Kidney transplantation in the absence of the infrarenal vena cava.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Cook.
Explore the source record for details and available documents.
Effects of inhibition of nitric oxide (NO) synthesis on the cerebrovascular autoregulatory vasodilator response to hypotension were studied in conscious rats. Cerebral blood flow (CBF) was determined with [14C]iodoantipyrine in a saline-treated control group and in three groups following inhibition of NO synthase activity by twice daily intraperitoneal injections of 50 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME) for four days. In the saline-control group (n = 8) and in the L-NAME-treated Group (a) (n = 8) CBF was determined while systemic mean arterial blood pressure (MABP) remained at its resting level (means +/- S.D., 128 +/- 6 and 151 +/- 11 mmHg, respectively). In the other groups CBF was determined after MABP was reduced by blood withdrawal to 118 +/- 9 and 88 +/- 8 mmHg in Groups (b) (n = 8) and (c) (n = 8), respectively. Despite the elevated MABP, global CBF was significantly lower in L-NAME-treated Group (a) than in the saline-controls (P < 0.005), indicating cerebral vasoconstriction resulting from inhibition of NO synthesis. Global CBF was not significantly reduced further in the two groups with hypotension. Local CBF in the hypotensive rats showed no significant reductions below values in L-NAME-treated control rats (Group (a)) in 31 of 32 brain structures; the only exception was in the auditory cortex of the severely hypotensive rats (Group (c)). The autoregulatory mechanism for cerebral vasodilatation to compensate for reduced arterial blood pressure is maintained following inhibition of NO synthesis.
A case-control study was conducted in El Paso County, Colorado to estimate differences in risk of head injury among persons in motorcycle crashes who were or were not wearing helmets. There were 71 cases, motorcyclists with head injuries from crashes, and 417 controls, motorcyclists in crashes without head injuries. Motorcyclists not wearing helmets were 2.4 times as likely to sustain head injuries (95% confidence limits: 1.23, 4.70) than motorcyclists wearing helmets. This odds ratio was adjusted for age and crash characteristics, using logistic regression. Alcohol intoxication and severity of motorcycle damage were also associated with significantly elevated odds ratios related to sustaining a head injury.
Panum's limiting case--a perceived depth difference between two lines in one eye combined with only one in the other eye--has long been considered weak or reversible. In the last few years this has led to strong promotion of the view that Panum's case is not based on a stereoscopic process involving double fusion, that only one line is fused, with the depth of the other one attributable either to fixation disparity or to occlusion cues. This view is refuted in two ways. First it is shown that when the separation of the two lines, considered as a disparity, is within the range of 'patent stereopsis', depth is perceived with a precision and accuracy indistinguishable from regular stereopsis. The predictions of nonstereoscopic theories concerning the effects of fixation are not borne out at small disparities. Second, very compelling Panum versions of orientation and curvature disparity are introduced, which are difficult to account for except by a process of double fusion. Finally it is shown that at large disparities the depth in Panum's case deviates from prediction more frequently than does regular stereoscopic depth.
Unintentional carbon monoxide poisonings were identified through death certificates, by hyperbaric chambers, and by laboratories required to report carboxyhemoglobin levels greater than 12%. From 1986 to 1991, 981 cases were reported, including 174 deaths. Deaths most often resulted from fire-related carbon monoxide intoxication (36.2%), followed by motor vehicle exhaust (34.5%), and furnaces (10.3%). Among nonfatal cases, furnaces were the leading source of carbon monoxide exposure (44.3%), followed by motor vehicle exhaust (22.8%). The importance of furnaces and other home heating devices in carbon monoxide intoxication may be underappreciated if only mortality data are examined. Surveillance of carbon monoxide-related morbidity is a useful adjunct to mortality surveillance in guiding prevention efforts.
Recently a number of new medications have become available for the treatment of epilepsy. In addition, advances in diagnostic facilities, particularly imaging, have improved dramatically in recent years. Patients with medically refractory epilepsy should be considered for the use of these drugs or for surgical therapy.
The branchial region of the vertebrate head forms through complex interactions involving rhombomeric segments, neural crest and branchial arches. It is though that aspects of their patterning mechanisms are linked and involve Hox-2 genes, whose overlapping and spatially restricted expression domains represent a combinatorial code for generating regional diversity. Vertebrates possess four Hox clusters of Antennapedia class homeobox genes, related to each other by duplication and divergence from a common ancestral complex. In consequence, at equivalent positions in different clusters there are highly related genes known as subfamilies or paralogous groups. As Hox-2 genes cannot fully account for patterning individual rhombomeres, we investigated whether offsets in expression limits of paralogous genes could account for the generation of regional diversity. We report here that, with the exception of the labial subfamily, paralogues show identical expression limits in rhombomeres, cranial ganglia and branchial arches, providing a combinatorial Hox code for the branchial region that seems to be different in organization to that of the trunk.
Conditioned medium from human monocyte-macrophages incubated under various conditions was tested for its ability to stimulate fibrinogen mRNA levels in the hepatoma cell line HepG2. Recombinant human interleukin-6 (IL-6) stimulated fibrinogen mRNA levels 4.4-fold over control levels; this response was blocked by an anti-IL-6 antibody. Conditioned medium from 3-day-cultured monocyte-macrophages produced a slight stimulation of fibrinogen synthesis in HepG2 cells which was enhanced when the monocyte-macrophages had been treated with lipopolysaccharide (LPS). This stimulation was blocked by the anti IL-6 antibody. The cytokines, interleukin-1 (IL-1) and tumour necrosis factor (TNF) were also detected in the conditioned medium from the 3-day-cultured monocyte-macrophages. Monocyte-macrophages were cultured for 17 days and then incubated with acetylated low density lipoprotein (AcLDL) for 48 h. Such cells were 'foamy' in appearance and showed a 4-fold increase in apoE mRNA and a 10 to 50-fold increase in apoE secretion. This increase in apoE production was suppressed by almost a third when cells were coincubated with AcLDL and LPS. Conditioned medium from these 17-day-cultured AcLDL-treated human monocyte-macrophages did not stimulate fibrinogen mRNA synthesis in HepG2 cells, nor did the conditioned medium contain detectable levels of cytokines. These results suggest that cytokine production from foam cells in the atherosclerotic lesion is unlikely to be a major contributing factor in determining the elevated fibrinogen levels seen in the plasma of patients with IHD.
Reaches made without feedback to positions on an object's surface reflect the spatial form of the surface. In Experiment 1, the reaching pattern varied with the stimulus surface's spatial attributes, consistent with a point-by-point perceptual representation of the surface. In Experiment 2, systematic reaching errors were determined solely by target position regardless of surface structure, implying a highly consistent representation of location. In Experiment 3, illusory slant was imparted to a surface by an aniseikonic lens. Individual variations in directly judged slant were reflected in the reaching pattern, implying organization of local perceptual representation of location and global perception of spatial attributes of the stimulus into a coherent structure.
Murine Hox genes are organized into four clusters that share many features with the homeotic clusters of Drosophila. This evolutionary conservation and the clear relationships between the position of a gene within a cluster and its expression pattern have led to the suggestion that the structure of the cluster is essential for proper regulation. Using a Hox-2.6-lacZ reporter gene in transgenic mice we have shown that the overall expression pattern of the endogenous Hox-2.6 gene can be reconstructed when it is isolated from the complex. The transgene was expressed in the proper tissues, with the correct spatial distribution and temporal pattern. Furthermore, direct comparison by in situ hybridization revealed that the levels of transgene expression are similar to those of the endogenous gene. This has allowed us to define three elements that regulate particular aspects of the Hox-2.6 pattern, two of which act as spatially specific enhancers. One enhancer, region A, directed expression only in the neural tube, whereas the other, region C, specified the majority of the Hox-2.6 pattern. Both were also capable of imposing the correct boundaries of expression on heterologous promoters. The definition of such elements will allow the characterization of the trans-acting factors that mediate spatial regulation in the mammalian embryo.
A family is presented with paroxysmal dystonic choreoathetosis transmitted as a dominant trait over five generations. The family is unusual in the marked responsiveness of the episodes to short periods of sleep in several members, in the very variable age of onset, and in the association with prominent myokymia in some cases. These overlap features suggest a link between paroxysmal dystonic choreoathetosis and familial paroxysmal ataxia with myokymia.
In this study we have examined the expression of murine Hox homeobox containing genes by in situ hybridisation in the branchial region of the head. Genes from the Hox complexes display segmentally restricted domains of expression in the developing hindbrain, which are correlated with similar restricted domains in the neural crest and surface ectoderm of the branchial arches. Comparison of related genes from the different clusters shows that subfamily members are expressed in identical rhombomeres and branchial arches. These patterns suggest a combinatorial system for specifying regional variation in the head, which we refer to as a Hox code. The Hox genes also display dynamic dorso-ventral (D-V) restrictions in the developing neural tube which mirror the timing and spatial distributions of the birth of major classes of neurons in the CNS. Genes in the Hox-2 cluster all have a similar D-V distribution that differs from that of genes from the other Hox clusters, and suggests that members of a subfamily may be used to specify positional values to different subsets of cells at the same axial level. These results are discussed in terms of a system for patterning the branchial regions of the vertebrate head, and evolution of head structures. We have also examined aspects of the transcriptional regulation of Hox-2 genes in transgenic mice using a lacZ reporter gene. We have been able to reconstruct the major pattern of the Hox-2.6 gene on the basis of identical expression of the transgene and the endogenous gene with respect to timing, spatial restrictions and tissue-specific distributions. Deletion analysis has enabled us to identify three regions involved in generating this pattern. Two of these regions have the properties of enhancers which are capable of imposing spatially-restricted domains of expression on heterologous promoters. We have generated similar Hox-lacZ fusions that reconstruct the highly restricted patterns of the Hox-2.1 and Hox-2.8 genes in the developing nervous system, supporting our in situ analysis and the idea of a Hox code. These transgenic experiments are a useful step in examining regulation in the Hox cascade.
Ploidy of neoplastic large-bowel cells in lesions from which biopsies showed only adenoma tissue by histopathologic examination was investigated retrospectively by DNA flow cytometry. Biopsy and resected-specimen blocks gave interpretable ploidy profiles from 83 lesions. The expectation that adenomas will show diploidy in biopsies and that adenocarcinomas will show aneuploidy in biopsies was fulfilled in 80% of the lesions. In addition, four lesions with diploid biopsies were polyps with minimal invasion. Thus, diploidy would have correctly predicted that local resection was adequate treatment for 62 lesions and conversely that cancer resection was the appropriate treatment for 8 lesions, for an overall predictive success rate of 87%. In conjunction with endoscopic, radiologic and other data, DNA flow cytometry of biopsies from apparently benign large-bowel lesions could become a useful addition to therapeutic decision-making.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have isolated two genes, Hox-2.8 and Hox-2.9, from the mouse homeobox cluster Hox-2, located on chromosome 11. A 120-kilobase yeast artificial chromosome (YAC) containing a large region of the murine Hox-2 cluster, including 45 kilobases of sequence upstream of the most 5' gene, was cloned. The DNA sequence of the YAC is unrearranged relative to the genomic map. We have subcloned from the YAC insert a homeobox gene, Hox-2.8, whose homeodolmain is highly related to that of the Drosophila homeotic gene proboscopedia (pb). The expression pattern of Hox-2.8 during embryogenesis extends the trend established by genes from Hox-2.5 to -2.7 of successively anterior domains of expression in the neural tube. We have also subcloned and sequenced from a cosmid the labial (lab)-related Hox-2.9, the most 3' member of the cluster to date. These data lend further support to the idea of a common evolutionary origin of the mouse Hox and Drosophila HOM clusters. The YAC will enable us to construct modified forms of the Hox-2 cluster in yeast and to identify their effect on the phenotype of the animal in transgenic mouse strains.
The timing of renal transplantation in infants is controversial. Between 1965 and 1989, 79 transplants in 75 infants less than 2 years old were performed: 23 who were 12 months or younger, 52 who were older than 12 months; 63 donors were living related, 1 was living unrelated, and 15 were cadaver donors; 75 were primary transplants and 4 were retransplants. Infants were considered for transplantation when they were on, or about to begin, dialysis. All had intra-abdominal transplants with arterial anastomosis to the distal aorta. Sixty-four per cent are alive with functioning grafts. The most frequent etiologies of renal failure were hypoplasia (32%) and obstructive uropathy (20%); oxalosis was the etiology in 11%. Since 1983 patient survival has been 95% and 91% at 1 and 5 years; graft survival has been 86% and 73% at 1 and 5 years. For cyclosporine immunosuppressed patients, patient survival is 100% at 1 and 5 years; graft survival is 96% and 82% at 1 and 5 years. There was no difference in outcome between infants who were 12 months or younger versus those who were aged 12 to 24 months; similarly there was no difference between infants and older children. Sixteen (21%) patients died: 5 after operation from coagulopathy (1) and infection (4); and 11 late from postsplenectomy sepsis (4), recurrent oxalosis (3), infection (2), and other causes (2). Routine splenectomy is no longer done. There has not been a death from infection in patients transplanted since 1983. Rejection was the most common cause of graft loss (in 15 patients); other causes included death (with function) (7), recurrent oxalosis (3), and technical complications (3). Overall 52% of patients have not had a rejection episode; mean creatinine level in patients with functioning grafts is 0.8 +/- 0.2 mg/dL. Common postoperative problems include fever, atelectasis, and ileus. At the time of their transplants, the infants were small for age; but with a successful transplant, their growth, head circumference, and development have improved. Transplantation in infants requires an intensive multidisciplinary approach but yields excellent short- and long-term survival rates that are no different from those seen in older children or adults. Living donors should be used whenever possible. Patients with a successful transplantation experience improved growth and development, with excellent rehabilitation.