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Biomedical subjects

M P Sullivan

Publications and source records attributed to M P Sullivan.

At least 19 recordsLinked to original sources

Correlation between micturitional urethral pressure profile and pressure-flow criteria in bladder outlet obstruction.

PURPOSE: We correlate micturitional urethral pressure profilometry with pressure-flow diagnoses of outlet obstruction. MATERIALS AND METHODS: Urodynamic evaluation was done of 86 consecutive men with voiding symptoms. Obstruction criteria were a micturitional urethral pressure profile (MUPP) gradient greater than 5 cm. water, Schäfer's linear passive urethral resistance relation (PURR) greater than grade 1 and Abrams-Griffiths nomogram. RESULTS: Interpretable results were completed in 99% of the patients undergoing MUPP and 60% undergoing pressure-flow studies (p < 0.00001). MUPP diagnosis agreed with PURR (p = 0.0015) and Abrams-Griffiths nomogram results (p = 0.00004). MUPP gradients correlated well with PURR (r = 0.70, p < 0.00001). Using optimum cutoff values (11 cm. water), the sensitivity of MUPP was 83%, specificity 82% and positive predictive value 94%. CONCLUSIONS: MUPP correlates well with and yields interpretable results more often than pressure-flow studies.

Aged

Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism.

The precise role of the American Urological Association (AUA) symptom index in the management of benign prostatic hyperplasia (BPH) is not well established. The AUA symptom index has been recommended only for quantifying the symptoms of BPH but not for its diagnosis. However, to our knowledge the ability to discriminate obstructive from nonobstructive BPH using the AUA symptom index has never been investigated. To establish the relationship between the AUA symptom index and prostatic obstruction 125 men (mean age 67.7 +/- 8.4 years) with voiding dysfunction presumably related to BPH were analyzed. Patients were given the AUA symptom questionnaire, following which video urodynamic studies were done, including micturitional urethral pressure profilometry for specifically diagnosing outlet obstruction. The patients were divided into 2 groups: group 1-78 with primary BPH dysfunction and group 2-47 with prostatism of ambiguous etiology. The mean AUA symptom index in group 1 (15.5 +/- 7.1) was not statistically different from that in group 2 (14.8 +/- 7.9). In both groups the mean AUA symptom index in the patients with obstruction (15.3 +/- 7.2 for group 1 and 13.9 +/- 7.9 for group 2) was not statistically different from that in the nonobstructed group (17.0 +/- 5.4 and 16.1 +/- 7.9, respectively). Of the severely symptomatic patients 22% did not have obstruction whereas all mildly symptomatic patients did. No significant correlations were found between the severity of obstruction and the AUA symptom index in either group. These observations indicate that the AUA symptom index cannot discriminate obstructed from nonobstructed BPH cases, not all severely symptomatic BPH patients will have outlet obstruction, a significant proportion of mildly symptomatic BPH patients can have outlet obstruction and voiding dysfunctions in elderly men, regardless of the etiology, produce similar symptoms.

Aged

Continuous occlusion test to determine detrusor contractile performance.

PURPOSE: A study was conducted to determine the merits of the continuous occlusion test as a method of detrusor contractility assessment by comparing it with other stop tests and with contractility derived from pressure-flow analysis. MATERIALS AND METHODS: The continuous occlusion test was performed in elderly men by occluding the bladder outlet before the onset of a detrusor contraction and it was repeated to assess reproducibility. The magnitude of the isovolumetric contraction, maximum slope of the detrusor contraction, and duration of detrusor activation were determined. Voluntary and mechanical stop tests were performed during the mid voiding phase. Continuous occlusion test parameters were compared with the pressure-flow contractility parameters. RESULTS: The continuous occlusion test was evaluated in 159 patients. The maximum isovolumetric contraction pressure of the continuous occlusion test was significantly higher than that of the voluntary stop test (49 patients). Continuous occlusion test contractility parameters were reproducible. The maximum isovolumetric contraction pressure and the maximum slope of the detrusor contraction of the continuous occlusion test significantly correlated with the estimated maximum isovolumetric contraction pressure and estimated velocity of shortening (derived from pressure-flow), respectively (r = 0.79, p < 0.0001 and r = 0.385, p = 0.016, 39 patients). The watts factor was well correlated with maximum isovolumetric contraction pressure (r = 0.75, 39 patients). CONCLUSIONS: Our study suggests that the continuous occlusion test can be used as an effective alternative method of assessing detrusor contractility.

Adult

Cisternal Na+ transport inhibition and the ventilatory response to CO2.

When PCO2 rises transiently, glia or neurons may move ions across their cell membranes to restore intracellular pH, in the process changing extracellular pH. Inhibiting ion transport would result in a different extracellular fluid pH (a putative stimulus for the medullary chemoreceptors) and, therefore, in an altered ventilation in response to PCO2. We infused two ion transport inhibitors, amiloride and bumetanide, into the cisterna magna of anesthetized rabbits and compared their ventilatory response to a rebreathing maneuver with sham rabbits receiving no inhibitor. Amiloride (10(-5)-10(-3) M) had no effect; 3 h of 10(-2) M amiloride increased the frequency of breathing and decreased tidal volume but had no net effect on minute ventilation. Bumetanide (10(-3) M) had no effect after 1 h of infusion, but by 3 h it had decreased tidal volume and minute ventilation at 6 and 7% end-tidal CO2 fraction, respectively, during the rebreathe. Three hours of infusion of amiloride and bumetanide did not affect ventilation in a manner consistent with our predictions from previous studies of ionic changes in cerebrospinal fluid. During the 1st h, when neuronal and glial ion transport in the ventrolateral medulla should be inhibited, we found no effect of ion transport inhibition. We conclude that, during the transient hypercapnia of a rebreathing maneuver, Na+/H+ exchange and Na(+)-K(+)-2Cl- cotransport do not play a significant role in immediate rapid pH homeostasis by cellular ion transport in the microenvironment of the medullary chemoreceptors.

Amiloride

Inhibition of atherosclerosis by dietary pectin in microswine with sustained hypercholesterolemia.

Sustained hypercholesterolemia is a known risk factor for development of atherosclerosis. In animal studies, grapefruit pectin fed concurrently with a high-lipid diet inhibits hypercholesterolemia and atherogenesis. The purpose of the present study was to determine if grapefruit pectin affects cholesterol levels and atherogenesis of animals with established hypercholesterolemia. Microswine were fed an atherogenic diet to establish hypercholesterolemia. Plasma cholesterol levels rose rapidly and for 360 days were sustained at levels 6- to 12-fold the normal level. Then, half the microswine, selected at random, were fed a diet in which 3% grapefruit pectin was substituted for cellulose, and the remaining animals received the original diet. Animals were killed 270 days later, and the extent of atherosclerosis was determined. In animals with established hypercholesterolemia, pectin did not lower their cholesterol levels. However, pectin reduced the extent of atherosclerosis in both the aorta and coronary arteries. The mean surface area covered by atherosclerosis in the aorta was 13.6% in the group that did not receive pectin compared with 5.3% in the group that did receive pectin. The mean coronary artery narrowing was 45% without pectin and 24% with pectin. We conclude that pectin may have a direct beneficial effect on atherosclerosis by a mechanism independent of cholesterol levels.

Animals

Evidence for identity inhibition during selective attention in old adults.

Previous studies of negative priming have shown that, relative to young adults, old adults can effectively suppress location information associated with stimuli, but not information about the identity of stimuli. S.L. Connelly and L. Hasher (1993) attributed this dissociation to an age-related decrement in the inhibitory processes that suppress meaning-bearing information. In this study, the authors report both identity negative priming and distractor interference in a group of young and old adults. Their results force a reconsideration of an age-related decrement in the inhibitory processes underlying the suppression of meaning-bearing information. The results also suggest that whether a relationship between negative priming and interference is observed may depend on whether the 2 measures index the same level of processing.

Adolescent

The gerbil, hamster, and guinea pig as rodent models for hyperlipidemia.

The purpose of this study was to compare the effects of a hyperlipidemic diet on three different rodent models to evaluate them on how their responses simulate human serum lipid diseases. Forty hamsters, 40 gerbils, and 20 guinea pigs were given either a chow diet or a modified high-fat, high-cholesterol diet (HF/HC) for 7 days. Food was withheld from half of the animals on each diet for 12 hours prior to collecting the blood for analysis of total cholesterol and triglyceride concentration. In all species, HF/HC feeding resulted in at least a 370% increase in total cholesterol concentration. Withholding food significantly decreased total cholesterol concentration in hamsters and gerbils fed HF/HC but had no effect on animals fed chow diet. Triglyceride concentrations were increased by the HF/HC in the hamster and the gerbil. As with total cholesterol, triglyceride concentration was decreased after food was withheld in these two animal groups. We suggest that the guinea pig is the most appropriate model for studying hypercholesterolemia because of its moderate plasma cholesterol response and normal triglyceride response to a HF/HC. We also suggest that the hamster is a good model for studying hypertriglyceridemia since increased serum triglyceride concentrations can be easily maintained on a HF/HC.

Animals

Effect of chloride transport blockade on the MAC of halothane in the rat.

There is a growing evidence that central nervous system chloride transport via gamma-aminobutyric acid (GABAA) related Cl- conductance or Cl-/HCO3- exchange affects anesthetic requirements. To delineate the effects of GABAA-related Cl- conductance blockade versus Cl-/HCO3- exchange inhibition, we determined the change in minimum alveolar anesthetic concentration (MAC) of halothane in rats after intracisternal infusion of 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). DIDS inhibits Cl-/HCO3- exchange transport in concentrations greater than 1 microM and in GABAA-related Cl- channels in concentrations greater than 0.1 mM. After control MAC determination, rats were given intracisternal mock cerebrospinal fluid (n = 6), 1.0 microM DIDS (n = 8), or 1 mM DIDS (n = 8) at a rate of 2 microL/min for 30 min. Mock cerebrospinal fluid did not change the MAC of halothane. The MAC of halothane increased significantly (P less than 0.001) from 0.96% +/- 0.02% to 1.11% +/- 0.03% (mean value +/- SEM) with 1 microM DIDS and from 0.94% +/- 0.02% to 1.16% +/- 0.04% with 1 mM DIDS. The increases in MAC with 1 microM and 1 mM DIDS were not statistically different. This suggests that Cl-/HCO3- exchange inhibition increases halothane requirements, whereas GABAA-related Cl- channel blockade does not.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Childhood malignant non-Hodgkin lymphomas of uncommon histology.

Uncommon histologies were identified in 36 of 1336 cases (2.7%) of newly diagnosed childhood non-Hodgkin lymphoma (NHL). Seventeen cases were classified as follicular (six cases as mixed small and large cell, nine as large cell, and two as small non-cleaved cell) and 19 cases as diffuse (18 cases as mixed small and large cell, and one as small cell lymphocytic). The follicular pattern group included a preponderance of male patients; the median age at diagnosis was 11.7 years. These children presented primarily with low-stage disease involving lymph nodes or tonsils. All patients except one achieved complete remission and remain disease-free for 11 months to 18.8 years (actuarial 5-year event-free survival, 94%). The group with diffuse histologies was similar in sex ratio, age at diagnosis (median = 12.1 years), and nodal involvement, but tended to have more advanced-stage disease. Moreover, only 14 of 19 (74%) children with diffuse intermediate-grade histologies are alive in continuous complete remission (actuarial 5-year event-free survival, 70%). These results suggest that follicular pattern childhood NHL has an excellent prognosis, whereas cases with diffuse intermediate-grade histology are prognostically similar to those with diffuse high-grade histologies.

Adolescent

Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study.

Of 2947 children with acute lymphocytic leukemia (ALL), treated during three consecutive studies of the Pediatric Oncology Group (1974-1986), 52 (1.8%) had Down's Syndrome (DS). Comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count, racial distribution, sex ratio, platelet count, incidence of mediastinal mass, lymphadenopathy or hepatosplenomegaly, or percentage of blood or bone marrow blasts for children with ALL with or without Down's Syndrome (DS-ALL or NDS-ALL, respectively). However, children with DS-ALL were slightly older at the time of presentation and had higher hemoglobin values. The relative frequency of each major immunophenotype (early pre-B, pre-B, T, or B) was also comparable for patients with or without DS. For this report, treatment regimens were categorized as either conventional (no consolidation therapy) or intensive. Cox regression analysis revealed that the presence of DS, a higher leukocyte count, black race, or age older than 10 years was independently associated with a poorer event-free survival (EFS) for children treated with conventional chemotherapy. However, for the cohort of children who received intensive chemotherapy, DS was no longer an independent risk factor. In fact, event-free survival (EFS) was markedly improved to a level comparable with that observed in the children diagnosed as having NDS-ALL. On the other hand, serious toxicity, requiring interruption of treatment, was significantly more frequent in the intensively treated children with DS compared with similarly treated patients with NDS-ALL, although deaths resulting from toxicity occurred infrequently.

Antineoplastic Combined Chemotherapy Protocols

Results of a changing treatment philosophy for children with stage I Hodgkin's disease: a 35-year experience.

Over the last four decades, significant changes have occurred in the management of childhood stage I Hodgkin's disease. Between 1949 and 1984, 50 children, ages 4 to 16 years, were treated for stage I Hodgkin's disease at The University of Texas M. D. Anderson Cancer Center. Nineteen children had clinically staged (CS) disease. Thirty-one patients were pathologically staged (PS). Thirty-four children were treated with radiotherapy only, 12 were treated with both radiotherapy and chemotherapy, and 3 patients were treated with combination chemotherapy alone. All patients were followed from 32 to 311 months (median 170 months). Five-, 10-, and 15-year actuarial survival rates for all patients were 94, 89, and 84%, respectively. The corresponding freedom from relapse (FFR) rates were 76, 69, and 69% respectively. The 10-year actuarial survival and FFR rates for CS patients were 79 and 42%. The corresponding rates for PS patients were 97 and 86%. In patients with PSI disease, actuarial 10-year FFR rates of 100% were obtained either with regional radiotherapy alone or with combination chemotherapy and involved field radiotherapy. The following delayed adverse effects of treatment were observed: growth abnormalities in 17, aspermia in 3, thyroid abnormalities in 11 (two carcinomas), and second malignancies beyond the radiotherapy fields in 2. We conclude with a recommendation of combined chemotherapy and involved field radiation for children who have not fulfilled their growth potential, to achieve high cure rates, while minimizing morbidity.

Adolescent

High-dose cyclophosphamide-high-dose methotrexate with coordinated intrathecal therapy for advanced nonlymphoblastic lymphoma of childhood: results of a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) investigated a high-dose cyclophosphamide (CPM) high-dose methotrexate (MTX) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkin's lymphoma (NHL) (stages III and IV) and B-cell acute lymphatic leukemia (B-ALL) in children. Another goal was to determine the comparative effectiveness of shortened maintenance treatment (2 versus 6 courses) in the study population. Systemic induction therapy included vincristine, prednisone, cyclophosphamide, and intermediate-dose MTX with leucovorin rescue. Superimposed intrathecal (IT) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX. Intrathecal MTX was given 3 times during induction. At the end of induction, 2 days of triple (hydrocortisone, MTX, and cytosine arabinoside) therapy were given intrathecally (TIT). All patients then received a consolidation course of 4 doses of TIT, 2 doses of cyclophosphamide, and 4 more courses of vincristine and MTX with leucovorin rescue. Patients were then randomized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue. The TIT was given with each cycle. Complete response rates by histology and Murphy stage (1) were as follows: undifferentiated lymphoma (DUL) stage III, 84/105 (80%): stage IV, 5/12 (42%); and other NHL [primarily large cell lymphoma (LCL)] stage III, 21/28 (75%); stage IV, 2/3 (67%). Event-free survival (EFS) at greater than 2 years was similar for patients with DUL and LCL, i.e., 65 and 61%, respectively. No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments (p = .76). Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Comparative effectiveness of two combined modality regimens in the treatment of surgical stage III Hodgkin's disease in children. An 8-year follow-up study by the Pediatric Oncology Group.

The Pediatric Oncology Group compared two regimens that employed involved field radiotherapy 3,500 rad and either MOPP + Bleo or A-COPP chemotherapy, given in a sandwich fashion, as treatments for stage III Hodgkin's disease in children under the age of 18 years. Eighty-four surgically staged children from the United States and Mexico who had been randomly assigned to treatment during the period from July 1976 through October 1982 were evaluated. Unfavorable disease characteristics were distributed equally between the treatment groups. The percentages of children achieving complete remission by regimen were 84% for MOPP + Bleo and 92% for A-COPP. For those continuing in complete remission, the percentages were 71% for MOPP + Bleo and 72% for A-COPP. For those surviving 9 years, the percentage was 84% for MOPP + Bleo and 85% for A-COPP. The presence of low abdominal disease at diagnosis did not adversely influence response to therapy or survival. All deaths among MOPP + Bleo cases occurred within 4 years of study entry; 3 late deaths in A-COPP cases at 8-10 years were due to osteosarcoma, cardiopathy, and recurrent Hodgkin's disease. The preferred treatment regimen for future use cannot be determined until the cardiotoxicity of Adriamycin is eliminated by the development of drug delivery techniques that reduce cardiotoxicity or anthracycline congeners that are not cardiotoxic.

Abdomen

The intergroup Hodgkin's disease in children. A study of stages I and II.

A total of 228 previously untreated and eligible children with pathologic Stage I or II Hodgkin's disease were registered in the Intergroup Study of Hodgkin's Disease in Children between February 1977 and April 1981. Patients were randomized in the Southwest Oncology Group (later the Pediatric Oncology Group [POG] to involved-field (IF) radiotherapy alone or IF radiotherapy followed by six courses of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy; patients in the Children's Cancer Study Group (CCSG) and Cancer and Leukemia Group B (CALGB) were randomized to receive extended-field (EF) radiotherapy or IF radiotherapy followed by six courses of MOPP. An estimated 97% of patients receiving IF + MOPP were relapse-free and surviving (RFS) at 5 years, which was significantly better than 41% for patients receiving IF alone; however there was essentially no overall difference in survival experience between groups. Patients in CCSG and CALGB receiving IF + MOPP had significantly superior RFS at 5 years than patients receiving EF. Survival rate was not different between these two groups, an estimated 93% of patients surviving 5 years or longer. Although patients were not randomized between IF or EF radiotherapy, they were similar with respect to patient characteristics. There was some statistical evidence that RFS was superior at 5 years for patients receiving EF than for IF; however, there was no evidence of a difference in survival experience. The percentages of patients with late effects of therapy were not significantly different by treatment. The most common types of late effects were endocrine dysfunction and impaired resistance to infection. Overall, the response rate to therapy for relapse patients was good, being 83% among all patients who relapsed. Patient characteristics related to poor prognosis were the presence of constitutional (B) symptoms (fever, night sweats, and weight loss) and poor performance status.

Adolescent

Is distal sampling of end-tidal CO2 necessary in small subjects?

The authors compared PaCO2 with end-tidal CO2 (ETCO2) sampled at multiple sites along the endotracheal tube (ETT) in seven anesthetized rabbits (weight, 2.7-3.6 kg) to determine the most convenient, yet accurate, sampling location. Comparisons were made during spontaneous and controlled ventilation with fresh gas flows (FGF) of two and ten times the minute ventilation using a Mapleson D circuit. An Engstrom Eliza analyzer with a continuous sampling rate of 100 ml/min was used to measure ETCO2. A 0.75-mm ID polyethylene tube inserted in the side of the ETT sampled ETCO2 at the distal tip and at the 6-, 12-, and 15-cm marks on the ETT. ETCO2 was also measured at the standard proximal connector. The differences (P less than 0.05) between PaCO2 and ETCO2 at the distal, 6-, 12-, and 15-cm marks were 2.9 +/- 0.4, 3.1 +/- 0.4, 3.6 +/- 0.4, and 4.6 +/- 0.5 mmHg (mean +/- SEM), respectively, and did not change with FGF or mode of ventilation. The difference between PaCO2 and ETCO2 measured at the proximal connector was always large but significantly (P less than 0.05) greater during spontaneous than controlled ventilation (24.2 +/- 1.5 versus 15.0 +/- 1.4 mmHg) and at higher FGF (19.4 +/- 1.3 versus 16.8 +/- 1.6 mmHg). The differences (P less than 0.05) between ETCO2 at the distal tip and ETCO2 at the 6-, 12-, and 15-cm marks were 0.24 +/- 0.07, 0.73 +/- 0.11, and, 1.77 +/- 0.20 mmHg, respectively. This demonstrates that the change in ETCO2 between the distal tip and the 12-cm mark on the ETT is less than 1 mmHg, and that this clinically insignificant difference is independent of FGF and mode of ventilation. The 12 cm-mark is outside of the mouth on a newborn, and sampling ETCO2 at that point, which may be accomplished simply by inserting a small needle in the side of the ETT, may be the most appropriate sampling location.

Analysis of Variance

Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials.

Thirty-two children or adolescents had B cell acute lymphocytic leukemia (ALL) diagnosed by demonstration of surface immunoglobulin expression on greater than 10% of their bone marrow blasts. All patients had greater than 25% bone marrow lymphoblasts. Only five of 32 patients (16%) presented with an abdominal mass; however, 24 cases (75%) had FAB L3 morphology. By comparison with findings in common ALL, these 32 children were older (median age, 8 years) and had a higher incidence of central nervous system disease at presentation (22%); all but one were white, and 24 were males. Blast cells from individual cases expressed mu kappa (n = 13), mu lambda (n = 9), gamma kappa (n = 1), alpha kappa (n = 1), or mu with an undetermined light chain (n = 8). The most frequently identified cytogenetic abnormality was the classic B cell-associated t(8;14)(q23;q24) (n = 4); the t(1;19)(q23;p13.3), t(9;22)(q23;q11), and t(1;22) were observed in single cases. Twenty patients were treated uniformly on a single protocol designed for children with advanced B cell malignancy; therapy for the other 12 children varied. Nine children (28%) are surviving event-free; all but one for 3 years or more. We conclude that approximately 25% of children with B cell ALL are curable with intensive multiagent chemotherapy and that classification by immunophenotyping is superior to use of clinical and/or lymphoblast morphologic features.

Adolescent

Diffuse small noncleaved cell lymphoma in children, Burkitt's versus non-Burkitt's types. Results from the Pediatric Oncology Group and St. Jude Children's Research Hospital.

The clinical relevance of a morphologic distinction between Burkitt's (B) and non-Burkitt's (NB) types of small non-cleaved cell (SNC) non-Hodgkin's lymphoma (NHL) has been controversial. Numerous attempts to discern an important clinical difference between the subtypes have failed to provide a convincing reason to maintain this distinction for other than descriptive purposes. Because of conflicting reports in the literature, the authors have analyzed 183 cases of SNC NHL in children from the Pediatric Oncology Group and 129 from St. Jude Children's Research Hospital (Memphis, TN). The results from both series, which consist of approximately the same proportions of B and NB subtypes, (i.e., approximately 54%-58% B, 36% NB, and 6%-10% not otherwise specified) show no significant differences in age at presentation, extent of disease, primary site of involvement, or survival. The authors conclude that the morphologic distinction between B and NB types of SNC NHL in children lacks demonstrable clinical importance.

Burkitt Lymphoma