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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 19 recordsLinked to original sources

Excitotoxin paraventricular nucleus lesions: stress and endocrine reactivity and oxytocin mRNA levels.

Electrolytic lesion of the paraventricular nucleus (PVN) of the hypothalamus blocks the tachycardia response to stress. The current study examined the effects of chemical lesion of PVN parvocellular neurons on the cardiovascular and endocrine responses to stress and on the content of hypothalamic oxytocin (OT) mRNA levels. Acute footshock stress increased heart rate in both ibotenic acid lesion and control groups of animals; however, the tachycardia was significantly lower in animals with a PVN lesion than the controls. Lesion of the PVN also attenuated the increase in plasma OT induced by stress, 4-fold in the lesion group versus 20-fold for the controls. There was not a generalized decrease in hormonal responsiveness since the OT response to an osmotic challenge was exaggerated in the lesion group. There was no difference between the groups in the arterial pressure and vasopressin responses to acute stress. Neurotoxin lesions of the PVN also resulted in significant depletions of VP and OT in all levels of the spinal cord and decreased OT levels in the dorsal brainstem. Ibotenic acid lesions of the PVN resulted in no significant changes in OT mRNA in the PVN, SON and PP. In addition, the 48-h dehydration resulted in a significant increase in plasma OT and OT mRNA in the PVN. These data indicate that the parvocellular neurons of the PVN play a role in integration of cardiovascular and endocrine responses to both stressful and osmotic stimuli and provide further evidence that parvocellular OT and VP neurons project to the brainstem and spinal cord.

Animals

Basal and stimulated plasma atrial natriuretic peptide (ANP) concentrations and cardiac ANP contents in old and young rats.

To investigate the ability of the ageing heart to release atrial natriuretic peptide (ANP) we compared the response of awake, trained, chronically catheterized old (20-21 months) and young (4 months) rats to an acute, hypertonic saline challenge. There were no differences between young and old rats in basal plasma concentration of sodium (PNa; old: 141 +/- 3 meq/l; young: 143 +/- 3 meq/l) or ANP (old: 61 +/- 5 pg/ml; young: 67 +/- 12 pg/ml). Five minutes after acute saline challenge, PNa rose in both groups (old: 146 +/- 2 meq/l; young 149 +/- 1 meq/l) and approximately 3-fold increases in plasma ANP levels (182 +/- 24 pg/ml; young: 179 +/- 42 pg/ml). Hearts of old and young rats were assayed for atrial and ventricular ANP content. Atrial ANP levels were similar in old and young rats (13.5 +/- 3.6 vs. 24.9 +/- 8.7 micrograms/g atrial tissue), whereas ventricular ANP content was approximately 4-fold higher in old vs. young rats (153.7 +/- 39.3 vs. 47.5 +/- 6.4 ng/g ventricular tissue). Thus, the ageing rat heart responds equally as well as the young rat to an acute NaCl challenge.

Aging

Minimally invasive vulvar carcinoma: an indication for conservative surgical therapy.

It has been proposed that squamous carcinoma of the vulva with 1 mm or less of stromal invasion can be treated with local resection without inguinal node dissection. A retrospective review of 255 cases of stages I and II vulvar carcinoma demonstrated 24 cases of minimally invasive carcinoma. All cases were subjected to detailed chart review and pathologic confirmation. Mean age at diagnosis was 60 years. Seven patients had a preoperative diagnosis of preinvasive disease, ten had stage I disease, and seven had stage II disease. Fifteen cases had associated vulvar carcinoma in situ. Treatment consisted of local excision in 2 patients, radical wide excision in 11, hemivulvectomy in 5, and radical vulvectomy in 6. Eleven patients had either unilateral or bilateral inguinal node dissection. Five-year life-table survival was 89%. Four patients (17%) developed recurrent dysplasia and four (17%) developed invasive recurrences. One invasive recurrence was in an inguinal node in a patient previously treated with a hemivulvectomy and negative ipsilateral superficial node dissection. Univariate analysis revealed no statistically significant associations between recurrence and age, symptom duration, margin status, location, FIGO stage, or coexisting VIN. Large areas of coexisting dysplasia and variable gross appearance make meaningful application of FIGO staging criteria difficult in lesions with minimal focal invasion. Wide excision or radical wide excision of lesions with "high-risk" VIN or those showing less than or equal to 1 mm of stromal invasion on biopsy is adequate therapy. If final pathologic review demonstrates deeper invasion, a selective lymph node dissection can be performed as a second procedure. Careful surveillance with liberal use of colposcopy and biopsies is indicated in these patients.

Adult

The effect of prolonged cisplatin-based chemotherapy on progression-free survival in patients with optimal epithelial ovarian cancer: "maintenance" therapy reconsidered.

From 1978 until 1988, 116 patients with epithelial ovarian cancer were entered onto one of three consecutive prospective clinical trials involving cisplatin-based combination chemotherapy. They had the following characteristics: (1) stage III or IV disease, (2) grade 2 or 3 tumors, and (3) optimally debulked tumors (residual disease < or = 2 cm). The purpose of the study was to investigate the influence of duration of chemotherapy on survival. The treatment plans were as follows: Trial 1, 12 cycles of cisplatin/melphalan (43 patients); Trial 2, 12 cycles of cisplatin/cyclophosphamide (24 patients); and Trial 3, 6 cycles of cisplatin/cyclophosphamide (49 patients). The total dose of cisplatin was 60 mg/m2 in the first trial and 50 mg/m2 in the second and third trials. Median survival times for the three groups were 58, 29, and 35 months, respectively (NS). Median progression-free survival (PFS) times were 37, 23, and 15 months, respectively (P = 0.0008). Combining patients from the first two trials, the median PFS for patients receiving 12 planned cycles of chemotherapy was 30 months versus 15 months for patients receiving 6 planned cycles (P = 0.0004). Using a forward stepwise Cox proportional hazard model, the use of 12 cycles of therapy and melphalan predicted increased PFS (P = 0.0001 and P = 0.0002, respectively). In view of these results, the lack of published data supporting the superiority of 6 over 12 cycles of chemotherapy, and the rather recent availability of less toxic maintenance therapy (i.e., carboplatin), we believe that a multiinstitutional trial comparing the 6-cycle regimen with more prolonged chemotherapy is justifiable.

Adult

Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide.

Between July 1986 and February 1991, 10 patients with small cell carcinoma of the cervix were prospectively treated with combination chemotherapy using cisplatin (50 mg/m2) and doxorubicin (50 mg/m2) on Day 1 and etoposide (75 mg/m2) on Days 1-3. All patients underwent an extensive pretreatment metastatic survey and had histologic confirmation of small cell carcinoma prior to entry in the study. Seven patients had stage Ib, 1 stage IIa, and 2 stage IIb. Nine patients received chemotherapy at primary presentation and 1 was treated for recurrent disease. In 6 cases, chemotherapy was given and then followed by radiation therapy. Three patients received chemotherapy following radical hysterectomy and 1 was treated for persistent disease after radiation therapy. Patients received a median of four courses of chemotherapy (range 2-6). Neutropenia was the dose-limiting toxicity with 9 of 10 patients requiring a dose reduction. There was no instance of neutropenic sepsis or other major toxicity. Seven patients had measurable disease at the start of therapy. Three of these patients had a complete clinical response, 1 had a partial response, 2 had stable disease, and 1 had progressive disease (response rate = 57%). The median survival was 28 months. At the time of this report, 4 of 6 patients with stage Ib cancers given primary treatment on this regimen remained free of disease (with 28 months the median follow-up). Our pilot study indicates that this chemotherapy regimen has activity in small cell carcinoma of the cervix and should be further evaluated as an adjuvant to surgery or radiation in patients with early stage disease.

Adult

Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC).

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.

Adult

Superficially invasive squamous cell carcinoma of the cervix.

The microscopic pathologic features of early invasive squamous cell cervical carcinoma are used as determinants for the treatment of these lesions. This study is a retrospective review of 180 patients with squamous cell cervical carcinoma with invasion to a depth of 5 mm or less. Invasion of less than or equal to 1 mm, greater than 1 but less than or equal to 3 mm, greater than 3 but less than or equal to 5 mm was noted in 37, 84, and 59 patients, respectively. The median follow-up was 6.5 years. Four (2.2%) patients developed carcinoma in situ of the vagina and four (2.2%) patients progressed to invasive squamous carcinoma. Pelvic lymph node metastases were rare (1%). No patient has died from recurrent disease. Analysis of numerous clinical and pathological variables identified no risk factors for recurrence. Most (54/68) patients with tumor invading beyond 3 mm or with tumor demonstrating vascular invasion were treated by traditional "radical" methods. This limited a meaningful analysis of the risk of conservative treatment. The reliability of using the existing definitions of microinvasive disease for the guidance of treatment remains controversial. Further clarification may be rendered only with prospective clinical-pathologic studies performed by cooperative groups.

Adult

Bulky endocervical carcinoma: a 23-year experience.

Between 1962 and 1985, 371 patients had initial treatment for bulky endocervical carcinomas of the uterine cervix at The University of Texas M.D. Anderson Cancer Center. All patients had concentric expansion of the cervix by tumors that measured at least 6 cm in greatest transverse diameter. Of the 361 patients treated with curative intent, 211 (57%) had FIGO Stage I disease that was believed to be confined to the uterus, 59 (16%) had FIGO Stage IIA disease, and 101 patients (27%) had FIGO Stage IIB disease. Median follow-up time of surviving patients was 130 months. Actuarial survival rates of 361 patients treated with curative intent were 54% and 48% at 5 and 10 years, respectively. The actuarial pelvic disease control rate was 76% at 10 years. Patients whose tumors were less than 8 cm in maximum diameter (279 patients) had a better survival rate than those with tumors greater than or equal to 8 cm in diameter (92 patients) (p less than 0.01). Of the 282 patients who underwent lymphangiography, survival rate was significantly better for those with negative studies than it was for the 113 patients (40%) with positive or suspicious studies (p less than 0.01). There was no correlation between FIGO stage and survival rate (p = 0.64) or pelvic control rate (p = 0.59). Of patients treated with curative intent, treatment was by radiation alone (RT) in 244 (68%) or by radiation followed by hysterectomy (RT+S) in 117 (32%). Although there has been an overall shift in policy away from the use of adjuvant hysterectomy during the past decade, many patient selection factors also influenced the choice of treatment during the study years, resulting in a significantly higher proportion of patients with adverse prognostic features in the RT group. Patients chosen for treatment with RT alone had a greater likelihood of having tumors greater than or equal to 8 cm (p = 0.03), FIGO stage IIB (p less than 0.01), positive lymphangiogram (p = 0.02), and persistent palpable parametrial disease after external radiotherapy (p less than 0.01). Patients treated with RT alone also had a lower overall survival rate at 10 years than patients treated with RT+S (45% vs 64%, p less than 0.01). Although multivariate analysis suggested that treatment had an independent influence upon survival rate, it was difficult to draw firm conclusions about the value of adjuvant surgery because of the numerous biases in patient selection, some of which may have been difficult to quantify.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Central and systemic oxytocin release: a study of the paraventricular nucleus by in vivo microdialysis.

The mechanisms controlling central and systemic oxytocin (OT) release were examined using in vivo microdialysis of the paraventricular (PVN) region. Dialysate and plasma samples were collected from conscious male rats and stimuli were administered via the dialysate fluid. Characterization studies showed that microdialysis was a viable technique for the study of peptide secretion in the conscious animal. OT was consistently detected in the PVN dialysate and a partially purified extract crossreacted in parallel fashion with the synthetic peptide. In vitro studies showed that peptide recovery was positively correlated with the pore size of the dialysis membrane and that there was an inverse relationship between flow rate and recovery. Hypertonic saline administered centrally caused an increase in dialysate and plasma oxytocin while the intravenous injection affected only plasma oxytocin. The excitatory amino acid, glutamate (0.05-0.5 M), caused an increase in plasma, but not dialysate oxytocin, while depolarization with potassium chloride (0.05-0.15 M) had no significant effects. Histological examination showed that the dialysis probe was located in the rostral, lateral PVN. Our results show that in vivo microdialysis provides a method for the delivery of drugs into specific brain regions as well as a useful technique for the evaluation of in vivo neuropeptide release.

Analysis of Variance

When loyalties are divided between teachers and patients.

Three situations are described where a junior doctor is required by his consultant to do something that he thinks is not in the patient's best interests. The dilemma is explored from the perspective of patients' interests being the doctor's first concern; of the importance of respect for medical teachers, and of the implications of an apprenticeship model of postgraduate medical training.

Consensus

Alterations in oxytocin prohormone processing during early development in the fetal sheep.

Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma.

Animals

Sinoaortic denervation does not increase cardiovascular/endocrine responses to stress.

Sinoaortic baroreceptor denervation is reported to produce exaggerated centrally derived cardiovascular and endocrine responses. We examined the effect of sinoaortic denervation (SAD) on the cardiovascular and endocrine responses to two acute stressors, footshock and immobilization, in male Sprague-Dawley rats. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and plasma levels of oxytocin (OT) and vasopressin (VP). Baseline MAP was elevated in the SAD group (approximately 25 mm Hg) and footshock stress increased arterial pressure equivalently in both groups. This stress caused tachycardia and increased plasma OT, with a tendency for the SAD group to show blunted responses. Immobilization increased HR but caused no change in MAP and no significant difference between the groups. This form of stress also increased plasma OT, and again the SAD group showed a diminished response. Plasma VP was not significantly altered by either stressor. The results of these studies indicate that SAD does not uniformly increase the cardiovascular and endocrine responses to all stressors or centrally derived stimuli. These results also suggest that the lack of an increase in plasma VP is not related to baroreceptor-mediated inhibition of secretion under stressful conditions.

Animals

Presymptomatic testing for Huntington's disease in Wales 1987-90.

Between 1987 and 1990 a large series of at-risk individuals has been referred to our Huntington's disease (HD) presymptomatic testing programme. A detailed protocol for assessment and counselling has been followed. Out of 238 serious inquiries, 36% were potentially suitable for the testing programme, but 19% chose not to continue. Reasons for exclusion included the presence of clinical features of HD and being under the age of 18 years. Out of 40 final results given to 38 individuals, 23 indicated a lowered risk, 11 an increased risk, while five results were uninformative, two of these becoming informative on repeat testing. This series contained more women than men, and was disproportionately from the higher socio-economic groups. Motives for requesting a test principally related to child-bearing, informing existing children, and planning for the future. No significant psychiatric symptoms have been reported in the short term, but difficult counselling problems were presented by the high proportion of applicants who already showed clinical signs of HD. It is concluded that a detailed counselling protocol is essential in testing for HD, as many applicants are ill-prepared; this will assume even greater importance when the HD gene is identified and a test for specific mutations is available. The experience of presymptomatic testing for HD provides important general lessons which are likely to be applicable to other inherited neurological and psychiatric disorders.

Adaptation, Psychological

The ABCs of DRGs.

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Abstracting and Indexing

Reasons for inappropriate simple hysterectomy in the presence of invasive cancer of the cervix.

We evaluated 148 women who had had simple hysterectomy in the presence of invasive cervical cancer between the years 1973-1987. Two had microinvasive squamous carcinoma for which hysterectomy was not a planned procedure. The remaining 146 women all had either adenocarcinoma or squamous carcinoma exhibiting greater than 3 mm of stromal invasion of lymph-vascular space involvement. Medical records were reviewed retrospectively to determine the reasons for hysterectomy. Causes of inappropriate hysterectomy were as follows: inadequate evaluation of an abnormal Papanicolaou smear or cervical biopsy (21%), failure to perform an indicated conization (12%), deliberate hysterectomy for grossly invasive cancer of the cervix (11%), lack of preoperative Papanicolaou smear (7%), conization margins positive or not evaluated (7%), misreading of pathology results (5%), emergent operation because of bleeding (3%), failure to check cytology preoperatively (1.5%), and failure to biopsy a gross cervical lesion (1.5%). The remaining 31% of cases had normal or inflammatory Papanicolaou smears and negative cervical examinations. Although 93% of this latter group complained of abnormal bleeding, 78% did not have endocervical or endometrial sampling preoperatively. Despite the increasing emphasis on cervical cancer screening, the number of referrals following hysterectomy performed in the presence of cervical carcinoma is not decreasing. Most cases could be avoided by careful adherence to well-established guidelines for cervical cancer detection.

Adenocarcinoma

Pelvic exenteration in the elderly patient.

Advanced age is frequently considered a contraindication to radical exenterative surgery. We reviewed the outcomes of 63 patients age 65 years or older who underwent pelvic exenteration between 1960-1991 at The University of Texas M. D. Anderson Cancer Center. Sixty-three percent had preexisting medical illnesses. Major or potentially life-threatening complications were noted in 38% of the patients. An additional 38% experienced minor complications. Sixty percent experienced one or more infectious complications, including pyelonephritis, wound infection, sepsis, and flap necrosis. When both major and minor complications were considered, infectious morbidity was the single largest category. Although they are not life-threatening, nonspecific infectious morbidity and transient confusion were the most frequent individual complications, occurring in 26 and 24% of patients, respectively. Twenty-four percent of the patients experienced no complications. Thirty-four percent of the postoperative survivors suffered late major morbidity. Operative mortality was 11%; multisystem failure was the most frequent cause of death. After a mean follow-up of 4 years, 22 patients were alive with no clinical evidence of disease. Twenty-one patients died of recurrent disease, with a median time to recurrence of 9.6 months. The 5-year survival rate for the group was 46%. In comparison, 363 patients younger than age 65 who underwent exenteration during the same period experienced an operative mortality rate of 8.5% and a 5-year survival rate of 45%, neither of which were significantly different from the rates found for the older group (P = .51 and .52, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors