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Biomedical subjects

J Garland

Publications and source records attributed to J Garland.

At least 19 recordsLinked to original sources

Sandostatin LAR (long-acting octreotide acetate) for malignant carcinoid syndrome: a 3-year experience.

BACKGROUND: Somatostatin analogues are the best therapy for controlling the symptoms of malignant carcinoid syndrome. Octreotide acetate given as subcutaneous injection up to three times daily, intramuscular Lanreotide injection given once per 1-2 weeks and monthly intramuscular Sandostatin LAR have demonstrated similar efficacy in short-term studies. AIM: To assess the long-term effect of Sandostatin LAR on the management of patients with malignant carcinoid syndrome. METHODS: This was a 3-year retrospective study. Twenty-seven patients were assessed with a median follow-up of 23 months. Thirteen patients were switched from subcutaneous octreotide and 14 patients were octreotide naive. All patients showed avid uptake on indium-111 octreotide imaging. RESULTS: Ten of the 13 patients previously on subcutaneous octreotide and 13 of the 14 patients who were octreotide naive had good symptom control on Sandostatin LAR. Over the period of follow-up, many patients showed progression of their tumour and required additional therapies. Patients expressed a preference for monthly intramuscular Sandostatin LAR as opposed to daily subcutaneous injections of octreotide. Although Sandostatin LAR was difficult to administer in certain instances, overall it was well tolerated. CONCLUSIONS: Sandostatin LAR provides good long-term symptomatic control in patients with malignant carcinoid syndrome; it is well tolerated and patients expressed improved satisfaction in their management.

Adult↗

Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study.

OBJECTIVE: The objective of this study was to determine the renoprotective effects of ground flaxseed in patients with lupus nephritis. METHODS: Forty patients with lupus nephritis were asked to participate in a randomized crossover trial of flaxseed. Twenty-three agreed and were randomized to receive 30 grams of ground flaxseed daily or control (no placebo) for one year, followed by a twelve-week washout period and the reverse treatment for one year. At baseline and six month intervals, serum phospholipids, flaxseed sachet counts, serum creatinine, 12-hour urine albumin excretion and urine albumin to creatinine ratios, serum viscosity and plasma lipids were measured. RESULTS: There were eight drop-outs and of the 15 remaining subjects flaxseed sachet count and serum phospholipid levels indicated only nine were adherent to the flaxseed diet. Plasma lipids and serum viscosity were unaltered by the flaxseed supplementation whereas serum creatinine in the compliant patients during flaxseed administration declined from a mean of 0.97+/-0.31 mg/dL to a mean of 0.94+/-0.30 mg/dL and rose in the control phase to a mean of 1.03+/-0.28 mg/dL [p value <0.08]. Of the fifteen patients who completed the study, similar changes were noted [p value <0.1]. The nine compliant patients had lower serum creatinines at the end of the two-year study than the 17 patients who refused to participate [p<0.05]. Microalbumin at baseline declined in both control and flaxseed time periods, but there was a trend for a greater decline during flaxseed administration [p<0.2]. CONCLUSIONS: Flaxseed appears to be renoprotective in lupus nephritis, but this interpretation is affected by under powering due to poor adherence and potential Hawthorne effects.

Albuminuria↗

Response of soybean rhizosphere communities to human hygiene water addition as determined by community level physiological profiling (CLPP) and terminal restriction fragment length polymorphism (TRFLP) analysis.

In this report, we describe an experiment conducted at Kennedy Space Center in the biomass production chamber (BPC) using soybean plants for purification and processing of human hygiene water. Specifically, we tested whether it was possible to detect changes in the root-associated bacterial assemblage of the plants and ultimately to identify the specific microorganism(s) which differed when plants were exposed to hygiene water and other hydroponic media. Plants were grown in hydroponics media corresponding to four different treatments: control (Hoagland's solution), artificial gray water (Hoagland's+surfactant), filtered gray water collected from human subjects on site, and unfiltered gray water. Differences in rhizosphere microbial populations in all experimental treatments were observed when compared to the control treatment using both community level physiological profiles (BIOLOG) and molecular fingerprinting of 16S rRNA genes by terminal restriction fragment length polymorphism analysis (TRFLP). Furthermore, screening of a clonal library of 16S rRNA genes by TRFLP yielded nearly full length SSU genes associated with the various treatments. Most 16S rRNA genes were affiliated with the Klebsiella, Pseudomonas, Variovorax, Burkholderia, Bordetella and Isosphaera groups. This molecular approach demonstrated the ability to rapidly detect and identify microorganisms unique to experimental treatments and provides a means to fingerprint microbial communities in the biosystems being developed at NASA for optimizing advanced life support operations.

Bacteria↗

Apoptosis in factor-dependent haematopoietic cells is linked to calcium-sensitive mitochondrial rearrangements and cytoskeletal modulation.

Apoptosis in murine haematopoietic interleukin (IL)3-dependent cell lines is induced within 6-8 h by IL-3 withdrawal. Direct introduction of cytochrome c by electroporation induces apoptosis within 2 h and was inhibited by caspase inhibitors, such as Z-VADfmk and Z-Dfmk. We report here that apoptosis induced by IL-3 withdrawal was refractory to these inhibitors but was accompanied by striking redistribution of mitochondria, which aggregated into an area associated with centrioles without loss of Deltapsim. Both mitochondrial redistribution and apoptosis were inhibited by the calcium ionophore, ionomycin. Nocodozole, an inhibitor of microtubule assembly, also induced apoptosis, which was unaffected by caspase inhibitors. Although nocodozole did not alter mitochondrial distribution, it significantly reduced Deltapsim, and both reduction of Deltapsim and apoptosis were inhibited by ionomycin. Oligomycin, which inhibits the mitochondrial FoF1 ATPase, similarly induced apoptosis, which was unaffected by caspase inhibitors but was inhibited by ionomycin. Further, oligomycin stimulated the novel formation and release of surface membrane-derived vesicles containing mitochondria with intact Deltapsim; ionomycin also inhibited their production. In all these conditions, Bcl-2 protected cells from apoptosis. Our studies show that apoptosis induced by three very different agents shares insensitivity to caspase inhibitors, suppression by ionomycin and effects on mitochondria, which all appear to be linked to cytoskeletal/microtubule activity. They suggest that microtubules and the cytoskeleton play an important role in apoptosis through mechanisms affecting mitochondria but which are independent of cytochrome c release.

Animals↗

Cigarette smoking patterns in patients after treatment of bladder cancer.

BACKGROUND: Assessment of smoking status and identification of those most likely to continue smoking are important in the management of patients who have bladder cancer, because continued smoking following diagnosis and treatment increases the likelihood of treatment-related complications, recurrence, second primary malignancies, and morbidity and mortality. METHODS: Patients (n = 224) receiving follow-up care of previously treated bladder cancers completed a brief written survey assessing their post-diagnosis smoking patterns. RESULTS: Despite the risks of continued smoking, 69% of the patients who had been active smokers at the time of diagnosis (n = 84) reported smoking at some point following the diagnosis and 45% reported smoking at the time of assessment. Patients diagnosed at earlier stages were more likely to continue smoking. Patients diagnosed at later stages were 2.80 times more likely to be continuous abstainers than those diagnosed sooner (95% CI, 1.08-7.25). CONCLUSIONS: The findings underscore the need to assess smoking status and provide smoking-cessation advice and counseling within routine comprehensive care of bladder cancer patients.

Adult↗

Clinical suggestions for management of stimulant treatment in adolescents.

Children with attention-deficit hyperactivity disorder (ADHD) do not typically outgrow this condition in adolescence, which is a challenging period of development. Management of ADHD in adolescence requires specific accommodations. These include providing adolescents with as much control over treatment as possible, so that they perceive treatment to be widening their autonomy rather than limiting it. Wherever possible, medication needs to be long-acting to facilitate compliance and to minimize problems with rebound misbehaviour and moodiness. Comorbid psychiatric symptoms and syndromes need to be evaluated carefully both pre- and posttreatment. Ongoing psychoeducation and support can help to restructure the demands that an adolescent with ADHD faces at home and school so that they are more manageable. With active treatment it may be possible to prevent the serious morbidity associated with ADHD during this period and to lay a foundation for adulthood.

Adolescent↗

Influence of smoking status on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma of the bladder.

BACKGROUND: The aim of this study was to assess the influence of tobacco exposure, at the time of diagnosis, on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma (TCC) of the bladder. METHODS: A retrospective cohort study was performed using the MSKCC Registry to identify all institutional cases of "noninvasive" TCC (n = 1632) between 1985 and 1995. After employing exclusion criteria, 286 cases of incident tobacco-associated superficial TCC were divided into 3 strata of tobacco exposure (127 ex-smokers, 51 quitters, and 108 continued smokers) by chart review and post hoc questionnaires (n = 82). Measured outcomes included recurrence free survival and survival free of adverse events (defined a priori as disease progression or other urinary tract TCC). RESULTS: There were no significant differences among ex-smokers, quitters, and continued smokers in terms of stage, grade, tumor size, multifocality, up-front bacillus Calmette-Guérin therapy, or median follow-up. Ex-smokers presented at a later age than individuals who continued to smoke. Post hoc questionnaires and chart reviews were compared in terms of smoking status at time of diagnosis, and reliability was excellent (kappa = 0.89). Multivariate analyses revealed diminished recurrence free survival among continued smokers versus quitters or ex-smokers. Univariate analyses revealed diminished adverse event free survival among continued smokers versus quitters or ex-smokers. Multivariate models assessing adverse event free survival revealed a similar trend (P = 0.06). CONCLUSIONS: Continued smokers experience worse disease-associated outcomes than patients who quit smoking. Smoking cessation should thus be employed as a tertiary prevention strategy for patients with superficial TCC.

Adult↗

Regulation of prelamin A endoprotease activity by prelamin A.

The maturation of lamin A is completed by the endoproteolytic cleavage of its farnesylated precursor protein, prelamin A. In the absence of this cleavage, prelamin A can neither give rise to lamin A nor assemble into the nuclear lamina. We call the enzyme which catalyzes this endoproteolytic step the 'prelamin A endoprotease'. In this study, we begin characterization of the regulation of prelamin A endoprotease. In particular, we address the question as to whether prelamin A endoprotease activity is constitutive in cells or responds to expression of prelamin A. To do this, we compared the activity of this novel endoprotease in cells which express prelamin A with those that do not. Our data shows that the enzymatic activity of prelamin A endoprotease is enhanced by the expression of prelamin A.

Chromatography, Thin Layer↗

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Attention Deficit Disorder with Hyperactivity↗

Verapamil sensitive incessant ventricular tachycardia in the newborn.

Incessant VTs in infancy are often poorly tolerated. Response to conventional antiarrhythmic therapy is disappointing. The present case involves a 3-week-old infant with an incessant VT of a left bundle branch block, and normal axis morphology. This tachycardia was inducible with both atrial and ventricular pacing, but not by premature stimulation. Tachycardia persisted despite treatment with adenosine, esmolol, procainamide, and flecainide. Intravenous verapamil suppressed tachycardia and prevented inducibility, and no further recurrences were seen on oral verapamil. This case suggests that some incessant VTs in infancy may be due to calcium channel related afterdepolarizations or triggered activation.

Anti-Arrhythmia Agents↗

Pulmonary hemorrhage risk in infants with a clinically diagnosed patent ductus arteriosus: a retrospective cohort study.

OBJECTIVE: To determine if an early, clinically detectable patent ductus arteriosus (PDA) was associated with pulmonary hemorrhage (PH) in infants who received rescue artificial surfactant therapy. METHODS: This retrospective cohort study of 233 low birth weight infants (< or = 1700 g) who received artificial surfactant therapy for respiratory distress syndrome compared antenatal and postnatal characteristics of infants with PH and without PH. Pulmonary hemorrhage was defined by an onset of bright red blood from the endotracheal tube in quantities that resulted in increased ventilatory support and a new infiltrate on a chest radiograph. RESULTS: Pulmonary hemorrhage occurred in 6% (15/233) of the infants. Thirty-three percent (5/15) of the infants with PH died within 14 days of the hemorrhage. Of the 15 PH, 73% occurred within 48 hours of the first surfactant dose. Pulmonary hemorrhage was more common in male infants and infants of mothers who received antibiotic therapy during labor (P < or = .04). Infants with PH received surfactant earlier than those without PH (P = .04). Nursery events or therapies occurring following surfactant therapy that were associated with PH included: little improvement in ventilatory efficiency index (P = .01), dopamine infusion (P = .04), and the presence of a clinically detectable PDA before, or at the time of, the PH [60% (9/15) vs 33% (71/217), P = .03]. After adjusting for severity of illness before surfactant therapy, risk of PH remained greater in infants who developed symptoms of a PDA. Dopamine support appeared to modify the association between PDA and PH. CONCLUSIONS: In this retrospective cohort study, pulmonary hemorrhage, was associated with the presence of a clinically detectable patent ductus arteriosus before, or at the time of, pulmonary hemorrhage.

Cohort Studies↗

Treatment of severe imipramine poisoning complicated by a negative history of drug ingestion.

The wide use of imipramine (Tofranil) for the treatment of nocturnal enuresis continues in spite of the unique dangers associated with this drug. Young children are particularly susceptible to the potentially lethal central nervous system and cardiovascular toxicities, yet the toxic potential of imipramine remains unrecognized by both parents and too many physicians. Management of severe imipramine intoxication can be difficult. This report describes a 12-month-old patient with severe imipramine intoxication whose treatment was complicated by a negative history at presentation.

Acute Disease↗

Ventral pallidum projections to mediodorsal nucleus of the thalamus: an anatomical and electrophysiological investigation in the rat.

Horseradish peroxidase (HRP) and single unit recording experiments were done in rats to investigate neural connections from the ventral pallidal region to the mediodorsal nucleus of the thalamus (MD). In the first series, following the diffusion or iontophoretic injection of HRP into the MD, retrogradely labeled neurons were observed throughout the rostrocaudal extent of the ipsilateral ventral pallidum. Most of the labeled neurons were found in an area between the nucleus of the diagonal band and the ventral aspect of the substantia innominata subcommissuralis. Additional labeled neurons were found in the ventral aspect of the globus pallidus and substantia innominata sublenticularis. In the second series, the region shown to contain labeled neurons was explored for single units antidromically activated by single pulse stimulation of the MD in urethane anesthetized rats. One hundred and fifty-nine single units in the subpallidal area were antidromically activated with latencies corresponding to conduction velocities of 0.2-3.9 m/s. A greater percentage of units in the subcommissural region (50.3%) were activated antidromically as compared to the sublenticular region (27.4%). In the third series, the MD was explored for single units which responded orthodromically to stimulation of the ventral pallidum. Fifty-eight percent (40/69) of MD units responded to stimulation of the subcommissural substantia innominata, whereas 90% (72/80) MD units responded to stimulation of the sublenticular substantia innominata. The most frequent type of orthodromic response observed in MD neurons was inhibition with short onset latencies (less than 10 ms). These data provide anatomical and electrophysiological evidence for the existence of direct pathways from the ventral pallidum to the MD and suggest that this projection is part of a corticosubcortical loop through which the frontal cortex with the ventral striatum and pallidum may contribute to motor function.

Animals↗

Adaptation skills in the elderly, their supporters and carers.

The elderly, their supporters and carers are a large group, relatively neglected by psychologists. They appear to have need of training in adaptation skills in areas which include: orientation; activities of daily living; coping with relocation; memory and reminiscence; problem solving; self-care of health; coping with depression or anxiety; facing bereavement and other loss; and confronting dying. For care staff, promoting independent behaviour in elderly residents, maintaining positive attitudes and implementing organizational change are important, and for supporters effective use of resources and coping with caregiving strain. Reality orientation, behaviour modification, memory and reminiscence training, individual and group counselling, bibliotherapy and psychotherapy have been widely used but rarely evaluated thoroughly. Texts and training programmes for carers and supporters abound, but their effectiveness awaits detailed investigation.

Activities of Daily Living↗

Stimulation of interleukin-3 dependent cell growth by specific antibody.

We are attempting to raise antibodies against interleukin-3 receptors by immunizing mice with one cloned line of IL-3 dependent cells. In syngeneic mice immunized with a basophil cell line AC-2, serum contains stimulatory activity preferential for the immunizing cells but largely inactive against an alternative IL-3 dependent line of different phenotype. The serum activity corresponds to a fraction containing a cell agglutinin. Supernatants from hybridomas constructed from immune spleen cells raised by direct spleen immunization also contain binding antibodies, of which a select number show phenotype-restricted proliferative activity. We suggest that such antibodies may be recognizing receptors for IL-3, and that phenotypically different IL-3 dependent cells may express different membrane epitopes concerned with interacting with IL-3.

Animals↗

Distinct mechanisms may account for the growth-promoting activity of interleukin 3 on cells of lymphoid and myeloid origin.

We have investigated whether interleukin 3 (IL-3) supports the growth of cells of different lineages by the same mechanism(s). The experiments were carried out with Ea3 cells, a mouse pre-B cell line, and S-480-3 cells, a mouse basophil cell line, both of which are totally IL-3 dependent. We found that Ea3 lymphocytes but not S-480-3 basophils absorb partially purified IL-3. Both Ea3 and S-480-3 cells respond to IL-3 by increasing anaerobic glycolysis as determined by lactic acid production. S-480-3 cells responded to exogenous ATP by maintaining proliferation and reducing lactic acid production, but Ea3 lymphocytes are refractory to exogenous ATP. We conclude that there may be two distinct mechanisms by which cells respond to IL-3, indicated by early events concerning the binding of IL-3 and the effect of exogenous ATP on respiratory metabolism. One appears to be a ligand-receptor-mediated mechanism in lymphoid cells and the other to be a mechanism that is partially replaceable by exogenous ATP in nonlymphoid cells not associated with lymphoid-like receptors. Our findings may explain (i) the apparent variety of cell lineages promoted by IL-3 by a widely available mechanism that supports glycolysis and, therefore, enables both proliferation and possibly expression of binding sites for lineage specific differentiation factors and (ii) the existence of lymphocytes that express receptors specific for IL-3 and are inducible for other characteristics and functions in a regulated manner.

Animals↗