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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 91 records · Page 5Linked to original sources

Serous borderline tumors of the ovary with noninvasive peritoneal implants.

BACKGROUND: The authors conducted this study to update their experience with patients who have ovarian serous borderline tumors with noninvasive peritoneal implants, with the objectives of gaining additional insight into the biologic behavior of these tumors and understanding better the effects of postoperative treatment. METHODS: Seventy-three patients who had ovarian serous borderline tumors with noninvasive peritoneal implants were identified in a retrospective review. Major end points selected for analysis were surgicopathologic response, time to relapse, type of relapse, progression free survival, and overall survival. Univariate and multivariate regression analyses were also performed. RESULTS: The median follow-up time was 10.3 years. Of 20 patients with macroscopic residual disease at completion of initial surgery who subsequently underwent second-look surgery, 3 (15%) had a response to chemotherapy. Twenty-two of 73 patients (30%) either developed progressive disease or had a relapse. The median time from the date of diagnosis to relapse was 7.1 years. Tissue was available from 20 of the 22 patients who had a relapse; 14 (70%) had invasive low grade serous carcinomas, and 6 (30%) had recurrent borderline tumors. Age was the only factor studied that had a significant influence on survival (P = 0.03). In both univariate and multivariate proportional hazards models, age and residual disease were found to be of borderline significance in predicting cancer specific survival. CONCLUSIONS: Approximately 30% of patients who have ovarian serous borderline tumors with noninvasive peritoneal implants will develop progressive or recurrent tumors, most commonly serous carcinomas. The presence of macroscopic residual disease appears to be a predictor of disease free survival. In this study, however, the authors were unable to elucidate the role of postoperative therapy or determine criteria for selecting patients for such therapy.

Adolescent↗

Plasma oxytocin levels in autistic children.

BACKGROUND: Social impairments are central to the syndrome of autism. The neuropeptide oxytocin (OT) has been implicated in the regulation of social behavior in animals but has not yet been examined in autistic subjects. METHODS: To determine whether autistic children have abnormalities in OT, midday plasma samples from 29 autistic and 30 age-matched normal children, all prepubertal, were analyzed by radioimmunoassay for levels of OT. RESULTS: Despite individual variability and overlapping group distributions, the autistic group had significantly lower plasma OT levels than the normal group. OT increased with age in the normal but not the autistic children. Elevated OT was associated with higher scores on social and developmental measures for the normal children, but was associated with lower scores for the autistic children. These relationships were strongest in a subset of autistic children identified as aloof. CONCLUSIONS: Although making inferences to central OT functioning from peripheral measurement is difficult, the data suggest that OT abnormalities may exist in autism, and that more direct investigation of central nervous system OT function is warranted.

Autistic Disorder↗

Stress increases oxytocin release within the hypothalamic paraventricular nucleus.

Evidence indicates that the hypothalamic paraventricular nucleus (PVN) and oxytocin (OT) neurons in particular play a role in the physiological response to stress. Microdialysis (MD) experiments were performed to determine whether OT is released into the PVN during shaker stress. Male rats were prepared with venous catheters and PVN guide cannulae. OT and vasopressin (VP) release into PVN and peripheral blood were measured under basal conditions and during and after shaker stress (10 min at 110 cycles/min). Stress produced a specific increase in PVN and plasma OT. Dialysate OT levels were 0.3+/-0.1, 2.8+/-1.2 and 1.3+/-0.6 pg/sample (control, stress and recovery, respectively). Plasma OT was significantly increased during stress (3.7+/-1.2 vs. 11.7+/-2.3 pg/ml, basal vs. stress, respectively). When MD probes were located outside the PVN, there was no increase in OT release, demonstrating site specificity. Stress produced no change in VP levels, either in dialysate or plasma. These results show that OT, but not VP, is released into the PVN and peripheral blood in response to shaker stress. The data raise the possibility that local release of OT into the PVN plays a role in the neuroendocrine stress cascade.

Animals↗

Abnormalities in the stride length-cadence relation in parkinsonian gait.

The purpose of this investigation was to clarify abnormalities in the stride length-cadence relation in gait hypokinesia in Parkinson's disease (PD). A second aim was to investigate the effect of levodopa medication on the foot-step pattern. In the first experiment, 20 subjects with idiopathic PD and 20 age-, sex-, and height-matched controls performed a series of 10 m walking trials at cadence rates ranging from 40 steps/min to 180 steps/min. Cadence rates were set by an electronic metronome, and gait patterns were measured by using a footswitch stride-analyzer system. By instructing subjects to concentrate on walking in time to the metronome beat, the baseline stride length could be monitored for a range of velocities with the compensatory effects of cadence removed. Linear-regression analysis revealed that the mean slope for the regression of stride length against cadence was not different from normal in PD, although there was a statistically significant difference in mean intercept between the PD group (0.25) and the control group (0.59); [t (19) = -4.76; p = 0.0001]. The second experiment evaluated the effects of levodopa on stride-length regulation in 10 subjects with idiopathic PD on average 45 min before and after the first morning dose was administered. There was a statistically significant increase in stride length for all cadence rates from premedication to postmedication phases and the maximal stride length was achieved at higher cadence rates after medication. The slope of the regression of stride length against cadence did not alter according to medication status, although the mean intercept was significantly lower before levodopa (-0.06) compared with after levodopa (0.27); [t (9) = -3.83; p = 0.004]. These results suggest that defective scaling of stride length underlies gait disturbance in PD.

Aged↗

A phase II study of prolonged oral etoposide in advanced or recurrent carcinoma of the cervix.

OBJECTIVE: To evaluate the efficacy and toxicity of prolonged oral etoposide as single agent chemotherapy in patients with advanced or recurrent carcinoma of the cervix. METHODS: Between May 1991 and February 1993, 44 patients with advanced or recurrent carcinoma of the cervix were entered onto this study. Patients were eligible if they had received no more than two prior cytotoxic regimens. The initial dose of etoposide was 37.5 mg/m2 administered orally on a daily basis on days 1-21 of a 28-day cycle. Subsequent doses were unchanged, reduced, escalated, or omitted according to toxicity. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria. RESULTS: Forty-four patients were evaluable for response and toxicity. The overall response rate was 9.1% (2 CR, 2 PR). In patients with no prior chemotherapy the response rate was 4/25 compared to 0/19 for those who had prior therapy. The mean response duration was 2.7 months and the median survival from treatment for all patients was 7.7 months. The major toxicity was granulocytopenia, with 11% of patients having grade 3 or 4 toxicity. Gastrointestinal toxicity of some degree occurred in 11% of patients, and alopecia was universal. CONCLUSION: Prolonged oral etoposide has limited activity in advanced or recurrent carcinoma of the cervix. Its use as palliative therapy for this disease is not indicated.

Administration, Oral↗

A phase I study of a daily x3 schedule of intravenous vinorelbine for refractory epithelial ovarian cancer.

PURPOSE: To determine the toxicity and activity of intravenous vinorelbine given daily for 3 consecutive days every 3 weeks in patients with platinum-resistant epithelial ovarian cancer. PATIENTS AND METHODS: Between September 1994 and October 1995, 23 women with refractory epithelial ovarian cancer were entered onto this phase I study. All patients had measurable disease and platinum-resistant tumor, and prior therapy was limited to a maximum of two prior regimens. Nineteen (83%) were assessable for toxicity and 20 (87%) were assessable for response. Vinorelbine was administered intravenously daily for 3 consecutive days; this was repeated every 21 days. The starting dose was 20 mg/m2 daily x3, with dose escalation by 5 mg/m2 daily x3. Dose-limiting toxicity (DLT) was defined as grade 4 granulocytopenia for >3 days, grade 4 thrombocytopenia, neutropenic fever, or grade 3 or greater nonhematologic toxicity. The maximal tolerated dose (MTD) was defined as the highest dose level at which <50% of patients developed a DLT. Once the MTD of vinorelbine without granulocyte colony-stimulating factor (filgrastim) support was defined, dosing was begun at the MTD level and administration of 5 microg/kg filgrastim was initiated on day 4 and continued until WBC counts reached >10,000/microL. Clinical response, progression-free survival, and survival were also determined. RESULTS: Nineteen patients evaluable for toxicity received a total of 135 cycles of vinorelbine. The major DLT was neutropenia. The MTD of vinorelbine without filgrastim support was established as 20 mg/m2 daily x3. The MTD of vinorelbine with filgrastim support was established as 25 mg/m2 daily x3. Of 20 patients evaluable for response, 2 patients (10%) had a complete response and 4 (20%) had a partial response, for an overall response rate of 30%. CONCLUSION: These results warrant further study of vinorelbine in patients with platinum-resistant epithelial ovarian cancer. However, further study of the daily x3 schedule may not be warranted because of failure to achieve higher weekly dose intensity and because of nonhematologic toxicity in the form of intense bone pain.

Adult↗

Depressor role of angiotensin AT2 receptors in the (mRen-2)27 transgenic rat.

The (mRen-2)27 transgenic rat (Tg+), a hypertensive model dependent on increased expression of the renin angiotensin system, was used to explore the role of angiotensin AT2 receptors in the control of cardiovascular and renal excretory function. Experiments tested the effect of blockade of AT2 receptors on basal blood pressure and the pressor, renal excretory, and vasopressin (VP) responses to intravenous hypertonic saline (HS). Chronically catheterized male Tg+ and normotensive Sprague-Dawley rats (Tg-) were housed in metabolic cages. PD123319 (AT2 antagonist) or 0.9% NaCl was given by intravenous bolus (3 mg/kg) followed by infusion (50 microg/kg/ min). Blockade of AT2 receptors both in Tg+ and Tg- rats produced no change in basal mean arterial pressure (MAP). The pressor response to intravenous HS (10% NaCl; 325 microL/100 g body weight) was significantly greater in Tg+ than in Tg- rats. PD123319 did not affect the peak rise in MAP but extended the time course of the response only in Tg+ rats. MAP was increased 39+/-4 and 36+/-3 mm Hg in Tg+ rats with and without the antagonist as compared to 20+/-2 and 24+/-2 mm Hg in Tg- rats. In the antagonist-treated Tg+ rats, MAP remained elevated for 60 min as compared to 5 min for Tg+ control or Tg- control or antagonist-treated rats. Hypertonic saline caused similar increases in plasma Na, VP, and in the natriuretic and diuretic responses in both Tg+ and Tg- rats, with no effect of antagonist treatment. These results demonstrate that Tg+ rats are sensitive to the effects of peripheral osmotic stimulation showing an increased pressor response, not attributed to greater secretion of VP or diminished natriuresis. These data also suggest that angiotensin AT2 receptors play a depressor role in the sodium-induced pressor response in this model.

Angiotensin Receptor Antagonists↗

Association of obsessive-compulsive disorder and pathological gambling with Huntington's disease in an Italian pedigree: possible association with Huntington's disease mutation.

This paper describes a pedigree with Huntington's disease (HD), in which three cases of obsessive-compulsive disorder (OCD) and two cases of pathological gambling (PG) were identified. The mutation analysis of the HD gene was carried out in the examined individuals who were at risk for HD. In fact, OCD and PG only occurred in carriers of the HD expansion. The possible implications of this finding are discussed.

Adolescent↗

Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry.

OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK.

Acyl-CoA Dehydrogenase↗

Cardiovascular, endocrine, and body fluid-electrolyte responses to salt loading in mRen-2 transgenic rats.

We previously demonstrated that mRen-2 transgenic [Tg(+)] rats are sensitive to chronic high NaCl intake, showing increased arterial pressure and vasopressin (VP) secretion. In this study, we determined the effect of a chronic osmotic challenge, 4 days of drinking 2% NaCl, on direct arterial blood pressure, heart rate, fluid-electrolyte balance, circadian rhythm of mean arterial pressure (MAP), and changes in plasma VP and catecholamines. Under baseline conditions, male Tg(+) rats showed a significant shift in the peak in circadian MAP into the light portion of the day-night cycle. Substitution of 2% NaCl for drinking water caused a rapid increase in MAP, 20 +/- 5 mmHg in Tg(+) rats within 6 h. Whereas the amplitude of circadian MAP fluctuations increased in salt-loaded Tg(+) rats, there was no significant change in the circadian timing of peak MAP with salt loading. Tg(+) rats showed exaggerated osmotic-induced increases in plasma VP, norepinephrine (NE), and epinephrine (Epi) compared with Tg(-) rats. Plasma NE and Epi were increased two- and fourfold, respectively, in the hypertensive rats with no significant change in the Tg(-) rats. Intravenous administration of a VP antagonist did not alter arterial pressure in either Tg(+) or Tg(-) rats. Tg(+) and Tg(-) rats showed a positive sodium balance with no significant difference observed between the groups. Tg(+) rats showed a significant increase in salt consumption, plasma sodium, osmolality, and hematocrit, accompanied by a negative water balance. We conclude that Tg(+) rats are sensitive to acute and chronic osmotic stimuli in terms of blood pressure, fluid-electrolyte balance, and plasma VP and catecholamines. Whereas elevated plasma VP does not contribute to the hypertensive response, increased sympathetic drive may mediate the salt-induced blood pressure changes in this model.

Animals↗

Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix.

PURPOSE: To evaluate the efficacy and toxicity of intravenous vinorelbine as single-agent chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between August 1993 and July 1995, 35 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Patients had received no prior therapeutic chemotherapy. The initial dose of vinorelbine 30 mg/m2 was administered as a weekly intravenous infusion. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group (GOG) and World Health Organization criteria, respectively. RESULTS: Thirty-three of 35 patients were assessable for response and 35 of 35 for toxicity. The overall response rate was 18% (one complete response [CR], five partial responses [PR]). The mean response duration was 5.2 months and the median survival from treatment for all patients was 11.0 months. The major toxicity was leukopenia, with 61% of patients who had grade 3 or 4. Gastrointestinal and neurotoxicity were infrequent and mild. CONCLUSION: Vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Further studies of combination regimens with this agent are justified in this patient population.

Adult↗

Chemotherapy for cervical carcinoma: factors determining response and implications for clinical trial design.

PURPOSE: To identify characteristics that predict response to chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between January 1986 and May 1996, 190 chemotherapy-naive patients with advanced or recurrent squamous cell carcinoma of the cervix not amenable to curative radiation therapy or surgery were treated on 14 different chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were retrospectively reviewed for patient demographics, tumor and treatment characteristics, and patterns of response and survival. RESULTS: Of 190 patients, 22 had advanced or persistent disease and 168 had recurrent disease. Patients were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens. The overall response rate was 20.0% (4.2% complete response; 15.8% partial response), with a median response duration of 4.8 months. Race, socioeconomic class, tumor stage and grade, mode of primary treatment, time from primary diagnosis to disease recurrence, initial performance status, and use of platinum-based therapy were not significant predictors of response. Age at time of chemotherapy (P=.001) and site of recurrence (P=.044) were significant determinants by multivariate analysis. Patients who were older were more likely to respond to therapy, and the response rate for patients in whom disease recurred outside the irradiated field was 25.2%, compared with a 5.3% response rate for patients with recurrent disease limited to a previously irradiated field. CONCLUSION: The site of disease recurrence and patient age should be taken into account when designing chemotherapy trials and also when considering chemotherapy in the patient with recurrent cervix cancer.

Adult↗

Panel discussion. Data needs in cancer.

A prospective, comprehensive outcomes database was recently initiated by the National Comprehensive Cancer Network (NCCN) after a 2-year study to test data collection methods and systems. It started with data on 400 patients with newly diagnosed breast cancer at five NCCN sites, and over the next 3 years is projected to grow to include more than 12,000 patients with common cancers treated at all eligible NCCN sites. Among the goals of the database are: 1) to establish the capability to select, analyze, and report patterns of care and outcomes; 2) to allow NCCN members to assess their compliance with NCCN clinical practice guidelines and benchmark their performance against the rest of the NCCN; 3) to establish a true databased continuous quality improvement program; 4) to support clinical disease-oriented research and methodologic studies; and 5) to provide the NCCN with a vehicle for forging partnerships with others in the health-care field, such as the pharmaceutical industry, regulatory agencies, and accrediting bodies. Many of those potential partners were represented on this panel. Panelists discussed the data needs of their organizations, what they are doing to meet those needs, and how a comprehensive database will ultimately help improve patient care.

Aged↗

Methodologic issues in the measurement of oxytocin in human neonates.

Oxytocin's (OT) role in the onset and maintenance of labor and in the letdown reflex is well known. OT also has been recognized as a neurotransmitter having functions in the central nervous system, including an influence on behavior (e.g., initiation of maternal behavior). This research was conducted to (1) evaluate whether human tactile contact in the human newborn would increase urine OT levels and alter infant behavioral state, and (2) determine the reliability of measuring OT in human infant urine. Although the data did not support the hypotheses, it was noted that OT levels significantly decreased in infants who cried during the study period and that there was no correlation between infant's chronologic age and OT levels. The findings illustrate several methodologic and measurement problems in the study of OT in human infants and that urine sampling in the neonate is not the most reliable method to evaluate change in OT levels. Some general issues concerning research with human infants also are discussed. Further research is recommended to document baseline levels of OT in neonates and to explore the use of salivary OT to measure short-term responses to interventions.

Crying↗

High-performance liquid chromatographic analysis of complex N-linked glycans derivatized with 2-aminoacridone.

2-Aminoacridone (2-AMAC) has been used to derivatize mixtures of N-linked oligosaccharides released from alpha(1)-acid glycoprotein and immunoglobulin G. In each case, the HPLC profile obtained for the derivatized glycans was compared to that obtained after digestion with sialidase and a two-enzyme array system made up of sialidase and alpha-fucosidase, prior to derivatization by 2-AMAC. These studies are rapid and provide a wealth of preliminary information about the degree of sialylation and core fucosylation in the corresponding parent glycans. Moreover, collection of glycans from one single injection has provided enough material for molecular weight determination by MALDI-MS analysis. In this study we have also carried out limited MS-MS studies on enriched fractions of 2-AMAC-glycans using a nanospray orthogonal quadrupole time-of-flight mass spectrometer.

Aminoacridines↗

Renal transplantation in children; the Auckland experience 1980-96.

AIM: To review the experience and outcome of renal transplantation in children who received a renal allograft at the Auckland Children's Hospital between January 1980 and June 1996. METHODS: Retrospective review of patient records and access to data collected through the ANZDATA Registry. Forty one renal transplants were undertaken in 39 children. Prednisone and Azathioprine were the mainstay of the immunosuppressive regimen from 1980 to 1985, then cyclosporin A was introduced in 1986. Median age of first graft was 11 years (range 1.6-14 years). There were 34 living related and 7 cadaveric grafts and 17 males and 22 females. Thirteen children (33%) had a primary glomerular disorder as the cause of renal failure. Another 9 (28%) had reflux nephropathy and a further 8 (18%) had congenital renal dysplasia/hypoplasia either as primary cause or secondary to lower urinary obstruction. RESULTS: Survival analysis showed that 93% of grafts were functioning at 12 months and 73% were still functioning at 5 years. Longest surviving transplant is 16 years. Ten primary grafts were lost with the most common cause being chronic rejection, accounting for 50% of all transplants lost. Recurrence of primary disease was the second most common (4 of 13) cause of graft failure. There was one malignancy in this series with a child developing a Kaposi's sarcoma. CONCLUSIONS: Renal transplantation is a successful treatment of endstage renal failure in children. Chronic rejection remains a major cause of graft loss and better immunosuppressive strategies are required to deal with this problem.

Adolescent↗

Cognitive neuropsychological analysis and neuroanatomic correlates in a case of acute anomia.

We describe an analysis of lexical processing performed in a patient with the acute onset of an isolated anomia. Based on a model of lexical processing, we evaluated hypotheses as to the source of the naming deficit. We observed impairments in oral and written picture naming and oral naming to definition with relatively intact semantic processing across input modalities, suggesting that output from the semantic system was impaired. In contrast to previous reports, we propose that this pattern represents an impairment that arises late in semantic processing prior to accessing mode-specific verbal and graphemic output lexicons. These deficits were associated with a lesion in the posterior portion of the middle temporal gyrus or area 37, an area of supramodal association cortex that is uniquely suited as a substrate for the multimodal deficit in naming.

Aged↗