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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 37 records · Page 2Linked to original sources

[Endoscopic treatment of colorectal obstruction with self-expandable metal endoprosthesis].

Relief of colo-rectal obstruction by means of self-expandable metal mesh stents (SEMS) has been suggested for palliation and acute decompression followed by optimization of the patients' general condition prior to definitive surgery. Twelve patients with high operative risk and/or metastatic disease were selected for stenting with a dedicated colorectal partly covered SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). Stent deployment was successful in nine, two of whom had total obstruction. In one a guidewire perforation was treated conservatively. In two patients (one benign stricture, and one rectal cancer) the stents migrated within three weeks. One re-obstructed. In the remaining six patients colonic decompression was achieved, and the stents have been patent until death (33-175 days, four patients) or are still patent (follow-up 35-80 days). These results are promising, but data from several centres should be compiled prospectively in a standardized fashion in order to allow for assessment of the method's safety and success rates before randomized trials can be initiated.

Aged↗

Electroosmosis- and pressure-driven chromatography in chips using continuous beds.

The application range of microchips can be extended to any mode of chromatography by filling the narrow channels with continuous polymer beds, exemplified by electrochromatography and ion-exchange chromatography. "Wall effects" are eliminated by anchoring the bed to the wall of the channel, an arrangement which has the additional advantage that no frits to support the bed are required. The design of the equipment is based on a quartz chip with all auxiliary pieces (for example, electrode vessels and fluid transfer fittings) placed in a rack, which permits a flexibility of great importance for automation. The same resolution and van Deemter plots were obtained in experiments performed in fused-silica capillaries and in chips for both low-molecular-weight (alkyl phenones, antidepressants) and high-molecular-weight substances (proteins). A sample of uracil, phenol, and benzyl alcohol was separated by electrochromatography in less than 20 s.

Chromatography, High Pressure Liquid↗

Ligand binding characteristics of a glycosylphosphatidyl inositol membrane-anchored HeLa cell folate receptor epitope-related to human milk folate binding protein.

The folate receptor (FR) in HeLa cells was characterized as to ligand binding mechanism, antigenic properties and membrane anchor in order to obtain information to be used for the design of biological agents targeting FR in malignant tumors. The receptor displayed the following binding characteristics in equilibrium dialysis experiments (37 degrees C, pH 7.4) with [3H] folate: a high-affinity type of binding that exhibited positive cooperativity with a Hill coefficient > 1.0 and an upward convex Scatchard plot, a slow radioligand dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition in the presence of other folates. The molecular size of the receptor was 100 kDa on gel filtration with Triton X-100, or similar to that of high molecular weight human milk folate binding protein (FBP). The latter protein represents a 25 kDa molecule which equipped with a hydrophobic glycosylphosphatidyl inositol (GPI) membrane anchor susceptible to cleavage by phosphatidylinositol specific phospholipase C (PI-PLC) forms micelles of 1kDa size with Triton X-100. The HeLa cell FR immunoreacted with antibodies against purified human milk FBP in ELISA, and in a fluorescence activated cell sorting system, where HeLa cells exposed to increasing concentrations of antibody showed a dose-dependent response. Exposure to PI-PLC decreased the fraction of immunolabeled cells indicating a linkage of FR to cell membranes by a GPI anchor. HeLa cells incubated with radiofolate showed a continuous uptake with time, however, with a complete suppression of uptake in the presence of an excess of cold folate. Prewash of cells at acidic pH to remove endogenous folate increased the uptake. Binding and uptake of [3H] folate was increased in cells grown in a folate-deprived medium. The HeLa FR seems to be epitope related to human milk FBP.

Binding Sites↗

Middle cerebral artery circulation during carotid surgery. A transcranial Doppler study.

OBJECTIVE: Perioperative carotid cross-clamping might induce low stump pressures as well as hypoperfusion of the middle cerebral artery. In this study blood flow velocities in the middle cerebral artery were compared with intraoperative measurements of the poststenotic carotid blood pressure. DESIGN: Forty-one patients with internal carotid artery stenosis were operated on without shunting, under general anesthesia. Poststenotic carotid pressures and middle cerebral artery flow velocities were measured before and during cross-clamping. The hemodynamic responses to preoperative carotid compressions and intraoperative cross-clamping were evaluated. RESULTS: In seven patients the poststenotic carotid blood pressure decreased on clamping despite unchanged or even increased middle cerebral artery blood flow velocities. In all other patients, pressure changes were significantly correlated to the decrease in middle cerebral artery blood flow velocities. Autoregulatory blood flow velocity responses after preoperative common carotid artery compression were not reproducible by cross-clamping. CONCLUSIONS: Stump blood pressure measurements may not reflect middle cerebral artery perfusion in about 20% of thrombendarterectomies performed under general anesthesia. A possible explanation might be dimished cerebral autoregulation and changes in collateral flow distributions.

Adult↗

High diastolic flow velocities in severe internal carotid artery stenosis: a sign of increased surgical risk?

PURPOSE: We reviewed the history and preoperative investigations of patients with early postoperative neurologic events after carotid thromboendarterectomy in an attempt to identify risk factors for neurologic complications. METHODS: Patients with neurologic events/complications (S group, n = 14 patients) were compared with an age- and disease-matched control group (C group, n = 42 patients) selected from the whole carotid thromboendarterectomy material between 1987 and 1996. In this retrospective study, we re-evaluated the maximum systolic and end diastolic flow velocities within the internal carotid artery (ICA) using video recordings of preoperative Duplex ultrasound scan investigations. The flow velocity variables were compared with preoperative carotid angiography and intraoperative ICA stump pressure measurement. RESULTS: S-group did not differ from C-group concerning either cardiovascular risk factors or diseases, ipsilateral and contralateral angiographic grade of ICA stenosis, or history of cerebral infarctions. Nevertheless, in contrast to control subjects, patients with early postoperative major stroke had higher end diastolic flow velocities and lower ICA stump pressures. Patients with postoperative minor stroke, transient ischemic attack, or amaurosis fugax did not differ significantly from the control subjects. Among patients with ICA stenosis of 75% or more, end diastolic flow velocities were correlated to the diastolic stump pressures. CONCLUSION: Diastolic flow velocities within severe internal carotid artery stenosis are dependent on the level of the collateral perfusion pressure distally to the stenosis (ie, high values indicate a low internal carotid artery stump pressure), which seems to be a risk factor for early postoperative strokes.

Aged↗

Endoscopic placement of self-expanding metal stents for treatment of colorectal obstruction with long-term follow-up.

INTRODUCTION: Relief of colorectal obstruction by means of self-expandable metal mesh stents (SEMS) has been suggested for palliation and acute decompression followed by optimization of the patients' general condition prior to definitive surgery. METHODOLOGY: Twelve patients with high operative risk and/or metastatic disease were selected for stenting with a dedicated colorectal partly covered SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). RESULTS: Stent deployment was successful in nine, two of whom had total obstruction. In one a guidewire perforation was treated conservatively. In two patients (one benign stricture, and one rectal cancer) the stents migrated within three weeks. One re-obstructed. In the remaining six patients colonic decompression was achieved, and the stents have been patent until death after median 116 days (33-292 days). CONCLUSION: These results are promising, but data from several centres should be compiled prospectively in a standardized fashion in order to allow for assessment of the method's safety and success rates before randomised trials can be initiated.

Aged↗

Changes in levels of factor VII and protein S after acute myocardial infarction: effects of low-dose warfarin.

Persistent coagulation activity after an acute myocardial infarction may increase the risk of reinfarction. We prospectively investigated the effects on plasma coagulation of a low, fixed dose of warfarin in combination with aspirin after myocardial infarction. We also evaluated the influence of coagulation activity on clinical outcome. Plasma samples from 97 patients, randomised to 1.25 mg of warfarin daily in combination with 75 mg of aspirin or aspirin alone were drawn 4 days, 1 month, and 6 months after myocardial infarction. Patients receiving warfarin had a greater reduction in factor VII coagulation activity (FVII:C) after 6 months: 0.18 vs. 0.06 U/mL,(95% CI, 0.02-0.22), whereas no differences were seen in levels of protein C, protein S, or prothrombin fragment 1+2. In the acute phase, the level of free protein S was lower than after 6 months in both groups: 25.6 vs. 28.8% (95% CI, 4.19--2.35). Cardiovascular mortality, reinfarction, and stroke were evaluated after 4 years (median). In a survival analysis, every 0.1 U/mL increase in the level of FVII:C1 month after myocardial infarction was associated with an 15% increase in risk of cardiovascular events (95% C1, 1.01-1.30). Warfarin at 1.25 mg daily reduces FVII:C but not systemic thrombin generation measured as prothrombin fragment 1 +2. Low levels of the anticoagulant protein S may contribute to a procoagulant state.

Adult↗

[Hypertension in general practice].

A group of 15 Danish general practitioners performed a medical audit on hypertension control consultations consisting of three registrations of each 15 days during 1995 through 1997. Between the first and second registration an interventional programme was set up by establishing different kinds of CME activity and by publishing local guidelines for discovering, diagnosing, treating and controlling hypertension. The blood pressure reductions achieved were only moderate even though the doctors were rather compliant to the recommendations; in 1997 no less than 70% of the patients were above the recommended target value for systolic blood pressure (140 mmHg) whereas 20% were above the target value for diastolic blood pressure (90 mmHg). Present aspects of the epidemiology of hypertension and its treatment as performed by general practitioners today are described, and possible reasons for shortcomings are discussed.

Adult↗

High-affinity folate receptor in human ovary, serous ovarian adenocarcinoma, and ascites: radioligand binding mechanism, molecular size, ionic properties, hydrophobic domain, and immunoreactivity.

High-affinity folate receptors are expressed in normal ovaries and ovarian carcinomas. Binding of [3H]folate in human ovary, serous ovarian carcinoma tissue, and ascites is a complex process that has not been well characterized. This study shows changes in binding affinity and mechanism of binding with decreasing receptor concentration, inhibition by folate derivatives, and a slow radioligand dissociation at pH 7.4 becoming rapid and complete at pH 3.5. The receptor seems to be positively charged since it elutes in the front effluent of a DEAE-Sepharose CL-6B ion-exchange column at pH 6.3. The gel filtration profile of Triton X-100-solubilized tissue and ascites contained two peaks of radioligand-bound receptor (25 and 100 kDa). Exposure of ascites to cleavage by phosphatidylinositol-specific phospholipase C resulted in a partial conversion of the 100-kDa peak to a 25-kDa peak. This suggests that the receptor may be anchored to the membrane by a glycosylphosphatidyl residue that inserts into Triton X-100 micelles, resulting in a large molecular size on gel filtration. The receptor in ovarian carcinoma tissue immunoreacts with antibodies against purified human milk folate receptor protein as shown by enzyme-linked immunosorbent assay, immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting (a single band of 45 kDa), and immunohistochemistry. In only three of seven ovarian carcinomas did expression of radioligand-bound receptors exceed levels found in five normal ovaries. However, only receptors in ovarian carcinoma specimens showed a high degree of immunoreactivity. Hence, even without elevations of the total receptor level, a folate receptor isoform homologous to human milk folate receptor protein seemed to prevail in serous ovarian carcinomas.

Ascites↗

Characterization of a high-affinity folate receptor in normal and malignant human testicular tissue.

We have characterized the folate receptor in normal and malignant tissue from male gonads. Radioligand binding displayed characteristics typical of other folate receptors. Those included a high-affinity type of binding (K = 10(10M-1)), apparent positive cooperativity changing into non-cooperativity at low receptor concentrations, a tendency to increased binding affinity with decreasing receptor concentrations, a slow dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition by folates, in particular oxidized forms. The gel filtration profile of Triton X-100 solubilized tissue contained a 25 and 100 kDa peak of radioligand-receptor. The latter peak could represent receptor equipped with a hydrophobic membrane anchor that inserts into Triton X-100 micelles. The concentration of radiolabelled receptor ranged from 0.41 nmol/g protein to 1.68 nmol/g protein in specimens of normal testicular tissue from patients with prostatic carcinomas and from 1.54 nmol/g protein to 3.82 nmol/g protein in testicular tissue from young individuals. Compared to normal testicular tissue the concentration of receptor in seminoma tissue was low (0.38-1.27 nmol/g protein) but showed a higher degree of immunoreactivity in the presence of antibodies against human milk folate binding protein as evidenced by ELISA and immunohistochemistry data. Hence a folate receptor isoform homologous to human milk folate binding protein is apparently expressed in seminomas where the total expression of receptor, however, seems to be lower than in normal testicles.

Aged↗

Factor V Q506 (resistance to activated protein C) and prognosis after acute coronary syndrome.

Factor V:Q506 causing resistance to activated protein C (APC-resistance), is a risk factor for venous thrombosis. Some studies have indicated an association with arterial disease, especially in women. We investigated the prevalence of the FV:Q506 allele prospectively in 295 patients with acute coronary syndrome. Mortality and myocardial infarction rate were evaluated after 30 days and after 2 years. The FV:Q506 allele was found in 38 patients. In a Cox proportional hazards model, smokers carrying FV:Q506 had a higher risk of infarction or death within 30 days, compared to non-smokers with a normal genotype (relative risk 2.9 [95% CI 1.2-7.0]). The difference remained significant after 2 years (relative risk 2.8 [95% CI 1.2-6.5]). The effect of the FV:Q506 allele on clinical outcome in acute coronary syndrome has not previously been described. Our results demonstrate a gene-environment interaction between smoking and the FV:Q506 allele, with an increased risk of early complications after an acute ischemic event.

Activated Protein C Resistance↗

A folate binding protein in ascitic fluid, serum and ovarian tissue of patients with ovarian adenocarcinoma immunoreacts with antibodies against human milk folate binding protein.

The presence of a folate binding protein which immunoreacts with antibodies against human milk folate binding protein was demonstrated in ascitic fluids from seven patients with ovarian adenocarcinoma. Ascitic fluids collected from two patients with other malignancies contained non-immunoreactive FBP. Tumor tissue specimens from five patients with ovarian carcinoma contained immunoreactive FBP. By contrast to normal ovaries ovarian carcinoma tissue showed positive immunostaining on immunohistochemistry. Ascitic fluids from two patients with ovarian carcinoma exhibited single distinct bands on SDS-PAGE immunoblotting. The gel filtration profile of ovarian carcinoma tissue homogenate from two patients contained 25 and 1OOkDa peaks of radioligand-bound and immunoreactive folate binding protein, while ascitic fluid from one of the patients exhibited a large 100 kDa immunoreactive peak with no radioligand binding activity. The immunoreactive non-functional 100 kDa FBP could represent unprocessed precursor FBP. Future studies are necessary to evaluate whether determination of immunoreactive FBP in ovarian adenocarcinomatosis is of any diagnostic value.

Adenocarcinoma↗

Selectivity of superficial vein occlusion at the ankle and calf level: a methodological study in healthy volunteers.

Judgement of deep venous function may be necessary before surgery for superficial vein incompetence is performed. Assessment of deep venous function needs selective entrapment of superficial venous compartments between the ankle and knee, which may not be guaranteed if conventional tourniquets are used. This study was, therefore, aimed at modifying the technique of selective compression of superficial vein compartments. Twenty apparently normal legs of 10 volunteers were investigated on two study days. The subjects were in a supine position with the feet resting 30 cm above heart level. Ankle cuffs (3 cm wide) were placed just above the malleoli and stepwise inflated with air. The steady-state venous volume of the forefoot as a function of the pressure within the ankle cuff was measured with a mercury-in-rubber strain gauge. The maximum venous outflow velocity from the foot was also measured at each cuff pressure step after the addition of conventional thigh vein occlusion. The same protocol was used on the second study day: calf cuffs (3 cm wide) were then used instead of the ankle cuffs. In the forefoot, venous volume increased and the maximum venous outflow velocity decreased significantly either at ankle cuff pressures > 30 mmHg or at calf cuff pressures of > 60 mmHg. By using small cuffs, selective superficial vein occlusion seems to occur at cuff pressures ranging between 10 and 30 mmHg (ankle) and between 30 and 60 mmHg (calf), provided the feet are 30 cm above heart level. Higher cuff pressures seem to interact with deep venous function.

Adult↗

A high-affinity folate binding protein in fluid of benign cysts of human liver and mammary gland.

The presence of a folate binding protein in fluid of benign cysts of human liver and mammary gland was demonstrated. Radioligand binding was of a high-affinity type (K approximately 10(10) M -1). The gel filtration profile of cystic fluid contained two peaks of radiolabelled folate, a large one of 25 kDa and a small one of 100 kDa. The concentration of radioligand bound protein in samples of cystic fluid ranged from nil to 6 nM. In most cases the protein immunoreacted with antibodies against human milk folate binding protein. The data suggest that fluid of human liver and mammary gland cysts contains a folate binding protein which appears to be homologous to human milk folate binding protein.

Binding, Competitive↗