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Biomedical subjects

P Rogers

Publications and source records attributed to P Rogers.

At least 55 records · Page 3Linked to original sources

Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

PURPOSE: To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%. PATIENTS AND METHODS: Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death. RESULTS: Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy. CONCLUSION: Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.

Adolescent↗

The rate of diagnosis and demography of pelvic inflammatory disease in general practice: England and Wales.

Knowledge of pelvic inflammatory disease (PID) epidemiology is essential to the understanding of reproductive morbidity in women. This paper estimates the rate of PID diagnosis in general practice (GP) and the level of association between PID diagnosis and demographic factors. Diagnoses of PID were made at 1.7% of attendances amongst women aged 16 to 46. Increased risk of PID was associated with smoking (P<0.0001), younger age groups (P<0.0001) and lower socioeconomic groups (P<0.0001). Compared to patients who were married, increased risk was also associated with those patients who were widowed, separated or divorced and not cohabiting (adjusted rate ratio (RR)=1.62; confidence limits (CL) 1.35 to 1.97), and with those who were unmarried but cohabiting (adjusted RR=1.32; 95% CL 1.11 to 1.56). General practice is an important focus for the diagnosis and treatment of PID. If intervention and surveillance are to be undertaken effectively, more has to be known about the epidemiology of this important public health problem.

Adolescent↗

Feline herpesvirus infection in a group of semi-captive cheetahs.

Clinical disease caused by feline herpesvirus type-1 in wild felid species is similar to that in domestic cats. Herpesviruses are endemic in free-ranging lions in South Africa but actual clinical disease due to them has not been reported in free-ranging felids. The first reports of feline herpesvirus infection associated with clinical disease in wild felids came from Australia and the USA in 1970. Subsequent reports of clinical disease in cheetahs and other wild felid species were limited to captive animals. This report deals with clinical disease in a group of semi-captive cheetahs in which 18 animals were affected, and included 12 adult males, 4 adult females and 2 subadults. No mortalities occurred in this group, the most common clinical signs being sneezing, nasal discharge and loss of appetite.

Acinonyx↗

Bladder microvasculature in women with interstitial cystitis.

PURPOSE: A cardinal cystoscopic finding in women with interstitial cystitis is mucosal small vessel hemorrhage or glomerulations after hydrodistention. We quantified and compared microvascular density and endothelial proliferation in the bladder biopsies of women with interstitial cystitis and a control group of women who were undergoing incontinence or prolapse surgery. MATERIALS AND METHODS: We performed computer assisted image analysis and immunohistochemical studies to compare differences in the blood vessel count, and proportional area in the bladder suburothelium and deeper submucosa of bladder biopsies of 52 women, including 26 with interstitial cystitis. Routine light microscopy features were examined and correlated with microvascular density. RESULTS: In the bladder biopsies of women with interstitial cystitis there was a lower blood vessel count (p = 0.01), and a lower proportion of the total image consisted of blood vessel wall (p = 0.03) in the suburothelium than in control biopsies. We noted no difference in the blood vessel count of the deeper submucosa or in the degree of endothelial cell proliferation. Suburothelial blood vessel differences correlated with the degree of histological change, such as edema, inflammatory infiltrate and vascular congestion. CONCLUSIONS: We found decreased microvascular density in the suburothelium but not in the deeper submucosa in bladder biopsies of women with interstitial cystitis.

Cystitis, Interstitial↗

Prevalence of helicobacteriosis and gastritis in semicaptive cheetahs (Acinonyx jubatus).

Endoscopic biopsy specimens were obtained from the cardiac, fundic, and pyloric stomach regions of 28 semicaptive cheetahs (Acinonyx jubatus) to look for signs of helicobacteriosis and gastritis. Impression smear cytology and urease tests were positive in 23 and 26 of the cheetahs, respectively. Histopathology showed mild or no lesions in 27 cheetahs; only one cheetah had moderate gastritis. Gastritis was uncommon in these semicaptive cheetahs, and stress could play a major role in the development of helicobacteriosis-associated gastritis in the captive cheetah.

Acinonyx↗

The relationship of HIV prevalence in pregnant women to that in women of reproductive age: a validated method for adjustment.

OBJECTIVE: To devise and validate a method for adjusting HIV seroprevalences in pregnant women to estimate population prevalences among all women in their child-bearing years. DESIGN: Birth and termination rates from women with known HIV infection in the United Kingdom were calculated according to the likely route of HIV infection and whether HIV infection was diagnosed. METHODS: Birth and termination rates were weighted and combined to produce summary statistics. Comparisons were then made with population birth and termination rates to derive summary relative inclusion ratios (RIRs), the relative probabilities of including HIV-infected and uninfected women in seroprevalence surveys of pregnant women. RESULTS: The derived RIRs for women having live births were close to unity: 1.03 [95% confidence intervals (CI) 0.90-1.17] for London and 0.80 (Cl, 0.71-0.89) for elsewhere in England and Wales. This indicates that currently observed overall seroprevalences among pregnant women having live births in London would be similar to those among all women of the same age, while elsewhere it would be slightly underestimated. Sensitivity analysis indicated that RIRs could, however, vary three-fold (0.47-1.56) according to the proportion of diagnosed maternal infections and the mix of maternal HIV-exposure categories. The method was validated by using it to predict the ratio of unlinked seroprevalences between women having terminations and live births in London. It predicted a ratio of 1.74: 1, which is close to the observed ratio of 2.07 : 1. CONCLUSIONS: Application of HIV seroprevalences from pregnant women to whole populations may need adjustment for fertility rates among HIV-infected women. A general method for this has been derived and validated. Gathering fertility data for HIV-infected women is a useful adjunct to serosurveillance.

Birth Rate↗

ras mutation and platinum resistance in human ovarian carcinomas in vitro.

A panel of 16 human ovarian carcinoma cell lines comprising cisplatin naive as well as those with acquired cisplatin resistance was studied to determine if there was a relationship between ras status and cisplatin sensitivity. From the ras expression studies alongside data produced by direct DNA sequencing, there was very little to suggest that ras overexpression or mutation plays a role in the cisplatin sensitivity of the panel of human ovarian carcinoma cell lines tested. A weak correlation (r2 = 0.53) was found between total Ras protein levels and resistance to cisplatin. No relationship was found between Kirsten-Ras protein levels and cisplatin sensitivity (r2 = 0.0). Only one ras mutation (codon 13, Kirsten exon 1, glycine --> aspartate in the HX62 cell line) was observed in the cisplatin naive cell lines from the panel which comprised both cisplatin sensitive and resistant models. Of interest, however, was that the HX62 cell line was the most resistant to cisplatin. No ras mutations were found in those cell lines which had repeatedly been exposed, and acquired resistance, to cisplatin. The A2780 and CH1 human ovarian carcinoma cell lines were transfected with activated, mutant Harvey-ras and, as a result, were shown to display elevated MAP kinase phosphorylation in low serum concentration growth medium. No changes in cisplatin sensitivity were found following transfection with activated Harvey-ras in these 2 human ovarian carcinoma tumor cell models which, importantly, differed greatly in their expression of Bcl-2. Therefore, when conducted under similar conditions to previously published studies, very little evidence was found to support Harvey-ras activation as a factor which can either sensitize or confer resistance to cisplatin in human ovarian carcinoma cell lines.

Carcinoma↗

Comparison of newborn hearing screening by transient otoacoustic emissions and auditory brainstem response using ALGO-2.

The aim of this study is to compare pass rates for two different hearing screening methods in well newborns as a function of age. A previous study by this group compared click evoked otoacoustic emissions (EOAE) and automated auditory brainstem response (ABR) using the ALGO-1 infant hearing screener (Natus Medical, Foster City, CA). Since that study, a new generation automated ABR screener, the ALGO-2, has been developed. In this study, 232 ears in 116 healthy newborn infants aged 5-48 h were tested using the ALGO-2 screener and EOAE. Overall, 92% of ears passed the ABR, while 57% passed the EOAE screen. The ABR pass rate was higher than in the previous study, where 88.5% of ears passed the ABR screen using ALGO-1. The EOAE pass rate in the present study was lower than in the previous study, in which 79% passed the EOAE screen. Pass rates for both EOAE and ABR improved significantly with increasing infant age. There was no significant difference in the test time required for ALGO-2 (5.7 min) compared with EOAE (5.2 min). The results are compared with earlier studies and implications for universal hearing screening are discussed.

Acoustic Stimulation↗

Predictors of medication use, compliance and symptoms of hypotension in a community-based sample of elderly men and women.

OBJECTIVE: To investigate use of prescription and non-prescription drugs, predictors of drug use and symptoms of postprandial and postural hypotension were examined in 765 men and 846 women. METHOD: A questionnaire mailed to 6324 subjects randomly chosen from the electoral roll. RESULTS: Drug use, both prescription and non-prescription, was greater (P < 0.0001) in women (mean 4.1 total drugs, CI 3.9, 4.3) than in men (3.5 drugs, CI 3.3, 3.7); 41% of women and 36% of men used at least four drugs. Total drugs used were significantly greater in women (standardized regression coefficient (b) = 0.101, P < 0.0001), and increased with the number of diagnoses (b = 0.461, P < 0.0001) and taking antidepressants (b = 0.160, P < 0.0001). Use of non-prescription drugs was also greater in women (b = 0.094, P < 0.0001) and in association with arthritis (b = 0.053, P = 0.036) but decreased with age (b = -0.013, P < 0.0001). Potentially important drug interactions occurred in 10% of subjects and included hypoglycaemic agents with b-blockers and asthma with b-blockers. Symptoms of postprandial hypotension, reported in 2.6% of subjects, increased with the number of drugs used (OR 1.17, CI 1.05, 1.31) and with diabetes (OR 2.27, CI 1.05, 4.89). Symptomatic postural hypotension, recorded by 13% of subjects, related significantly to age (OR 1.04, CI 1.02, 1.06), tranquillisers (OR 1.98, CI 1.11, 3.54), antidepressants (OR 2.23, CI 1.30, 3.84) and ACE inhibitors (OR 2.14, CI 1.42, 3.22). CONCLUSION: Reduction in the number and frequency of drug doses and better knowledge about drugs may improve compliance. Observed associations with polypharmacy or hypotension suggest possible approaches to decreasing drug-related illness and limiting the adverse effects of hypotension in the elderly.

Aged↗

Regulation of T cell subsets from naive to memory.

To gain insights into the development and regulation of immune responses, we have studied the phenotype, cytokine profiles, activation requirements, and susceptibility to apoptosis of naive CD4, Th1, Th2 polarized effectors, resting memory, and memory effector cells. T cell receptor (TCR) transgenic mice were utilized as a source of enriched naive cells that could be used to generate effector and memory populations. The direct comparison of these populations, which all bear the same TCR, has revealed some interesting distinctions. When restimulated with antigen, effector populations secrete high titers of cytokines in polarized patterns. Retaining their polarized profile, memory cells secrete low levels and memory effector cells secrete very large levels of cytokine. Unlike naive CD4 T cells, effector cell proliferation is not dependent on classic co-stimulation but does require a threshold level of TCR signaling that can be enhanced by accessory interactions. Memory cells have intermediate requirements for co-stimulation/accessory interactions. However, different thresholds of activation are required for production of various cytokines, with requirements for production of interleukin (IL) 2 >> interferon-gamma > IL-4. CD4 subsets also differ dramatically in their susceptibility to apoptosis. Naive Th2 effectors and resting memory cells undergo activation-induced cell death (AICD) 4-7 days after antigen stimulation. In contrast, both primary and memory Th1 effectors undergo rapid AICD mediated by Fas/FasL within 0.5-2 days after stimulation. AICD is substantially blocked by IL-2 and transforming growth factor-beta1, resulting in impressive effector expansion. The process of memory development from effector populations remains mysterious, but these studies suggest roles for cytokines in promoting survival.

Animals↗

Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and mortality.

A prospective cohort study of 129 consecutive patients developing pulmonary infiltrates in the surgical ICU was conducted to determine the predictors and outcome of pulmonary infiltrates. Most common etiologies of pulmonary infiltrates were pneumonia (30%), pulmonary edema (29%), acute lung injury (15%), and atelectasis (13%). Enteral nutrition was associated with a significantly lower incidence of acute lung injury as compared with pneumonia (22% vs 58%, p = 0.012). Patients with liver disease were significantly more likely to have pulmonary infiltrates due to acute lung injury as compared with other etiologies (p = 0.02). Clinical pulmonary infection score (Pugin score) > 6 virtually excluded acute lung injury, pulmonary edema, or atelectasis as etiologies of pulmonary infiltrates. Nosocomial Haemophilus/pneumococcal pneumonia occurred significantly earlier in the ICU as compared with Gram-negative (p = 0.05) or methicillin-resistant Staphylococcus aureus pneumonia (p = 0.01). Pneumonia in trauma patients was significantly more likely to be due to Haemophilus/pneumococcus as compared with all other ICU patients (54% vs 0%, p = 0.0004). These data have implications for treatment of patients with nosocomial pneumonia in the ICU.

APACHE↗

Adjunctive use of inhaled nitric oxide during implantation of a left ventricular assist device.

BACKGROUND: The aim of this study was to evaluate the efficacy of inhaled nitric oxide in the prevention and reversal of pulmonary hypertension during and after left ventricular assist device implantation. METHODS: Inhaled nitric oxide (20 ppm) was administered to seven consecutive patients undergoing implantation of a left ventricular assist device at the time of implantation and for the first 24 hours after operation. RESULTS: Withdrawal of inhaled nitric oxide at 24 hours after operation was associated with a significant rise in both the transpulmonary gradient (from 8+/-1 to 14+/-2 mm Hg, p < 0.01) and in pulmonary vascular resistance (from 110+/-19 to 196+/-32 dynes x sec x cm[-5], p < 0.01). In two patients, the rise in pulmonary vascular resistance resulted in a critical fall in left ventricular assist device flow and hemodynamic deterioration, necessitating urgent reinstitution of inhaled nitric oxide. CONCLUSION: The administration of inhaled nitric oxide at the time of left ventricular assist device implantation prevents rises in pulmonary vascular resistance that in some patients result in critical reductions in left ventricular assist device flow. We suggest that inhaled nitric oxide is a useful adjunctive treatment that should be routinely available at the time of left ventricular assist device implantation.

Administration, Inhalation↗

Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis.

T helper cell (Th) 1, but not Th2, effectors undergo rapid Fas/Fas ligand (FasL)-mediated, activation-induced cell death upon restimulation with antigen. Unequal apoptosis is also observed without restimulation, after a longer lag period. Both effectors undergo delayed apoptosis induced by a non-Fas-mediated pathway. When Th1 and Th2 effectors are co-cultured, Th2 effectors survive preferentially, suggesting the responsible factor(s) is intrinsic to each population. Both Th1 and Th2 effectors express Fas and FasL, but only Th2 effectors express high levels of FAP-1, a Fas-associated phosphatase that may act to inhibit Fas signaling. The rapid death of Th1 effectors leading to selective Th2 survival provides a novel mechanism for differential regulation of the two subsets.

Animals↗

High dose rate Microselectron moulds for Kaposi sarcoma of the palate.

PURPOSE: External beam radiotherapy for Kaposi sarcoma of the palate in HIV positive patients has often severe acute side-effects. As alternative treatment, a high dose Microselectron brachytherapy technique was developed. METHODS AND MATERIAL: A customised dental plate with afterloading tubes was made; from outlines, three dimensional coordinates of source positions and surface points were input to a Target 2 treatment planning computer. For the best dose-distribution on the mould surface, weighting of each source dwell position was adjusted, a plan produced, and a test run with TLD measurements performed. RESULTS: We planned and treated six patients and seven lesions with this technique. A median surface dose of 24 Gy (range 14-39.9 Gy) in 3 fractions over 3 to 10 days was prescribed. There was a complete response for all lesions with only mild mucositis. No relapse occurred in the treated areas. CONCLUSIONS: Kaposi sarcoma of the palate treated with a high dose rate Microselectron dental plate is convenient for the patient, achieves local control and has less acute toxicity compared with external beam radiotherapy.

Adult↗

Effect of inhaled nitric oxide on normal human left ventricular function.

OBJECTIVES: This study determined the effects of inhaled nitric oxide (NO) on load-independent indexes of normal human left ventricular (LV) function. BACKGROUND: Inhaled NO is a potent and selective pulmonary vasodilator. However, when it is used in patients with congestive heart failure, the decrease in pulmonary vascular resistance (PVR) is often associated with an increase in pulmonary capillary wedge pressure. NO has been shown to have a negative inotropic action, but it is not known whether it affects LV chamber function when delivered by inhalation. METHODS: Eleven subjects (51 to 69 years old) with normal LV function (mean ejection fraction 72% [range 60% to 80%]) were studied. Four patients had concomitant coronary artery disease. Pressure-volume loop recordings were used to determine end-systolic and end-diastolic pressure-volume and preload recruitable stroke work relations. NO was delivered at 20 ppm for 10 min. In an additional group of patients with normal LV function, PVR (n = 5) and NO metabolites (n = 9) were measured. RESULTS: There was no effect of inhaled NO on steady state LV pressures, volumes, contractility, contraction duration, active relaxation (time constant of relaxation, peak negative first derivative of left ventricular pressure), diastolic compliance or PVR. NO metabolites (methemoglobin and nitrate) were present in the LV cavity at the same concentration as right atrial venous blood, suggesting inactivation of free NO before arrival in the LV chamber. This study had a power of 0.995 to detect a 5% change in contractility (slope of preload recruitable stroke work relation) for alpha = 0.05, based on the multiple linear regression model used. CONCLUSIONS: These results indicate that 20 ppm of inhaled NO does not have significant effects on normal LV function. This lack of effect may be due in part to rapid inactivation of free NO in transit to the heart.

Administration, Inhalation↗

Temporal bisection in humans with longer stimulus durations.

Normal adults were tested in eight temporal bisection conditions, using 500-Hz tones as stimuli. Stimulus lengths matched, or overlapped with, durations normally used in bisection experiments with animals, and chronometric counting was prevented by using a concurrent digit-shadowing task. Four experimental groups were used to investigate any effects of stimulus spacing, and stimuli were logarithmically or linearly spaced between standard "short" and "long" durations of 1 and 4, or 2 and 8 sec. A slight leftward shift of the psychophysical function was found in the logarithmic spacing condition, relative to linear spacing. Four other groups tested the conjecture that the ratio of the short and long standards might play some role in determining the location of the bisection point, and conditions with long/short ratios of 2:1 and 5:1 were used. In all cases the bisection point was close to the arithmetic mean of the short and long standards, rather than the geometric mean, as in animal studies. Overall, however, smaller long/short ratios (which may indicate more difficult temporal discriminations) produced more sensitive timing. When the long/short ratio was held constant, however, data showed nearly perfect superimposition, indicating conformity to scalar timing. In general, results were similar to those from experiments with humans that used much shorter durations, indicating the animal/human differences in bisection do not depend on the absolute lengths of the stimuli used.

Humans↗

Epidemiology of genital Chlamydia trachomatis in England and Wales.

OBJECTIVE: To describe the recent epidemiology of genital Chlamydia trachomatis infection in England and Wales. DESIGN: Retrospective study of routinely available surveillance datasets and ad hoc prevalence studies. METHODS: Numbers of new cases of genital C trachomatis infection, obtained from the Department of Health and Welsh Office, were combined with the estimated mid-year resident population of England and Wales. Rates were analysed for trend over time using a log linear age period model in GLIM4. Ad hoc prevalence and case finding studies carried out over the past 20 years were critically assessed in terms of study design and testing methodologies. RESULTS: Attendance rates at genitourinary medicine (GUM) clinics were higher for women than men over the period 1989 to 1994 as were the number of laboratory reports. The highest rate of attendance (GUM clinic data) was for women aged 16 to 19 years. There was an overall significant linear decrease in the attendance rates over time for both men (p = 0.0172) and women (p = 0.0000) between 1989 and 1994. There was considerable variation in the prevalence of genital C trachomatis infection detected within different clinical settings, together with a substantial level of asymptomatic infection. CONCLUSIONS: Genital C trachomatis infection is broadly distributed throughout the sexually active population, with a substantial reservoir of asymptomatic infection among those generally perceived to be at low risk of a sexually transmitted infection. Young people, particularly women aged 16 to 19 years, are at highest risk of genital C trachomatis infection. This is of concern since younger women are more susceptible than older women to developing complications of chlamydial infection, such as pelvic inflammatory disease. The broad distribution of infection across all sexually active health service attenders and the high level of asymptomatic infection suggest that a new, screening based, approach to the control of genital C trachomatis infection is required. Recommendations are made as to the epidemiological research required to guide such work.

Adolescent↗