Biomedical subjects
Publications and source records attributed to M Hart.
Asymmetric channel-cut monochromators have been tested at the SRS. Results from both focused and unfocused beamlines have shown a threefold improvement in flux when compared with the flux obtained from a symmetric cut Si(111) monochromator. Some problems with using such monochromators and possible modifications are described.
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Multipole wigglers in storage rings already produce X-ray power in the range up to a few kilowatts and planned devices at third-generation facilities promise up to 30 kW. Although the power density at the monochromator position is an order of magnitude lower than that from undulators, the thermal strain field in the beam footprint can still cause severe loss of performance in X-ray optical systems. For an optimized adaptive design, the results of finite-element analysis are compared with double-crystal rocking curves obtained with a laboratory X-ray source and, in a second paper [Quintana, Hart, Bilderback, Henderson, Richter, Setterson, White, Hausermann, Krumrey & Schulte-Schrepping (1995). J. Synchotron Rad. 2, 1-5], successful tests at wiggler sources at CHESS and ESRF and in an undulator source at HASYLAB are reported.
X-ray wigglers which produce tens of kilowatts of photon power within the white beam will soon become available at third-generation sources of synchrotron radiation. Insertion devices that produce several kilowatts already exist and we have used those at CHESS, ESRF and HASYLAB to test adaptive 111 silicon water-jet-cooled monochromators at up to 2 kW total incident beam power. This development from earlier work at the Brookhaven National Synchrotron Light Source (NSLS) uses the pressure in the water coolant to provide active compensation of the strain field in the thermal footprint, nulling its effect to within residual variations in Bragg angle of only a few arc s. The design is robust, vacuum compatible and uses no moving mechanical parts.
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In the Patients' Charter, a standard is laid down that all patients who attend out-patient clinics should be seen within 30 minutes of their appointment time. Discusses how a statistical monitoring system using a "low technology" approach was implemented at Leicester General Hospital during 1992-93. This was instrumental in raising the proportion of patients seen within 30 minutes from under 50 per cent to over 80 per cent in 15 months. Points to the fact that statistical monitoring alone is not sufficient to deliver quality improvements. Suggests that only enlightened management action which brings both management and clinicians into a quality improvement programme is likely to be effective. Discusses some of the measurement problems involved. Warns against the fact that over-reliance on purely quantitative measures (as indicated in "Charter" standards) to the neglect of more qualitative measures may be counterproductive. Suggests that qualitative approaches need to complement the normal statistical monitoring.
We have developed several high-resolution assays for the nucleotide state of a rho-subfamily low molecular weight GTP-binding protein, Cdc42Hs. The first involves the use of the fluorescent N-methylanthraniloyl derivative of GDP (mant-GDP). As has been shown for the ras protein, mant-dGDP fluorescence is significantly enhanced (approximately 20%) upon binding to Cdc42Hs. It was further found that the binding of mant-nucleotides results in an efficient energy transfer between the single tryptophan residue of Cdc42Hs and the mant moiety. The exchange of mant-dGDP for GDP bound to Cdc42Hs, as read-out either by the enhancement of the mant fluorescence or by energy transfer, is inhibited by physiological (mM) Mg2+ concentrations and correlates exactly to the rate of [3H]GDP exchange observed in filter-binding assays. Moreover, changes in the fluorescence of mant-dGDP are also sensitive to nucleotide dissociation induced by the dbl-oncogene product, a known nucleotide exchange factor for Cdc42Hs. A second fluorescence read-out for the nucleotide-bound state of Cdc42Hs involves the measurements of intrinsic fluorescence of a single tryptophan residue (W97) which is highly sensitive to whether GDP or GTP is bound in the nucleotide pocket. The hydrolysis of GTP to GDP by Cdc42Hs results in an approximately 30% enhancement of the protein fluorescence. The rate of this fluorescence change corresponds well to the rate of conversion of [gamma-32P]GTP to GDP plus [32P]Pi as measured by filter-binding assays.(ABSTRACT TRUNCATED AT 250 WORDS)
A 42-year-old woman with negative family history had the insidious onset of weakness in her lower extremities 8 years before, in 1983. The disorder slowly progressed to include cramps and muscle twitches. The diagnosis of adult spinal muscular atrophy (SMA) was made when electromyography showed large rapidly firing motor unit-potentials, positive waves, and fibrillation potentials, and when muscle biopsy of the quadriceps revealed severe alterations consistent with neurogenic atrophy. The patient also had severe chronic constipation for many years. More recently she had developed unremitting diarrhea. Gastrointestinal studies showed no evidence of peristaltic contractions in the rectum, delayed gastric emptying, and abnormal jejunal manometry with altered propagation of the migrating myoelectrical complex.
We studied a 9-year-old girl with progressive weakness of her extremities for two years. Her neurologic evaluation showed weakness of proximal muscles but no ophthalmoparesis. With the exception of elevated serum lactic acid, the general blood screen, EMG, nerve conduction velocity tests, and ECG were normal. Light and electron microscopy of a muscle biopsy showed proliferation of mitochondria containing disorganized cristae. Activities of respiratory chain enzymes containing mitochondrial DNA (mtDNA)-encoded subunits were significantly impaired in muscle homogenates. A G-->A transition at position 15990 previously detected in this patient's muscle was not present in peripheral blood cells of her mother or sister. However, the patient's WBCs appeared to contain a very small percentage of mutant mtDNAs, indicating that the mutation may have originated during early embryogenesis.
OBJECTIVE: To assess hypertension detected under 40 in a general practice population. DESIGN: Prospective case-control study. SETTING AND SUBJECTS: Former coal mining community in south Wales. Systematic case finding for hypertension and associated risk factors applied to a mean total population of 1945 from age 20 on a five year cycle through 21 years. Mean population aged 20-39, 227 men and 213 women. Case criteria: age < 40 and mean systolic pressure > or = 160 mm Hg or diastolic pressure > or = 100 mm Hg. Age and sex matched controls randomly sampled from the same population. MAIN OUTCOME MEASURES: Mean initial pressures and pressures at follow up in 1989 or preceding death, and all cardiovascular events. RESULTS: 25 men and 16 women met criteria. Estimated five yearly inceptions were 26/1000 for men and 18/1000 for women. Male group mean initial blood pressure was 164/110 mm Hg for cases, falling to 148/89 mm Hg at follow up. Five male cases died at mean age 47.8, compared with two controls at 49.5. Female group mean initial pressure was 172/107 mm Hg for cases, falling to 145/86 mm Hg at follow up. One female case died aged 50, no controls. 10 male cases had non-fatal cardiovascular events at mean age 40.2, compared with two controls at mean age 50.5. Four female cases had non-fatal events at mean age 47.2, compared with one control aged 58. Male differences were statistically significant. CONCLUSIONS: Hypertension under 40 is dangerous, commoner in men than women, rarely secondary to classic causes, and may be controlled in general practice on a whole community basis.
Thirty-one patients underwent limited hepatic resection with Roux-en-Y biliary-enteric anastomosis and placement of biliary stents for cholangiocarcinoma of the hepatic duct bifurcation (Klatskin tumor). Resection included wide tumor excision and bile duct resection at the liver hilum without major hepatic resection and was undertaken in all patients unless precluded by intraoperative evidence of vascular invasion. All patients were operated on by a single surgeon during the 10 years between 1981 and 1991. Similar procedures were performed for both curative (n = 17) and palliative (n = 14) treatment of this disease entity. In this series, the overall mean postoperative survival of these patients was 17 months. The mean postoperative survival of patients undergoing surgery with curative intent was 21 months in contrast to 12 months for those undergoing planned palliation. One patient in this series has been alive for more than 6 years with no evidence of disease. Five patients experienced major postoperative complications (16%), and there were two perioperative deaths (6%). This retrospective review supports an aggressive surgical approach in patients with Klatskin tumor.
Neutrophil recruitment and activation are thought to play an important role in tissue damage observed in septicemia. Interleukin-8 (IL-8) is a small cytokine with important neutrophil-activating and chemoattractant properties. IL-8 release was studied after injection of human volunteers with low doses of either endotoxin (2 ng/kg of body weight) or tumor necrosis factor-alpha (TNF alpha) (50 micrograms/m2). After TNF-alpha injection, IL-8 appeared at 30 min, whereas increased levels were first observed after 90 min in endotoxin-challenged volunteers. Peak levels were measured at 120 min after both endotoxin (192 +/- 193 ng/L) and TNF alpha (500 +/- 236 ng/L) injection. These data indicate that IL-8 is released in humans after injection of endotoxin and TNF alpha and suggest that endotoxin-induced IL-8 release is mediated by TNF alpha.
Patients treated with continuous ambulatory peritoneal dialysis (CAPD) may suffer from recurrent peritonitis episodes caused by Staphylococcus epidermidis. Early recruitment of granulocytes from the peripheral blood is important for the peritoneal antibacterial defense of CAPD patients. In this study, human peritoneal mesothelial cells were shown to produce high levels of interleukin-8 (IL-8) in response to IL-1 beta and tumor necrosis factor-alpha (TNF alpha) but not lipopolysaccharide or S. epidermidis. Coculture of peritoneal macrophages with S. epidermidis induced high levels of IL-1 alpha, IL-1 beta, and TNF alpha in 24-h-conditioned medium. Preincubation of this medium with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta partially blocked stimulation of IL-8 production by mesothelial cells. Added together, these antibodies abolished IL-8 production to a level just above background. Migration of granulocytes to the stimulated mesothelial cell-conditioned medium could be totally blocked with rabbit polyclonal anti-IL-8 antibody. Thus, mesothelial cells are important for the recruitment of granulocytes into the peritoneal cavity.
A meaningful definition of the CNS has been difficult to express because of the versatility of the role, yet a clear understanding of the role responsibilities is essential to ensure successful implementation of the CNS position within a select client population. Adolescence is a period in the life-span that represents such a population. Adolescents undergo certain cognitive changes that render them vulnerable to health-damaging behaviors often initiated during this stage of development. Health promotion self-care strategies by the CNS are important in helping the young person incorporate positive health practices in daily activities. A conceptual model, based on Orem's general theory of nursing, has been developed through literature review and refined through practical application. It is presented as a framework by which health promotion needs of the adolescent may be predicted, recognized, and satisfied through components of the CNS role, the basic concepts of Orem's model, and characteristics of adolescent cognitive development.
It has been a typically busy Saturday night in the emergency department. Then, near midnight, a trauma casualty was admitted and an incident occurred that would occupy Suzanne Smith's thoughts for months to come. When starting an intravenous line on this patient, Suzanne spiked herself with a needle. Later the patient was taken to the intensive care unit and placed on a ventilator. Suzanne was overcome with fear that she might have contracted AIDS. Her fears intensified when she learned that the patient, Mr. Norman, was a heroin addict.
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Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis.