that influenza vaccine induces interferon production and may potentially depress hepatic metabolism of theophylline, serum interferon concentrations were monitored for 6 days after vaccination. Lymphocytes from 6 subjects were incubated in vitro with dilute whole virus vaccine (WVV) or dilute split virus vaccine (SVV) to assess their immunocompetence and the immunogenic potential of the 2 vaccine preparations. Additionally, influenza antibody response was monitored by prevaccination and postvaccination serum antibody titers in 11 subjects. No significant change in half-life, total body clearance, volume of distribution of maximal serum theophylline concentration compared to prevaccine values was observed at either 2 or 6 days after vaccination. No interferon production was detected in vivo up to 6 days after vaccination. In vitro lymphocyte interferon induction assay demonstrated mean interferon levels of 12,252 +/- 9,819 IU/ml for WVV and 888 +/- 1,180 IU/ml for SVV (p less than 0.05), demonstrating the immunocompetence of the subject's lymphocytes and confirming the greater immunogenic potential of WVV. Seven of 11 subjects (64%) showed a 4-fold rise in influenza antibody titer to at least one of the vaccine antigens. We conclude that whole virus influenza vaccine does not alter theophylline pharmacokinetics. In addition, it has greater immunogenic potential than split virus vaccine in vitro but does not induce significant interferon production in vivo. This study adds further evidence supporting the safety of the concomitant use of influenza vaccine in patients taking theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The versatile midface degloving approach.

The exposure obtained using the degloving approach is superb and the absence of resultant facial scar or deformity provides a dramatic new addition to the otolaryngologist's surgical repertoire. The advantages of the degloving technique in exposure of the midface, nasal cavities, paranasal sinuses, nasopharynx, skull base, and clivus have led to its increasing importance in the otolaryngology literature. Within 2 years of the technique's introduction in our department, it had been used 48 times for a wide variety of problems, including inverting papilloma, juvenile angiofibroma, chordoma and selected cases of fungal disease of the sinuses. This article describes the procedure, reports the results from a panel of 48 patients, and discusses potential complications. The authors' experience with this procedure indicates that it should become a procedure of choice for management of inverting papilloma and juvenile angiofibroma, as well as a major alternative method in many other circumstances.

Face↗
PubMed1988

Induction of HLA-DR antigen on human squamous carcinoma by recombinant interferon gamma.

The antigen recognition system which plays the major role in immunologic attraction mechanisms, including graft rejection, is the class II major histocompatibility complex containing the HLA-DR locus. Few types of cells constitutively express this antigen, as it is a potent immunological activating signal usually confined to antigen processing cells, activated lymphocytes, and endothelium. Using indirect immunofluorescence, we have observed induction of the HLA-DR glycoprotein in selected head and neck squamous cell carcinoma tissue cultures treated with recombinant interferon gamma. This occurs in concert with growth arrest and morphological changes after rHuIFN-gamma treatment. This report describes the induction of a surface antigen that may have profound prognostic significance. Understanding the kinetics of HLA-DR induction will aid in the design and assessment of adoptive immunotherapy with rHuIFN-gamma.

Carcinoma, Squamous Cell↗