Altruism can have its rewards.
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Adolescent↗
Biomedical subjects
J Keating
Publications and source records attributed to J Keating.
Mechanical environment affects allograft incorporation.
In a bilateral canine tibial model, the mechanical, radiologic, and histologic characteristics of intercalary allografts stabilized with locked intramedullary nails were compared with those of allografts fixed with compression plates. Both methods of fixation achieved healing to host bone. Tibiae that were plated had more callus with statistically greater mean torsional rigidity and strength than those treated with nails (paired t-test, p </= 0.05). On average, tibiae which had been plated had much higher bending rigidity than those fixed with locked nails; however, the difference in means was not statistically significant. Histomorphometric analysis showed an overall greater total bone formation in those limbs treated with plates compared to nails (paired t-test, p </= 0.04). The mechanical environment created by the different fixation methods are thought to be responsible for the observed differences in healing pattern. The traditional concept of fixation for allografts to achieve maximum rigidity of the construct may not necessarily promote the most appropriate host healing response in all situations. A less rigid fixation method (plates) produced more callus resulting in superior torsional and bending properties. These data show that in this canine intercalary allograft model, limbs fixed with plates produced more external callus resulting in stronger, more rigid healing.
Animals↗
Substance misuse in early pregnancy and relationship to fetal outcome.
UNLABELLED: To establish the frequency of substance misuse in early pregnancy in an urban UK population, 807 consecutive positive pregnancy test urine samples were screened for a range of drugs, including cotinine as an indicator of maternal smoking habits. A positive test for cannabinoids was found in 117 (14.5%) samples. Smaller numbers of samples were positive for other drugs:- opiates (11), benzodiazepines (4), cocaine (3) and one each for amphetamines and methadone. Polydrug use was detected in nine individuals. Only two samples tested positive for ethanol. The proportion with a urine cotinine level indicative of active smoking was 34.3%. The outcome of the pregnancy was traced for 288 subjects. Cannabis use was associated with a lower gestational age at delivery (P < 0.005), an increased risk of prematurity (P < 0.02) and reduction in birth weight (P < 0.002). Whilst maternal smoking was associated with a reduction in infant birth weight (P < 0.05), this was less pronounced than the effect of other substance misuse. CONCLUSION: This study suggests that one in six women in South London are using drugs in early pregnancy and that cannabinoid use is associated with a poorer pregnancy outcome.
Female↗
Phase II trial of high-dose liposome-encapsulated doxorubicin with granulocyte colony-stimulating factor in metastatic breast cancer. TLC D-99 Study Group.
PURPOSE: To estimate the toxicity and response rate of high-dose liposome-encapsulated doxorubicin (TLC D-99, Evacet, The Liposome Company Inc, Princeton, NJ) in patients with advanced breast cancer. PATIENTS AND METHODS: Fifty-two breast cancer patients with bidimensionally measurable metastatic disease and no prior chemotherapy for metastatic disease received a 135 mg/m2 intravenous (i.v.) bolus of TLC D-99 with 5 microg/kg of granulocyte colony-stimulating factor via subcutaneous injection every 21 days. RESULTS: The median number of treatment cycles of TLC D-99 was three (range, one to 10 cycles), and the median total cumulative dose of TLC D-99 was 405 mg/m2 (range, 135 to 1,065 mg/m2). Grade IV neutropenia, thrombocytopenia, and mucositis were experienced by 48 (92%), 46 (88%), and 10 (19%) patients, respectively. Twenty (38%) of patients experienced cardiac toxicity: four (8%) experienced a decrease of 20% or more in left ventricular ejection fraction (LVEF) to a final value > or = 50%, nine (17%) experienced a decrease of 10% or more in LVEF to a final value less than 50%, and seven (13%) developed symptomatic congestive heart failure (CHF), including one patient who died of cardiomyopathy after receiving a total dose of 1,035 mg/m2. In a stepwise logistic regression model, the significant risk factors for the development of CHF were the cumulative dose of prior adjuvant doxorubicin (P = .007) and the total cumulative dose of TLC D-99 (P = .032). The overall response rate was 46% (95% confidence interval [CI], 32% to 61%) on an intent-to-treat basis. The median duration of response was 7.4 months (95% CI, 6.1 to 19.6 months) and the median progression-free survival was 6.1 months (95% CI, 5.4 to 7.5 months). CONCLUSION: There was no added therapeutic benefit to the dose escalation of TLC D-99 in this study. A high rate of cardiotoxicity was also observed, especially among patients who had received prior adjuvant doxorubicin. This was probably attributable to the dose and schedule of TLC D-99 used in this trial, as well as the patient's lifetime cumulative doxorubicin dose. Administration of high-dose TLC D-99 at 135 mg/m2 every 3 weeks by i.v. bolus infusion does not warrant further investigation.
Adult↗
Monitoring therapeutic response in skeletal metastases using dual-energy x-ray absorptiometry: a prospective feasibility study in breast cancer patients.
Response to systemic therapy in breast cancer patients with lytic skeletal metastases manifests as a shift from increased bone resorption to new bone formation. We hypothesized that dual-energy x-ray absorptiometry (DXA) could be used to prospectively quantitate changes in bone mineral density (BMD) in metastatic skeletal lesions in breast cancer patients receiving systemic therapy. Nine metastatic breast cancer patients with one or more assessable lytic skeletal metastases receiving systemic therapy were prospectively evaluated with DXA, skeletal radiographs, computed tomography (CT), and radionuclide bone scans at baseline (t = 0 months, 2 months, and 6 months). The median (range) percentage change in BMD in skeletal lesions among patients responding to systemic therapy was 10.7% (0.1-21.85), 5.0% (-1.3-23.8), and 16.7% (-2.0-50.8) at 0-2, 2-6, and 0-6 months, respectively. Changes in BMD between 0-2, and 0-6 months were significant (Wilcoxin signed rank test; p = 0.013 and p = 0.017, respectively). The percentage change in BMD skeletal lesions between 0-2 and 2-6 months correlated with the changes imaged on skeletal x-rays (Spearman rank order correlation coefficient [Rs] = 0.511, p = 0.011) and CTs (Rs = 0.416, p = 0.046) but less so with bone scans (Rs = 0.293, p = 0.189). It is technically feasible to use DXA to prospectively monitor changes in lytic skeletal metastases in breast cancer patients receiving systemic therapy. The BMD of skeletal metastases increases in patients responding to treatment and was significantly correlated with the changes imaged on skeletal x-rays and CTs. Additional studies of DXA to evaluate response in skeletal metastasis are warranted.
Absorptiometry, Photon↗
Carbohydrate deficient transferrin in the assessment of alcohol misuse: absolute or relative measurements? A comparison of two methods with regard to total transferrin concentration.
Carbohydrate deficient transferrin (CDT) is now accepted as a potentially useful marker for the detection of alcohol misuse. It is not clear whether absolute values or values expressed relative to the total transferrin concentration provide the same diagnostic efficiency. CDT was measured in 35 patients with alcohol related liver disease, 35 subjects abusing alcohol without evidence of liver disease and 35 patients with chronic viral hepatitis using two commercial methods (CDTect and %CDT). To compare the methods, results were normalised by dividing the actual result by the upper limit of the reference range. Subtracting normalised %CDT results from the normalised CDTect results demonstrated a linear relationship between CDTect and total transferrin. This linear relationship could be abolished by calculating the CDTect/total transferrin ratio. The sensitivity of the methods was similar with CDTect (43 and 57%) being slightly superior to %CDT (40 and 46%). Specificity was similar (78%) for both methods. Calculation of the CDTect/total transferrin ratio improved the sensitivity and specificity slightly. The linear relationship between CDTect and total transferrin may produce misleading results in populations with a high prevalence of abnormal total transferrin concentrations and could cause difficulties in method comparisons unless taken into account.
Adolescent↗
Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers.
OBJECTIVE: The aim of the study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. METHODS: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg. 1(-1) and 12 mg . 1(-1), two doses of caffeine (predicted peak concentrations of 4.5 mg. 1(-1) and 9 mg. 1 (-1) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. RESULTS: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. CONCLUSION: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly.
Aged↗
Papular umbilicated granuloma annulare in association with Alagille syndrome.
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Alagille Syndrome↗
Identification of a recombination event narrowing the Lafora disease gene region.
Patients affected with progressive myoclonus epilepsy of the Lafora type present during late adolescence with a characteristic EEG pattern and Lafora bodies seen on skin biopsy. The critical region for the Lafora gene has been localised to chromosome 6q24 flanked by the dinucleotide repeat markers D6S292 and D6S420. This study for linkage of markers from the candidate gene region was performed in a previously unpublished family affected with Lafora disease. EEG and skin biopsy evaluation for Lafora bodies were performed on five of eight family members followed for seizure activity. Haplotype and linkage analysis of DNA from five family members were carried out using the nine dinucleotide repeat markers reported in the common region of homozygosity by Serratosa et al in 1995. The present study of an additional family affected by Lafora disease has narrowed the 17 cM critical region for the Lafora disease gene on chromosome 6q24 to a 4 cM region flanked by markers D6S308 and D6S311.
Chromosome Banding↗
A case of coeliac disease detected via raised 5-hydroxytryptamine and 5-hydroxyindoleacetic acid.
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Adult↗
Repetitive cycles of cyclophosphamide, thiotepa, and carboplatin intensification with peripheral-blood progenitor cells and filgrastim in advanced breast cancer patients.
PURPOSE: As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral-blood progenitor-cell (PBPC) and filgrastim (granulocyte colony-stimulating factor [G-CSF]) in advanced-stage breast cancer patients. PATIENTS AND METHODS: From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (n = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m2 by intravenous (IV) bolus with G-CSF 5 microg/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days for four cycles. PBPC were collected by 2-hour single-blood volume leukapheresis on 2 consecutive days at the time of hematologic recovery from each cycle of doxorubicin. Eighteen patients received 61 cycles of intensification with cyclophosphamide 1,500 mg/m2, thiotepa 125 mg/m2, and carboplatin 200 mg/m2 by IV continuous infusion with G-CSF 10 microg/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. RESULTS: Twelve of 20 patients (60%) completed all four planned cycles of doxorubicin induction followed by four cycles of one-quarter dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophage colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BFU-E) (median slope per day, -1.18; P = .006) were observed over the course of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67%) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensification regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, 100%, and 26% of cycles, respectively. The median duration of each CTCb cycle was 24 days (range, 18 to 63), and the median duration of an absolute neutrophil count (ANC) < or = 500/microL and platelet count < or = 20,000/microL during each cycle was 6 days (range, 2 to 15) and 4 days (range, 0 to 38), respectively. CONCLUSION: It is feasible to administer repetitive cycles of one-quarter dose CTCb intensification with PBPC and G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage over a single high-dose cycle.
Adult↗
Investigation of the association between the presence of cytoplasmic residues on the human sperm midpiece and defective sperm function.
Defective sperm function has been identified as one of the most common causes of human infertility. The aim of this investigation was to identify whether the presence of retained cytoplasm on the human sperm midpiece is associated with defective sperm function. Statistical analysis of data demonstrated a strong negative correlation between the presence of residual cytoplasm on the midpiece of spermatozoa in the inseminate and fertilization rate during IVF. Significant negative correlations were also identified between the percentage of spermatozoa in the ejaculate bearing cytoplasmic residues and (i) spermatozoa having membrane integrity and (ii) sperm concentration. A highly significant positive correlation was also revealed between the percentage of spermatozoa in the ejaculate with membrane integrity and the percentage of motile spermatozoa. These correlations suggest that retained cytoplasm is a cause of subfertility. Measurements of the percentage of spermatozoa bearing residual cytoplasm in the IVF inseminate could provide the basis for a simple predictive test before IVF.
Cytoplasm↗
Approach to ergodicity in quantum wave functions.
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Journal Article↗
Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.
Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.
Adult↗
A survey of the phenomenology and pharmacotherapy of compulsive and impulsive-aggressive symptoms in Prader-Willi syndrome.
Prader-Willi Syndrome (PWS) is a congenital disorder characterized by hyperphagia as well as by other behavioral disturbances such as self-mutilation and temper outbursts. Some of these symptoms have been reported to respond to psychotropic medications. A systematic survey was conducted to gather information on the phenomenology and pharmacotherapy of compulsive and impulsive-aggressive symptoms in PWS. Both compulsive and impulsive-aggressive symptoms are frequent in this population. Pharmacotherapeutic intervention may have a role in the management of these symptoms. Rigorous diagnostic and treatment studies should be undertaken in this population.
Adolescent↗
Abdominal tuberculosis.
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AIDS-Related Opportunistic Infections↗
Brief report: fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale.
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Aged↗
Measurement of plasma serotonin by high-performance liquid chromatography with electrochemical detection as an index of the in vivo activity of fluvoxamine.
A reversed-phase high-performance liquid chromatographic method is described for the measurement of plasma serotonin concentrations. Sample preparation is by a simple solid-phase extraction using C18 columns. An isocratic separation is used with electrochemical detection. The application of the method to the measurement of plasma serotonin concentrations following the administration of fluvoxamine (a serotonin re-uptake inhibitor), maprotiline (a noradrenaline re-uptake inhibitor) and placebo to normal subjects for a seven-day period is reported. Fluvoxamine significantly decreases plasma serotonin over this time period in a linear fashion. No effect on plasma serotonin was seen for maprotiline or placebo. Plasma serotonin concentrations can be used to monitor compliance with fluvoxamine therapy.
Adult↗