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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 181 records · Page 10Linked to original sources

Pelvic exenteration for primary and recurrent vulvar cancer.

Twenty-one patients who underwent pelvic exenteration for primary (n = 8) or recurrent (n = 13) vulvar malignancy at the M. D. Anderson Cancer Center between 1956 and 1989 were evaluated. A posterior exenteration was performed in 12 patients, anterior exenteration was performed in 6, and total exenteration was performed in 3. In patients with primary tumors, radical vulvectomy and inguinal lymphadenectomy were also performed. The median patient age was 57 years. The mean tumor diameters were 5 cm (primary) and 4 cm (recurrent). Infections were the most frequent postoperative complications (n = 15), followed by pulmonary (n = 4) and cardiac problems (n = 3). There were no treatment-related deaths. Five patients required further surgery to correct late postoperative sequelae. Four of eight patients experienced recurrence after treatment of their primary tumor; the recurrences were local only (n = 1), in the inguinal area (n = 2), or local and in the pelvis (n = 1). Nine of the 13 patients treated for recurrent tumors developed a second recurrence; the second recurrences were all within the pelvis, although two also had a distant component. The 5-year survival rates were 70% for patients treated for primary disease and 38% for patients treated for recurrent disease. Pelvic exenteration is indicated for selected patients with advanced vulvar malignancy.

Adult↗

Combined cisplatin and carboplatin chemotherapy for treatment of advanced epithelial ovarian cancer.

PURPOSE: The primary goal of this trial was to evaluate the clinical activity and the toxicity of a combination of cisplatin and carboplatin for women with advanced-stage epithelial ovarian cancer. PATIENTS AND METHODS: Fifty-one consecutive evaluable patients with untreated stage III and IV epithelial ovarian cancer received 360 mg/m2 carboplatin on Day 1 and 50 mg/m2 cisplatin on Day 2 administered intravenously every 28 days for six cycles. Drug doses were adjusted for hematologic toxicity based on nadir counts during the prior therapy course. Dose levels included 300-400 mg/m2 carboplatin and 50-75 mg/m2 cisplatin. Second-look surgery was optional. Endpoints were clinical response, surgical response, progression-free survival, and survival. RESULTS: Of 8 patients with measurable disease, 3 (37.5%) had a clinical compete response, and 3 (37.5%) had a clinical partial response, for an overall clinical response rate of 75%. Of 39 patients who began chemotherapy with abnormal serum levels of CA 125, 31 (79%) achieved normalization of CA 125 at the completion of chemotherapy. Thirteen patients underwent second-look laparotomy. Of these, 7 (54%) had a pathological compete response, and 2 (15%) had a partial response. The median progression-free survival was 14 months, and the overall median survival was 32.5 months. Neutropenia and thrombocytopenia were the main dose-limiting toxicities. In addition, 9 patients developed grade 2 and 3 developed grade 3 ototoxicity. CONCLUSION: This regimen is very active against advanced-stage epithelial ovarian cancer. The degree of ototoxicity observed is worrisome, but such toxicity may be ameliorated by limiting the dose of cisplatin and increasing the dose of carboplatin.

Adolescent↗

Adenocarcinoma as an independent risk factor for disease recurrence in patients with stage IB cervical carcinoma.

Between 1960 and 1989 1538 patients were treated with initial radiation therapy for FIGO Stage IB squamous cell carcinoma (SCC) of the cervix and 229 patients were treated for Stage IB adenocarcinoma (AC). The overall 5-year survival rates for patients with SCC and AC were 81 and 72%, respectively (P < 0.01). Patients with AC more often had a maximum cervical diameter < 4 cm than those with SCC (53% versus 47%). For 903 patients with tumors > or = 4 cm, 73% of those with SCC survived > or = 5 years compared with only 59% of those with AC (P < 0.01). Although there was no significant difference in the rate of pelvic disease recurrence for patients with AC or SCC tumors > or = 4 cm (17% versus 13%, P = 0.16), the rate of distant metastases was greater for patients with AC (37% vs 21%, P < 0.01). For patients with tumors > or = 4 cm, prognosis was strongly correlated with tumor size (P < 0.01) and lymphangiogram findings (P < 0.01) but not with age (P = 0.58) or tumor morphology (exophytic versus endocervical) (P = 0.33); a trend toward better survival in 165 patients who underwent adjuvant hysterectomy (78% versus 71%) was not significant (P = 0.09). Multivariate analysis confirmed a highly significant independent association between histology and survival; patients with tumors > or = 4 cm in diameter that were AC had an estimated risk of death 1.9 times that of patients with SCC (P < 0.01). These results provide strong evidence that patients with AC of the cervix have a poorer prognosis than those with SCC of similar stage and tumor diameter, reflecting primarily a higher rate of distant metastases in patients with AC.

Adenocarcinoma↗

Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva.

Twelve patients ages 37-85 years (mean, 59 years) with locoregionally advanced vulvar carcinoma were treated with a combination of irradiation and chemotherapy using prolonged continuous infusions of 5-fluorouracil (5-FU) and cisplatin. Eleven patients had advanced vulvar disease with tumors 5-18 cm in maximum diameter (mean, 8.7 cm), eight had palpable inguinal nodes with biopsy-proven metastatic carcinoma, and five had fixed nodes. Patients received weekly 96-hr infusions of cisplatin (4 mg/m2/day) and 5-FU (250 mg/m2/day) for a total of 64 mg/m2 of cisplatin and 4 g/m2 of 5-FU in 4 weeks. Concurrent radiation therapy was delivered to the lower pelvis, vulva, and inguinal nodes to a total dose of 40-50 Gy at 2 Gy per fraction in 11 patients. One patient who had been previously treated for cervical cancer received radiation only to the vulva with an appositional electron beam field. Chemoradiation was well tolerated with virtually no hematologic toxicity and no unscheduled breaks in treatment. Eleven of 12 patients had at least a partial clinical response; one patient had a minimal response of unresectable vulvar disease. Of eight patients who underwent vulvar resection 6 weeks after chemoradiation, four had no residual disease in the resected vulvar specimen and remain disease-free 17, 20, 25, and 37 months, respectively, after surgery. Another patient is disease-free 28 months after a complete clinical response without vulvar resection. However, of four patients who had residual disease in the vulvar surgical specimen, disease has recurred within the irradiation field in three. Overall, 6 of 12 patients treated with this chemoradiation regimen remain disease-free 17-30 months after treatment. This is a well-tolerated outpatient regimen that yields a high response rate in patients with massive vulvar carcinomas.

Actuarial Analysis↗

Fetal oxytocin and its extended forms at term with and without labor.

OBJECTIVE: We examined the concentrations of oxytocin and extended forms of oxytocin in umbilical plasma with and without labor. STUDY DESIGN: Umbilical venous and arterial blood were sampled in 27 term fetuses delivered vaginally and 13 delivered abdominally before labor. Extended forms and oxytocin were measured by radioimmunoassay and compared by analysis of variance or t test. RESULTS: Concentrations of extended forms were higher than oxytocin concentrations (24.7 +/- 3.1 vs 6.1 +/- 1.2 pg/ml, p < 0.01). Extended forms were higher in umbilical venous than in arterial plasma (29.6 +/- 5.0 vs 19.8 +/- 3.1 pg/ml, p < 0.05); oxytocin concentrations were not significantly different (4.7 +/- 1.6 vs 7.8 +/- 1.8 pg/ml). Concentrations of extended forms were markedly lower with than without labor (17.1 +/- 3.0 vs 37.1 +/- 5.7 pg/ml, p = 0.01). Ratios of extended forms over oxytocin decreased with labor. CONCLUSION: In umbilical plasma extended forms of oxytocin are more abundant than oxytocin. Extended forms originate in the uterus and decrease markedly with labor.

Female↗

Ovarian malignant mixed müllerian tumors treated with platinum-based chemotherapy.

OBJECTIVE: To characterize the clinical course of patients diagnosed with ovarian malignant mixed müllerian tumors treated with platinum-based chemotherapy. METHODS: Thirty-six patients received this treatment at The University of Texas M. D. Anderson Cancer Center in the period 1979-1993. The mean age was 59 years. Stage distribution was as follows: stage IA, one (3%) patient; stage IIIB, two (5.5%); stage IIIC, 21 (58%); and stage IV, two (5.5%). Ten (28%) patients were unstaged. Chemotherapy regimens included cisplatin, doxorubicin, and cyclophosphamide in 16 patients; cisplatin-ifosfamide in five; cisplatin-cyclophosphamide in four; carboplatinum in three; cisplatin-doxorubicin in three; and various other combinations in the remaining five. RESULTS: Of 16 patients evaluated for clinical response, seven (44%) had a complete response and four (25%) had a partial response, for a total clinical response rate of 69%. Nine patients were evaluated for surgical response: five (56%) had a complete response and one (11%) had a partial response, for a total surgical response rate of 67%. The median survival for the cohort was 18 months. At the time of this analysis, five (14%) patients were alive and disease-free, 25 (69%) had died of disease, five (14%) were alive with disease, and one had been lost to follow-up. CONCLUSION: This study suggests that the clinical course of patients with ovarian malignant mixed müllerian tumors treated with platinum-based chemotherapy is similar to the clinical course experienced by patients with high-grade epithelial carcinoma of the ovary.

Adult↗

Pediatric gonococcal infection: case report demonstrating diagnostic problems in remote populations.

The inability of Neisseria gonorrhoeae to survive prolonged transit times and hostile ambient temperatures has made its detection at referral laboratories by cultural methods untenable. In this situation, reliance upon antigen detection systems is attractive but when these tests are performed on vaginal specimens from children, false positive results are a significant concern. Some of the difficulties associated with the investigation of a gonococcal infection resulting from sexual abuse of a child in an isolated community are illustrated in this report.

Antigens, Bacterial↗

Fos activation in cultured tyrosine hydroxylase and oxytocin immunoreactive neurons.

Fos and other immediate early gene products are used as markers for neuronal activity. We identified Fos immunocytochemically after KCI-induced depolarization of cultured hypothalamic neurons. Five-day cultures were treated for 1 h with 50 mM KCI or media and fixed at 0, 0.5, 1, 2, and 4 h posttreatment. Sequential immunocytochemistry was performed to identify Fos immunoreactivity in tyrosine hydroxylase (TH)-immunoreactive (-ir) or oxytocin (OT)-ir neurons. Activated neurons [brown cells (TH-ir or OT-ir) with purple nuclei (Fos-ir)] were counted microscopically. KCI treatment resulted in an increased percentage of Fos-ir TH-ir and OT-ir neurons over control levels over the time course examined. Fos-ir peaked in TH-ir neurons at 0.5 to 1 h posttreatment, with levels returning to baseline at 4 h. Fos-ir in OT-ir neurons peaked at 2 h, and remained elevated at 4 h, showing prolonged activation. These results demonstrate that KCI-induced depolarization of cultured hypothalamic neurons increases Fos with a different time course in TH-ir vs. OT-ir neurons.

Animals↗

A phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent epithelial ovarian carcinoma. A Gynecologic Oncology Group Study.

In this series 49 patients with epithelial ovarian carcinoma previously treated with platinum-based chemotherapy received leucovorin 200 mg/m2 i.v. bolus followed by 5-fluorouracil at 370 mg/m2 i.v. bolus daily for 5 days every 4 weeks for the first two courses and subsequent courses were given every 5 weeks. Of this group, 47 patients were evaluable for toxicity and 44 for response. Of the patients evaluable for response, 15 were considered platinum-sensitive and 29 were platinum-refractory. The overall response rate was 6/44 (13.6%). There were two complete responders (4.5%) and four partial responders (9.1%). In the platinum-sensitive patients, there was one complete response, yielding a response rate of 6.6%, whereas in the platinum-refractory patients, there were four partial responses and one complete response for a response rate of 17.2%. Five responses were in the pelvis and there was one response at an extrapelvic site in the abdominal mesentery. The median number of courses delivered was three (range: 1-10). The major adverse effect was myelosuppression with 16/47 (34.0%) experiencing granulocytopenia < 1,000/mm3. The median white blood count nadir for the patients experiencing any leukopenia was 2,700 (range: 400-3,900/mm3). There was one episode of grade 3 thrombocytopenia. Grade 3 intestinal toxicity was seen in seven patients (14.9%). There were no treatment-related deaths. In this previously treated population, 5-fluorouracil with high-dose leucovorin exhibited activity of interest in the platinum-refractory population and warrants further investigation.

Adult↗

A phase II trial of merbarone (NSC 336628) as salvage therapy for squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Study.

Twenty-seven patients with previously irradiated unresectable recurrent squamous carcinoma of the cervix who had failed one prior cytotoxic regimen received 1,000 mg/m2 per day of merbarone given by continuous i.v. infusion for 5 days every 4 weeks through a central line. One patient was never treated, and four were inevaluable for response, leaving 26 patients evaluable for toxicity and 22 evaluable for response. The major adverse effect was myelosuppression with 6/26 (23%) experiencing Gynecologic Oncology Group (GOG) grade 3 or 4 leukopenia. There were two episodes (3.8%) of GOG grade 3 SGOT elevation. There were two patients (9.0%) who developed mental status changes classified as grade 3 neurotoxicity. This neurotoxicity may have been secondary to iatrogenic hyponatremia caused by the large volumes of 5% glucose infusion required at the original infusate concentration. After the concentration of the merbarone infusate was increased to 4 mg/ml, no further problems with hyponatremic neurotoxicity were encountered. The overall response rate was 2/22 (9.0%) (95% confidence interval 1.1-29.2%). In this pretreated population with recurrent squamous cervical carcinoma, merbarone exhibited only minimal activity.

Adult↗

Uterine leiomyosarcoma with clear cell areas.

An unusual case of a uterine leiomyosarcoma with a clear cell component in an 82-year-old woman who presented with vaginal bleeding and a mass protruding through the cervix is reported. Histologic examination of the biopsy sample showed only pleomorphic clear tumor cells and necrosis. Because the patient had a history of a breast carcinoma, and a computed tomography scan of the abdomen showed a renal cyst, these lesions created some problems in the differential diagnosis of the patient's clear cell neoplasm. The patient was treated with a hysterectomy, and examination of the uterus showed an epithelioid leiomyosarcoma with areas of clear cells. Four months after surgery, the patient presented with a vaginal recurrence, which was resected. Twelve months later, the patient had no evidence of recurrence.

Aged↗

Human immunodeficiency virus and hepatitis B virus seroprevalence in an urban trauma population.

OBJECTIVE: To determine the seroprevalence of the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) in patients of an urban level I trauma center. DESIGN: Prospective, blinded point prevalence study of serum HIV and HBV antibody and antigen. SETTING: An urban level I trauma center that participates in a trauma system serving three million people. PATIENTS: The study included 994 (94.8%) of 1049 consecutive trauma service patients treated between June 6, 1988 and September 22, 1988. The patients were 82.2% male and 73.1% black, with a mean age of 28.8 +/- 12.3 years. Blunt trauma was seen in 65.4% of patients, 5.2% were in shock, and 96.2% survived their trauma. MAIN OUTCOME MEASURES: HIV and HBV seroprevalence, using both antibody and antigen testing. RESULTS: HIV infection was seen in 43 patients (4.3%); 41 (95.3%) were HIV Ab+ and two (4.7%) were HIV Ab-/HIV Ag+. Infection with the HBsAg was seen in 31 patients (3.1%). Infection with either virus was seen in 70 patients (7%); four patients (0.4%) were infectious for both viruses. Infection was related to age 20 to 49 years, i.v. drug use, a hepatitis or sexually transmitted disease history, prior HIV testing, shock, and death (p < 0.05). Penetrating trauma was not predictive of infection. In a logistic regression model, IV drug use was the single significant predictor of infection (p < 0.05). CONCLUSIONS: Young urban trauma patients, because of drug-related intentional violence, are 15.3 to 17.6 times more likely to be HIV infected and 3.9 to 7.9 times more likely to be infectious for HIV or HBV than the trauma population overall. The 12 to 21% infection rates in critically injured patients who require shock resuscitation and/or die reinforces the need for mandated universal precautions and for clear policies which govern the performance of procedures by physicians in training. Primary HIV infection in critically injured patients may worsen their outcome and may adversely affect the exposed health care worker. Emergency departments and trauma units should develop a referral system to HIV primary care services (HIV counselling and testing) for high risk patients and for adversely exposed health care workers.

AIDS Serodiagnosis↗

Chronic cough with eosinophilic bronchitis: examination for variable airflow obstruction and response to corticosteroid.

The purpose of this study was to examine airway responsiveness, sputum cells and the effects of inhaled corticosteroid in the chronic cough syndrome associated with eosinophilic bronchitis. We studied nine consecutive referrals with chronic cough, sputum with > 10% eosinophils, normal spirometry, and normal methacholine airway responsiveness. Clinical assessment, sputum analysis, allergy skin tests and a methacholine inhalation test were performed at the first visit. Peak expiratory flow (PEF) was measured twice daily for 1 week followed by an adenosine monophosphate (AMP) inhalation test. Subjects were then treated with inhaled beclomethasone 0.4 mg twice daily for 7 days. Sputum analysis and measurement of methacholine responsiveness were then repeated. Excessive airway narrowing to methacholine was not present in any of the subjects. A methacholine plateau response was present in five subjects. Hyperresponsiveness to AMP was absent in six of the nine subjects, and PEF variability was not increased for eight subjects. Corticosteroid therapy led to a reduction in sputum eosinophil counts from 40.1 (SD 21.4)% to 4.0 (4.5)% but there was no significant change in metachromatic cell counts (0.8 SD 0.5% vs 0.6 SD 0.6%) or total cell counts. Methacholine responsiveness improved within the normal range in the three subjects in whom it could be determined. Chronic cough associated with eosinophilic airway inflammation can occur in the absence of variable airflow obstruction (asthma) and can improve after treatment with inhaled corticosteroid. This treatment can reduce the level of methacholine responsiveness within the normal range and reduces sputum eosinophils but not mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗

Central oxytocin mediates stress-induced tachycardia.

To address the role of oxytocin in the control of cardiovascular reactivity, we examined the effect of central injection of oxytocin, vasopressin and mixed base antisense oligodeoxynucleotides on stress-induced cardiovascular and endocrine changes. Antisense oligomers were injected into the paraventricular nucleus (PVN), 4 h prior to the stress test. The oxytocin antisense abolished the tachycardia produced by 5 min of shaker stress. The blood pressure and plasma oxytocin responses were not different between the groups. PVN levels of OT were reduced in the oxytocin antisense-treated group while brain stem levels were increased. These results demonstrate the importance of a specific peptide system, the PVN/oxytocin axis, in stress-induced tachycardia. Further, the data illustrate the effectiveness of short-term treatment with antisense oligomers on physiological responses.

Animals↗

Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats.

Observations that angiotensin-(1-7) [ANG-(1-7)] may oppose the vasoconstrictor actions of angiotensin II (ANG II) prompted an investigation of the effects of the heptapeptide on the maintenance of elevated blood pressure in spontaneously hypertensive rats (SHR). ANG-(1-7) (24 micrograms.kg-1.h-1) was infused into the jugular vein of 13-wk-old SHR (n = 64), Wistar-Kyoto (WKY, n = 50), and Sprague-Dawley (SD, n = 18) rats for 2 wk, with the use of osmotic minipumps. Blood pressure, fluid and electrolyte balance, plasma vasopressin, and urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured at days 2, 7, and 12 of the infusion. In SHR, ANG-(1-7) caused a sustained and significant reduction in plasma vasopressin concentration that was associated with an increase in urinary prostaglandin E2 and 6-keto-PGF1 alpha excretion at day 2 after the commencement of the infusion. These changes were accompanied by diuresis and natriuresis during the first 3 days of infusion in SHR but not in WKY or SD rats. Direct measurements of arterial pressure confirmed the lowering effect of ANG-(1-7) on systolic pressure of SHR on day 2 of treatment with a restoration of the pressure by days 7 and 12. These findings, along with our previous demonstration that ANG-(1-7) is an active depressor peptide in the intact animal, suggest that ANG-(1-7) may play a significant role as a vasodepressor system opposing the hemodynamic actions of ANG II in this genetic form of experimental hypertension.

Angiotensin I↗

Aging effects on human sympathetic neuronal function.

To study the effect of aging on human sympathetic nervous function, we applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20-30 yr) and older (aged 60-75 yr) healthy men. Mean plasma norepinephrine concentration was 66% higher in older men, attributable to 22% lower norepinephrine plasma clearance (P < 0.05) and 29% higher norepinephrine spillover to plasma (difference not statistically significant). Regional venous sampling disclosed that sympathetic outflow to all organs was not activated by aging. Renal norepinephrine spillover was normal in older men. Although spillover of norepinephrine from the heart was increased in older men, 21.1 +/- 11.4 ng/min compared with 11.4 +/- 8.6 ng/min (P < 0.05), diminished norepinephrine reuptake rather than increased cardiac sympathetic nerve firing was the most likely cause, although somewhat reduced intracardiac methylation of norepinephrine with aging also possibly contributed. The extraction of tritiated norepinephrine from plasma during transit through the heart was reduced, suggesting neuronal norepinephrine reuptake was lowered and overflow of the norepinephrine precursor dihydroxyphenylalanine and metabolites dihydroxyphenylglycol and 3-methoxy-4-hydroxy phenylglycol was normal, indicating that norepinephrine synthesis and release were not increased.

Adult↗

Effects of tetrodotoxin on osmotically stimulated central and peripheral vasopressin and oxytocin release.

Tetrodotoxin (TTX) was used to (1) distinguish between axonal and dendritic/somatic release of vasopressin (VP) and oxytocin (OT) within the supraoptic nucleus (SON) and (2) to determine whether neuronal inputs trigger intranuclear peptide release in the response to osmotic stimulation. Microdialysis was used to administer TTX (10(-6) M or 10(-4)M) bilaterally into the SON with simultaneous monitoring of central and peripheral peptide release and mean arterial pressure in urethane-anesthetized male rats. Osmotic stimuli were given via the microdialysis probe (1 M NaCl-artificial CSF) or injected intraperitoneally (3.5 M NaCl; 600 mu l/100 g b.w.) SON perfusion with TTX did not alter basal intranuclear VP or OT release or the intranuclear peptide response to direct NaCl stimulation of the SON. However, TTX treatment abolished the effect of peripheral osmotic stimulation on central peptide release. Basal plasma peptide levels were significantly reduced by TTX, e.g. decreases of 94.8 and 75.8% for VP and OT, respectively. TTX also blocked the peripheral endocrine and cardiovascular responses to both modes of osmotic stimulation. The TTX insensitivity of directly stimulated intranuclear release suggests nonsynaptic peptide release from dendrites and/or cell bodies. The ability of TTX to abolish the central peptide response to systemic osmotic stimulation demonstrates that intranuclear release is a part of a cascade produced by osmotic activation of multisynaptic pathways.

Animals↗