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Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

At least 55 records · Page 3Linked to original sources

Impact of attachment styles on dream recall and dream content: a test of the attachment hypothesis of REM sleep.

We tested the hypothesis (McNamara 1996; Zborowski and McNamara 1998) that dream recall and dream content would pattern with interpersonal attachment styles. In study I, college student volunteers were assessed on measures of attachment, dream recall, dream content and other psychologic measures. Results showed that participants who were classified as 'high' on an 'insecure attachment' scale were significantly more likely to (a) report a dream, (b) dream 'frequently', and (c) evidence more intense images that contextualize strong emotions in their dreams as compared with participants who scored low on the insecure attachment scale. In study II, 76 community dwelling elderly volunteers completed measures of attachment, and dream recall. Participants whose attachment style was classified as 'preoccupied' were significantly more likely to report a dream and to report dreams with higher mean number of words per dream as compared with participants classified as 'securely' attached or as 'avoidant' or as 'dismissing.' Dream recall was lowest for the avoidant subjects and highest for the preoccupied subjects. These data support the view that rapid eye movement (REM) sleep and/or dreaming function, in part, to promote attachment.

Adult↗

Pressure support noninvasive positive pressure ventilation treatment of acute cardiogenic pulmonary edema.

We assessed cardiogenic pulmonary edema (CPE) patient response to full mask pressure support noninvasive positive pressure ventilation (NPPV). Adult patients presenting to the emergency department (ED) in acute respiratory failure who clinically required endotracheal intubation (ETI) were studied. In addition to routine therapy consisting of oxygen, nitrates, and diuretics, patients were started on full mask NPPV using a Puritan Bennett 7200 ventilator delivering pressure support 10 cm H(2)O, PEEP 5 cm H(2)O, FiO(2) 100%. Pressure support was titrated to achieve tidal volumes of 5 to 7 mL/kg, and PEEP titrated to achieve oxygen saturation (SaO(2)) > 90%. Outcome measures included arterial blood gas (ABG), Borg dyspnea score, vital signs, and need for ETI. Twenty patients mean age 74.7 +/- 14.3 years were entered on the study. Initial mean values on FiO(2) 100% by nonrebreather mask: pH 7.17 +/-.13, paCO(2) 65.5 +/- 19.4 mmHg, paO(2) 73.8 +/- 27.3 mm Hg, SaO(2) 89.7 +/- 10.0%, Borg score 8.1 +/- 1.4, and respiratory rate(RR) 38 +/- 6.3. At 60 minutes of NPPV, improvement was statistically significant: pH 7.28 (difference.11; 95% CI.04-.19), paCO(2) 45 (difference 20.5; 95% CI 8-33), Borg score 4.1 (difference 4.0; 95% CI 3-5), and RR 28.2 (difference 9.8; 95% CI 5-14). NPPV duration ranged from 30 minutes to 36 hours (median 2 hours, 45 minutes). Eighteen patients (90%) improved allowing cessation of NPPV. Two patients with concomitant severe chronic obstructive pulmonary disease (COPD) required ETI. There were no complications of NPPV. NPPV using full face mask and pressure support provided by a conventional volume ventilator is an effective treatment for CPE and may help prevent ETI.

Acute Disease↗

Reflex sympathetic dystrophy with hidradenitis suppurativa exacerbation: a case report.

Reflex sympathetic dystrophy (RSD) or complex regional pain syndrome type 1, is characterized by spontaneous pain or allodynia and hyperalgesia disproportionate to the inciting event, multiperipheral nerve involvement, edema, vasomotor or sudomotor change, and possible loss of function. It has been described in relation to various insults, including a number of infectious and inflammatory conditions. We report a case of a patient who developed RSD 1 week after an exacerbation of hidradenitis suppurativa, a rare chronic inflammatory disease of apocrine sweat glands. The patient responded well to a combination of range-of-motion exercises, thermal modalities, and oral steroids. Hidradenitis suppurativa should be considered when searching for an etiology of new onset RSD.

Aged↗

Vasodilator pre-treatment of human radial arteries; comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro.

AIMS: The radial artery, increasingly used for coronary artery bypass grafting (CABG). has a potential for spasm which may increase peri-operative risk. Increased alpha-adrenoceptor activation is a key candidate for the spasm. We studied the effects of vasoconstriction in a radial artery, which had undergone brief exposure to the alpha-adrenoceptor antagonist phenoxybenzamine vs the opioid derivative papaverine. METHODS AND RESULTS: Using standard classical organ bath techniques, concentration responses were obtained to norepinephrine in segments of radial artery from 12 CABG patients pre- and post-incubation for 20 min in either phenoxybenzamine 10(-6) M or papaverine 3 x 10(-3) M. Responses were reassessed 2, 4 and 18 h after washout of phenoxybenzamine and 2, 4, 8 and 18 h after washout of papaverine. There was concentration-dependent constriction to norepinephrine (maximum response 0.89 +/- 0.20 (SEM) g x mm(-1), n=6). Constriction to norepinephrine was abolished immediately after incubation in phenoxybenzamine and remained completely inhibited for at least 18 h (P<0.0001 ANOVA phenoxybenzamine pre-treated vs controls). Most of the inhibition of concentration-dependent constriction to norepinephrine following pre-treatment with papaverine was lost 8 h later. CONCLUSION: Radial artery vasoconstriction induced by a clinically relevant agonist, norepinephrine, may be prevented for at least 18 h by pre-incubation in phenoxybenzamine, in contrast to the brief inhibition achieved by pre-treatment with papaverine. Adding phenoxybenzamine to radial artery graft bathing solution may improve early outcome following CABG.

Aged↗

The causes of fever in children attending hospital in the north of England.

OBJECTIVES: Fever is a common symptom in children presenting to casualty. Identifying the seriously ill is difficult. Previous studies, mainly from North America, suggest that symptoms, signs and simple investigations may help to do this. The aim of the present study was to assess the causes of fever and identify clinical and laboratory features suggesting serious disease in U.K. children presenting to hospital with temperatures >or=38 degrees C. METHODS: All children with a temperature of >or=38 degrees C seen in two hospitals between August and October 1999. RESULTS: One hundred and forty one children between 8 days and 16 years of age were studied, 64% male, 55% aged under 2 years. Eighty three percent had temperatures between 38 and 39 degrees C. Ninety six percent were casualty or GP referrals and 4% were tertiary referrals. Twenty nine percent (41/141) had serious disease but microbiologically or radiologically proven in only 22% (31/141); pneumonia (nine), meningitis (seven), sepsis (five), urinary tract infection (five), brain abscess (two), toxic shock syndrome (one), appendicitis (one), ischiorectal abscess (one). Forty two percent (5/12) of microbiologically proven meningitis and sepsis and 36% (8/22) of all meningitis and sepsis were meningococcal. Seventy one percent had non-serious diseases. In cases of serious disease the temperature was >39 degrees C in 15% (sensitivity: 14%, specificity: 82%, PPV: 25%). Poor feeding and restlessness predicted serious disease with a sensitivity of 78% and 76%, respectively. Full blood count (FBC) was taken in 50% of patients on admission; in 44% of serious and 24% of non-serious diseases WBC was between 5000 and 15,000/mm(3) and WBC >or=15,000/mm(3) was seen in 39% of serious diseases (sensitivity:10%, specificity: 95%, PPV: 44%). CONCLUSIONS: One out of three of children referred with fever had a serious disease. Degree of temperature and WBC count were poor predictors of serious disease. Interestingly, poor feeding and restlessness were more sensitive predictors, suggesting high fever and WBC count can not replace clinical assessment of the child with a temperature.

Adolescent↗

Patterns of spread in recurrent head and neck squamous cell carcinoma.

OBJECTIVE: To examine the pattern of spread regarding recurrent disease in primary head and neck squamous cell carcinoma. STUDY DESIGN AND SETTING: A retrospective study reviewed 128 patients who underwent primary tumor resection and postoperative radiation and/or chemoradiation for squamous cell carcinoma at Loyola University Medical Center from July 1993 to August 1998. Patterns of spread of recurrent disease were grouped according to site of recurrence and compared with the histopathology. RESULTS: Of 128 patients, 40 (32%) had recurrent disease, 22 (17%) died without disease, and 66 (51%) are disease free. Although the recurrences in patients who were N0 were primarily local-regional (8/11), the majority of recurrences in patients that were N+ with extracapsular nodal spread involved distant sites (18/24); 17/18 involved metastasis to the lung. SIGNIFICANCE: This study gives the first report at our institution of patterns of spread in recurrent head and neck squamous cell cancer and compares these patterns within subgroups of patients based on the extent of neck disease at the time of primary surgical resection. CONCLUSION: Not only was there a higher rate of recurrent disease in patients with extracapsular nodal spread, there was a much higher involvement of distant metastatic sites as opposed to local-regional recurrence more often seen with the N0 neck. The most common site of distant metastasis was the lung.

Carcinoma, Squamous Cell↗

The effects of increased rehabilitation therapy after brain injury: results of a prospective controlled trial.

OBJECTIVE: The objective was to investigate the effect of increased intensity of rehabilitation therapy provided to brain-injured subjects on the rate at which independence was regained and the duration of hospital admission. DESIGN: A two-centre, prospective, controlled study with random allocation to groups. SETTING: Two district general hospitals on the south coast of England. SUBJECTS: Fifty-six people with moderate and severe head injury consecutively admitted to Southampton and Poole hospitals between June 1995 and September 1997. INTERVENTIONS: Increased intensity of rehabilitation therapy input without change in content. RESULTS: Subjects receiving more intensive therapy made more rapid progress and were discharged home sooner. The different intensities of therapy employed in this study showed no evidence of a 'ceiling' effect and the 'intervention group' made significantly more rapid progress on tests of dependency during the period of admission. A clear response to increased therapy input was seen in one of the centres with more rapid functional improvement and a shorter length of hospital stay. This centre already had more therapy and better community facilities. No such benefits were seen at the other centre where the intervention group had a longer hospital stay than the routine group. CONCLUSION: Increasing the hours per week of therapy given to adults recovering from brain injury in hospital can accelerate the rate of recovery of personal independence and result in their being discharged from hospital sooner. Increased rehabilitation therapy after brain injury is associated with enhanced functional recovery and shorter hospital stay if provided in the context of an integrated service that can provide ongoing community support. There is no evidence of any ceiling effect of therapeutic intensity beyond which no further response is observed.

Adolescent↗

Prevalence of insomnia symptoms in patients with sleep-disordered breathing.

OBJECTIVE: To assess the prevalence of insomnia symptoms in patients with objectively diagnosed sleep-disordered breathing (SDB). DESIGN: Retrospective medical chart review of a representative sample of patients with SDB. SETTING: University sleep-disorders clinic and laboratory. PATIENTS: Two hundred thirty-one patients with SDB were selected from a pool of approximately 2,000 patients with sleep disorders. MEASUREMENTS: Data were extracted from intake questionnaires and polysomnographic studies. RESULTS: Of 231 patients with SDB diagnoses, 115 patients reported no insomnia complaints (SDB-only patients) and 116 patients reported clinically meaningful insomnia complaints (SDB-plus patients). Compared to SDB-only patients, SDB-plus patients reported significantly worse mean sleep characteristics consistent with insomnia, including sleep latency (17 min vs 65 min), total sleep time (7.2 h vs 5.6 h), and sleep efficiency (92% vs 75%). SDB-plus patients experienced significantly more psychiatric disorders, cognitive-emotional symptoms, and physical and mental symptoms that disrupted or prevented sleep. SDB-plus patients also reported greater use of sedative and psychotropic medications and had significantly more primary complaints of insomnia, restless legs or leg jerks, and poor sleep quality despite having relatively similar referral rates for sleep apnea or complaints of loud snoring. CONCLUSIONS: Problematic insomnia symptoms were reported by 50% of a representative sample of patients with objectively diagnosed SDB. Research is needed to determine the degree to which insomnia and related symptoms and behaviors interfere with SDB treatment.

Adult↗

Kidney cancer: the Cytokine Working Group experience (1986-2001): part I. IL-2-based clinical trials.

The Cytokine Working Group (CWG) was initially established in 1986 as the Extramural IL-2/LAK Working Group. With funding from the National Cancer Institute (NCI), the CWG was mandated to confirming data regarding the efficacy of the high-dose interleukin-2 (IL2)/lymphokine-activated killer cell (LAK cell) regimen piloted at the NCI in the treatment of renal cell cancer. Since those initial studies, the CWG has conducted a series of clinical trials, often with correlative immunologic investigations, to evaluate combination immunotherapy in attempts to enhance the efficacy of IL-2 or to reduce toxicity. Subsequently, the CWG conducted trials to demonstrate the activity of lower-dose outpatient combination cytokine regimens to help determine their role in the armamentarium of treatment for metastatic renal cell cancer. This has culminated in a phase III randomized trial comparing the activity of high-dose IL-2 with the activity of outpatient IL-2 plus interferon-alpha. The CWG also has honed the management of both high-dose IL-2 and outpatient IL-2 regimens to make these safer in the hands of experienced clinicians. In addition, the CWG has produced a series of carefully conducted clinical trials of new cytokines, again attempting to define their clinical efficacy as anticancer agents. These include studies of IL-4, IL-6, and IL-12. Currently, the CWG is conducting studies with new approaches to IL-2 therapy, as well as planning trials with new agents for treatment of renal cell cancer. This review describes these efforts conducted over the past 15 yr.

Antineoplastic Agents↗

Kidney cancer: the Cytokine Working Group experience (1986-2001): part II. Management of IL-2 toxicity and studies with other cytokines.

The Cytokine Working Group (CWG) was initially established in 1986 as the Extramural IL-2/LAK Working Group. With funding from the National Cancer Institute (NCI), the CWG was mandated to confirming data regarding the efficacy of the high-dose interleukin-2 (IL2)/lymphokine-activated killer cell (LAK cell) regimen piloted at the NCI in the treatment of renal cell cancer. Since those initial studies, the CWG has conducted a series of clinical trials, often with correlative immunologic investigations, to evaluate combination immunotherapy in attempts to enhance the efficacy of IL-2 or to reduce toxicity. Subsequently, the CWG conducted trials to demonstrate the activity of lower-dose outpatient combination cytokine regimens to help determine their role in the armamentarium of treatment for metastatic renal cell cancer. This has culminated in a phase III randomized trial comparing the activity of high-dose IL-2 with the activity of outpatient IL-2 plus interferon-alpha. The CWG also has honed the management of both high-dose IL-2 and outpatient IL-2 regimens to make these safer in the hands of experienced clinicians. In addition, the CWG has produced a series of carefully conducted clinical trials of new cytokines, again attempting to define their clinical efficacy as anticancer agents. These include studies of IL-4, IL-6, and IL-12. Currently, the CWG is conducting studies with new approaches to IL-2 therapy, as well as planning trials with new agents for treatment of renal cell cancer. This review describes these efforts conducted over the past 15 yr.

Antineoplastic Agents↗

Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index.

PURPOSE: The National Institutes of Health (NIH) chronic prostatitis symptom index was used to determine the prevalence of prostatitis-like symptoms among men (age 20 to 74 years) at risk in a community based study. MATERIALS AND METHODS: The study was a cross-sectional postal survey of men age 20 to 74 years in Lennox and Addington counties, which included a large rural area, 1 major town and a suburban area with a stable population of men representative of Canadian demographics. The questionnaire collected information on 2 domains of chronic prostatitis identified in the NIH chronic prostatitis symptom index, including pain (location, severity and frequency), voiding function (irritative, obstructive), demographics, quality of life, general health and health seeking behavior. The self-reported pain score was used to identify prostatitis-like symptoms in the most discriminating domain. Based on analysis of the index final validation study comparing patients with prostatitis to normal controls and those with benign prostatic hyperplasia, the 2 questions most specific for prostatitis, including perineal and/or ejaculatory pain/discomfort, and a total pain score (0 to 21) 4 or greater were used to identify men with significant prostatitis-like symptoms. RESULTS: A total of 2,987 eligible men received the survey, and it was completed by 868 (29%). Of the men 84 (9.7%) were identified as having chronic prostatitis-like symptoms (mean NIH chronic prostatitis symptom index pain score 9.1 +/- 0.3). The average age of the prostatitis population was 50 years compared with 52 years for men without prostatitis-like symptoms. Prevalence was 11.5% in men younger than 50 years and 8.5% in men 50 years or older. Of the sampled population 57 (6.6%) men had prostatitis-like symptoms and an index pain score 8 or greater (moderate to severe). The index voiding score (0 to 10) was 4.1 +/- 0.5 in men younger than 50 years compared with 1.5 +/- 0.1 for normal controls, and 4.7 +/- 0.4 in those 50 years or older compared with 1.9 +/- 0.1 for normal controls. Of the prostatitis group 60% sought medical help for their symptoms. CONCLUSIONS: In our opinion this community based study using the new prostatitis symptom index confirms that chronic prostatitis-like symptoms are common.

Adult↗

Predictors of patient response to antibiotic therapy for the chronic prostatitis/chronic pelvic pain syndrome: a prospective multicenter clinical trial.

PURPOSE: To our knowledge antibiotics are the most popular choice of therapy for all categories of the chronic prostatitis/chronic pelvic pain syndrome. We determine if culture, leukocyte and/or antibody status of prostate specific specimens predicts patient response to antibiotic therapy. MATERIALS AND METHODS: Patients clinically diagnosed with the chronic prostatitis/chronic pelvic pain syndrome according to the National Institutes of Health (NIH) definition had a lower urinary tract evaluation that included standard microscopy and culture of prostate specific specimens, and determination of the ratio of voided bladder 3 and voided bladder 2 antibody levels against a panel of identified prostate pathogens (enzyme linked immunosorbent assay methodology). Symptom evaluation consisted of the NIH chronic prostatitis symptom index (derived) pain scale 0 to 21, symptom severity index scale 0 to 100, symptom frequency questionnaire scale 0 to 50 and quality of life scale 0 to 6. Patients were stratified according to microscopy, culture and immune status, were treated with 12 weeks of ofloxacin, and were assessed at 4, 12 and 24 weeks with symptom scores as well as global assessments. RESULTS: Based on leukocyte and culture results, 102 evaluable patients were stratified into categories II (14%), IIIA (48%) and IIIB (38%) of the chronic prostatitis/chronic pelvic pain syndrome. Of the cases 23% were categorized as antibody positive and 77% as antibody negative. Average age was 42 +/- 10 years and 92% of patients were white. Of the patients 57% believed that they had moderate to marked improvement. All categories of the chronic prostatitis/chronic pelvic pain syndrome and patients in whom antibody was positive or negative had significant improvement in the NIH chronic prostatitis symptom index, symptom severity index, symptom frequency questionnaire and quality of life scores compared with baseline (p <0.001). There was no significant difference in patient response to the stratification based on culture, leukocyte, that is categories II, IIIA and IIIB had same beneficial response, or antibody status. CONCLUSIONS: Culture, leukocyte and antibody status of prostate specific specimens does not predict antibiotic response in patients with the chronic prostatitis/chronic pelvic pain syndrome. The perceived beneficial effect of antibiotics needs to be evaluated in a randomized placebo controlled trial.

Anti-Infective Agents↗

Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.

CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is converted by the bacterial enzyme nitroimidazole reductase (NTR) into a potent cytotoxic bifunctional alkylating agent, which can be delivered to tumors in adenoviral vectors as virus-directed, enzyme prodrug therapy. This report summarizes a Phase I and pharmacokinetic study of the prodrug, CB1954. Thirty patients, ages 23-78 years (median 62 years), with predominantly gastrointestinal malignancies were treated. CB1954 was administered by i.v. injection every 3 weeks or i.p. followed by 3-weekly i.v. injections, toward a maximum of six cycles. The dose was escalated from 3 to 37.5 mg/m2. No significant toxicity was seen until 24 mg/m2 (recommended i.v. dose). Dose-limiting toxicities (DLT) were diarrhea and hepatic toxicity, seen at 37.5 mg/m2. DLT has not been observed at the current i.p. dose of 24 mg/m2. There was no alopecia, marrow suppression, or nephrotoxicity. Clearance data suggest hepatic metabolism, and <5% of CB1954 was renally excreted. There was a nonlinear relationship between i.v. dose and area under the curve (AUC). At the recommended i.v. dose of 24 mg/m2, the AUC was 5.8 microM/h. Intraperitoneal administration (24 mg/m2) achieved an AUC of 387 microM/h, giving a considerable regional advantage. In vitro, the AUC required to achieve the IC50 for CB1954, in NTR-expressing cancer cells, ranges from 10-50 microM/h. Thus, CB1954 is well tolerated at a dose of 24 mg/m2, and sufficient serum/peritoneal levels are achieved for an enzyme-prodrug approach to be feasible. We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors.

Abdominal Pain↗