Pleomorphic Leimyoma of the scrotum: immunohistochemical stains.
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Genital Neoplasms, Male↗
Biomedical subjects
M Herbert
Publications and source records attributed to M Herbert.
Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial.
CONTEXT: Neisseria meningitidis is a common cause of meningitis and septicemia in infants worldwide. Whether a meningococcal C conjugate vaccine protects infants against the serogroup C strain is unknown. OBJECTIVES: To determine whether a meningococcal C conjugate vaccine is safe and immunogenic and induces immunologic memory in infants. DESIGN: Single-center, double-blind, randomized controlled trial in 1995 and 1996. SETTING: Community, Oxfordshire, England. PARTICIPANTS: One hundred eighty-two healthy infants. INTERVENTIONS: Participants were randomly assigned to receive vaccination with 0. 5-mL doses of 1 of 2 lots of meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or a hepatitis B control vaccine (group 3; n=62), administered with routine immunizations at 2, 3, and 4 months of age. Approximately half of each group received meningococcal C conjugate vaccine and half received plain meningococcal polysaccharide vaccine (MPS) at 12 months of age. MAIN OUTCOME MEASURES: Serum antibodies to meningococcal C polysaccharide, assayed by enzyme-linked immunosorbent assay, and serum bactericidal activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and systemic reactions, recorded for 6 days after each vaccination, compared by intervention group. RESULTS: Meningococcal C conjugate vaccine was well tolerated. After 3 doses, children in groups 1 and 2 achieved significantly higher meningococcal C IgG geometric mean concentrations (21 and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and 420, respectively, vs 4.1; P<. 001) than controls. At 12 months, antibody concentrations had decreased in all groups but remained significantly higher in children vaccinated with meningococcal C conjugate vaccine (SBA, 24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001). Following vaccination with MPS at 12 months of age, SBA in the meningococcal C conjugate vaccine group was significantly higher than in controls (SBA, 789 vs 4.5; P<.001). CONCLUSIONS: Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age. JAMA. 2000;283:2795-2801
Analysis of Variance↗
Embryonic development in vitro is compromised by the ICSI procedure.
The implantation rates achieved with intracytoplasmic sperm injection (ICSI) are equivalent to those with conventional in-vitro fertilization (IVF) but information on embryonic development in vitro after ICSI is scant. In this paper we compare blastocyst formation after IVF and ICSI; we have also investigated the effect of the ICSI procedure with internal control of extrinsic (including paternal) factors. The first series comprised cases of IVF treatment (n = 101) for tubal infertility and ICSI (n = 96) for male infertility. The proportions of embryos developing to the blastocyst stage was significantly lower after ICSI (8.9%, P < 0.001) than after conventional IVF (23.5%). In order to investigate the effect of the ICSI procedure in isolation, blastocyst formation was analysed in a second series of eight cases, in which sibling oocytes were non-selectively subjected to ICSI (n = 78) or IVF (n = 67) with spermatozoa from the same semen sample. It was found that 20% of ICSI embryos and 50% of IVF embryos formed blastocysts (P < 0.01), demonstrating that the ICSI procedure contributes to a reduced capacity for blastocyst formation in vitro.
Adult↗
Characterization of ferrochelatase (hemH) mutations in Haemophilus influenzae.
Haemophilus influenzae lacks most of the biosynthetic enzymes for hemin synthesis. However, the organism has retained ferrochelatase activity, which we identified to be encoded by a hemH-homologous gene. In this report we characterize the growth physiology conferred by hemH mutations under infection and laboratory conditions.
Animals↗
Advanced applications of MRI in human brain science.
Magnetic resonance imaging of the brain is now generally indispensable to state of art clinical medicine. Robust, high resolution imaging systems are currently available worldwide. The availability of MRI has, in little more than a decade, revolutionized the certainty and efficiency of clinical diagnosis and management. As a dividend of this revolution, clinicians and radiologists who are expert in the many and varied applications of MRI methods are able to relate this expertise to a confident mastery of the topographic anatomy of the brain as revealed in magnetic resonance images. Whereas the yield to clinical objectives has been massive, the clinician as yet draws upon a relatively limited sampling of the potential informational harvest from this technology which in theory could further enrich both clinical concerns and those of fundamental neuroscience. Here we will review early explorations into these other offerings with the expectation that the coming decade will see them established comfortably with current uses. We will also consider potential offerings of the extended applications of brain MRI to the characterization and insights into biological origins of certain obscure developmental disorders.
Artificial Intelligence↗
CRG launches genetic bill of rights.
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Eugenics↗
Poor response to hib (PRP-T) vaccine when combined with an acellular pertussis/diphtheria/tetanus vaccine for primary immunization of infants.
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Antibody Formation↗
Severe ovarian hyperstimulation syndrome following salvage of empty follicle syndrome.
We report a case of severe ovarian hyperstimulation syndrome (OHSS) following a rescue of empty follicle syndrome (EFS). This suggests that the risk of developing OHSS remains unaltered even in the presence of EFS. The case supports the possibility of obtaining oocytes that fertilize and cleave normally after a second dose of human chorionic gonadotrophin (HCG) and a repeat oocyte retrieval. It supports the suggestion that the follicles are not necessarily empty in EFS. It demonstrates further that OHSS cannot be prevented by aspiration of follicular fluid and patients with large numbers of follicles and EFS must be warned of this potential complication.
Adult↗
Interleukin-2-induces development of denditric cells from cord blood CD34+ cells.
Dendritic cells (DC) have been shown to develop along a myeloid or lymphoid lineage of differentiation propagated from bone marrow or early thymic precursor cells with hematopoietic cytokines. In our study, we have induced growth and differentiation of DC from cord blood CD34+ cells initiated in interleukin-2 (IL-2) alone or in IL-2 + stem cell factor (SCF) + tumor necrosis factor alpha (TNF-alpha)-supplemented medium and cultured with IL-2 or IL-2 + SCF for 28-35 days. Dendritic morphology and antigenic phenotype of DC grown with IL-2 were characteristic for DC cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Growth and differentiation of DC was followed by an increase in expression of MHC II and co-stimulating molecules CD80 and CD86. We have also shown the expression of the IL-2 receptor (IL-2R) gamma-chain in CD34+ cells after 2-3 days of culture with IL-2 alone. The co-expression of the IL-2R alpha, beta, and gamma subunits in both DC cultured with IL-2- or GM-CSF-containing cocktail of cytokines was also shown. The time curve for induction of IL-2R demonstrated low levels of subunit expression at the beginning of culture. The number of CD1a cells co-expressing CD25, CD122, and CDgamma increased to about 24-68 and to 78-95% after 21 and 28-35 days, respectively. Development of natural killer cells was shown along with DC. The proportion of CD56+ cells and cytotoxicity increased in a time-dependent manner.
Antigens, CD↗
Critical issues in the assessment of child sexual abuse.
This article explores the feasibility of using standardized psychometric methods in the initial stages of an investigation of child sexual abuse; methods that are less intrusive and therefore less damaging to children and their families. We review the complex conceptual and research issues that arise from attempts to assess the many-sided aspects of child sexual maltreatment. Among those considered in both the clinical and research spheres are problems of definition and diagnosis; limitations of clinical interviews, and a variety of direct and indirect psychological instruments used for investigating sexual maltreatment and risk assessment; the inadequacies of experimental designs; and also the political, practical, and ethical restraints that hinder research in this area. It is argued that there is insufficient evidence based on controlled studies or standardized normative tests to advocate any simple, unidimensional methodology for the screening task. However, recommendations are put forward for the cautious, conjoint use of several procedures in a multidimensional approach to assessing child sexual abuse. Suggestions are also made for future research and development.
Case-Control Studies↗
Effects of profound suppression of luteinizing hormone during ovarian stimulation on follicular activity, oocyte and embryo function in cycles stimulated with purified follicle stimulating hormone.
The effects of profound suppression of circulating luteinizing hormone (LH) during the follicular phase of in-vitro fertilization cycles were explored in normal women during treatment with a gonadotrophin-releasing hormone analogue and exogenous purified follicle stimulating hormone. Ovarian responses to treatment and the capacity of supernumerary embryos to undergo blastocyst formation were examined in groups of patients defined by the concentration of plasma LH in the mid-follicular phase. Concentrations < or = 0.5 IU/I diagnosed the group with profoundly suppressed LH (<LH, n = 20), which was compared with the remaining patients (nLH, n = 41). The <LH group showed lower oestradiol concentrations at human chorionic gonadotrophin administration, while the total follicular development estimated by the total follicular diameters was similar in both groups. The oestradiol secreted per follicle, estimated by the circulating concentration per mm total follicular diameter, was significantly lower in the <LH group. The combined effects of a trend to lower yield of oocytes (not significant) and a lower fertilization rate (not significant) resulted in a significantly reduced quantity of embryos available for cryopreservation after the fresh transfer. Supernumerary embryos were cultured for 7 days to determine blastocyst development rates, and the degree of LH suppression made no difference to embryo developmental competence (nLH, 23%; <LH, 27%), or the rates of blastocyst formation. The group of patients with profoundly suppressed mid-follicular phase LH showed a reduced yield of oocytes and embryos which resulted in significantly fewer embryos available for cryopreservation. However, the developmental potential of those embryos, represented by the ability to form blastocysts in vitro, was unaffected.
Adult↗
An investigation of the possible neurotoxic effects of intrathecal midazolam combined with fentanyl in the rat.
In previous work, midazolam was injected intrathecally and produced reversible, segmental, spinally mediated anti-nociception sufficient for abdominal surgery in a rat model. The neurotoxic effect of midazolam, alone or combined with fentanyl, injected intrathecally repeatedly on 15 occasions over a period of 1 month, was studied in the same model. We sought to establish whether this would produce neurological damage or neurotoxic injury. Histopathological examination of the excised spinal cord and paraspinal tissues was carried out. Thirty Wistar strain rats with nylon catheters chronically implanted in the lumbar subarachnoid space were divided into five groups: group 1 (n = 6) received 40 microL of midazolam 0.1%; group 2 (n = 6) received 40 microL of fentanyl 0.005%; group 3 (n = 6) received 20 microL of midazolam 0.1% plus 20 microL of fentanyl 0.005%; group 4 (n = 6) received 40 microL of lignocaine 2%; group 5 (n = 6) received 40 microL of phenol in water. All substances were injected through the implanted catheters. The neurological recovery of all the animals in the four groups that received intrathecal midazolam alone, fentanyl alone, midazolam plus fentanyl and lignocaine alone was similar and complete. There were no significant differences in the histological changes in the neural tissues of these groups, despite repeated application of the test substances. Group 5 demonstrated the typical neurolytic lesions of phenol when injected intentionally into the subarachnoid space.
Analgesics, Opioid↗
The cart before the horse.
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Academies and Institutes↗
Effect of fibroblast growth factors on outgrowth of facial mesenchyme.
The ectoderm is required for outgrowth of facial prominences and facial ectoderm from all facial prominences is interchangeable. Signals provided by the ectoderm may include members of the fibroblast growth factor family (FGF). In order to test whether FGFs could replace facial ectoderm and promote outgrowth, stage 24 frontonasal mass or mandibular mesenchyme was grafted to a host chick limb and a bead soaked in FGF-2 or FGF-4 was placed on top of the mesenchyme. Following 7 days of incubation, the amount of outgrowth was quantified by measuring the rods of cartilage that formed from the grafts. FGF-2 and FGF-4 stimulated an increase in length of cartilage rods in mandibular grafts compared to mandibular mesenchyme grafted without ectoderm (P < 0.05). FGF-4 stimulated a small increase in length of frontonasal mass mesenchyme (P < 0.05) and both FGFs increased the frequency of egg tooth formation in frontonasal mass mesenchyme compared to frontonasal mass mesenchyme grafted without ectoderm. FGFs can partially but not completely replace facial ectoderm since homotypic recombinations of frontonasal mass and mandibular tissues were significantly longer than mesenchyme grafts treated with FGF-soaked beads (P < 0.05). The addition of a second FGF-soaked bead did not significantly increase the length of the frontonasal mass or the mandibular mesenchyme. We have determined that FGF-2 protein is expressed in facial ectoderm and could be an endogenous signal for outgrowth. In contrast, FGF-8 transcripts are not expressed in the ectoderm covering the areas of the face that were grafted; thus, it is less likely that FGF-8 is required for outgrowth. Our results indicate that FGFs are part of an endogenous signaling pathway involved in distal outgrowth and chondrogenesis of the facial prominences.
Animals↗
Detection of mosaic and non-mosaic chromosome abnormalities in 6- to 8-day old human blastocysts.
A reliable technique has been developed for the production of good quality G-banded chromosome preparations from 6- to 8-day-old human blastocysts (20-800 cell stage) from an in vitro fertilization programme. The technique involves a thymidine cell division synchronization step to reduce the exposure time to colcemid, in conjunction with a simple 70% acetic acid disaggregation procedure to produce discrete metaphases for analysis. Of 105 blastocysts processed by this technique, 9 were lost during handling and 10 showed no dividing cells. The remaining 86 produced useful separate metaphases with a mean mitotic activity of 6.5%. A full G-banded karyotype was obtained from 1-6 cells in 55 blastocysts (64%), incomplete G-banded analysis but with full information of ploidy was obtained from 18 blastocysts (21%), with 13 (15%) producing no useful cytogenetic results. Abnormalities observed included polyploidy, diploid/polyploid mosaicism, non-mosaic trisomy 16 (2 cases), 46,Xdel(X)-(q21)/46,XX (1 case) and several single cells with trisomies or structural anomalies in otherwise normal blastocysts. Variable levels of structural chromosome damage, with apparent interchanges, chromosome branching and anomalous chromatid pairing were also seen.
Aneuploidy↗
The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study.
BACKGROUND: Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies. METHODS: We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of > of 2 of the specific symptoms in a subject ascertained on prechallenge interview. RESULTS: Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p = 0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p = 0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p < 0.023), muscle tightness (p < 0.004), numbness/tingling (p < 0.007), general weakness (p < 0.040), and flushing (p < 0.016) occurred more frequently after MSG than placebo ingestion. CONCLUSIONS: Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex.
Administration, Oral↗
Development of calcium signalling mechanisms during maturation of human oocytes.
Sperm-induced Ca2+ signals mediate the events of oocyte activation at fertilization. In this study, the development of mechanisms involved in the generation of Ca2+ signals in human oocytes was investigated. The thiol reagent, thimerosal, which induces oscillations of intracellular Ca2+ ([Ca2+]i) similar to those seen during fertilization, was used to mobilize Ca2+ in in-vivo matured, immature and in-vitro matured human oocytes. There was an increase in the sensitivity to thimerosal during maturation of human oocytes, with oocytes from small antral follicles being relatively insensitive, compared with those from luteinized follicles, which displayed a large spike followed by sustained oscillations in [Ca2+]i. These oscillations were inhibited by caffeine which suggests that they were mediated by the inositol trisphosphate receptor Ca2+ release system. When immature oocytes were cultured in vitro they acquired the capacity to undergo a single large spike in [Ca2+]i, however, subsequent sustained oscillations were not observed, indicating that these oocytes failed to develop fully competent Ca2+ signalling mechanisms during culture in vitro. This finding may be a key factor in the poor developmental competence of in-vitro matured human oocytes.
Calcium↗