Bacteriophage therapy for bacterial infections. Rekindling a memory from the pre-antibiotics era.
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Biomedical subjects
Publications and source records attributed to K Ho.
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A series of sulfonated poly(N-vinylcarbazole) (PVK) samples have been systematically studied by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS). Negative TOF-SIMS results provided unambiguous evidence that sulfonate groups are chemically attached to the carbazole moiety of PVK. The positive SIMS spectrum of PVK was, however, little affected by the sulfonation reaction. The degree of sulfonation was quantitatively determined by XPS. Therefore, the combination of TOF-SIMS and XPS is useful to follow the sulfonation reaction, both qualitatively and quantitatively. The SIMS intensities of some characteristic fragments are linearly related to the degree of sulfonation, suggesting that quantitative analysis is possible from TOF-SIMS data.
Twenty-four 4-alkylidene glutamic acids were synthesised and tested as potential subtype selective GluR5 and 6 ligands. It was found that a critical size of alkylidene group gave potent and selective GluR5 receptor agonists. LY339624 had Kis of 0.0326 and >100 microM on GluR5 and 6 receptors, respectively.
The present study was intended to examine the relaxant effects of berberine in rat isolated mesenteric arteries. Berberine produced a rightward shift of the concentration-response curve to phenylephrine and significantly reduced the maximal contractile response to phenylephrine. Berberine (10(-7)-3x10(-5) M) also relaxed the phenylephrine- and 9,11-dideoxy-11alpha, 9alpha-epoxy-methanoprostaglandin F(2alpha)-precontracted arteries with respective IC(50) values of 1.48+/-0.16x10(-6) and 2.23+/-0. 22x10(-6) M. Removal of a functional endothelium significantly attenuated the berberine-induced relaxation (IC(50): 4.73+/-0. 32x10(-6) M) without affecting the maximum relaxant response. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of berberine, and L-arginine (10(-3) M) partially antagonized the effect of L-NAME. In contrast, pretreatment with 10(-6) M glibenclamide or 10(-5) M indomethacin had no effect. Berberine (10(-5) M) reduced over by 50% the transient contraction induced by caffeine or phenylephrine in endothelium-denuded rings bathed in Ca(2+)-free Krebs solution. Pretreatment with putative K(+) channel blockers, such as tetrapentylammonium ions (1-3x10(-6) M), 4-aminopyridine (10(-3) M), or Ba(2+) (3x10(-4) M), significantly attenuated the berberine-induced relaxation in endothelium-denuded arteries. In contrast, tetraethylammonium ions (3x10(-3) M), charybdotoxin (10(-7) M) or glibenclamide (10(-6) M) were without effect. Berberine reduced the high-K(+)-induced sustained contraction and the relaxant response to berberine was greater in rings with endothelium (IC(50): 4.41+/-0.47x10(-6) M) than in those without endothelium (IC(50): 8.73+/-0.74x10(-6) M). However, berberine (10(-6)-10(-4) M) did not affect the high-K(+)-induced increase of intracellular [Ca(2+)] in cultured aortic smooth muscle cells. Berberine did not affect active phorbol ester-induced contraction in Ca(2+)-free Krebs solution. In addition, berberine inhibited proliferation of cultured rat aortic smooth muscle cells with an IC(50) of 2.3+/-0.43x10(-5) M. These findings suggest that berberine could act at both endothelium and the underlying vascular smooth muscle to induce relaxation. Nitric oxide from endothelium may account primarily for the berberine-induced endothelium-dependent relaxation, while activation of tetrapentylammonium-, 4-aminopyridine- and Ba(2+)-sensitive K(+) channels, inhibition of intracellular Ca(2+) release from caffeine-sensitive pools, or a direct relaxant effect, is likely responsible for the berberine-induced endothelium-independent relaxation. Mechanisms related to either Ca(2+) influx or protein kinase C activation may not be involved. Both vasorelaxant and antiproliferative effects may contribute to a long-term benefit of berberine in the vascular system.
Lack of a nocturnal decline in blood pressure (BP) has been associated with more severe end organ damage in hypertensives, and blacks appear less likely than whites to have a > 10% drop in nighttime BP ("dipping"). Little information is available about the relationship between treatment regimens, ethnic group classification, and dipping in treated hypertensive patient populations. We obtained 24-h ambulatory BP readings in 438 adult white (n = 103), black (n = 200) and Hispanic (n = 135) treated hypertensives. Tycos monitors were connected in patients' homes before their usual morning medication dose time. Research assistants administered a quality-of-life questionnaire, recorded patients' drug regimen, and observed the patients take their morning dose. Monitors were programmed to record BP every 30 min. Dippers were defined as persons who had a drop of > or = 10% decline in average daytime (08:00 to 22:00) compared to nighttime (00:00 to 04:00) BP. Logistic regression modeling was used to assess the relationship between demographic and treatment variables and probability of dipping. Twenty-four-hour average BP was similar in all three ethnic groups. However, the absence of a systolic dip was significantly more common in black and Hispanic men than in white men (OR black v white = 11.54, 95% CI = 3.92 to 34.01; OR Hispanic v white = 7.32, 95% CI = 2.47 to 21.68). There were no ethnic group differences in probability of systolic dipping among women. Absence of a diastolic dip was approximately twice as common in blacks and Hispanics than in whites, with no marked gender-by-ethnic-group interaction in the magnitude of the association. Of the 10 most commonly prescribed antihypertensives, no single drug was positively associated with nocturnal BP decline. Later versus earlier morning dose time, but not once-a-day dosing, was associated with absence of dipping. Treated black and Hispanic hypertensives are less likely to "dip" than non-Hispanic whites. No particular drug was positively associated with dipping.
In February 1999, a workshop was held in Cortina, Italy to develop a consensus defining the criteria for cure of acromegaly. The workshop was sponsored by the University of Brescia and hosted by the Italian Society of Endocrinology. Invited international participants included endocrinologists, neurosurgeons, and radiotherapists skilled in the management of acromegaly. This statement summarizes the consensus achieved in these discussions.
Both genetic and environmental factors have been hypothesized to explain the higher prevalence of hypertension in US African Americans compared to populations still residing in western Africa. Studies of first-generation immigrants can help to identify risk factors for increased chronic disease expression in the developed world. Since we could identify no prior studies of hypertension in African immigrants to the United States, we conducted a cross-sectional survey of African-born and US-born African-American health professionals to compare the two groups for the prevalence of hypertension (blood pressure > or = 140/90 mm Hg or use of antihypertensive medication) and risk factors for hypertension (body mass index, lifestyle factors, and psychosocial variables hypothesized to relate to hypertension). Subjects were registered pharmacists and nurses recruited by mail. For the 182 individuals who completed study measurements (95 US-born and 87 African-born), the unadjusted odds ratio for hypertension associated with birthplace was 2.16 (95% CI = 1.12, 3.98). After adjustment for body mass index and age, the OR for birthplace was 1.92 (95% CI = 0.92, 4.00). No lifestyle or psychosocial variables were associated with hypertension prevalence. We conclude that there is a lower prevalence of hypertension in first-generation African immigrants that cannot be readily explained by the environmental effects measured in this study. Larger scale studies with African immigrants could advance understanding of the causes of the increased hypertension prevalence in US-born African Americans.
Ruptured abdominal aortic aneurysm (RAAA) is a surgical emergency associated with a high mortality often requiring postoperative intensive care. Our objectives were to assess the outcome of RAAA management in a nontertiary community hospital intensive care unit (ICU) and to compare this with historical data from tertiary hospitals. We also sought to identify variables related to outcome and evaluate the potential of an organ failure score to identify patients at increased risk of death. The study was a retrospective chart review of patients with RAAA over 11 years (1986-1996 inclusive) at Manly District Hospital, a 210 bed community teaching hospital with eight intensive care beds. Forty patients were identified in the study period as having been admitted to ICU after RAAA surgery. There was an overall hospital mortality rate of 47.5% and intensive care mortality rate of 42.5% for successfully operated RAAA. Five variables were significantly different between survivors and non-survivors. These were age, total amount of blood products required, duration of operation, development of hypotension (systolic blood pressure < 90 mmHg) in ICU postoperatively, and APACHE II score at Day 1 ICU. A trend was also found between mortality rate and the number of failed systems after 48 hours intensive care stay. Mortality for a patient with zero failed systems was 38%, one failed system 42%, two 58% and three 67%. Based on these results, management of RAAA in a non-tertiary setting appears appropriate with postoperative care occurring in an ICU where there is adequate equipment and medical and nursing staff experienced in the care of complex critical illness.
The ROMK1 (Kir 1.1a) channel is formed by a tetrameric complex of subunits, each characterized by cytoplasmic N- and C-termini and a core region of two transmembrane helices flanking a pore-forming segment. To delineate the general regions mediating the assembly of ROMK1 subunits we constructed epitope-tagged N-terminal, C-terminal, and transmembrane segment deletion mutants. Nonfunctional subunits with N-terminal, core region, and C-terminal deletions had dominant negative effects when coexpressed with wild-type ROMK1 subunits in Xenopus oocytes. In contrast, coexpression of these nonfunctional subunits with Kv 2.1 (DRK1) did not suppress Kv 2.1 currents in control oocytes. Interactions between epitope-tagged mutant and wild-type ROMK1 subunits were studied in parallel by immunoprecipitating [35S]-labeled oocyte membrane proteins. Complexes containing both wild-type and mutant subunits that retained H5, M2, and C-terminal regions were coimmunoprecipitated to a greater extent than complexes consisting of wild-type and mutant subunits with core region and/or C-terminal deletions. The present findings are consistent with the hypothesis that multiple interaction sites located in the core region and cytoplasmic termini of ROMK1 subunits mediate homomultimeric assembly.
PURPOSE: To test the effectiveness of a bioptic form of a peripheral vision-enhancement lens in patients with retinitis pigmentosa (RP), choroideremia, and Usher's syndrome Type II. METHODS: Fifteen patients with peripheral visual field loss were trained in the use of the amorphic lenses for driving and other everyday activities for a 3-month period. A cross-over study design was used, where one group of eight patients received training during the first 3 months of the 6-month study, and another group of seven patients received training during the second 3 months. All patients were administered a battery of clinical, psychophysical, functional, mobility, and driving assessment tests at the beginning of the study, at 3 months, and at 6 months. The assessment tests were coded according to the primary visual skill involved in the task. These visual skills included: recognition, peripheral detection, scanning, tracking, visual memory, and mobility. RESULTS: After training, the patients showed improvement in all visual skills categories on the assessment tests, with overall improvement of 37%. There was no significant difference in the levels of improvement between the two groups. Those with smaller visual field extents showed significantly greater improvement on peripheral detection and scanning tasks. Those patients trained during the first 3 months of the study maintained their skills when tested at the 6-month point. CONCLUSION: Patients with peripheral vision loss may benefit from a rehabilitation program which combines low vision training with amorphic lenses in a bioptic configuration.
The structure of ATP-sensitive K+ (KATP) channels in excitable cells has been elucidated recently. These channels consist of a pore-forming inward rectifier K+ (Kir) channel and four sulfonylurea receptor proteins. In the distal nephron, Kir 1.1 (ROMK) channels probably contribute to the formation of epithelial (KATP) channels. Current findings suggest the possibility that these renal KATP channels consist of Kir 1.1 channel-CFTR complexes and therefore represent structural analogues of classical KATP channels.
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Low-molecular-weight (LMW) heparin has recently been used for anti-coagulation in maintenance hemodialysis. The LMW heparin was administered as a single bolus in hemodialysis that usually lasted for four hours or less. The regimen for administering LMW heparin in hemodialysis of longer duration (5 hours or more) is not well documented and manufacturers recommend a supplementary dose equivalent to one-quarter of the initial dose to be given at 4 hours after the commencement of hemodialysis. In this study, we explored whether administering a single dose of LMW heparin is feasible in hemodialysis of longer duration. Maintenance five-hour hemodialysis sessions were performed in nine uremic patients with two different heparin regimens: single dose of LMW heparin (nadroparin) 12,500 ICU AXa at the beginning of dialysis or a priming dose of nadroparin 10,000 ICU AXa at the beginning of dialysis followed by a supplementary dose of nadroparin 2,500 ICU AXa at the beginning of the fifth hour of dialysis. Clots in the airtraps or clotting of the dialyser were not observed in hemodialysis with the single dose heparin regimen. The anti-Xa activities at different time intervals during dialysis were above the therapeutic range of 0.5 U/ml except towards the end of the hemodialysis treatment. There was no difference between anti-Xa activities determined in dialysis sessions using two different regimens of LMW heparin at any individual time interval. The anti-thrombotic effect determined by the area under the time response curve for anti-Xa activity was comparable in the two LMW heparin regimens. Hence, our findings suggest a single bolus dose of LMW heparin (nadroparin) at 12,500 ICU AXa provides adequate, safe, and effective anti-coagulation for five-hour hemodialysis. This practice is convenient and avoids the necessity of administering a double dose of LMW heparin.
In Drosophila intracellular gradients establish the pattern of segmentation by controlling gene expression during a critical syncytial stage, prior to cellularization. To investigate whether a similar mechanism may be exploited by other insects, we examined the timing of cellularization with respect to blastoderm formation in an insect with extreme short-germ development, the African desert locust, Schistocerca gregaria. Using light and electron microscopic techniques, we show that the islands of cytoplasm surrounding cleavage nuclei are largely isolated from their neighbours, allowing cleavage to proceed asynchronously. Within a short time of their arrival at the surface and prior to blastoderm formation, nuclei become surrounded by complete cell membranes that block the free uptake of dye (10,000 kDa) from the yolk. Our results imply that the formation of the blastoderm disc involves the aggregation of cells at the posterior pole of the egg and not the migration of nuclei within a syncytial cytoplasm. These findings suggest that the primary cleavage syncytium does not play the same role in patterning the locust embryo as it does in Drosophila. However, we do identify a syncytial nuclear layer that underlies the forming blastoderm and remains in continuity with the yolk.
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OBJECTIVE: To assess the value of an ankle effusion on plain radiographs as a predictor of radiographically occult fracture after acute ankle trauma. PATIENTS: Consecutive patients with acute ankle trauma and radiographic evidence of an ankle joint effusion. Patients were excluded if ankle trauma was sustained more than 48 h previously or if a fracture was visible on initial photographs. METHODS: All subjects (n = 26) underwent computed tomography (CT) of the ankle in sagittal and coronal planes. Ankle effusion size was measured from initial lateral ankle radiographs. RESULTS: Twelve patients (46%) had radiographically occult fractures identified with CT. Fracture sites included: posterior or lateral malleoli (n = 4), calcaneus (n = 1), or talus (n = 7). Ankle effusion size was 11.2 mm in the group without fracture and 17.1 mm in the group with fracture (P < 0.0001). The positive predictive value of an effusion 15 mm or greater was 83%. CT detected significant soft-tissue injuries in four (15%) patients including peroneal retinaculum tear (n = 1), anterior talofibular ligament avulsion (n = 1), and tears of the peroneus longus (n = 1) and tibialis posterior (n = 1) tendons. CONCLUSIONS: The presence of a large ankle effusion of radiographs after acute ankle trauma suggests an underlying fracture. An ankle effusion of > or = 15 mm is a reasonable threshold to prompt additional imaging. Computed tomography provides good visualization of subtle bone injuries and may detect clinically imported soft-tissue injuries.
STUDY OBJECTIVES: To determine the incidence of occult ankle fractures and to determine whether an ankle effusion identified radiographically correlated with the presence of an occult fracture. METHODS: Attending physicians in the emergency department of a university hospital prospectively identified patients with acute ankle injuries that produced ecchymosis or edema over two or more major ligaments of the ankle. Plain radiographs of these patients demonstrated ankle effusions without fractures. A consecutive sample of patients with acute ankle injuries was selected. Thirty-six of 1,151 patients were eligible to enter the study; 2 of these patients subsequently were excluded from the data analysis. All eligible patients underwent plain ankle tomography at 3-mm intervals in the coronal and sagittal planes. The types and frequencies of occult ankle fractures identified on plain film tomography were noted. The distention of the ankle joint capsule of enrolled patients was measured to determine if the degree of effusion correlated with the presence of an occult fracture. RESULTS: The minimum incidence of occult fractures in the general population with ankle injuries was 1%. Twelve of 34 patients (35%) with acute, severe injuries had occult fractures. Depending on the size, an effusion was correlated with the presence of an occult fracture in 35% to 85% of the study population. CONCLUSION: Plain film tomography should be used when evaluating ankle injuries if both edema or ecchymosis over two or more stabilizing ligaments and radiographic evidence of an effusion are present simultaneously.