Is germ cell harvest and storage justified in minors treated for cancer?
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Biomedical subjects
Publications and source records attributed to D Walker.
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Ethyl methacrylate (ethyl 2-methyl-2-propenoate, EMA) has been implicated in the development of neurologic impairment following occupational exposure. The potential of EMA to produce neurotoxicity was investigated in adult male Sprague-Dawley rats in two experiments. In the first experiment, animals were administered 100, 200, 400, or 800 mg/kg by daily intraperitoneal (i.p.) injections for 60 d. Control rats received daily i.p. injections of 1 ml saline/kg. Clinical observations, spontaneous motor activity, and performance in the Morris water maze were assessed. Alterations in clinical parameters in the higher dose groups included lethargy, impaired breathing, decreased weight gain, and increased mortality. Alterations in motor activity were observed at 100 mg/kg, a dose that did not cause alterations in clinical parameters, body weight gain, or mortality. There was also a dose-dependent impairment in performance in the Morris water maze. In the second experiment, animals were administered EMA in drinking water at concentrations of 0.1, 0.2, or 0.5% for 60 d. Control rats were administered tap water. Animals were perfused at the termination of exposure and samples of brain, spinal cord, and sciatic nerve were prepared for histological examination. Spongiform alterations were observed in fiber tracts of the forebrain, brainstem, and spinal cord. Clusters of axonal swellings were scattered throughout the dorsal, ventral, and lateral columns of the spinal cord, and typically involved internodal segments of two or three neighboring axons. Shrunken axons with separated myelin lamellae and large axons with thinner than normal myelin sheaths were apparent in the sciatic nerve. The patterns of alterations in the white matter of the spinal cord and the sciatic nerve are consistent with myelinopathy, but additional experiments are necessary to confirm whether oligodendroglia and Schwann cells are the primary sites of injury. In addition to the alterations associated with myelin, there was a decrease in the density of neurons in the ventral horn of the spinal cord. While the observed effects of EMA on the nervous system of rats are consistent with neurologic symptoms of workers exposed to EMA, additional experiments are necessary to determine if the level and route of exposures associated with occupational use produce these impairments in experimental animals.
A complementary pair of rapid methods for the energy calibration of solid-state detectors have been developed. Each method requires only a single measurement from either (i) a glass sample containing elements chosen to produce fluorescence lines over a suitable energy range when exposed to a polychromatic beam of X-rays, or (ii) a powder diffraction standard in the presence of diffraction slits. The fluorescent glass method has the advantage of allowing simultaneous energy calibration of a number of detectors without requiring diffraction slits. There is the potential for the glass material to be incorporated into virtually any sample holder to allow a continuous in situ calibration. Complementary observations of a powder diffraction standard allow simultaneous calibration of diffraction 2theta and monitoring of the detector for drift.
Limited health care budgets have emphasized the need for providers to use resources efficiently. Accordingly, there has been a rapid increase in the number of economic evaluations of communicable disease health programmes in developing countries, as there is a need to implement evidence-based policy decisions. However, given the prohibitive cost of many economic evaluations in low-income countries, interest has also been generated in pooling data and results of previously published studies. Yet, our review demonstrated that very few published economic evaluations have been performed during 1984-1997 (n=107). Certain diseases and geographical areas have also been neglected. Of those studies published, appropriate analytic techniques have been inconsistently applied. In particular, there are four immediate concerns: the narrow perspective taken-dominance of the health care provider viewpoint and reliance on intermediate outcomes measures; bias-some costs were excluded from estimates; the lack of transparency-sources of data not identified; and the absence of a critical examination of findings-many papers failed to perform a sensitivity analysis. The usefulness of previously published economic evaluations to help make resource allocation choices on an individual basis and, therefore, for the purpose of international comparisons, pooling or meta-analysis, has to be questioned in light of the results from this study.
OBJECTIVES: To evaluate laparoscopic tubal sterilisation, as compared to minilaparotomy in terms of operative morbidity and mortality. Trials comparing laparoscopy or minilaparotomy with culdoscopy were also included in the review. Different methods used to interrupt tubal patency (excision, occlusion and coagulation) and comparison of different forms of anaesthesia will be considered in different reviews. SEARCH STRATEGY: Randomised controlled trials (RCTs) have been identified by using the search strategy of the Cochrane Collaboration. The Cochrane Controlled Trials Register has been searched. Reference lists of identified trials have been searched. SELECTION CRITERIA: All randomised controlled trials comparing laparoscopy, minilaparotomy and/or culdoscopy for tubal sterilisation. Except in one trial [Taner 1994] where 4 women underwent curettage at the same time, all women requested tubal sterilisation as an interval procedure. DATA COLLECTION AND ANALYSIS: Trials under consideration were evaluated for methodological quality and appropriateness for inclusion. Data were extracted independently by the reviewers. Results are reported as odds ratio for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: Minilaparotomy vs laparoscopy: There was no difference in major morbidity between the 2 groups. Minor morbidity was significantly less in the laparoscopy group (Peto OR 1.89; 95% CI 1.38, 2.59). Duration of operation was about 5 minutes shorter in the laparoscopy group (WMD 5.34; 95% CI 4. 52, 6.16). Minilaparotomy vs culdoscopy: Women undergoing culdoscopy had more major morbidity than women for whom minilaparotomy was performed (Peto OR 0.14; 95% CI 0.02, 0.98). Duration of operation was about 5 minutes shorter in women undergoing culdoscopy (WMD 4. 91; 95% CI 3.82, 6.01). Laparoscopy vs culdoscopy: In the one trial comparing the two interventions there were no significant differences between the groups with regard to major morbidity. Significantly more women suffered from minor morbidities in the culdoscopy group compared to the laparoscopy group (Peto OR 0.20; 95% CI 0.05, 0.77). REVIEWER'S CONCLUSIONS: Major morbidity seems to be a rare outcome for both, laparoscopy and minilaparotomy. The included studies had limited power to demonstrate significant differences especially for the relatively rare but potentially serious outcomes. Personal preference of the woman and/or of the surgeon can guide the choice of technique. Practical aspects (e.g. cost, maintenance, and sterilisation of the instruments) must be taken into account before implementing the more sophisticated endoscopic techniques in settings with limited resources. Culdoscopy is not recommended as it carries a higher complication rate.
The effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, was studied alone or in combination with postnatal hyperthermia, on the structural and neurochemical development of the postnatal brain at 1 and 8 weeks. Pregnant guinea pigs (n = 11) were exposed to 200 p.p.m CO for 10 h/day from midgestation until term (68 days), whereas control mothers (n = 10) breathed room air. On postnatal day 4, neonates from the control and CO-exposed pregnancies were exposed to hyperthermia (35 degrees C) for 75 min or remained at ambient (23 degrees C) temperature. Using semiquantitative immunohistochemical techniques the following neurotransmitter alterations were found in the medulla at 1 week: a decrease in met-enkephalin-immunoreactivity (IR) following postnatal hyperthermia and an increase in 5-hydroxytryptamine-IR following a combination of CO and hyperthermia. No alterations were observed in substance P- or tyrosine-hydroxylase-IR in any paradigm. At 8 weeks of age the combination of prenatal CO exposure followed by a brief hyperthermic stress postnatally resulted in lesions throughout the brain and an increase in glial fibrillary acidic protein-IR in the medulla. Such effects on brain development could be of relevance in cardiorespiratory control in the neonate and could have implications for the etiology of Sudden Infant Death Syndrome, where smoking and hyperthermia are major risk factors.
People find unexpected bad news aversive and often brace themselves by predicting the worst. Three experiments examined whether the pessimism is influenced by personal need. Students who differed in financial need learned that a billing error meant that some students would receive an additional bill from their university. Financially needy students were consistently pessimistic in predicting their likelihood of receiving a bill, whereas non-needy students were not. In addition, the experiments reveal that (a) the pessimism occurred for potential losses but not potential gains, (b) needy students were pessimistic about their own chances but not the chances of a friend, (c) the pessimism was not attributable to needy students' being more readily primed by the news of a possible bill or to needy students' having more experience with billing errors, and (d) the pessimism was specific to monetary losses and did not generalize to other events.
Sooty tern (Sterna fuscata) rookeries are scattered throughout the tropical oceans. When not nesting, individuals wander great distances across open seas, but, like many other seabirds, they tend to be site-faithful to nesting locales in successive years. Here we examine the matrilineal history of sooty terns on a global scale. Assayed colonies within an ocean are poorly differentiated in mitochondrial DNA sequence, a result indicating tight historical ties. However, a shallow genealogical partition distinguishes Atlantic from Indo-Pacific rookeries. Phylogeographic patterns in the sooty tern are compared to those in other colonially nesting seabirds, as well as in the green turtle (Chelonia mydas), an analogue of tropical seabirds in some salient aspects of natural history. Phylogeographic structure within an ocean is normally weak in seabirds, unlike the pronounced matrilineal structure in green turtles. However, the phylogeographic partition between Atlantic and Indo-Pacific rookeries in sooty terns mirrors, albeit in shallower evolutionary time, the major matrilineal subdivision in green turtles. Thus, global geology has apparently influenced historical gene movements in these two circumtropical species.
It was estimated that in 1990, major parasitic diseases accounted for 11.7% of the disease burden from communicable disease. As advances in the prevention, diagnosis and treatment of parasitic diseases are made and implemented, there is a growing economic literature to help decision-makers choose the most efficient control method. The aim of this paper is to identify, describe and analyse the available published data on the efficiency of control strategies against parasitic diseases. Internal validity is assessed through the quality of economic evaluations over time using a series of standard questions, and external validity is assessed in terms of the potential to extrapolate results to other settings. This leads to a discussion of the legitimacy and feasibility of pooling data or results from studies for priority setting in the health sector, resulting in three recommendations: to increase the coverage of economic evaluations for parasitic diseases and types of interventions; to improve the internal validity of studies through guidelines and review procedures; and to explore the external validity of research results by examining their predictive validity across settings.
We report the clinico-pathological features and management of a 49-year-old male with a 30-year history of Type 1 diabetes mellitus who had nephropathy (proteinuria 1.81 g/24 h, creatinine 136 micromol/l), proliferative retinopathy and severe somatic and autonomic neuropathy. A sural nerve biopsy demonstrated marked myelinated fibre loss with unmyelinated fibre degeneration and regeneration combined with extensive endoneurial microangiopathy. The management of the patient's blood pressure problems (supine hypertension) and symptomatic postural hypotension is discussed.
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Nearly all of the 906 embryos from a male-tended nest of the sand goby (Pomatoschistus minutus) were genotyped at two hypervariable microsatellite loci to document conclusively the number of mothers and their relative genetic contributions to the nest. The true number of mothers determined by this nearly exhaustive genetic appraisal was compared to computer simulation treatments based on allele frequencies in the population, assumptions about reproductive skew, and statistical sampling strategies of progeny subsets. The "ground-truthed" appraisal and the theoretical estimates showed good agreement, indicating that for this nest a random sample of approximately 20 offspring would have sufficed for assessing the true number of biological parents (but not necessarily their relative genetic contributions). Also, a general dilocus matrix procedure is suggested for organizing and interpreting otherwise cumbersome data sets when extremely large numbers of full-sib and half-sib embryos from a nest are genotyped at two or more hypervariable loci.
Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in the fetal guinea pig. Pregnant guinea pigs were exposed to 200 p.p.m CO for 10 h per day from day 23-25 of gestation (term = 68 days) until day 61-63, at which time fetuses were removed and brains collected for analysis. Using immunohistochemistry and quantitative image analysis, examination of the medulla of CO-exposed fetuses revealed a significant decrease in tyrosine hydroxylase-immunoreactivity (TH-IR) in the nucleus tractus solitarius, dorsal motor nucleus of the vagus (DMV), area postrema, intermediate reticular nucleus, and the ventrolateral medulla (VLM), and a significant increase in choline acetyltransferase-immunoreactivity (ChAT-IR) in the DMV and hypoglossal nucleus compared with controls. There was no difference between groups in immunoreactivity for the m2 muscarinic acetylcholine receptor, substance P- or met-enkephalin in any of the medullary nuclei examined, nor was there evidence of reactive astrogliosis. The results show that prenatal exposure to CO affects cholinergic and catecholaminergic pathways in the medulla of the guinea pig fetus, particularly in cardiorespiratory centers, regions thought to be compromised in SIDS.
The complex between the ribonuclease domain of the ribosome-inactivating colicin E3 and its protein inhibitor, the cognate immunity Im3, has been crystallized and preliminary X-ray characterization has been performed. Single crystals of the 1:1 complex were grown from hanging-drop vapour-diffusion experiments using 2-propanol as a precipitant. The space group is P3(1)21 or P3(2)21, with unit-cell parameters a = b = 93.7, c = 76.2 A. When cryocooled, these crystals diffract to a resolution of 2.4 A. A search for suitable conventional heavy-atom derivatives was unsuccessful and so Im3 mutants containing engineered cysteine or methionine residues have been produced for mercury soaks and selenomethionine-labelling experiments, respectively.
The 1.9 A X-ray structure of a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis is reported. This enzyme, MurG, contains two alpha/beta open sheet domains separated by a deep cleft. Structural analysis suggests that the C-terminal domain contains the UDP-GlcNAc binding site while the N-terminal domain contains the acceptor binding site and likely membrane association site. Combined with sequence data from other MurG homologs, this structure provides insight into the residues that are important in substrate binding and catalysis. We have also noted that a conserved region found in many UDP-sugar transferases maps to a beta/alpha/beta/alpha supersecondary structural motif in the donor binding region of MurG, an observation that may be helpful in glycosyltransferase structure prediction. The identification of a conserved structural motif involved in donor binding in different UDP-sugar transferases also suggests that it may be possible to identify--and perhaps alter--the residues that help determine donor specificity.
Ovine Johne's disease, or paratuberculosis, occurs in many countries. In Australia, surveillance using serology is used as part of a control program, but the testing regime is costly relative to its sensitivity. For this reason, culturing of Mycobacterium avium subsp. paratuberculosis in fecal samples pooled from a number of sheep was evaluated. Initially, the effect of pooling on the sensitivity of fecal culture was evaluated using samples from 20 sheep with multibacillary paratuberculosis and 20 sheep with paucibacillary paratuberculosis, each confirmed histologically. All multibacillary cases and 50% of paucibacillary cases were detected by culturing of feces at a pooling rate of 1 infected plus 49 uninfected sheep. In a pilot-scale study in 1997, M. avium subsp. paratuberculosis was detected by pooled fecal culture on 93% of 27 infected farms which were identified originally based on history, clinical signs, and one or more rounds of testing using serologic and histopathologic examinations. Pooled fecal culture was compared with serologic examination for submissions from 335 farms where both tests had been conducted on the same sheep and was significantly more sensitive (P<0.001). Computer simulation of random sampling indicated that the testing of 6 pools of 50 sheep would provide 95% confidence in detecting > or =2% prevalence of infection. The estimated laboratory cost of pooled fecal culture when applied as a flock test is approximately 30% that of serologic examination, and sample collection costs are lower. It is recommended that pooled fecal culture replace serologic examination for detection of M. avium subsp. paratuberculosis infection at the flock level.
OBJECTIVE: To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters. ANIMALS: 44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters. PROCEDURE: Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated. RESULTS: The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE. CONCLUSIONS: Genetic transmission of GSE is under the control of a single major autosomal recessive locus.
SETTING: St. Francis Hospital in Katete District, Eastern Province, Zambia. OBJECTIVE: To compare the incremental cost-effectiveness of examining serial sputum smears for screening suspects for pulmonary tuberculosis at a rural district hospital in Zambia. DESIGN: An incremental cost-effectiveness analysis of serial sputum smear examinations for diagnosing pulmonary tuberculosis based on laboratory results collected during 1997 and 1998 in a rural district hospital in Zambia. The cost analysis took a health service provider perspective, and used the ingredients approach. The cost-effectiveness is expressed in terms of the incremental cost per tuberculosis case diagnosed. Relevant information was obtained from various sources, including administrative records, interviews and direct observation. RESULTS: Of a total of 166 acid-fast bacilli positive suspects who had three sputum smears examined sequentially, 128 (77.1%) were found on the first smear, a further 25 (15%) on the second smear and 13 (7.9%) additional cases were identified on the third smear. The economic analysis shows that the incremental cost of performing a third test, having already done two, increases rapidly with only a small gain in terms of additional cases of tuberculosis identified. CONCLUSION: A policy of examining two samples should be considered in resource-poor settings, if the remaining steps of the national diagnostic algorithm can be adhered to with respect to smear-negative suspects.