Elective caesarean section on request. Pregnant women should have choices.
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Biomedical subjects
Publications and source records attributed to R J Howard.
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Fifty patients with visual hallucinations and illusions secondary to degenerative eye disease reported remarkably stereotyped experiences. Questionnaire responses revealed five previously recognized categories of pathological vision (perseveration, illusory visual spread, polyopia, prosopometamorphopsia and micro/macropsia) and three novel categories (tessellopsia, hyperchromatopsia and dendropsia). Identical pathologies of vision occur in a range of clinical and experimental settings, suggesting that they reflect fundamental visual processes. The known neurophysiology of the visual cortex helps explain the phenomenology of the experiences and provides the basis for a neurobiologically based classification of positive and negative visual perceptual disorders.
OBJECTIVE: The authors investigated, by whole brain functional magnetic resonance imaging (MRI), the neural substrate underlying processing of emotion-related meanings. METHOD: Six healthy subjects underwent functional MRI while viewing 1) alternating blocks of pairs of pictures and captions evoking negative feelings and the same materials irrelevantly paired to produce less emotion (reference pairs); 2) alternating blocks of picture-caption pairs evoking positive feelings and the same materials irrelevantly paired to produce less emotion; and 3) alternating blocks of picture-caption pairs evoking positive feelings and picture-caption pairs evoking negative feelings. RESULTS: Compared with the reference picture-caption pairs, negative pairs activated the right medial and middle frontal gyri, right anterior cingulate gyrus, and right thalamus. Compared with the reference picture-caption pairs, positive pairs activated the right and left insula, right inferior frontal gyrus, left splenium, and left precuneus. Compared with the negative picture-caption pairs, positive pairs activated the right and left medial frontal gyri, right anterior cingulate gyrus, right precentral gyrus, and left caudate. CONCLUSIONS: Contrasts of both 1) negative and reference picture-caption pairs and 2) positive and negative picture-caption pairs activated networks involving similar areas in the medial frontal gyrus (Brodmann's area 9) and right anterior cingu-late gyrus (areas 24 and 32). The area 9 sites activated are strikingly similar to sites activated in related positron emission tomography experiments. Activation of these same sites by a range of evoked affects, elicited by different methods, is consistent with areas within the medial prefrontal cortex mediating the processing of affect-related meanings, a process common to many forms of emotion production.
The effects of increased salinity on plant growth were examined in a greenhouse experiment with four species common to oligohaline marshes of the northern Gulf of Mexico: Eleocharis palustris, Panicum hemitomon, Sagittaria lancifolia, and Scirpus americanus. Effects of final salinity reached (6 or 12 g/L), salinity influx rate (3 d or 3 wk), and duration of exposure (1, 2, or 3 mo) were investigated. Sagittaria lancifolia was the first species to show visible signs of stress, with browning and curling of older leaf edges. The salt effect was delayed for 6-8 wk in P. hemitomon, but this species had the highest aboveground tissue mortality rate at 12 g/L as exposure continued. Final salt concentration affected all species to a greater degree than did salinity influx rate. No aboveground mortality occurred at 6 g/L, but growth suppression was apparent and varied with species. The magnitude of growth suppression in response to salinity increased for all species as the duration of exposure increased. Overall, we ranked the species as follows, in order from least to most salt tolerant: Panicum hemitomon < Sagittaria lancifolia < Eleocharis palustris < Scirpus americanus. This ranking reflects the field occurrence of these species along a gradient of increasing salinity in northern Gulf of Mexico coastal habitats from freshwater wetlands through oligohaline areas to mesohaline wetlands.
The ability of common oligohaline marsh macrophytes of the northern Gulf of Mexico coast to recover from pulses of increased salinity was investigated in a greenhouse experiment with Eleocharis palustris, Panicum hemitomon, Sagittaria lancifolia, and Scirpus americanus monocultures. Components of salinity pulses applied were final salinity reached (6 or 12 g/L), salinity influx rate (3 d or 3 wk), and duration of exposure (1, 2, or 3 mo). After each exposure period, we placed plants into freshwater until the end of the 120-d experiment to determine recovery potential. The four species varied in their ability to recover from the salinity pulses. Within a species, recovery varied with final salinity level and duration of exposure, and to a lesser extent with salinity influx rate. Scirpus americanus, growth of which was stimulated by <3 mo of exposure to 6 g/L, was able to recover even under the most extreme conditions of exposure to 12 g/L salinity for 3 mo. Ability to recover decreased with increased salinity and increased duration of exposure for the remaining three species. Recovery of specific aspects of growth was also suppressed in these species by a rapid salinity influx rate compared to a slow influx rate. The complex variations in recovery patterns displayed by the different species may lead to changes in species dominance following the short-term salinity pulses that can occur during storm events, which in turn may affect marsh plant community composition and structure.
We report two functional magnetic resonance imaging experiments which reveal similarities and differences between perceptual and imaginal networks within the single visual submodality of colour. The first experiment contrasted viewing of a coloured and grey-scale Mondrian display, while the second contrasted a relative colour judgement with a spatial task and required the generation of mental images. Our results show that colour perception activates the posterior fusiform gyrus bilaterally (area V4), plus right-sided anterior fusiform and lingual gyri, striate cortex (area V1), and the left and right insula. Colour imagery activated right anterior fusiform gyrus, left insula, right hippocampus and parahippocampal gyrus, but not V4 or V1. The findings reconcile neurological case studies suggesting a double dissociation between deficits in colour imagery and perception and point to anterior fusiform, parahippocampal gyri and hippocampus as the location for stored representations of coloured objects.
Evidence is reviewed that dysplastic brain development in the second half of pregnancy predisposes to schizophrenia. We suggest that an important corollary of aberrant development at this stage of ontogenesis is abnormal afferentation of the cortical plate, and that this may be macroscopically measurable in terms of abnormal correlational structure in adult brain imaging data. This prediction is tested by analysis of multiple cortical volume measures on magnetic resonance imaging data acquired from 35 male right-handed schizophrenics and 35 matched controls. There are no significant differences between groups in global, intra-hemispheric or inter-hemispheric correlational structure; but schizophrenics are shown to have significantly reduced dependencies between frontal and temporal lobe volumes, and frontal and hippocampal volumes, in the left hemisphere. We conclude that anatomical dysconnectivity (between frontal and temporal cortex) in schizophrenia may be caused by dysplasia.
BACKGROUND: There is a strong association between delayed graft function (DGF) and reduced graft survival (GS) of cadaveric renal transplants. This study was performed to identify donor characteristics that might predict adverse outcomes. METHODS: We reviewed the folders of 509 consecutive organ donors for 586 renal transplant recipients receiving grafts between 1990 and 1995. A uniform immunosuppression protocol was employed. RESULTS: The factors that did not alter the rate of DGF were procurement year, local versus shared organs, donor gender, race, hypotension, serum creatinine level and trend, blood transfusions, and vasopressor use and dose. The factors that did alter the frequency of DGF were cause of death (P=0.0053), donor age (P=0.0017), cold ischemic time (P=0.0009), anastomotic time (P=0.0012), combined cold ischemic time and anastomotic time (P=0.00018), and body mass index (P=0.009). All of the factors with the exception of body mass index were of comparable import when analyzed by multiple logistic regression. One-year GS of patients without DGF was 93.2%, and the GS of those with DGF was 76.6% (P < 0.0001). However, none of the donor factors correlated with 1-year GS. Seventy-seven donors were the source of paired transplants performed by our program. Sixty percent were concordant for immediate function, 32% were discordant for DGF with equal numbers affecting the first or second graft, and in only 8% did DGF affect both grafts. CONCLUSIONS: Donor factors associated with DGF were increased ischemia, donor age, and cause of death. Although there is a close association between DGF and reduced GS, there is no association between these donor factors and GS. This seeming paradox suggests that unknown variables contribute heavily to early graft outcome.
BACKGROUND: Hyperparathyroidism is common in patients with renal disease. These patients may require operation for this disease if it cannot be controlled by medical therapy. Because these patients continue to have renal failure, the risk of recurrence and reoperation is high. METHODS: Sixty-nine patients with renal failure underwent operation for hyperparathyroidism. These patients were followed up on dialysis or after transplantation. RESULTS: Sixty-nine patients, aged 2 to 71 years old, with end-stage renal disease required parathyroidectomy for hyperparathyroidism 6.2 +/- 4.2 (standard deviation) years after beginning dialysis. Thirty-six patients had undergone renal transplantation (creatinine = 1.6 +/- 0.4 mg/dL). All patients had elevated parathyroid hormone (PTH) levels. Sixty-eight patients had hyperplasia; 1 patient had adenoma. Six patients required reoperation for recurrent hyperparathyroidism 30 to 123 months after their initial parathyroidectomy. CONCLUSION: Patients with end-stage renal disease are prone to abnormalities of calcium metabolism. They frequently develop parathyroid hyperplasia. Recurrence can occur following operation because of continuing renal failure.
OBJECTIVES: We conducted a multicenter retrospective study to determine the results of treatment for prostate cancer in solid organ transplant recipients. METHODS: A retrospective analysis of all patients diagnosed with prostate cancer after organ transplantation at five centers was conducted. Data were obtained by chart review and a multipoint data sheet was used to abstract the data from the patient charts. RESULTS: Eighteen cases of prostate cancer were identified from six institutions. Most (84%) of the cancers were clinically localized at the time of diagnosis. Nine (50%) of 18 patients underwent radical prostatectomy, which was the predominant mode of treatment. Overall survival at a mean follow-up of 32 months was 66%, with a cancer specific mortality of 16%. Mortality was 13% for the 15 patients with localized disease and 33% for the 3 patients with metastatic disease at the time of diagnosis. CONCLUSIONS: Most of the patients with prostate cancer being detected after solid organ transplantation were diagnosed with localized disease. Aggressive therapeutic intervention as in the general (nontransplant) population yields good results and should be pursued. Diligent surveillance for prostate cancer in this population using periodic digital rectal examination, serum prostate-specific antigen, and prostate needle biopsy as needed will ensure earlier cancer detection and allow for definitive therapeutic intervention.
Despite recent advances in functional neuroimaging, the apparently simple question of how and where we see--the neurobiology of visual consciousness--continues to challenge neuroscientists. Without a method to differentiate neural processing specific to consciousness from unconscious afferent sensory signals, the issue has been difficult to resolve experimentally. Here we use functional magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet syndrome, for whom visual perception and sensory input have become dissociated. We found that hallucinations of color, faces, textures and objects correlate with cerebral activity in ventral extrastriate visual cortex, that the content of the hallucinations reflects the functional specializations of the region and that patients who hallucinate have increased ventral extrastriate activity, which persists between hallucinations.
Adherence of mature parasitized erythrocytes (PE) of Plasmodium falciparum to microvascular endothelial cells contributes directly to the virulence and pathology of this human malaria. The malarial variant antigen, P falciparum erythrocyte membrane protein 1 (PfEMP1), has been implicated as the PE receptor for CD36 on endothelial cells. We identified the region of PfEMP1 that mediates adherence of PE to CD36 and showed that a recombinant protein fragment from this region blocked and reversed adherence of antigenically different parasites. Sequence variation was evident in the CD36 binding domain of different PfEMP1 genes, yet many highly conserved residues, particularly cysteine residues, are evident. This suggests a highly conserved shape that mediates adherence to CD36. Immunization with the CD36-binding domain elicited sera that are cross-reactive with the different recombinant proteins but are strain-specific for the PE surface. Novel anti-adherence therapeutics and a malaria vaccine may derived from exploitation of the structure of the CD36 binding domain of PfEMP1.
We have used whole brain fMRI and canonical variate analysis to investigate the anatomical location of brain activity subserving episodic memory encoding and recognition. Recognition of previously presented words did not specifically activate right prefrontal areas although right-sided activations were seen during transitions between the target and reference phases of the paradigm. Encoding was associated with left sided prefrontal activation, but this was within Broca's area rather than dorsolateral prefrontal cortex. The temporal resolution of fMRI, combined with analysis of the apparent functional connectivity of activations observed, revealed activity within complex networks each functionally specialized for the demands of particular aspects of a cognitive task.
The significance of a positive cross-match in liver transplantation remains controversial, as documented by a number of recent conflicting reports. In this study, we evaluated 195 consecutive orthotopic liver transplant recipients in whom the cross-match was either negative or positive for T or B cells. Special emphasis was placed on the outcome of patients with high levels of preformed IgG antibodies directed against donor T cells. IgG anti-donor antibodies were confirmed by flow cytometry in all cases. Of 10 patients with strong T-cell antibodies, there was one early death due to nonimmunological causes. Transplantation was successful in 9/10 patients followed for 3 months to 3 years. Graft survival, incidence of acute rejection, and number of liver biopsies in patients with a positive cross-match (strong T, weak T, or B cell) were not significantly different from those of patients with a negative cross-match. In the strong T cell antibody group, one patient had early graft dysfunction, with extensive hepatic necrosis and histological signs of antibody-induced damage. Two other patients also showed some evidence of possible antibody-mediated events, such as neutrophil infiltration and hepatocyte swelling. These lesions were reversible, and the patients had uneventful recoveries. Thus, in our experience, preformed antibodies did not preclude good graft survival.
We report a novel method to identify brain regions generically activated by periodic experimental design in functional magnetic resonance imaging data. This involves: 1) registering each of N individual functional magnetic resonance imaging datasets in a standard space; 2) computing the median standardised power of response to the experimental design; 3) testing median standardised power at each voxel against its nonparametrically ascertained distribution under the null hypothesis of no experimental effect; and 4) constructing a generic brain activation map. The method is validated by analysis of 6 null images, acquired under conditions when the null hypothesis was known to be true; 8 images acquired during periodic auditory-verbal stimulation; and 6 images acquired during periodic performance of a covert verbal fluency task.
DNA shuffling is a practical process for directed molecular evolution which uses recombination to dramatically accelerate the rate at which one can evolve genes. Single and multigene traits that require many mutations for improved phenotypes can be evolved rapidly. DNA shuffling technology has been significantly enhanced in the past year, extending its range of applications to small molecule pharmaceuticals, pharmaceutical proteins, gene therapy vehicles and transgenes, vaccines and evolved viruses for vaccines, and laboratory animal models.
BACKGROUND: Many studies have separately reported abnormalities of frontal and temporal lobe structures in schizophrenia, but little is known of structural fronto-temporal associations in this condition. We investigated whether male patients with chronic schizophrenia would show abnormal patterns of correlation between regional brain volumes. METHODS: Structural magnetic resonance images of the brain in 42 patients were compared with 43 matched unaffected controls. We explored the pattern of association between regional brain volumes by correlational analyses, and non-parametrically tested for significance of between-group differences by randomization. RESULTS: The schizophrenics demonstrated significant volume deficits in several brain regions (left temporal lobe and hippocampus, right dorsolateral prefrontal cortex), and significant volume increases in the ventricular system (third ventricle and left temporal horn of the lateral ventricle). Controls demonstrated large positive correlations (r > 0.4) between prefrontal and temporal lobe regions. By contrast, inter-regional correlations significantly reduced in schizophrenics included those between prefrontal, anterior cingulate and temporal regions, and between posterior cingulate and hippocampus (P < 0.05). The most salient abnormality in patients was a dissociation between prefrontal and superior temporal gyrus volumes (P < 0.01). CONCLUSIONS: These results support the existence of a relative 'fronto-temporal dissociation' in schizophrenia which we suggest may be due to lack of mutually trophic influences during frontal and temporal lobe development.