Splenic flexure volvulus presenting as proximal small intestinal obstruction.
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Biomedical subjects
Publications and source records attributed to J Harvey.
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PURPOSE: To identify possible abnormalities in regional cerebral glucose metabolism in patients with benign essential blepharospasm or Meige syndrome using positron emission tomography. METHODS: Ten patients with benign essential blepharospasm and one patient with Meige syndrome were examined using positron emission tomography with deoxyglucose labeled with fluorine 18. The severity of muscle spasm at the time of positron emission tomography was recorded in each patient. In five patients, positron tomography was performed on two occasions (once before and again 1 to 2 weeks after botulinum injection) to look for reproducibility of the findings on positron emission tomography also to see if there was any correlation between the severity of symptoms and positron emission tomography findings. RESULTS: The mean reference ratio for fluorodeoxyglucose F18 metabolism was significantly elevated in the striatum compared with the frontal, temporal, or parietal regions. Glucose metabolism was also elevated in the thalami. There was no correlation between the severity of blepharospasm and the degree of hyperactivity in the striatum. In the patients who underwent positron emission tomography scanning on two occasions, there was no significant difference between the two studies in any of the regions analyzed. CONCLUSIONS: The authors' findings support the hypothesis that benign essential blepharospasm and Meige syndrome may be associated with overactivity of the striatum and the thalamus. Positron emission tomography may prove to be a useful research tool and a possible adjunct diagnostic technique for benign essential blepharospasm and Meige syndrome.
An eight-year-old, sexually intact, male, 37 kg crossbred dog was referred for investigation of two acute episodes of intestinal bleeding and severe anaemia within a five-month period. There was no evidence of coagulopathy or underlying systemic disease. Technetium-labelled red blood cell scintigraphy suggested the colon as the site of bleeding. Colonoscopy identified a focal area of dilated and tortuous mucosal blood vessels. Histopathology of the resected colon revealed vascular ectasia (angiodysplasia). At nine months post-resection, the dog remained healthy and free of any overt intestinal haemorrhage.
As we move into the 21st century, we are faced with an increasing number of childhood cancer survivors who are living into their middle adult years and beyond. Providing appropriate, comprehensive follow-up care is a challenge for health care providers and one that can be met by developing quality follow-up programs for all childhood cancer survivors. The focus of these programs should be to educate these survivors on strategies to maximize their health and well being. This article discusses the evolution of survivor clinics, strategies for developing a quality program, and the role of nursing in the care of childhood cancer survivors.
The mechanisms controlling the formation of osteolytic bone metastases in patients with breast cancer are still poorly understood. To explore the role of motility in the establishment of osteolytic bone metastases, we have used a model of bone metastasis in which MDA-MB-231 breast cancer cells exhibiting low (hsp27-transfectants) and high (control-transfectant) endogenous cell motility were compared. We found that MDA-MB-231 cells exhibiting low cell motility were less capable of establishing osteolytic lesions. The number and the area of the osteolytic lesions in mice inoculated with low motility cells were both significantly smaller. Histomorphometry of bone lesions also demonstrated less tumor area in mice bearing hsp27 transfectants although there was no difference in the osteoclast number per square millimeter of tumor-bone interface. These data suggest that cell motility may be an important mechanism in the metastatic cascade of breast cancer cells to the bone and that controlling cell motility may be a useful target to prevent the establishment of osteolytic bone metastases.
Based on parent and teacher ratings of primary school children on a scale comprising the 18 DSM-IV AD/HD symptoms, this study used confirmatory factor analysis to compare three models: all items in one factor; inattention in one and hyperactivity and impulsivity items in a separate factor; and inattention, hyperactivity, and impulsivity items in three separate factors. It also examined the prevalence rates of the three AD/HD Types, and gender and age differences. Results supported both the two- and three-factor models, with the three-factor model only slightly better than the two-factor model. Based on parent-teacher agreement, the prevalence rates were 1.6, 0.2 and 0.6% for the Inattentive, Hyperactive-Impulsive, and Combined Types, respectively. Overall, the male to female ratio was 5: 1, and boys were rated higher than girls by both parents and teachers. Age differences were minimal. The implications of the findings in relation to some of the assumptions made in DSM-IV for AD/HD are discussed.
Capillary blood of febrile children was lysed by using a lysis buffer containing ascorbic acid. MxA quantitation was performed by an immunochemiluminescent assay. The MxA values were significantly higher in capillary blood of infants with viral infections due to adenovirus (n = 5), rotavirus (n = 15), or respiratory syncytial virus (n = 28), than in capillary whole blood from infants with bacterial infections (n = 6) and healthy control patients (n = 20). A strong correlation was found between the MxA values in capillary whole blood and peripheral whole blood (r' = 0.86, P < 0.0001, n = 48). The MxA values found at these two sites were compared with the levels of IFN-alpha obtained by a dissociation enhanced lanthanide fluoroimmunoassay. A correlation between these two values was found. The results show that the combination of collection of blood by finger prick and specific immunochemiluminescent assay for MxA protein measurement may be of value for the diagnosis of viral infections in children.
Acute systemic, nonselective nitric oxide synthesis inhibition (NOSI) causes a marked pressor and renal vasoconstrictor response in the normal conscious chronically catheterized rat. The present studies directly address the question of how these vasoconstrictor responses are related to the combined vasoconstrictor activities of the sympathetic nervous system and angiotensin II. When the alpha adrenoceptors are blocked (with prazosin) the pressor and renal hemodynamic responses to NOSI are unaffected. Combined alpha adrenoceptor and angiotensin II receptor blockade at the same time as NOSI results in no net change in blood pressure while leaving the renal vasoconstrictor response intact. However, when the NOSI is delayed, a substantial and unblunted pressor response is seen. In contrast to the vasoconstrictor responses, the natriuretic and diuretic responses to acute NOSI are prevented by simultaneous alpha adrenoceptor blockade alone and combined with angiotensin II receptor blockade. These findings suggest that the hemodynamic actions of acute NOSI in the unstressed rat are independent of the sympathetic nervous system and angiotensin II. In contrast, the natriuretic/diuretic response to acute NOSI is apparently partly the result of some interaction with the sympathetic nervous system, not, as we had previously suggested, exclusively the result of a pressure natriuresis.
1. Using whole-cell and cell-attached recording configurations, the effects of insulin on leptin activation of ATP-sensitive K+ (KATP) channels were examined in the CRI-G1 insulinoma cell line. 2. Whole-cell recordings demonstrated that the leptin-induced hyperpolarization and increased potassium conductance are completely occluded by prior exposure to insulin (1-50 nM). In cell-attached recordings, insulin prevented leptin activation of tolbutamide-sensitive KATP channels. Furthermore, insulin (50 nM) slowly and completely reversed the effects of leptin (10 nM), an action not attributable to direct inhibition of KATP channels per se. 3. Low concentrations of insulin-like growth factor-1 (IGF-1; 10-100 nM) failed to prevent leptin activation of KATP channels, although higher concentrations (1 microM) did inhibit leptin actions. 4. The action of insulin was specific for leptin, as the hyperglycaemic agent diazoxide activated KATP channels following prior exposure to insulin. 5. Wortmannin (1-10 nM) and LY 294002 (10 microM) prevented leptin activation of KATP channels, indicating an involvement of phosphoinositide 3-kinase (PI 3-kinase). 6. In conclusion, leptin activation of KATP channels is counter-regulated by insulin in the CRI-G1 insulinoma cell line. This feedback mechanism may be important in the local integration of hormonal signals which regulate insulin secretion and in alterations of metabolic homeostasis associated with obesity and non-insulin dependent diabetes mellitus (NIDDM).
1. Using whole-cell and cell-attached recording configurations, the role of phosphorylation in leptin activation of ATP-sensitive K+ (KATP) channels was examined in the rat CRI-G1 insulinoma cell line. 2. Whole-cell current clamp recordings demonstrated that, following dialysis with the non-hydrolysable ATP analogue 5'-adenylylimidodiphosphate (AMP-PNP; 3-5 mM), the leptin-induced hyperpolarization and increase in K+ conductance were completely inhibited. 3. Under current clamp conditions, application of the broad-spectrum protein kinase inhibitor H-7 (10 microM) had no effect on the resting membrane potential or slope conductance of CRI-G1 insulinoma cells and did not occlude the actions of leptin. 4. Application of the tyrosine kinase inhibitors genistein (10 microM), tyrphostin B42 (10 microM) and herbimycin A (500 nM) all resulted in activation of KATP channels. In cell-attached recordings, the presence of tyrphostin B42 (10 microM) in the pipette solution activated tolbutamide-sensitive KATP channels in CRI-G1 cells. In contrast, the inactive analogues of genistein and tyrphostin B42 were without effect. 5. The serine/threonine-specific protein phosphatase inhibitors okadaic acid (50 nM) and cyclosporin A (1 microM) did not prevent or reverse leptin activation of KATP channels. In contrast, whole-cell dialysis with the tyrosine phosphatase inhibitor orthovanadate (500 microM) prevented the actions of both leptin and tyrphostin B42. 6. In conclusion, leptin activation of KATP channels appears to require inhibition of tyrosine kinases and subsequent dephosphorylation. This process is likely to occur prior to activation of phosphoinositide 3-kinase (PI 3-kinase) as wortmannin prevented activation of KATP channels by tyrphostin B42.
Interferon alpha (IFNalpha), a type I interferon, can be considered as a viral infection marker because this cytokine is induced during many viral infections. However, it is quite difficult to detect IFNalpha in sera. Investigations are interested in various intra-cellular IFNalpha-induced proteins as viral infection markers. However the activity of these enzymes increased not only in response to type I IFNs but also to type II IFN. MxA protein can be detected in the cytoplasm of IFNalpha/beta-treated cells, whereas other cytokines, including IFNgamma, are poor inducers. Using an immunochemiluminescent assay, we studied MxA protein in whole blood of 34 patients with various viral infections. The whole blood was drawn into sterile vacuum tubes containing heparin or EDTA. MxA values were relatively similar in heparin-treated samples and EDTA-treated samples, with differences not exceeding 1 ng/ml. The levels of MxA protein were compared in whole blood obtained by using two different lysis procedures. A correlation was found between the MxA levels obtained by using procedure I and procedure II, but higher amounts of MxA protein were found with procedure II. The second procedure is rapid and more convenient than the other and it is carried out in one step which reduce technical problems. High levels of MxA protein were found in peripheral blood cells of patients with acute viral infections (Rotavirus, Adenovirus, RSV, CMV), but MxA protein was not elevated in bacterial infections. The MxA levels were also studied in peripheral blood of 32 HCV positive patients. MxA protein was not found in most of IFNalpha-untreated patients, even those with high viral load. In contrast, high levels of MxA protein were found in IFNalpha-treated patients. MxA quantitation can be considered as a specific marker of acute viral infections, and could be useful in the management of treatment with IFNalpha.
1. The effects of the antidiabetic agent englitazone and the anorectic drug ciclazindol on ATP-sensitive K+ (K(ATP)) channels activated by diazoxide and leptin were examined in the CRI-G1 insulin-secreting cell line using whole cell and single channel recording techniques. 2. In whole cell current clamp mode, the hyperglycaemic agent diazoxide (200 microM) and the ob gene product leptin (10 nM) hyperpolarised CRI-G1 cells by activation of K(ATP) currents. K(ATP) currents activated by either agent were inhibited by tolbutamide, with an IC50 for leptin-activated currents of 9.0 microM. 3. Application of englitazone produced a concentration-dependent inhibition of K(ATP) currents activated by diazoxide (200 microM) with an IC50 value of 7.7 microM and a Hill coefficient of 0.87. In inside-out patches englitazone (30 microM) also inhibited K(ATP) channel currents activated by diazoxide by 90.8+/-4.1%. 4. In contrast, englitazone (1-30 microM) failed to inhibit K(ATP) channels activated by leptin, although higher concentrations (> 30 microM) did inhibit leptin actions. The englitazone concentration inhibition curve in the presence of leptin resulted in an IC50 value and Hill coefficient of 52 microM and 3.2, respectively. Similarly, in inside-out patches englitazone (30 microM) failed to inhibit the activity of K(ATP) channels in the presence of leptin. 5. Ciclazindol also inhibited K(ATP) currents activated by diazoxide (200 microM) in a concentration-dependent manner, with an IC50 and Hill coefficient of 127 nM and 0.33, respectively. Furthermore, application of ciclazindol (1 microM) to the intracellular surface of inside-out patches inhibited K(ATP) channel currents activated by diazoxide (200 microM) by 86.6+/-8.1%. 6. However, ciclazindol was much less effective at inhibiting KATP currents activated by leptin (10 nM). Ciclazindol (0.1-10 microM) had no effect on K(ATP) currents activated by leptin, whereas higher concentrations (> 10 microM) did cause inhibition with an IC50 value of 40 microM and an associated Hill coefficient of 2.7. Similarly, ciclazindol (1 microM) had no significant effect on K(ATP) channel activity following leptin addition in excised inside-out patches. 7. In conclusion, K(ATP) currents activated by diazoxide and leptin show different sensitivity to englitazone and ciclazindol. This may be due to differences in the mechanism of activation of K(ATP) channels by diazoxide and leptin.
Management of blowout fractures involving the orbital floor has been controversial over the past several decades. One school of thought recommends conservative treatment for 4 to 6 months while another recommends a 'wait and watch' period of 2 weeks before intervention. The authors have encountered a group of patients with such fractures, commonly children (less than 16 years of age), who have sustained a blow to the periocular area, yet have marked motility restrictions in up and down gaze, minimal soft tissue signs of trauma, lack of enophthalmos, and very minimal evidence of floor disruption on radiologic exam. A 2-week waiting period has been found to be of little benefit in these persons and possibly harmful to their motility. We advocate surgery within the first few days after injury as it may help to avoid permanent motility restriction. The authors have termed this entity 'the white-eyed blowout fracture.'
This retrospective study reviews 39 patients with primary subglottic cancer seen between 1955 and 1988 by the Department of Otolaryngology at Washington University. This number constitutes 1.8% of laryngeal cancer cases diagnosed during this period. Twenty-eight patients (71.8%) had epidermoid cancer, of which 19 (67.9%) had "early" disease (stages I and II), and nine (32.1%) had "advanced" (stages III and IV). Overall 5-year survival was 57.7%. Disease-free survival was 46.2%. Patients treated with radiotherapy alone, surgery alone, or both had disease-free 5-year survivals of 22.2%, 41.7%, and 100%, respectively. Combination therapy showed a significantly higher (P < .01) disease-free survival than radiotherapy alone.
We have identified a variant HLA-C allele, Cw*0805, in DNA isolated from a blood sample used in the UK National External Quality Assessment Scheme for Histocompatibility and Immunogenetics. The DNA was initially typed by PCR-SSP and PCR-SBT as Cw*0802, 1602 with a single mismatch in exon 2 of one of the alleles. The two HLA-C alleles were separated by locus- and allele-specific PCRs and sequencing analysis showed that the Cw*0802 allele was variant in this sample, with a single mismatch in exon 2 at position 289.
1. Peristalsis in the mammalian upper urinary tract (UUT) is mostly myogenic in origin, originating predominately in the proximal pelvicalyceal regions of the renal pelvis, an area that is enriched with specialized smooth muscle cells termed 'atypical' smooth muscle cells. Propagating peristaltic contractions are little affected by blockers of either autonomic nerve function or nerve impulse propagation; however, blockers of sensory nerve function or prostaglandin synthesis reduce both the frequency and the strength of the spontaneous contractions underlying peristalsis. 2. The electrical drive for these peristaltic contractions has long been considered to involve mechanisms analogous to the heart, such that 'atypical' smooth muscle cells generate spontaneous 'pacemaker' action potentials. These pacemaker potentials trigger the firing of action potentials and contraction in the muscular regions of the renal pelvis, which propagate distally to the ureter, propelling urine towards the bladder. 3. Recent intracellular microelectrode and single cell/channel patch-clamp studies have revealed that the ionic conductances underlying the action potentials recorded in the UUT are likely to involve the opening and slow closure of voltage-activated 'L-type' Ca2+ channels, offset by the time-dependent opening and closure of both voltage- and Ca(2+)-activated K+ channels. 4. In the present review we summarize the current knowledge of the ionic mechanisms underlying action potential discharge in the UUT, as well as present our view on how this electrical activity supports the initiation and conduction of UUT peristalsis.
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