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Biomedical subjects

J Kinzie

Publications and source records attributed to J Kinzie.

At least 19 recordsLinked to original sources
PubMed2001

Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: implications for vaccination strategy.

OBJECTIVES: Administration of vaccine for hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic hepatitis C (CHC) because of the potential for increased severity of acute hepatitis superimposed on existing liver disease. The aim of this study is to determine the prevalence of antibodies directed against HAV and HBV in patients with CHC, analyze demographic and risk factors associated with this prevalence, and develop a cost-effective vaccination strategy. METHODS: We reviewed records from 1092 CHC patients. Demographics and information regarding risk factors were obtained by history and questionnaire administered to all patients. The costs of vaccination and antibody testing were determined, based on standard laboratory and clinic charges at our institution. HAV and HBV markers were correlated to race, age, and risk factors. RESULTS: Of the total population studied (n = 1092), 72% were African-Americans, 27% white, and 1% others. Of 671 CHC patients tested for anti-HAV IgG, 252 (38%) were positive. Of 743 CHC patients tested for HBV antibodies (anti-hepatitis B core IgG or anti-hepatitis B surface), 494 (67%) were positive. African-Americans are more likely to have antibodies to HAV and HBV (67% and 75%, respectively) compared to whites (27% and 20%). The prevalence of anti-HAV was 76% in patients >60 yr, 34% in the 40- to 60-yr-old age group, and 21% in patients <40 yr. The highest prevalence of HBV antibodies was found in patients between the ages of 40-60 yr. No HCV risk factors were associated with increased HAV risk. In CHC patients with HBV antibodies, however, illicit injection drug use was the predominant risk factor. CONCLUSIONS: The prevalence of anti-HAV in patients with CHC was found to be similar to that of the general population in the United States (33% according to recent Centers for Disease Control data), consistent with the hypothesis that the two infections do not share risk factors. Because the prevalence of HAV immunity is low in CHC patients <40 yr, empiric HAV vaccination is cost effective. If two doses of vaccine are to be given, however, antibody testing of all HCV patients is indicated. In the subset of patients >60 yr of age or who are African-American, where the prevalence of HAV exposure is considerably higher, it would be cost effective to check the antibody ($36.00), before vaccination ($97.00). The prevalence of HBV antibodies, however, is significantly increased in patients with CHC compared with the general population (5.3% per the Centers for Disease Control), likely as a result of exposure to similar parenteral risk factors. HBV antibody testing ($26.00 per test) should, therefore, be undertaken in all CHC patients who are hepatitis B surface antigen negative, as this approach is cost-effective compared to empiric HBV vaccination ($438.00 for a three injection course).

Adult↗
PubMed1999

Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process.

Anticarcinogenic Agents↗
PubMed1997

Endogenous codeine and morphine in anorexia and bulimia nervosa.

The endogenous plasma alkaloids codeine and morphine were shown to be elevated in patients with anorexia nervosa and bulimia nervosa compared to control subjects. The role of these opioids in the pathophysiology of these eating disorders is discussed in relation to an auto-addiction opioid model. This model proposes that endogenous opioids are released during an initial period of dieting and reinforce a state of starvation dependence [1,2].

Adolescent↗
PubMed1997

High-dose naltrexone and liver function safety.

Studies have found naltrexone useful in the treatment of diseases other than opiate addiction in which endogenous opioids presumably play a role, such as alcoholism and eating disorders. Some of these studies involve high doses (100-200 mg bid). Because investigational studies with high doses (300 mg/day) reported clinically significant increases in liver enzyme levels, the authors measured a spectrum of liver function parameters in response to high doses of naltrexone in a double-blind, crossover trial (100 mg bid) followed by an open-label period (200 mg bid). They observed no adverse clinical or laboratory changes in liver function in association with high-dose naltrexone therapy in eating disorders.

Adult↗
PubMed1995

Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa.

Our auto-addiction model suggests that opiate blockade may be therapeutically useful in anorexia nervosa and bulimia nervosa. Naltrexone was administered to out-patient subjects in double-blind clinical trials with randomized cross-over designs. Reduction in binge-purge symptomatology was evident in the naltrexone period over placebo for 18 out of 19 subjects with either bulimia or anorexia nervosa of the bulimic subtype. In every case, the decoding of drug or placebo double blinding confirmed the assessments of both the investigator and the subjects, based on the blind analysis of the data and on their therapeutic response, respectively. Statistical analysis done on the total population and two diagnostic subgroups found highly significant differences.

Adult↗
PubMed1995

A detailed longitudinal analysis on the use of naltrexone in the treatment of bulimia.

In accord with our auto-addiction opioid model, naltrexone was previously reported to be effective in the treatment of bulimia in a controlled double-blind clinical trial with a randomized cross-over design. This is a detailed longitudinal analysis over a 16 month period of one subject from that study. Attenuation in bulimic symptoms in two-drug as compared to no-drug periods was demonstrated. The duration for which the drug was needed was also addressed. The subject is an illustration of a therapeutic response on multiple parameters including binges, purges, urges to perform both behaviors, eating patterns, scaled feelings and Eating Disorder Inventory questionnaire scores. A rare allergic reaction to the drug is reported. It appeared to be heat and photosensitive, even in the presence of sun screen, occurred after a delay and did not appear immediately on skin testing. Use of naltrexone after desensitization is also reported.

Adult↗
PubMed1995

Are axillary recurrence and overall survival affected by axillary extranodal tumor extension in breast cancer? Implications for radiation therapy.

PURPOSE: To determine the overall survival and local recurrence significance of axillary lymph node extranodal tumor extension (ETE) and whether axillary/chest-wall irradiation influenced any of these outcomes. MATERIALS AND METHODS: The records of 81 breast cancer patients treated with radical or modified radical mastectomy at a single surgical practice were eligible for study. Thirty-four patients had ETE: 17 with focal ETE (< 10 x high-power field) and 17 with extensive ETE (> 10 x high-power field). RESULTS: With a median follow-up duration of 92 months, only two patients had an axillary recurrence (2%): one had focal ETE and one had no ETE. Neither of these patients received axillary radiation therapy. Overall survival and recurrence-free survival were significantly decreased with ETE in patients whether axillary radiation therapy had been administered or not. Analysis showed that the age of the patient correlated significantly with extensive ETE (P = .04) and that the number of positive lymph nodes (< or = three v > three) correlated significantly with ETE (whether focal or extensive) (P = .0001). A multivariate analysis of extranodal tumor extension and number of positive lymph nodes showed that ETE was associated with decreased survival (P = .05), although to a lesser degree than number of positive lymph nodes (P = .003). CONCLUSION: These results show that ETE is associated with decreased survival and increased recurrence rates regardless of the extent of the radiation therapy field. Also, ETE does not necessarily indicate a significantly increased incidence of axillary recurrence. Therefore, axillary irradiation based on this pathologic finding may not be indicated.

Age Factors↗
PubMed1995

Binge eating disorder: response to naltrexone.

Binge eating disorder (BED) is characterized by a bulimic binge eating pattern without the compensatory behaviors of purging or laxative abuse. It is often associated with obesity. The treatment response characteristics are more like bulimia than other forms of obesity. We have shown the opiate antagonist naltrexone to attenuate bulimia nervosa in controlled clinical trials. We report here a response to naltrexone in a subject with BED similar to that previously reported for the larger population of bulimic subjects. Three consecutive periods of drug, placebo and double dose drug were used, with the order of the first two periods double blind until after the data analysis. Symptoms were reduced in the naltrexone compared to placebo period. Statistical significance was demonstrated using time series analysis for this 'n of one' study. Psychotherapy was carried out throughout all periods. Naltrexone plus psychotherapy may be more efficient than psychotherapy alone.

Adult↗
PubMed1993

Use of ultrasound to guide radiation boost planning following lumpectomy for carcinoma of the breast.

PURPOSE: To determine if sonographic localization of the breast lumpectomy site is feasible and useful in boost planning. METHODS AND MATERIALS: The operative beds following lumpectomy were localized by ultrasound in 22 patients (15-infiltrating ductal, 7-ductal carcinoma in situ; size: .4-2.0 cm). Twelve patients had two ultrasound examinations on different days for a total of 34 examinations. Twenty-one patients had their course of boost electron therapy planned using ultrasound to guide field placement. While the patient was in the treatment position, the surgical scar was placed at the machine's isocenter. With the electron cone in place, the ultrasound transducer was placed within the cone on top of the surgical scar. The biopsy site was localized and the light field maneuvered so that it's central axis would follow the axis of the transducer, transecting both the scar and biopsy site. RESULTS: The operative bed was highly visible in 26 ultrasound examinations, visible in 7, and subtly visible in 1. Every biopsy site showed some hypoechoic area but most appeared as the mixed hypoechoic pattern. Ultrasound appearances were mixed or mostly hypoechoic (28), anechoic with irregular walls (4), and echoic (hypoechoic compared to parenchyma) (2). In two cases the surgeon placed surgical clips in the operative bed, and in both cases several of these clips could be identified at the margins of the operative bed as hyperechoic foci with shadowing. The mean depth of the operative bed was 21 mm (range 17-36 mm). In 12 patients, two ultrasound examinations were performed on different days, and the mean depth difference between these scans was 2 mm with a range of 0-5 mm. Among patients with two scans we found that both the location and appearance of the operative bed was highly reproducible. CONCLUSION: Ultrasound can successfully be used to localize the biopsy site and facilitate boost field placement in patients treated with lumpectomy and radiation.

Biopsy↗
PubMed1989

Chemotherapy following surgery for head and neck cancer. A Radiation Therapy Oncology Group Study.

The feasibility of chemotherapy of three courses of cis-platin and 120-h 5-fluorouracil (5-FU) infusion after definitive surgery, followed by standard radiotherapy, in patients with resectable locally advanced head and neck cancer was carried out in Radiation Therapy Oncology Group (RTOG). Seventy-nine percent of the patients had stage IV cancer, 65% of the tumors were moderately differentiated, and primary sites were 38% oropharynx and 28% larynx. Toxicity to chemotherapy was acceptable, with no life-threatening side effects. Nausea and vomiting were the most common side effects (78%) and were severe in 26%; 30% of patients experienced had leukopenia, 22% had anemia, 13% had thrombocytopenia, and 9% had renal impairment--all of which were mild and reversible. In six patients, chemotherapy was not given for medical conditions or because of patient refusal. Of 23 patients started on cis-platin and 5-FU postsurgery, 18 (78%) completed all three courses. Ninety-six percent of the patients finished adequate radiotherapy according to the protocol. With minimum follow-up of 24 months, 62% of the patients were alive. Of the expired patients, 5 died from other causes, without evidence of recurrence at the time of their death. It is our conclusion that chemotherapy with cis-platin and 5-FU infusion following definitive surgery is feasible on the group level, and a Phase III trial comparing this combined modality therapy to standard treatment of surgery and post-operative radiotherapy is underway by the Head and Neck Cancer Intergroup.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Low-dose continuous infusion 5-fluorouracil and cisplatin: phase II evaluation in advanced colorectal carcinoma.

A study was performed to evaluate the combination of low-dose continuous infusion 5-fluorouracil (LDCI-FU) (300 mg/m2 daily for 28 days) and cisplatin (20 mg/m2 days 1-5 and 24-28). Patients were treated for 28 days with a subsequent 14-day rest period. A total of 24 patients were entered on the study and were evaluable for response and toxicity. All patients were previously untreated, with a median age of 61.5 years and median performance status of 70% (Karnofsky). Bidimensional measurable disease was required. Complete responses were noted in 2 of 24 (8%) patients lasting 8+ and 9 months. Partial responses were observed in 8 of 24 (33%), with a median duration of response of 6 months. Median survival for the 24 patients was 9+ months. Toxicities included nausea and vomiting (25%), hand-foot syndrome (21%), diarrhea (4%), myelosuppression (21%), neurotoxicity (13%), gastric ulceration (13%), mucositis (17%), nephrotoxicity (4%), and subclavian vein thrombosis (21%). This combination demonstrated antineoplastic activity; however, its efficacy parallels other trials utilizing both single agent 5-fluorouracil (5-FU) and different variations of the 5-FU/cisplatin in combination. The impact of this combination on survival and comparison to other regimens requires a randomized trial.

Adenocarcinoma↗
PubMed1987

Induction chemotherapy in advanced head and neck cancer. A Radiation Therapy Oncology Group Study.

Cisplatin (cis-platinum, 100 mg/m2) and fluorouracil (1000 mg/m2/d), for 120 hours' infusion every three weeks for three courses, produced a 93% overall response rate and a 54% complete clinical response at the single-institution level. The same combination was tested in the Radiation Therapy Oncology Group to evaluate the effectiveness and feasibility of this combination. An overall response rate of 86% was obtained, with a 38% complete clinical response. Only 27 of 42 patients completed planned surgery. Compliance with chemotherapy and radiation therapy was substantially better. No additional morbidity after surgical resection or postoperative radiation therapy was identified as secondary to the induction chemotherapy. We conclude that the combination of cisplatin and fluorouracil infusion is effective, with high complete clinical response rate in patients with advanced, previously untreated head and neck carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Pilot study of combination 5-fluorouracil, cisdiamminedichloroplatinum II, and radiation therapy for grade III and IV astrocytomas.

Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.

Adolescent↗
PubMed1987

Nonoperative therapy for squamous-cell cancer of the esophagus.

Based on the surgical pathology and survival for patients in previous trials using a neoadjuvant program of chemotherapy (5-fluorouracil [5-FU]-cisplatin) and radiation (3,000 cGy) before surgery for squamous-cell cancer (SCC) of the esophagus, a nonoperative pilot trial was designed to test if survival and recurrence would differ from our historical controls if routine esophagectomy was eliminated. Twenty patients were treated. The protocol called for the delivery of 5-FU infusion (1,000 mg/m2/d X 4 d) days 1 to 4 and 29 to 32 with cisplatin (100 mg/m2) day 1 and 29 sandwiched around external beam radiation (3,000 cGy over 3 weeks). Mitomycin C (10 mg/m2) day 57 was administered with bleomycin infusion (20 U/d X 4 d) days 57 to 60 and 78 to 81. A radiation boost of 2,000 cGy was administered 200 cGy/d days 99 to 103 and 106 to 110. Clinical pulmonary toxicity forced withdrawal of bleomycin and mitomycin C in the last four patients treated; two further courses of 5-FU-cisplatin were administered instead. The median measurement of the 20 esophageal lesions by barium swallow was 7 cm. Four patients underwent salvage surgery to prevent life-threatening aspiration pneumonia. The median survival for the 20 patients is 22 months, with a range from 6 to 39+ months. The six patients clinically without cancer are alive 22+ to 39+ months (median, 35+ months). Three patients died manifesting only local (infield) recurrence; five died manifesting only distant recurrence; and five developed local and distant recurrence. While the toxicity of the four drug regimen as administered was prohibitive, the survival and quality of survival is superior to the regimen previously used, which routinely used surgery after preoperative chemotherapy and radiation.

Aged↗
PubMed1986

The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy.

The response to initial treatment with cisplatin-containing combination chemotherapy as well as survival, were correlated with tumor differentiation (well, moderate or poorly differentiated) in 164 patients with advanced, untreated squamous cell carcinoma of the head and neck. Thirty-three percent of the tumors were graded as poorly differentiated, 59% moderately differentiated, and 8% were well differentiated. The overall clinical response rates were nearly equal for the three grades of differentiation: 79% for well differentiated, 86% for moderately differentiated, and 89% for poorly differentiated. The complete response rate was somewhat higher for poorly differentiated tumors: 46% as compared to 32% and 29% for moderately and well differentiated respectively, but the differences were not statistically significant. The median survival for each morphologic group was 22, 16, and 12 months for well differentiated, moderately differentiated and poorly differentiated tumor, respectively (P = 0.097). For patients achieving a complete clinical response to chemotherapy, there was a difference in survival when stratified according to degree of histologic differentiation. Patients who were complete responders and had well or moderately differentiated tumors attained 75% and 38% survival at 36 months, respectively, versus 19% for patients with complete response and poorly differentiated tumors (P = 0.064). The degree of differentiation of previously untreated squamous cell cancers of the head and neck does not conclusively predict tumor response to combination chemotherapy, but may reflect differences in natural history. Survival is improved in patients with differentiated tumors as compared to those with poorly differentiated tumors. Morphologic grading in patients achieving a complete response reveals a decrease in survival for patients with poorly differentiated tumors.

Adult↗
PubMed1986

Prognostic significance of tumor growth during radiation therapy.

A retrospective review of 282 consecutive patients with squamous cell carcinoma of the head and neck that were seen in the Radiation Oncology Department from January 1, 1980, through December 31, 1983, was performed. From this population a subgroup of six patients was identified that experienced growth of tumor in the radiation field during treatment. All except one of these patients expired from progression of cancer within 16 months. At the time of writing, the one remaining patient has progressive cancer in spite of additional therapy. Growth of cancer in the radiation field during therapy is unusual. It appears to be associated with a very poor prognosis even with aggressive salvage therapy. This observation should be taken into consideration in the medical/surgical management of these patients.

Carcinoma, Squamous Cell↗
PubMed1986

Upper gastrointestinal endoscopy for diagnosis of complications of regional hepatic chemotherapy.

Seven of 26 patients undergoing insertion of "Infusaid" perfusion pumps with hepatic artery catheters for regional hepatic perfusion with 5 fluorodeoxyuridine were diagnosed to have gastritis (n = 5) or penetrating duodenal ulcers with catheter exposure (n = 2). Diagnosis is best achieved by esophagogastroduodenoscopy. The ulcers required removal of the pumps and gastric resections. The gastritis responded only to cessation of drug infusion. These complications represent a significant risk to regional hepatic chemotherapy. Physicians caring for this group of patients will be unable to predict which individuals will suffer these complications when using preoperative or postoperative parameters such as age, sex, tumor type, arterial anatomy or flow patterns on nuclear isotope scanning. A high index of suspicion must be maintained during the critical third and fourth cycles of chemotherapy in all patients undergoing regional hepatic chemotherapy.

Adult↗