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Biomedical subjects

B J Carroll

Publications and source records attributed to B J Carroll.

At least 37 records · Page 2Linked to original sources

Binuclear metal centers in plant purple acid phosphatases: Fe-Mn in sweet potato and Fe-Zn in soybean.

Purple acid phosphatases comprise a family of binuclear metal-containing acid hydrolases, representatives of which have been found in animals, plants, and fungi. The goal of this study was to characterize purple acid phosphatases from sweet potato tubers and soybean seeds and to establish their relationship with the only well-characterized plant purple acid phosphatase, the FeIII-ZnII-containing red kidney bean enzyme. Metal analysis indicated the presence in the purified sweet potato enzyme of 1.0 g-atom of iron, 0.6-0.7 g-atom of manganese, and small amounts of zinc and copper. The soybean enzyme contained 0.8-0.9 g-atom of iron, 0.7-0.8 g-atom of zinc per subunit, and small amounts of manganese, copper, and magnesium. Both enzymes exhibited visible absorption maxima at 550-560 nm, with molar absorption coefficients of 3200 and 3300 M(-1) cm(-1), respectively, very similar to the red kidney bean enzyme. Substrate specificities were markedly different from those of the red kidney bean enzyme. A cloning strategy was developed based on N-terminal sequences of the sweet potato and soybean enzymes and short sequences around the conserved metal ligands of the mammalian and red kidney bean enzymes. Three sequences were obtained, one from soybean and two from sweet potato. All three showed extensive sequence identity (>66%) with red kidney bean purple acid phosphatase, and all of the metal ligands were conserved. The combined results establish that these enzymes are binuclear metalloenzymes: Fe-Mn in the sweet potato enzyme and Fe-Zn in soybean. The sweet potato enzyme is the first well-defined example of an Fe-Mn binuclear center in a protein.

Acid Phosphatase↗

Laparoscopic common bile duct exploration: long-term outcome.

HYPOTHESIS: Transcystic laparoscopic common bile duct exploration (LCBDE) with biliary endoscopy results in excellent long-term clinical outcome and patient satisfaction. DESIGN: Prospective cohort study of unselected patients found to have common bile duct stones during laparoscopic cholecystectomy between October 1989 and April 1998. A mailed survey assessed symptoms, outcome, and satisfaction. SETTING: A large community teaching hospital. PATIENTS: Two hundred seventeen patients with common bile duct stones. INTERVENTION: Transcystic LCBDE with choledochoscopy. MAIN OUTCOME MEASURES: Success of LCBDE, morbidity, postoperative symptoms, and satisfaction. RESULTS: One hundred sixteen surveys (54%) were returned. Mean follow-up was 60 months. The LCBDE procedure failed in 6 patients and endoscopic retrograde cholangiopancreatography was performed in 4 patients (3%). One patient had unsuspected retained stones. No patient had late recognition of retained stones or a bile duct stricture. Abdominal pain was present in 90 patients (89%) preoperatively and in 29 patients (26%) postoperatively (P = .001). The LCBDE procedure reduced 3 specific pain profiles: epigastric, from 47% (n = 54) to 7% (n = 8); back, from 31% (n = 36) to 6% (n = 7); and shoulder, from 18% (n = 21) to 2% (n = 2). When pain persisted, it was different in character in 15%. All nonpain symptoms (such as nausea, bloating, indigestion, and gas) were reduced from 78% (n = 91) to 34% (n = 39) (P = .001) except diarrhea. Diarrhea was present in 24 patients (22%) preoperatively and postoperatively, though it was a new postoperative symptom in 11 patients (11%). One hundred two patients (95%) were satisfied or mostly satisfied with LCBDE. CONCLUSIONS: Pain and nonpain symptoms, while reduced significantly after LCBDE, may persist. The LCBDE procedure does not result in common bile duct strictures or a significant rate of retained stones. This relatively new treatment for common bile duct stones is safe and effective.

Cholecystectomy, Laparoscopic↗

Candidate neuroanatomic substrates of psychosis in old-aged depression.

1. The authors investigated the candidate neuroanatomic substrates underlying delusional thought disorder in old-aged depressed patients by using magnetic resonance imaging (MRI), and examined the relationship between volumes for individual brain structures and clinical correlates of particular relevance to depression: executive cognitive impairment and global severity of depression. 2. MR morphometry was performed on nineteen deluded depressed patients and 26 non-deluded depressed patients, all older than 55 years of age. Subjects were administered a neuropsychological test battery and measures of depression. 3. The absolute volume of prefrontal cortex (PFC) was smaller in the deluded depressed group than in non-deluded depressed group (131.79 +/- 37.26 ml vs. 152.65 +/- 26.13 ml, p = 0.03); a difference that was statistically significant even after adjusting for the effect of whole brain volume (p = 0.01). No group differences were observed in the volumes of the basal ganglia, the temporal lobes, the superior temporal gyri, the amygdala-hippocampal complex, the lateral ventricles, or whole brain. The relative volume of PFC correlated inversely and significantly with the index of Wisconsin Card Sorting Test (WCST) performance (r = -0.76, p < 0.01) in depressed patients. 4. PFC may be one of the candidate neuroanatomic substrates underlying delusional thought disorder in old-aged depression.

Aged↗

Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients.

OBJECTIVE: Disturbance in glucose homeostasis in psychiatric populations has been suggested since the early part of this century. Increased comorbidity of diabetes mellitus in persons with major mood disorders has also been suggested. The goal of this study was to determine whether subjects diagnosed with bipolar disorder have an elevated rate of comorbid diabetes mellitus. METHOD: Three hundred forty-five hospitalized patients, aged 20-74 years, who met the DSM-III-R criteria for bipolar disorder, manic or mixed subtype, were evaluated for a comorbid diagnosis of diabetes mellitus. The frequency of diabetes mellitus in the study group was determined and compared with the expected frequency, calculated as a weighted average based on sex and age from national norms. Variables characterizing the course and severity of the affective disorder in the group of diabetic bipolar subjects and a group of nondiabetic age-matched bipolar subjects were compared. RESULTS: The prevalence of diabetes mellitus among these bipolar patients was 9.9%, significantly greater than expected from national norms (3.4%). The patients with comorbid diabetes mellitus had significantly more lifetime psychiatric hospitalizations than the nondiabetic subjects, but age at first hospitalization and duration of psychiatric disorder were similar in the two groups. CONCLUSIONS: The frequency of diabetes mellitus in hospitalized patients diagnosed with bipolar disorder is higher than in the general population. Manic-depressive patients with diabetes mellitus have a more severe course of illness, as indicated by a greater number of psychiatric hospitalizations. Possible reasons for this increased comorbidity include a genetic relationship between the disorders, a causal relationship in which hypercortisolemia induces diabetes or diabetic vascular lesions contribute to mania, an overlapping functional disturbance affecting similar regions of the brain, or the effect of psychotropic medications.

Adult↗

Plasma dexamethasone concentration and cortisol response during manic episodes.

BACKGROUND: Despite the widespread study of the dexamethasone suppression test (DST) in patients diagnosed with major depression, it has been less well studied during manic and mixed states of bipolar disorder. METHODS: Cortisol response to the administration of 1 mg of dexamethasone was studied in 44 patients diagnosed bipolar disorder, manic (n = 37) or mixed (n = 7). Dexamethasone levels and cortisol responses were compared between these groups. Four patients initially meeting criteria for bipolar disorder, mixed, and 7 patients initially meeting criteria for bipolar disorder, manic, all of whom were characterized as DST nonsuppressors, were retested after remission. RESULTS: Dexamethasone levels were lower and cortisol levels higher in those patients diagnosed bipolar disorder, mixed. An inverse correlation was found between log-transformed dexamethasone levels and log-transformed cortisol levels at 3 PM (r = -.619, p < or = .001) and 10 PM (r = -.501, p < or = .001). In those subjects retested after remission, dexamethasone levels were higher and cortisol levels lower than during the manic and mixed states. CONCLUSIONS: Disturbances in the hypothalamic-pituitary-adrenal axis are observed frequently during mixed states of bipolar disorder, but are also not uncommon in purely manic episodes. These changes appear to be state dependent and revert with treatment.

Adolescent↗

Tryptophan depletion in recently manic patients treated with lithium.

BACKGROUND: Serotonin has been repeatedly implicated in the mechanism of action of lithium against acute mania. Its role, however, has never been directly confirmed. METHODS: We studied recently manic patients successfully treated with lithium using a tryptophan depletion methodology. RESULTS: Patients remained euthymic despite a confirmed decrease in serum tryptophan levels. CONCLUSIONS: These data do not suggest that serotonin plays a critical role in the acute antimanic effect of lithium.

Adult↗

A factor analysis of the signs and symptoms of mania.

BACKGROUND: No adequate factor analyses of signs and symptoms of mania have been reported. From limited past reports, the view has arisen that 2 main symptom clusters (euphoric-grandiose and paranoid-destructive) occur in patients with mania, along with so-called core symptoms of psychomotor pressure. In this view, dysphoric mania is associated with paranoid-destructive symptoms and with psychosis. METHODS: We rated 237 patients with DSM-III-R-defined bipolar disorder, manic (n = 204) or mixed (n = 33), on 15 classic features of mania and 5 features related to dysphoric mood. Principal components factor analysis was applied to the ratings. RESULTS: Five clearly interpretable and clinically relevant factors were identified. The first and strongest factor represented dysphoria in mania, with strong positive loadings for depressed mood, lability, guilt, anxiety, and suicidal thoughts and behaviors and a strong negative loading for euphoric mood. Factors 2 through 5 represented psychomotor acceleration, psychosis, increased hedonic function, and irritable aggression, respectively. The distribution of weighted scores on factor 1 was bimodal, whereas the corresponding distributions of factors 2 through 5 were unimodal. Contrary to all past reports, no general factor denoting overall severity of mania was found. Factors previously proposed by Beigel and Murphy were not confirmed. CONCLUSIONS: Five independent factors representing dysphoric mood, psychomotor pressure, psychosis, increased hedonic function, and irritable aggression were identified. The conventional view of symptom factors in mania was not confirmed. Dysphoric features are statistically salient in patients with mania, and the bimodal distribution of the dysphoria factor is consistent with the possibility that mixed bipolar disorder is a distinct state.

Adolescent↗

Comparison of laparoscopic and open staging in Hodgkin disease.

BACKGROUND: Staging laparotomy provides useful information for management of Hodgkin disease but has fallen into disfavor because procedure-related morbidity exceeds that of new chemotherapeutic regimens. OBJECTIVE: To determine the feasibility, effectiveness, and safety of laparoscopic staging for Hodgkin disease compared with those of open staging. PATIENTS: Fifty-five patients with Hodgkin disease of cell types including nodular sclerosis in 43 (78%), mixed cellularity in 9 (16%), and lymphocyte predominance in 3 (5%). STUDY DESIGN: Concurrent evaluation of laparoscopic staging (n = 15) and retrospective review of open staging (n = 40). INTERVENTIONS: Laparoscopic and open techniques of surgical staging for Hodgkin disease, including splenectomy, liver biopsies, and lymph node sampling. MAIN OUTCOME MEASURES: Operative time, duration of postoperative ileus and of postoperative hospitalization, morbidity, number of lymph nodes retrieved, alteration in pathologic stage, recurrence, and survival. RESULTS: For laparoscopic staging vs open staging groups, mean operative time was 202 vs 144 minutes (P=.001); mean postoperative ileus was 1.9 vs 3.2 days (P<.001); mean postoperative hospitalization was 4.4 vs 6.7 days (P<.001); complications occurred in 3 patients (20%) vs 11 patients (28%) (P=.57); and mean number of lymph nodes retrieved was 8.5 vs 4.6 (P=.05). In the laparoscopic staging group, 2 cases (13%) were upstaged and 2 cases (13%) were downstaged. In the open staging group, 6 cases (15%) were upstaged and 3 cases (7.5%) were downstaged. Follow-up data were available for all patients in the laparoscopic staging group, at a mean of 23.5 months postoperatively. All were alive, none had recurrent disease below the diaphragm, and 2 (13%) had residual mediastinal disease. Follow-up data were available for 31 patients (78%) in the open staging group at a mean of 52.5 months postoperatively. All were alive, 27 (87%) were disease free, 3 (10%) had had relapses above the diaphragm, and 1 (3%) had residual mediastinal disease. CONCLUSIONS: Compared with open staging, laparoscopic staging of Hodgkin disease is oncologically equivalent and functionally superior. These data should encourage reappraisal of the role of operative staging in the management of Hodgkin disease.

Adolescent↗

Common bile duct injuries during laparoscopic cholecystectomy that result in litigation.

BACKGROUND: Iatrogenic common bile duct injury is the worst complication of laparoscopic cholecystectomy. The goal of this study is to increase awareness of the problem and educate surgeons about the consequences of these injuries. METHODS: A total of 46 bile duct injuries were analyzed by review of medical records, cholangiograms, videotapes, and surgeon statements. All cases were involved in malpractice litigation. RESULTS: All types of injuries were represented. There were 15 transections, 11 excisions, 6 lacerations, 8 clip impingements, 3 burns, 2 bile leaks, and 1 cystic duct leak. In all, 72% of these injuries occurred in elective cases in which there was no acute inflammation. Cholangiograms were performed in 16 cases, but they were misinterpreted in 11 of them. Injury type and severity was similar in patients with and without cholangiography. A total of 80% of these injuries were not detected at the initial surgery. The average delay in diagnosis was 10 days. Complications were worse in patients with delayed diagnosis. Primary surgeons had less successful outcomes from repairs than referral surgeons (27% versus 79%). In 86% of cases, litigation was resolved in favor of plaintiffs by settlement or verdicts. The average award was $214,000. CONCLUSIONS: Factors that predispose to lawsuits include treatment failures in immediately recognized injuries, complications that result from delays in diagnosis, and misinterpretation of abnormal cholangiograms. Injury prevention can be improved by increased awareness of common mistakes,. Improved cholangiographic technique and interpretation should decrease injury severity, delays in diagnosis, and subsequent morbidity.

Adult↗

Signs and symptoms of mania in pure and mixed episodes.

BACKGROUND: Debate continues about the diagnosis of mixed mania and the restrictiveness of the DSM-III-R and DSM-IV criteria for Bipolar Disorder, mixed. Although awareness of dysphoric features during mania continues to grow, standard mania rating instruments do not adequately assess mixed states and there is a striking disparity between the dysphoric signs and symptoms emphasized in research studies and the commonly employed DSM criteria. METHODS: Three hundred sixteen inpatients meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed, were evaluated by rating 20 signs and symptoms. The frequencies of these signs and symptoms were computed for both diagnostic subtypes and compared using chi2 statistics and conditional probability parameters. RESULTS: The most frequently noted signs and symptoms in mania are motor activation, accelerated thought process, pressured speech and decreased sleep. Although euphoric mood was present in a large portion of the cohort, irritability, dysphoric mood and mood lability were also prominent in the entire cohort. Dysphoric mood, mood lability, anxiety, guilt, suicidality, and irritability were the only symptoms significantly more common in the mixed group. In contrast, grandiosity, euphoric mood, and pressured speech were significantly more often observed in the pure manic group. Contrary to popular belief, paranoia did not differ significantly between the two groups. Suicidality was present in a non-trivial 7% of the entire cohort, including some subjects who did not meet the criteria for mixed mania. LIMITATIONS: The comparison of mixed and manic episodes requires the appropriate definition of mixed states. In the current report we use the DSM-III-R definition of Bipolar Disorder, mixed, which may be too rigid. CONCLUSIONS: The data underscore that mania is not a purely euphoric state. Substantial rates of dysphoria, lability, anxiety and irritability were noted in the "pure" manic patients, as well as in those who meet the full DSM criteria for Bipolar Disorder, mixed, suggesting, that perhaps a less restrictive definition of mixed states would be more appropriate.

Adolescent↗

Transposon tagging of the Defective embryo and meristems gene of tomato.

The shoot and root apical meristems (SAMs and RAMs, respectively) of higher plants are mechanistically and structurally similar. This has led previously to the suggestion that the SAM and RAM represent modifications of a fundamentally homologous plan of organization. Despite recent interest in plant development, especially in the areas of meristem regulation, genes specifically required for the function of both the SAM and RAM have not yet been identified. Here, we report on a novel gene, Defective embryo and meristems (Dem), of tomato. This gene is required for the correct organization of shoot apical tissues of developing embryos, SAM development, and correct cell division patterns and meristem maintenance in roots. Dem was cloned using transposon tagging and shown to encode a novel protein of 72 kD with significant homology to YNV2, a protein of unknown function of Saccharomyces cerevisiae. Dem is expressed in root and shoot meristems and organ primordia but not in callus. The expression pattern of Dem mRNA in combination with the dem mutant phenotype suggests that Dem plays an important role within apical meristems.

Amino Acid Sequence↗

Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits.

Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.

Administration, Oral↗

Serotonin transporter expression in rat brain regions and blood platelets: aging and glucocorticoid effects.

Hyperactivity of the hypothalamus-pituitary-adrenal axis is more common in elderly depression than in younger cohorts and glucocorticoids are known to influence serotonergic systems. The current study explores the interaction of glucocorticoids with aging on serotonin transporter expression and function. Continuous infusions of dexamethasone (26 days) reduced transporter expression in the aged brain but the ability of imipramine to inhibit synaptosomal [3H]serotonin uptake was unimpaired. These effects were unique to aged animals, as prior work with young adults found no effects of dexamethasone on transporter expression. In contrast to the effects in the brain, there were no differences in platelet transporter expression between young and old rats nor did dexamethasone treatment affect the values in the aged group: thus, the platelet may not reliably model these aspects of CNS function. The results suggest that there are basic biologic differences in the effects of glucocorticoids in aged vs. young brain that could contribute to lowered effectiveness to antidepressants in elderly depression; if transport capacity is already reduced by the effects of increased glucocorticoids, further inhibition of transport by antidepressants would have proportionally less impact on synaptic serotonin concentrations.

Aging↗

Dexamethasone suppression test identifies a subset of elderly depressed patients with reduced platelet serotonin transport and resistance to imipramine inhibition of transport.

Dysregulation of the hypothalamus-pituitary-adrenal axis (HPA) is more common in elderly patients with depression than in younger depressed patients, and glucocorticoids are known to influence serotonergic function. Elderly depressed patients are also reportedly more resistant to therapeutic effects of antidepressants. In the current study, we measured platelet serotonin transporter binding sites and transport function in young and elderly depressed patients and determined the relationship to HPA status as assessed with the dexamethasone suppression test (DST). The density and affinity of transporter molecules showed no differences between young and elderly depressed patients, regardless of DST results. Nevertheless, transporter function showed a substantial interaction of aging with DST: elderly DST suppressors showed a deficit in [3H]serotonin uptake capabilities and resistance to imipramine inhibition of uptake. No such defects were seen in the young depressed cohort, regardless of DST status, nor in elderly depressed DST non-suppressors. These results are consistent with the view that depression in the elderly exhibits basic biological differences from depression in earlier life, and that such distinctions may account in part for therapeutic ineffectiveness of antidepressants in specific subgroups, associated with the presence or absence of appropriate HPA regulation.

Adult↗

Final score in laparoscopic cholecystectomy. Cholangiogram 1207, no cholangiogram 116.

BACKGROUND: The role of intraoperative fluorocholangiography (IOC) in laparoscopic cholecystectomy (LC) is controversial. We evaluated the use of IOC at an institution where the study is performed routinely. METHODS: Records of all patients undergoing LC during a 3-year period ending January 1, 1996 were reviewed. RESULTS: A total of 1207 patients received IOC, whereas 116 patients did not. IOC findings were categorized as follows: normal, 1016 cases (84%); CBD stone, 149 cases (12.3%); anomalies, 23 cases (1.9%); duodenal diverticula, 10 cases (0.8%); ductal strictures, four cases (0.3%); and CBD diverticula, 5 cases (0.4%). In the 116 patients who did not receive IOC, 35 of the procedures could not be performed, whereas 81 were not attempted. Of the 149 IOC that showed CBD stones, two were false positives. Anomalies included accessory right hepatic ducts (11 cases), cystic ducts joining the right hepatic duct (seven cases), and abnormal cystic duct entries (five cases). Duct injuries occurred in 5 cases (0.4%), three before and two after IOC. Four injuries were minor; IOC prevented CBD transection. CONCLUSIONS: Routine IOC is feasible, safe, accurate, and provides critical information of immediate use during LC. By treating ductal stones at operation and identifying patients without CBD stones, IOC minimizes need for postoperative studies, including endoscopic retrograde cholangiography (ERC).

Cholangiography↗

The performance of DSM-III-R major depression criteria in the diagnosis of bipolar mixed states.

Two hundred thirty-seven (237) manic patients diagnosed by DSM-III-R criteria as either purely manic (204) or mixed bipolar (33) were reviewed for analysis of the diagnostic performance of the DSM-III-R criteria required to diagnose the mixed bipolar state. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic efficiency of each of the 9 DSM-III-R criteria for major depression in this cohort. As predicted, four of the major depression criteria had low diagnostic utility, with PPV's less than 0.3. Those items were: weight change; sleep disturbance; psychomotor change; and diminished ability to think or concentrate or indecisiveness. Four symptoms: anhedonia, fatigue, feelings of worthlessness or guilt, and recurrent thoughts of death or suicidal ideation had acceptable utility for the diagnosis of mixed states.

Adolescent↗