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Biomedical subjects

M O'Brien

Publications and source records attributed to M O'Brien.

At least 109 records · Page 6Linked to original sources
PubMed1998

Bioavailability of phylloquinone from an intravenous lipid emulsion.

This randomized, controlled study evaluated the bioavailability of phylloquinone from an intravenous lipid emulsion. A mild vitamin K deficiency was induced in 12 healthy adult men and women by dietary restriction of phylloquinone (40 microg/d, days 1-11) and by administration of warfarin (1.0 mg/d, days 5-11). On day 11, subjects received a 500-mL intravenous solution of either lipid or saline, both of which contained 154 microg phylloquinone. Bioavailability was assessed by serial measurements of plasma phylloquinone, vitamin K1-2,3-epoxide. PIVKA-II (proteins induced by vitamin K absence or antagonists-II), and percentage undercarboxylated osteocalcin. As a result of vitamin K deficiency and minidose warfarin, vitamin K1-2,3-epoxide, PIVKA-II, and percentage undercarboxylated osteocalcin increased significantly between days 1 and 11 (P = 0.05, 0.016, and 0.001, respectively). With the infusions, plasma phylloquinone increased in both groups (P = 0.001). After the infusions vitamin K,-2,3-epoxide decreased in both groups (P = 0.002). Changes in plasma phylloquinone and vitamin K1-2,3-epoxide were no different in the two groups (mean areas under the curves +/- SEM: 116+/-13 nmol x h/L for the saline group and 102+/-20 nmol x h/L for the lipid group for phylloquinone; 38.6+/-7.5 nmol x h/L for the saline group and 31.3+/-9.0 nmol x h/L for the lipid group for vitamin K1-2,3-epoxide). PIVKA-II decreased significantly from baseline values (P = 0.005) in both groups after the infusions. Intravenous lipid reversed the effects of minidose warfarin and of dietary restriction of phylloquinone on hemostasis and vitamin K nutritional status. This reversal was no different from that seen with the infusion of phylloquinone in a saline solution.

Adult↗
PubMed1998

Phase I trial and pharmacokinetic study of pyrazoloacridine in children and young adults with refractory cancers.

PURPOSE: To define the maximum-tolerated dose (MTD), quantitative and qualitative toxicities, recommended phase II dose, and pharmacokinetics of pyrazoloacridine (PZA) administered as a 1- or 24-hour infusion in children and young adults with refractory cancers. PATIENTS AND METHODS: Twenty-two patients received PZA as a 1-hour infusion at doses of 380 mg/m2 (n = 3), 495 mg/m2 (n = 6), 640 mg/m2 (n = 6), and 835 mg/m2 (n = 7). An additional four patients received PZA as a 24-hour infusion at the MTD (640 mg/m2) for the 1-hour infusion schedule. Plasma samples were obtained for pharmacokinetic analysis in 17 patients. PZA concentration in plasma was measured by reverse-phase high-performance liquid chromatography (HPLC). A two-compartment pharmacokinetic model was fit to the PZA plasma concentration data. RESULTS: On the 1-hour infusion schedule, dose-limiting myelosuppression (neutropenia more than thrombocytopenia) was observed in two of seven patients at the 835-mg/m2 dose level. Myelosuppression did not appear to be ameliorated by prolonging the infusion to 24 hours. Nonhematologic toxicities were minor. Significant neurotoxicity, which was dose-limiting in adults treated with a 1-hour infusion of PZA, was observed in one patient treated at 640 mg/m2, but was not dose-limiting. There was marked interpatient variability in plasma PZA concentrations at all dose levels. The pharmacokinetic profile of PZA was characterized by an initial rapid decline (alpha half-life [t(1/2)alpha], 0.5 hours) followed by a prolonged elimination phase (t(1/2)beta, 30 hours). The volume of distribution at steady-state (Vd(ss)) was 700 L/m2 and the clearance was 300 mL/min/m2. There was no evidence of dose-dependent clearance. The area under the PZA concentration-time curve (AUC) correlated poorly with dose and was more predictive of the degree of myelosuppression than was PZA dose. CONCLUSION: PZA administered as 1- or 24-hour infusion is well tolerated by children and young adults. The dose-limiting toxicity (DLT) is myelosuppression. Neurotoxicity is not prominent in this age group. There was marked interpatient variation in plasma concentrations of PZA. The recommended dose for phase II studies is 640 mg/m2.

Acridines↗
PubMed1998

Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (<6.5 hour) ischemic stroke.

BACKGROUND: Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are powerful new techniques for the assessment of acute cerebral ischemia. However, quantitative data comparing the severity of clinical neurologic deficit with the results of DWI or PWI in the earliest phases of stroke are scarce. Such information is vital if MRI is potentially to be used as an objective adjunctive measure of stroke severity and outcome. OBJECTIVE: The authors compared initial DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score in acute stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI lesion volume at 1 week to assess the accuracy of these MRI techniques for the detection of acute cerebral ischemia. METHODS: Patients with stroke underwent MRI scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were also compared with T2W lesion size at 1 week. RESULTS: There was a high correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r = 0.96, p < 0.001) or DWI (r = 0.67, p = 0.03). A similar high correlation was seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r = 0.99, p < 0.00001). CONCLUSIONS: Both DWI and PWI are highly correlated with severity of neurologic deficit by 24-hour NIHSS score. These findings may have substantial implications for the use of MRI scanning in the assessment and management of acute stroke patients.

Acute Disease↗
PubMed1998

Measurement of inhibin-A (alpha beta A dimer) during the oestrous cycle, after manipulation of ovarian activity and during pregnancy in ewes.

A new two-site ELISA was validated for ovine plasma and used to measure circulating inhibin-A concentrations during a synchronized oestrous cycle in four ewes and throughout pregnancy in six ewes. Inhibin A concentrations were also determined in four ewes during chronic treatment with a GnRH agonist and after subsequent exposure to pregnant mares' serum gonadotrophin (PMSG) to stimulate ovarian follicular development. Concentrations of FSH, LH, oestradiol and progesterone were determined by radioimmunoassay. The detection limit of the inhibin-A ELISA was approximately 50 pg ml-1 and no significant crossreaction was observed with a range of related molecules including activin-A, inhibin-B, activin-B, follistatin and alpha 2-macroglobulin. Inhibin-A concentrations were below the detection limit in plasma from hypophysectomized and ovariectomized ewes. During the oestrous cycle, plasma inhibin-A concentrations (approximately 0.3-0.4 ng ml-1) did not vary during the follicular phase whereas plasma oestradiol increased approximately tenfold. After the preovulatory LH/FSH surge, inhibin-A fell to a nadir (approximately 0.15 ng ml-1) coincident with the peak of the postovulatory FSH rise. During the next 2 days, FSH concentrations fell to basal values as inhibin-A concentrations increased (P < 0.05) to a peak (approximately 0.5 ng ml-1) 3 days after the preovulatory LH/FSH surge. Over the following 3 days, FSH values increased again (P < 0.05) as inhibin-A concentrations fell to approximately 0.25 ng ml-1 (P < 0.05). Chronic GnRH agonist treatment suppressed FSH concentrations by about 50%, while inhibin-A and oestradiol concentrations fell below detection limits. Within 2 days after the PMSG injection, concentrations of inhibin-A (approximately 4.5 ng ml-1) and oestradiol (approximately 20 pg ml-1) had increased to very high values, while FSH concentrations had been reduced by a further 50%. Plasma concentrations of inhibin-A and FSH were similar to those in nonpregnant ewes during the first 60 days of gestation, but inhibin-A values fell markedly (sevenfold; P < 0.01) between days 60 and 90, coincident with a twofold decrease in FSH (P < 0.05). Inhibin A and FSH concentrations remained low for the remainder of gestation and were positively correlated throughout pregnancy (r = 0.48; P < 0.005). These observations support an endocrine feedback role for ovarian inhibin-A and oestradiol in controlling the secondary (postovulatory) FSH surge in ewes, but indicate that an increase in oestradiol is responsible for the characteristic reduction in FSH during the early to mid-follicular phase. The reduced secretion of FSH from mid- to late pregnancy cannot be attributed to increased inhibin-A secretion by the feto-placental unit, but most likely reflects increased steroid secretion from this source.

Analysis of Variance↗
PubMed1998

Mental health professionals' attire.

OBJECTIVE: Our aim was to obtain mental health patients' views on psychiatrists' and case managers' attire. METHODS: Eighty-six patients treated at a community mental health service were surveyed. Various types of commonly worn attire were listed. Respondents were asked to choose what they thought was most appropriate for their psychiatrist and case manager to wear. RESULTS: Over 50% of respondents felt that psychiatrist or case manager dress was not an important issue. However, those who felt that it was preferred less formal attire. CONCLUSIONS: Psychiatrists and case managers in a community mental health team could consider adopting less formal attire. This conclusion is limited by the small sample and may be relevant to rural areas only. Further research is needed in urban centres. Implications of these findings are discussed.

Adult↗
PubMed1998

An approach to switching patients from baclofen to tizanidine.

With the introduction of the antispasticity agent, tizanidine hydrochloride (Zanaflex), physicians have requested information about the optimal way to switch appropriate patients from baclofen to tizanidine. A group of neurologists and rehabilitation specialists with a particular interest in spasticity was therefore asked to draw up a suitable approach to changing treatment.

Baclofen↗
PubMed1997

Non-oxidative modification of low density lipoprotein by ruptured myocytes.

In this study, the interaction of ruptured cardiac myocytes with low density lipoprotein (LDL) has been investigated and the consequent extent of uptake by macrophages. The results show that lysate released from ruptured myocytes is capable of inducing LDL oxidation and that the resulting modified form is recognised and degraded by macrophages. Peroxyl radical scavengers inhibit the LDL oxidation but not the macrophage uptake suggesting that LDL can be modified by mechanisms that are independent of oxidative processes by intracellular constituents of cardiac myocytes.

Animals↗
PubMed1997

A new classification and diagnostic criteria for invasive fungal sinusitis.

OBJECTIVE: To develop criteria for the diagnosis of invasive fungal sinusitis. DESIGN: Review of the literature on invasive fungal sinusitis in the context of a population of 30 patients with fungal sinusitis and 24 patients with chronic bacterial sinusitis. SETTING: Tertiary care medical center. RESULTS: Our review revealed no consensus in the literature on the classification of the syndromes of invasive fungal sinusitis and no criteria for their diagnosis. Moreover, the existing syndromes of invasive fungal sinusitis lacked specificity and one of the more commonly cited syndromes, primary aspergillosis of the paranasal sinuses, is a granulomatous disease that occurs rarely outside Africa. Two of our 30 patients with fungal sinusitis had a previously unrecognized form of invasive disease. Both were middle-aged adults with well-controlled type 2 diabetes mellitus, apical orbital syndrome, and a similar course: proptosis resulting from fungal expansion out of an ethmoid sinus, a protracted illness of 6 months or longer, visual changes, late neurological symptoms reflecting cavernous sinus invasion, and death. The syndrome in these 2 patients is distinct from the syndrome of fulminant invasive fungal sinusitis, (eg, mucormycosis) with nasal eschar, intracerebral fungal dissemination by vascular invasion, and death in days, and the granulomatous form. CONCLUSIONS: We conclude that there are 3 forms of invasive fungal sinusitis and propose that they be termed (1) granulomatous, (2) acute fulminant, and (3) chronic invasive. The latter category reflects the syndrome seen in our 2 patients. Furthermore, the following 2 diagnostic criteria for invasive fungal sinusitis are proposed: (1) sinusitis confirmed by radiological imaging and (2) histopathological evidence of hyphal forms within sinus mucosa, submucosa, blood vessels, or bone. The specificity of hyphae within sinus mucosa for tissue invasion was supported by the absence of stainable hyphae in the mucosa of patients with chronic bacterial sinusitis or in the mucosa of our described patients with allergic fungal sinusitis and mycetoma.

Adult↗
PubMed1997

Enterococcal bacteremia in the surgical intensive care unit. Does vancomycin resistance affect mortality? The Johns Hopkins SICU Study Group.

OBJECTIVE: To determine the incidence and mortality rate associated with nosocomial bacteremia caused by vancomycin-resistant Enterococcus in a surgical intensive care unit. DESIGN: A retrospective study. SETTING: The surgical intensive care unit of a large university hospital tertiary referral center. PATIENTS: All patients in the surgical intensive care unit with a documented nosocomial bacteremia between January 1, 1992, and December 31, 1994. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Mortality rate. RESULTS: Of the 134 nosocomial bacteremic episodes, 30.6% involved enterococci; 24.4% of the enterococci were resistant to vancomycin. Patients with vancomycin-resistant enterococcal bacteremia had a significantly longer hospital stay (mean +/- SD, 28 +/- 18 vs 12 +/- 10 days; P = .005) and were more likely to have been treated with vancomycin (70% vs 10.3%; P = .001) than patients with vancomycin-sensitive enterococcal bacteremia. The mortality (41.0%) associated with enterococcal bacteremia was similar to the overall bacteremic mortality (41.7%). There was no difference in episode-specific mortality associated with vancomycin-resistant enterococci (40%) vs vancomycin-sensitive enterococci (38.7%). Of the 4 deaths associated with vancomycin-resistant enterococcal bacteremia, only 2 occurred within 14 days of the bacteremia, as did 8 of 12 deaths associated with vancomycin-sensitive enterococcal bacteremia (P = .64). CONCLUSIONS: Enterococci were the most commonly isolated nosocomial blood-borne pathogens in the surgical intensive care unit. Nearly 25% of the enterococcal bacteremic episodes were resistant to vancomycin. Vancomycin-resistant Enterococcus is associated with a prolonged hospital stay and with vancomycin use. Nevertheless, vancomycin resistance itself does not increase the mortality rate associated with enterococcal bacteremia.

Adult↗
PubMed1997

Criteria for the diagnosis of sinus mycetoma.

Recent improvements in the treatment options for fungal disease of the sinuses make rapid distinction between the syndromes of invasive and noninvasive sinusitis necessary. On the basis of the extensive review of the literature detailed here, we developed case-finding criteria for the noninvasive syndrome of sinus mycetoma. Using these criteria, we identified 20 cases of sinus mycetoma in the medical literature and compared findings in these patients to those of five patients with mycetoma evaluated in our clinics. Like those in the literature, our patients appeared immunocompetent and were often first seen for evaluation of symptoms other than those usually associated with sinusitis. Two were first seen with a new-onset seizure disorder and one with nasal obstruction alone. Patients from both groups more commonly had mycetoma in their maxillary sinuses, and fungus failed to grow from the cheesy, grey-green, hyphae-rich material removed at the time of surgery. Clinical features in our five patients, which are not noted in published reports of sinus mycetoma, included frequent atopy, nasal polyps, calcification within the sinus on computed tomography, and an excellent response to surgical treatment. Serendipitously, one patient had both allergic fungal sinusitis and a mycetoma in the same sinus. On the basis of this experience, we have modified our case-finding criteria into proposed diagnostic criteria for sinus mycetoma. The elements of these criteria are designed to: (1) exclude patients with invasive fungal sinusitis and (2) differentiate sinus mycetoma from other forms of noninvasive fungal sinusitis on the basis of specific histopathologic findings. This study and the criteria presented reflect our view that sinus mycetoma represents a distinct but not necessarily isolated element in the spectrum of noninvasive fungal disease of the sinuses.

Adult↗
PubMed1997

Urinary assays for desmosine and hydroxylysylpyridinoline in the detection of cirrhosis.

BACKGROUND/AIMS: Non-invasive markers of liver fibrosis have great potential for both the diagnosis and therapy of liver disease and cirrhosis. The aim of this study was to evaluate the potential of urinary amino acids desmosine (DES) and isodesmosine (IDES) derived from the breakdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) derived from fibrillar collagen in diagnosing chronic liver disease. METHODS: We studied 48 patients with chronic liver disease who had varying degrees of liver fibrosis, graded 0-6 using a modified Knodell score, and 20 control subjects without liver disease. Urinary DES (microg/g creatinine) and HP (nmol/mmol creatinine) were measured by an isotope dilution, high performance liquid chromatography method. For liver disease patients, aminoterminal propeptide of type III procollagen (PIIINP) and alanine aminotransferase were determined. The urine and serum markers were correlated to degree of fibrosis and inflammation on liver biopsies. Differences between groups were analyzed by ANOVA and multiple linear regression was applied to determine independence of variables. Sensitivity, specificity and receiver operating curves were derived for each marker. RESULTS: In the 17 patients with liver fibrosis score of 5-6, mean urinary DES, IDES, HP and LP were all significantly greater than in the control group (p<0.05). Urinary DES and IDES correlated best with fibrosis score, r=0.61 for both markers. The correlation coefficient between serum PIIINP and fibrosis score was 0.47. Urinary DES and HP each had an overall diagnostic accuracy of 77% for fibrosis. Combining markers improved accuracy to over 80%. No correlation was seen between the urinary markers and inflammation scores. CONCLUSIONS: Urinary DES and HP are potentially useful clinical markers for liver fibrosis, especially when used in combination or in association with PIIINP.

Adult↗
PubMed1997

A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).

Adenocarcinoma↗
PubMed1997

Prevalence of specific language impairment in kindergarten children.

This epidemiologic study estimated the prevalence of specific language impairment (SLI) in monolingual English-speaking kindergarten children. From a stratified cluster sample in rural, urban, and suburban areas in the upper midwest, 7,218 children were screened. The language screening failure rate was 26.2%. Children who failed the screening and a similar number of controls were then administered a diagnostic battery (n = 2,084) that provided for a diagnosis of SLI using common diagnostic standards. Results provided an estimated overall prevalence rate of 7.4%. The prevalence estimate for boys was 8% and for girls 6%. Variation in prevalence was found among children of different racial/cultural backgrounds; however, these background variables were found to be correlated with parental education, which was also associated with SLI. The parents of 29% of the children identified as SLI reported they had previously been informed that their child had a speech or language problem. The prevalence estimates obtained fell within recent estimates for SLI, but demonstrated that this condition is more prevalent among females than has been previously reported. Also, the clinical identification of these children remains low among kindergarteners.

Child↗
PubMed1997

Normal variation in cutaneous blood content and red blood cell velocity in humans.

This study was designed to determine normal variations in cutaneous blood content, red blood cell content and skin thickness in healthy human volunteers. The blood content (BC) of human skin and the velocity of red blood cells (RBV) has been comprehensively mapped over 30 anatomical sites in 28 volunteers between the age of 7 and 77 years using reflectance spectrophotometry (RFS) and laser Doppler (LD) techniques respectively. Total skin thickness, which may have a relationship with blood content, has been mapped at the same anatomical sites in six of the volunteers using two-dimensional array, 12 MHz ultrasound equipment. The major determinant of BC and RBV was found to be anatomical site. Regardless of age, gender or prior sun exposure, anatomical sites above the waist produced higher readings than below. BC and RBV were found to be dependent on age and gender at most sites with higher readings being observed in males and younger volunteers. The largest difference was seen in males under 55 years whose RFS readings above the waist were significantly higher than in older males or females of any age. Heavy prior sun exposure and skin thickness could not be demonstrated to impact on either RFS or LD readings independently of the effects of anatomical site, gender or age. In general, RFS and LD readings paralleled one another and correlated linearly at most anatomical sites. While RFS readings tended to decrease in the cranio-caudal direction, LD readings were relatively uniform across the body except for the head and groin where they were higher, and the abdomen where they were lower. The site-to-site variations in RFS readings observed in this study correspond well to capillary density variations noted in previous studies.

Adolescent↗