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Biomedical subjects

K Johansen

Publications and source records attributed to K Johansen.

At least 19 recordsLinked to original sources

Automated analysis of free and total concentrations of three antiepileptic drugs in plasma with on-line dialysis and high-performance liquid chromatography.

A fully automated method for determination of the free and total concentration of drugs with a varying degree of protein binding is described. The antiepileptic drugs phenytoin, carbamazepine and phenobarbitone were chosen to demonstrate the utility of this technique. The method was based on the ASTED system and combined on-line equilibrium dialysis at 37 degrees C with concentration of the dialysate on a trace enrichment column and HPLC determination with UV detection. The dialysis cell was a modification of the ASTED dialysis cell and 22% of the free concentration of the drugs were recovered in the recipient channel of the dialyser after 10 min of dialysis at 37 degrees C. The free concentration, the total concentration as well as the drugs protein binding could be determined. The method was shown to be well suited for routine monitoring of the free and the total concentrations of the drugs in plasma from epileptic patients.

Anticonvulsants

Pharmacologic intervention to prevent graft failure.

Lower extremity vascular grafts, either vein or synthetic, fail for diverse reasons. Technical defects or poor surgical judgment doom a graft beyond any benefit pharmacotherapy can offer. Graft failure due to spontaneous thrombosis particularly affects prosthetic conduits, and use of antiplatelet agents (dextran, ASA) or anticoagulants (heparin, warfarin) is probably useful in this setting. An effective way to inhibit vein graft or anastomotic intimal hyperplasia remains elusive. Perhaps the most permanent and longstanding influence on lower extremity graft survival can be made through risk factor intervention aimed at arresting the progression of atherosclerosis. Aggressive treatment of hyperlipidemia, hypertension, smoking, and other known risk factors should be routinely and aggressively pursued in patients with lower extremity grafts, either autogenous or prosthetic. Lower extremity graft patency is optimally ensured by technically adept insertion of a proper autologous conduit in a well-selected patient. Pharmacotherapy may have a significant adjunctive role in the maintenance of graft patency, especially in high-risk settings such as limb salvage with associated poor outflow, a marginal vein graft, or the obligatory use of prosthetic material.

Anticoagulants

Essential thrombocytosis: underemphasized cause of large-vessel thrombosis.

PURPOSE: The purpose of this study was to describe the clinical course of patients seen with large-vessel thrombosis in association with essential thrombocytosis (ET). METHODS: This study was a retrospective review of all patients treated for large-vessel thrombosis caused by ET during a 2-year period at University of Washington teaching hospitals. RESULTS: Five patients presented with arterial (femoral-popliteal-tibial: aortic), portal (two cases), or systemic venous (inferior vena cava) thrombosis and required operation. Two were known to have ET; in three others ET was diagnosed after operation when platelet counts persistently in excess of 500,000/mm3 were noted. The diagnosis of ET was established in each case by ruling out causes of reactive thrombocytosis and (in the three new cases) by evidence for megakaryocyte hyperplasia on bone marrow biopsy. Platelet counts in all five patients were reduced to normal levels by cytoreductive therapy, and no further thrombotic episodes have occurred during 18 months (mean) of follow-up. During this 2-year period ET accounted for more large-vessel thrombotic complications in our institutions than all other more frequently described hypercoagulable states combined. CONCLUSIONS: ET is an underemphasized cause of large-vessel thrombosis.

Adult

Specific pathway selection by the early projections of individual peripheral sensory neurons in the embryonic medicinal leech.

In leech, the central annulus of each midbody segment possesses seven pairs of sensilla, which are mixed clusters of primary peripheral sensory neurons that extend their axons into the CNS where they segregate into distinct fascicles. Pathway selection by individual afferent growth cones of sensillar neurons was examined by double labeling using intracellular dye-filling with antibody labeling in early Hirudo medicinalis embryos. The monoclonal antibody Lan3-2 was used because sensillar neuronal tracts are specifically labeled by this antibody. Examining 68 individually filled neurons we found that sensillar neuron growth cones bifurcate within the CNS, that they project long filopodia capable of sampling the local environment, and that all of them appeared to choose a single particular CNS fascicle without apparent retraction or realignment of growth cones. Furthermore, each side of the bifurcating afferent growth cones always chose the same fascicle, implying a specific choice of a distinct labeled pathway. By dye-filling individual central neurons (P-cells), we show that there are centrally projecting axons present at the time sensillar afferents enter the ganglionic primordia and select a particular fascicle, and we confirm that at least the dorsal peripheral nerve is likely to be pioneered by central neurons, not by the peripheral afferents. In the sensillum studied here, we found examples of sensory neurons extending axons into one of all the available fascicles. Thus, an individual embryonic sensillum possesses a heterogeneous population of afferents with respect to the central fascicle chosen. This is consistent with the idea that segregation into distinct axon fascicles may be based upon functional differences between individual afferent neurons. Our findings argue strongly in favor of specific pathway selection by afferents in this system and are consistent with previous suggestions that there exists a hierarchy of cues, including surface glycoconjugates that mediate navigation of the sensillar growth cones and the fasciculation of their axons.

Animals

Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection.

A human IgA-radioimmunoprecipitation assay (IgA-RIPA) utilizing the galactose-binding lectin jacalin from the jack-fruit Artrocarpus integrifolia was developed. Among the human immunoglobulins, jacalin binds specifically to immunoglobulin A. The IgA-RIPA was used to characterize the serum IgA response to individual rotavirus polypeptides in nine paired sera from children (8-34 months of age) with an acute rotavirus infection. In acute sera the IgA response was mainly directed against the inner capsid proteins VP2 and VP6, with VP2 surprisingly being the most immunogenic protein while in the convalescent sera, the IgA response was directed not only against structural but also against non-structural proteins.

Antibodies, Viral

Biomaterials for hemodialysis access.

While the optimal vascular conduit for hemodialysis is undeniably an arterialized autogenous subcutaneous vein, only a minority of end-stage renal disease patients can count on such access: the remainder require implantation of a biomaterial conduit. This paper will briefly survey current biografts used for hemodialysis access, with an emphasis on their known limitations, and will delineate the questions to be asked--and answered--in the development of optimal dialysis access grafts.

Arteriovenous Shunt, Surgical

Symmetrical peripheral gangrene (purpura fulminans) complicating pneumococcal sepsis.

Bacterial sepsis is only infrequently accompanied by peripheral ischemia. However, we have managed 10 patients with symmetrical peripheral gangrene (purpura fulminans) accompanying pneumococcal sepsis (Streptococcus pneumoniae) during the past 15 years at a single institution. In only two (20%) of these patients could vasoconstrictor administration be implicated as contributory to gangrene. The clinical scenario was characterized by pneumococcal bacteremia, admission to the medical intensive care unit, normal proximal arterial perfusion, and symmetrical full-thickness digital and distal extremity ischemia leading to cutaneous gangrene. Three (30%) of these patients died. The failure of anticoagulant and antiplatelet agents as therapy and the successful reversal of impending digital gangrene in one patient by sympathetic blockade suggest that the initial underlining pathophysiology is vasoconstrictive rather than thrombotic in nature. Effective management includes appropriate antibiotic therapy, avoidance of early operative intervention, conservative local débridement, and secondary skin grafting.

Adrenal Cortex Hormones

[Arteriosclerosis of the lower extremities--patients' contacts with alternative therapists].

During the period July 1987-April 1988, ninety-one patients with arterial insufficiency in the lower limbs were referred to the Department of Thoracic and Vascular Surgery at Aalborg Hospital. The mean delay between contact with the general practitioner and the vascular surgeon was nine months. Twenty-nine of the patients contacted alternative therapists before referral to the vascular surgeon. Twenty-five of these patients had suffered from intermittent claudication for at least two years and the total cost of treatment was 76,013 Danish crowns (900 Danish crowns or approximately pounds 75 per patient).

Adult

Circulatory changes induced by portal venous diversion and mesenteric hypertension in rats.

We studied the hemodynamics in four groups of rats with combinations of mesenteric hypertension and portal diversion. Operations created three groups with mesenteric hypertension and different degrees of portal venous diversion: mesenteric vein stenosis, portal vein stenosis and end-to-side portacaval anastomosis with mesenteric vein stenosis, the fourth group had only portacaval anastomosis. A control group had sham operations. Cardiac output, splanchnic blood flows and portosystemic shunt indices were measured with radioactive microspheres. Mesenteric venous pressures in the mesenteric-stenosed, portal-stenosed, portacaval-shunted and end-to-side portacaval anastomosis with mesenteric vein stenosis rats were, respectively, 13.5 +/- 0.6, 15.3 +/- 0.7, 4.3 +/- 0.5 and 13.0 +/- 0.9 mm Hg, which were all significantly different from controls: 8.3 +/- 0.3 mm Hg. Portosystemic shunt indices were also significantly different from each other: controls, 0.4% +/- 0.02%; mesenteric-stenosed, 5.9% +/- 2.3%; and portal-stenosed, 52.1% +/- 4.9%. Cardiac output and splanchnic visceral blood flows were significantly increased in the portal-stenosed rats and the two groups with portacaval anastomoses, with the latter two groups having the highest values. The addition of mesenteric stenosis did not change the blood flows because mesenteric-stenosed rats did not differ from controls and end-to-side portacaval anastomosis with mesenteric vein stenosis rats did not differ from rats with portacaval anastomosis alone. These results suggest that mesenteric venous hypertension per se does not affect hemodynamics but that diversion of portal venous blood from the liver is a critical factor in the development of hyperkinetic circulation in portal hypertension.

Abdomen

N-acetylation polymorphism and diabetes mellitus among Saudi Arabians.

The acetylator phenotypes of 200 Saudi diabetics and an equal number of control subjects of the same origin were determined by measuring the peak height ratio of two urinary caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX), using a simplified high-performance liquid chromatographic method. Urine samples were collected from the diabetics and the control subjects who regularly drink coffee, tea, or caffeinated beverages as part of their normal daily diet. The patients were classified as either type 1 (insulin-dependent) (28 patients) or type 2 (insulin-independent) diabetics (172 patients) according to standard criteria. The reproducibility of acetylator phenotype was established by examining the peak height ratio of AFMU/1MX in 18 diabetics and 6 control subjects on different days. Significant differences in the proportion of rapid acetylators were observed between type 1 (53.6%) and type 2 (33.7%) diabetics (P < or = .0436), and between the control group (26%) and the overall diabetics (36.5%) (P < or = .024) or those with type 1 disease (P < or = .0028). Also, there was a significant (P < or = .0436) association between rapid acetylator status and type 1 diabetes mellitus.

Acetylation

Portal hypertension and bleeding esophageal varices.

Bleeding from esophageal varices exacts a high mortality and extraordinary societal costs. Prophylaxis--medication, sclerotherapy, or shunt surgery to prevent an initial bleeding episode--is ineffective. In patients who have bled from varices, endoscopic injection sclerotherapy can control acute bleeding in more than 90% of patients. Because recurrent bleeding frequently occurs and survival without definitive therapy is dismal, selection of a permanently effective treatment is mandatory once variceal bleeding has been controlled. Long-term injection sclerotherapy can be performed in compliant patients; it is relatively safe but is associated with a 30-50% rebleeding rate. Beta-blockers significantly reduce portal pressure and recurrent bleeding but have not been shown to diminish mortality from BEV. Portal decompressive surgery permanently halts bleeding in more than 90% of patients; the risk of operative mortality is high in decompensated cirrhotics, and long-term complications of encephalopathy and accelerated liver failure may limit indications for shunt surgery to good-risk cirrhotics who are not liver transplant candidates. Devascularization procedures have a low operative mortality and encephalopathy rate but unacceptably high rates of recurrent bleeding. Liver transplantation is curative therapy for bleeding esophageal varices and the associated underlying hepatic dysfunction; cost and availability of donor organs generally limit its use in this setting to variceal bleeders with end-stage liver disease not associated with active alcoholism.

Esophageal and Gastric Varices

Neurologic consequences of cerebrovascular injury.

Because of ongoing controversy, the issue of vascular repair or ligation for patients with cerebrovascular injuries and preoperative central neurologic deficits is frequently debated. A total of 133 patients with penetrating cerebrovascular injuries were analyzed. The frequency of preoperative neurologic deficit was 20% (27 patients). The common carotid and internal carotid arteries were the most frequently injured structures, with a 29% and 15% incidence of preoperative neurologic deficits, respectively. The results of carotid repair in all patients whose preoperative deficit was limited to weakness or paralysis were favorable (seven patients normal or improved, two patients unchanged). The results of repair in patients whose preoperative deficit was characterized by obtundation were variable (four patients improved, four patients worsened or died). The results of carotid ligation were also variable (one improved, one unchanged, three worsened or died). Limited numbers of patients with preoperative neurologic deficits and the retrospective nature of this review prohibit definite conclusions. Therefore a multicenter, prospective, randomized trial of ligation or vascular repair for comatose patients with cerebrovascular injuries is proposed.

Carotid Artery Injuries

Comparison of thyroglobulin and radioiodine scintigraphy during follow-up of patients with differentiated thyroid carcinoma.

OBJECTIVES: To compare serum thyroglobulin concentration and radioiodine scintigraphy during follow-up after thyroidectomy and radioiodine ablation for differentiated, non-medullary thyroid carcinoma. METHODS: One hundred fifty-eight patients received radiation ablation after thyroidectomy every 3-4 months until no pathological radioiodine uptake was seen on the scintigraphy. Simultaneously performed postablation scintigraphy and serum thyroglobulin measurement were related to clinical characteristics and mutually compared using kappa statistics (observed agreement not accounted for by chance divided by possible agreement not accounted for by chance). RESULTS: After three ablation doses, serum thyroglobulin concentration had fallen to below detection limit (5 micrograms/L) in 71% of the patients and 70% of the patients had achieved negative scintigraphy after a median radioiodine dose of 3700 MBq I-131 and a median follow-up time of 5 months. The observed agreement between serum thyroglobulin and scintigraphy after the third ablation dose was 62%. The chance agreement was 50% giving a kappa value of only 24%. The size of the thyroid cancer at admission was larger in patients with a positive scintigraphy after first ablation compared with patients with a negative scintigraphy (p = 0.005) and was correlated to thyroglobulin concentration (p = 0.05). Among patients with thyroglobulin level > 5 micrograms/L after thyroidectomy and first ablation dose, there were more patients who at admission had palpable lymph nodes in the neck (p = 0.06) and microscopically verified neck metastasis (p = 0.03) compared with the group with thyroglobulin < 5 micrograms/L. These differences were not seen when comparing patients with positive and negative scintigraphies. CONCLUSION: The low agreement between the two markers for thyroid cancer emphasizes the value of complementary use of thyroglobulin and scintigraphy in the follow-up of thyroid cancer patients. Patients with large tumours and neck metastasis probably need higher radioiodine doses for complete ablation.

Adenocarcinoma, Follicular

Prospective comparison of partial versus total portal decompression for bleeding esophageal varices.

Eighty-six patients underwent portacaval shunt (PCS) to treat bleeding esophagogastric varices during a period of four years. Twenty-eight patients (group 1) underwent emergency total portal decompression, while 58 patients (group 2) underwent elective partial PCS. Age, gender, preshunt and postshunt alcohol consumption and modified Child-Pugh classification at the time of operation, and at latest follow-up evaluation, did not differ significantly between the two groups. Early mortality was higher after emergency shunts than after elective operation (p < 0.01). However, partial portal decompression, when compared with total shunt, resulted in a significantly lower likelihood of late mortality (13 versus 39 percent) (p < 0.05), as well as portasystemic encephalopathy (8 versus 56 percent) (p < 0.0005). All shunts remained patent postoperatively and no patient had variceal rebleeding during follow-up evaluation averaging 2.2 years. Duplex sonography demonstrated hepatofugal portal flow in all patients in both groups. The results of the current study suggest that partial portal decompression is technically feasible, prevents further variceal hemorrhage and confers significant protection against late mortality and the development of postshunt neuropsychologic dysfunction.

Adult